Classification of patients at risk of IE: AHA guideline (1997) [47].
\r\n\t"
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He completed his thesis in electromechanics in September 1991 and received his third cycle degree. Dr. Lamchich received his Ph.D. from the same university in July 2001. His main activity is based on short-circuit mechanical effects in substation structures, control of different types of machine drives, static converters, active power filters. In the last decennia, his research interests have included renewable energies, particularly the control and supervision of hybrid and multiple source systems for decentralized energy production, and intelligent management of energy. He has published more than fifty technical papers in reviews and international conferences. With IntechOpen, he has published two chapters and was editor of the books “Torque Control” and “Harmonic Analysis”. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"43925",title:"History of Antimicrobial Prophylaxis Protocols for Infective Endocarditis Secondary to Dental Procedures",doi:"10.5772/56118",slug:"history-of-antimicrobial-prophylaxis-protocols-for-infective-endocarditis-secondary-to-dental-proced",body:'For several decades, the haematogenous spread of bacteria from the oral cavity has been considered a decisive factor in the pathogenesis of 10% to 15% of episodes of infective endocarditis (IE), suggesting that certain dental procedures may represent a significant risk factor [1]. Nowadays, however, this statement has its detractors; their main argument is that not all patients with heart valves infected by bacteria that typically colonize ecological niches of the oral cavity have undergone dental procedures. Furthermore, there is little evidence to date on the genetic similarity between bacteria isolated from the heart valves, from the bloodstream, and from the oral cavity of patients with IE [2,3].
Apart from its possible involvement in the development of episodes of IE, bacteraemia of oral origin has become of particular interest in the past 2 decades because it has been associated with the progression of atherosclerosis and may thus be related to ischemic processes, although the mechanism of action has not yet been fully elucidated [4-6]. A number of published clinical studies have demonstrated an association between periodontal disease and cardiovascular disease [7-9], and oral bacteria have been detected on heart valves and in atherosclerotic plaques and aortic aneurysms [10-12].
In 1935, Okell and Elliot [13] were the first authors to detect bacteraemia caused by Streptococcus species (in 64% of cases) after performing dental extractions on 138 patients. A year later, Burket and Burn [14] inoculated pigmented Serratia marcescens into the gingival sulcus of 90 patients before performing dental extractions and they subsequently isolated this bacterium in 20% of post-manipulation blood cultures. Those results confirmed that microorganisms from the oral cavity could enter the bloodstream after dental extraction. Between the mid 1930s and the early 1950s, numerous studies were published on the prevalence of post-dental extraction bacteraemia, with figures that varied between 2% and 83% [15-19]. In the early 1930s there was a growing awareness of the need for IE prophylaxis in patients with valvular heart disease undergoing certain dental manipulations, and the first guidelines recommending the use of certain sulfonamides to prevent IE of oral origin were published at the end of that decade. This chapter first provides a review of development of antimicrobial prophylaxis protocols for IE secondary to dental procedures between 1930 and 1955. Since the American Heart Association (AHA) published its first guideline for the prevention of IE secondary to dental procedures in 1955, several international committees formed mainly of cardiologists, infectious diseases specialists and pharmacologists have drawn up different prophylactic regimens based on findings published in the scientific literature. In the second part of this chapter we therefore review the changes in IE prophylaxis in the guidelines published by the AHA and the British Society of Antimicrobial Chemotherapy (BSAC) between 1960 and 2009, as well as those recently drawn up by other societies. Those guidelines provide a description of the susceptible patient, the at-risk dental procedures, the influence of the anaesthetic technique applied in dental treatment, the antibiotic prophylaxis protocols (antibiotics of choice, dose and route of administration) and the use of antiseptic prophylaxis.
In the early 1930s, Brown and Abrahamson [20,21] were 2 of the pioneers of the application of IE prophylaxis before performing certain dental manipulations in patients with valvular heart disease. Those investigators recommended the prophylactic use of autogenous vaccines. In 1938, Feldman and Trace [22] suggested cleaning and scraping the teeth before any manipulation in order to reduce contamination of the operative field; they performed only 1 or 2 dental extractions per session, and followed this by curettage and irrigation of the periodontal pockets with antiseptics. A year later, Elliott [23] proposed perialveolar cauterization of the gingiva as a prophylactic measure after dental extraction; this technique not only sterilized the sulcus but also sealed the gingival capillaries, preventing the entry of microorganisms into the bloodstream. The practice of dental extractions under local anaesthesia with epinephrine by the infiltration technique was also recommended, as some authors had shown that this type of anaesthetic applied in this way created a barrier, preventing vascular invasion by the bacterial inoculum [14,22]. Fish and Maclean [24] recommended that teeth be filled with cotton soaked in a paste of zinc oxide and oil of cloves and that this should be renewed every few days; those authors also recommended the administration of a dose of prontosil (azosulfamide) before a dental extraction, in addition to cauterization of the gingiva. However, Bender and Pressman [17] soon declared themselves contrary to the use of cauterization to prevent post-dental extraction bacteraemia, arguing that the teeth extracted in all the published series in which this technique was used were single rooted and a maximum of only 2 teeth were extracted in each session. According to those authors, cauterization of multirooted teeth damaged the adjacent periodontal tissues [17].
The first guideline for antibiotic prophylaxis for IE associated with dental manipulations in patients with valvular heart disease were soon developed and were based on the use of certain sulfonamides [25,26]. In 1939, Long and Bliss [27] published a book titled The Clinical and Experimental Use of Sulfanilamide, Sulfapyridine and Allied Compounds, in which they recommended the prophylactic administration of sulfanilamide to patients with rheumatic heart disease before performing dental extractions. In 1941, Kolmer and Tuft [28] drew up the most complete prophylactic guidelines published up to that time; those authors did not favour “massive dental extractions” and recommended not extracting more than 2 teeth in a single session; they also recommended the use of an autogenous streptococcal vaccine obtained from culture of the apical area of the first tooth extracted, which was to be administered before extraction of the following tooth. On the matter of antibiotic prophylaxis, those investigators proposed a regimen based on the use of 15 grains of sulfapyridine every 6 hours, starting 2 days before the manipulation and continuing for 2 or 3 days afterwards; they also endorsed the protocol for the prolonged administration of sulfonamides −previously proposed by Thomas et al [25]−for patients with acute rheumatic fever; that protocol consisted of the administration of 10 grains of sulfanilamide twice a day for a period that ran from November to June [28]. In 1941, Spink [29] indicated that sulfanilamide had to be administered between 8 and 12 hours before the dental manipulation in order to achieve a serum concentration of 7 mg/100 ml at the time of the manipulation. A year later, Budnitz et al [30] proposed a prophylactic protocol that consisted of an initial dose of 1 g of sulfapyridine followed by 0.5 g every 4 hours for 6 to 7 days, performing the dental extraction on the third or fourth day.
In 1943, Northrop and Crowley [31] were the first authors to evaluate the effect of the antibiotic sulfathiazole on the prevalence of post-dental extraction bacteraemia; their study group was formed of 73 patients who received 1 g of sulfathiazole every 4 hours, starting at 4 pm the day before the dental treatment and finishing at 12 noon the day of the procedure, 1 to 2 hours before the dental extraction. Blood samples were collected to perform the corresponding cultures at baseline and at 10 seconds and 10 minutes after the manipulation. All the baseline blood cultures and all those collected at 10 minutes after the dental extraction were negative, both in the controls and in individuals receiving antibiotic prophylaxis; however, at 10 seconds after the dental extraction, 13% of controls presented detectable bacteraemia compared to 4% of those who received antibiotic therapy (with blood levels of sulfathiazole of at least 3 mg/100 ml). These authors therefore concluded that a serum concentration of sulfathiazole of 4-5 mg/100 ml was effective for the prevention of post-dental extraction bacteraemia [31]. A year later, in the Journal of Oral Surgery, the same authors published another study based on the administration of a single dose of 5 g of sulfathiazole 3 hours before the dental manipulation, observing a reduction in the percentage of post-dental extraction bacteraemia from 16% to 4% [32]. Hopkins [16] and Budnitz et al [30], in their respective studies of patients at risk of IE, administered sulfanilamide or sulfapyridine before dental extraction; in both series all the post-dental extraction blood cultures were negative. In 1945, Bender and Pressman [17], in a study of the prevalence of post-dental extraction bacteraemia, created 3 randomly assigned study groups: a control group, a sulfanilamide group (this group was administered 4 doses of 1.35 g of the drug the previous day and 2 g 4 hours before the manipulation) and a cauterisation group (cauterisation of the free gingival border and of the full depth of the pocket was performed after the dental extraction). The mean serum levels of sulfanilamide were 7.5 mg/100 ml. In contrast to the results reported previously by other authors [16], the administration of sulfanilamide in this study did not reduce the prevalence of immediate post-dental extraction bacteraemia (83% in the control group versus 77% in the sulfanilamide group), although there was a detectable reduction in the number of positive blood cultures at 10 minutes after completion of the manipulation (33% in the control group versus 13% in the sulfanilamide group) and in the number of bacterial species isolated. Those authors indicated that the good results reported previously in the literature could be attributable to the absence of para-aminobenzoic acid (necessary to neutralise the sulfonamides) from the culture media used in some studies and based their findings mainly on the bacteriostatic action of this group of antibiotics [17].
In 1948, Hirsh et al [33] were the first authors to investigate the effect of penicillin on the prevalence of post-dental extraction bacteraemia. The study population was composed of a control group of 65 patients and a study group of 65 patients who received 600,000 IU of penicillin intramuscularly 3 to 4 hours before the dental extraction. Blood samples were collected immediately after the completion of surgery and at 10 and 30 minutes. Although the overall percentage of bacteraemia did not decline significantly (46% in controls versus 37% in the group that received penicillin), evaluation of only those cultures that were positive for streptococcal species showed a significant reduction in the prevalence of positive cultures in the group receiving prophylaxis compared to the control group (15% versus 34%), confirming that penicillin was effective in reducing the prevalence of streptococcal bacteraemia, although not bacteraemia caused by other microorganisms. Those authors speculated about 2 possible mechanisms of action of penicillin in the prevention of bacteraemia secondary to dental extractions: the first was that the penicillin present in the blood destroyed the microorganisms that reached the bloodstream, and the second that the antibiotic could inhibit bacterial growth in the oral cavity, thus reducing the size of the inoculum before vascular invasion occurred [33]. In another study on the efficacy of penicillin in the prevention of post-dental extraction bacteraemia published the same year, Glaser et al [34] administered 50,000 IU of penicillin intramuscularly every 2 hours for 24 hours prior to dental extraction, administering the final injection approximately 20 minutes before the manipulation. They then determined the sensitivity to penicillin of the microorganisms isolated from the blood cultures of patients who received the antibiotic therapy. In that study, prophylaxis with penicillin significantly reduced the prevalence of post-dental extraction bacteraemia (by 25%), as well as the number of bacteria isolated: there was a predominance of α-haemolytic streptococci in the control group (81% versus 29% in the group that received penicillin) and the majority of streptococci isolated in the penicillin group were non-haemolytic. However, none of the microorganisms isolated in the subjects who received prophylaxis were resistant to penicillin, confirming that this was not the cause of onset of the bacteraemia. Two very interesting findings of that study were that prophylaxis with penicillin was more effective in patients with periodontal disease and in those in whom only a single dental extraction was performed. Finally, those authors described a third mechanism of action of penicillin in the prevention of IE, the inhibition of bacterial growth after implantation of the microorganisms on the endocardium and before the resulting disease became clinically detectable [34]. Rhoads and Schram [35] evaluated the efficacy of penicillin and a new sulfonamide, 3,4-dimethyl-5-sulfanilamidoisoxazole (Gantrosan), for the prevention of post-dental extraction bacteraemia. Based on their optimal results, those authors were emphatic in their indication of the need to administer antibiotic therapy prior to performing dental extractions in patients with valvular heart disease [35].
The book on oral surgery published by Thoma in 1948 [36] was the first to include antibiotic prophylaxis prior to oral surgical procedures in patients with heart disease, although no specific regimen was described. In the first edition of Archer’s classic book on oral surgery published in 1952 [37], a complex prophylactic regimen was described based on the administration of an injection of procaine penicillin G the day before oral surgery and an injection of crystalline penicillin G 30 minutes before the procedure, followed by an injection of procaine penicillin G once a day for 3 days and an injection of bicillin together with the final injection of procaine penicillin G. A very similar antibiotic prophylaxis regimen appeared in another book on oral surgery published by Mead in 1954 [38], but the penicillin was limited to 3 doses: one the day before, one 20 to 30 minutes before the manipulation and the final one the day after the intervention.
In 1955, the Committee on Prevention of Rheumatic Fever and IE of the AHA, which at that time was formed exclusively by 7 physicians, developed the first prophylactic protocol for use in patients with IE undergoing dental procedures [39]. This protocol was recommended in patients with congenital or rheumatic heart disease who were undergoing dental extractions or other manipulations that affected the gingival tissues. The AHA experts stated that the aim of prophylaxis was to make high concentrations of the antibiotic available at the time of the manipulation and to maintain the presence of the drug in the bloodstream for several days in order to eliminate any bacteria that had adhered to the heart valves during the bacteraemic episode. The method chosen was an intramuscular injection of a dose of 600,000 IU of aqueous penicillin and 600,000 IU of procaine penicillin dissolved in oil with 2% aluminium monostearate administered 30 minutes before the dental procedure. Alternatively (although less desirable), they proposed the oral administration of 250,000-500,000 IU of penicillin 30 minutes before each meal and before bedtime, starting 24 hours before the dental treatment and continuing for 5 days afterwards, and with an extra dose of 250,000 IU of penicillin immediately prior to the manipulation. For patients with a history of allergy to penicillin, the AHA recommended the use of other antibiotics such as oxytetracycline, chlortetracycline or erythromycin for 5 days, with administration starting the day before dental treatment [39].
Since the AHA published its first protocol for the prevention of IE associated with dental procedures, numerous expert committees in different countries have drawn up different prophylactic regimens, many of which have subsequently been revised and modified based on subsequent epidemiological and clinical studies (prevalence of bacteraemia secondary to dental procedures, studies of the efficacy of antibiotic and antiseptic prophylaxis, pharmacokinetics of antibiotic prophylaxis, antimicrobial sensitivity of isolates identified in post-dental manipulation blood cultures) and on animal experimentation [40].
The AHA has published 9 IE prophylaxis protocols, the latest revision being in 2007 [39,41-48]. The BSAC published its first antibiotic prophylaxis regimen for IE in 1982; this was revised and modified in 1986, 1990, 1992 and 2006 [49-53]. The European Society of Cardiology (ESC), together with the group of experts of the International Society of Chemotherapy published a European Consensus on IE prophylaxis in 1995 [54]. In 2004, the ESC and the British Cardiac Society (BCS), in association with the Royal College of Physicians (RCP) of London, drew up guidelines for the prevention of IE associated with dental procedures [55,56]. In 2008, the National Institute for Clinical Excellence (NICE) of the United Kingdom published clinical guidelines entitled “Prophylaxis against IE: antimicrobial prophylaxis against IE in adults and children undergoing interventional procedures” [57]. In that document, the NICE reviewed 4 clinical guidelines on the prevention of IE, including those published by the BSAC in 2006 and the AHA in 2007. The NICE also reviewed the available evidence on the principal issues of IE of oral origin and reported their conclusions. In 2009, the Task Force of the ESC published a new guideline on the prevention, diagnosis and treatment of IE [58].
In its 2 protocols published in the 1960s on the prevention of IE associated with dental procedures, the AHA defined subjects considered to be at risk of IE as those with rheumatic heart disease or congenital heart disease [41,42]. In the early seventies, the AHA emphasised that IE represented one of the most serious cardiac complications as it was associated with a high morbidity and mortality, though it recognised that it was impossible to predict which patients with cardiac abnormalities were susceptible to developing IE after interventions (including those performed in the dental setting) [43]. However, they added patients with a past history of IE, including those with no detectable cardiac abnormalities, to the list of patients considered to be at risk of IE. For the first time, the AHA indicated that patients who were candidates for cardiac surgery should undergo an exhaustive dental examination in order to perform all necessary treatments in the weeks prior to the operation, with the aim of reducing the risk of postoperative IE. After cardiac surgery, patients would remain indefinitely in the category labelled at risk of IE (particularly those with prosthetic valves) and would therefore be candidates for antibiotic prophylaxis. In the opinion of the AHA, patients with atrial septal secundum defects repaired surgically by direct suturing, without the need for a prosthetic patch, and patients who had undergone surgical repair of a patent ductus arteriosus were not at risk of IE; in the AHA’s opinion, those patients would only need to receive antibiotic prophylaxis for dental treatment performed during the first 6 months after cardiac surgery [43].
Five years later, in its new guideline, the AHA pointed out that, despite advances in antimicrobial chemotherapy and cardiovascular surgery, IE continued to be associated with a significant morbidity and mortality [44]. For the first time, this Association listed those cardiac alterations considered to carry a risk of IE and in which the administration of antibiotic prophylaxis was indicated; the list included congenital heart disease, acquired valve disease (rheumatic fever), idiopathic hypertrophic subaortic stenosis, mitral valve prolapse with insufficiency and prosthetic valves, but not the presence of a secundum atrial septal defect. The AHA stated that mitral valve prolapse was associated with a relatively low incidence of IE and that the use of prophylaxis in these patients was therefore controversial. Antibiotic prophylaxis was not recommended for patients after coronary artery surgery, the insertion of pacemakers, those on renal dialysis with arteriovenous fistulae or hydrocephalic patients with ventriculoatrial shunts, although the it was added that “It will be the physician or dentist who takes the final decision about whether the patient requires the administration of antibiotic prophylaxis” [44].
In the first BSAC guideline on the prevention of IE secondary to dental procedures, patients considered to be at risk of IE included those with alterations of the endocardium due to congenital or acquired disease, those with valvular heart disease and those with prosthetic heart valves [49]. In 1984, the AHA stated that certain patients, such as those with prosthetic heart valves or surgically constructed systemic-pulmonary shunts, presented a higher risk of IE than patients with other heart conditions. This was the first guideline to include a discussion of the action to be taken in patients who were anticoagulated with heparin or dicoumarin derivatives, stating that the antibiotic prophylaxis should be administered intravenously or orally, and that intramuscular injections should be avoided because of the risk of causing haematomas [45].
In 1990, the AHA listed the heart conditions that did and did not require antibiotic prophylaxis [46]. On the subject of heart transplant patients, the AHA briefly commented that some experts considered these patients to be at risk of IE. In the case of patients with severe renal dysfunction, it was suggested that the second dose of antibiotic (gentamycin or vancomycin) proposed in some regimens should be omitted or modified [46]. Concerning the controversy over valve prolapse, in 1990, the BSAC gave its first opinion in favour of prophylaxis in mitral valve prolapse if the prolapse was associated with a systolic murmur [51].
The intense debate about IE prophylaxis that developed during the European Symposium held in Lyon in 1994 led an international group of experts to draw up a consensus protocol jointly with the Working Group on Valvular Heart Disease of the ESC [54]. The guideline was published in 1995 and it listed the heart conditions that required prophylaxis, establishing for the first time the conditions or diseases that were considered to carry a high risk of IE, such as prosthetic heart valves, cyanotic congenital heart disease and previous episodes of IE. The controversy concerning the administration of antibiotic prophylaxis in cases of mitral stenosis without valve incompetence was also discussed [54].
In 1997, the AHA adopted a more conservative attitude, admitting that the incidence of IE secondary to medico-surgical interventions in patients with cardiac abnormalities was low [47]. It was suggested that the indication for antibiotic prophylaxis should be conditioned by a number of factors such as the degree of risk of IE associated with the patient’s specific cardiac abnormality, the probability that the procedure performed might cause bacteraemia, possible adverse reactions to the recommended antibiotics and the cost-benefit relationship of the prophylactic regimens. One of the important novelties introduced by the AHA was the differentiation between cardiac diseases with distinct levels of risk of developing IE (as had previously been done by the ESC in the European Consensus of 1995), and consideration of the associated morbidity and mortality (Table 1) [47].
\n\t\t\t\tPROPHYLAXIS RECOMMENDED\n\t\t\t | \n\t\t\t\n\t\t\t\tPROPHYLAXIS NOT RECOMMENDED\n\t\t\t | \n\t\t
HIGH RISK OF IE -Valve prostheses -Previous episodes of IE -Cyanotic congenital heart diseasea\n\t\t\t\t -Surgically constructed systemic-pulmonary shunts or conduits MODERATE RISK OF IE -Structural heart defectsb\n\t\t\t\t -Acquired valve disease (e.g. due to rheumatic disease) -Hypertrophic obstructive cardiomyopathy -Mitral valve prolapse with regurgitation and/or thickened leaflets | \n\t\t\tLOW RISK OF IE -Isolated secundum atrial septal defect -Surgically repaired structural heart defects (after 6 months)c \n\t\t\t\t -Previous coronary artery bypass graft surgery -Physiological, functional or innocent heart murmursd\n\t\t\t\t -History of Kawasaki’s disease without valve dysfunction -History of rheumatic fever without valve dysfunction -Cardiac pacemakers or defibrillators | \n\t\t
Classification of patients at risk of IE: AHA guideline (1997) [47].
a- Including isolated ventricular defects, transposition of the great vessels and tetralogy of Fallot; b- Including ventricular septal defect, bicuspid aortic valve, primum atrial septal defects, patent ductus arteriosus and coarctation of the aorta; c- Including atrial and ventricular septal defects and patent ductus arteriosus; d- If the precise nature of the murmur is not known, specialist opinion should be sought.
The AHA also defined the profile of the patient with mitral valve prolapse in whom prophylaxis should be given as male, over 45 years of age, with mitral valve thickening and/or regurgitation. If the patient required emergency dental treatment and it was not known whether or not regurgitation secondary to the prolapse was present, the AHA recommended antibiotic prophylaxis. The AHA also stated that, whilst auscultation enabled innocent cardiac murmurs to be defined clearly in paediatric patients, their diagnosis in adults required complementary studies, such as echocardiography. Finally, the AHA reiterated that many professionals classified heart transplant recipients as having a moderate risk of IE indefinitely, as they were patients with a particular tendency to develop valve dysfunction (particularly during episodes of rejection) and because they were usually on immunosuppressants; these patients should therefore receive antibiotic prophylaxis [47].
In the guideline proposed by the ESC in 2004 [55], the classification of at-risk patients was similar to that published previously by the AHA in 1997 [47]. For the ESC, the classification represented a class I recommendation (when there is evidence and/or general agreement that a certain treatment or diagnostic approach is beneficial, useful or effective) with level C evidence (when there is expert consensus based on clinical trials or investigations). For the first time, the ESC added a number of so-called non-cardiac conditions in which antibiotic prophylaxis should be given: conditions that favour the development of nonbacterial thrombotic vegetations, those which compromise immune function and/or local non-immune defence mechanisms in the host and advanced age [55].
In 2004, the BSC and RCP indicated that the risk of developing IE varied according to the underlying cardiac abnormality and that, in the case of congenital heart disease, it depended on the haemodynamic repercussions of the condition and whether surgical treatment was palliative or curative [56]. To reflect these differences in susceptibility to IE, the experts established 3 risk groups (Table 2). The principal differences to be found on comparison with the classifications of at-risk patients published previously by the AHA [47] and ESC [55] were that mitral valve prolapse with regurgitation and/or thickening of the leaflets was incorporated into the high-risk group and that prophylaxis was recommended up to 12 months after atrial septal defect/patent foramen ovale (ASD/PFO) catheter-based closure procedures and only for the first 6 months after heart and/or lung transplant [56]. The BSC and RCP also recommended that all patients at risk of IE should have a card with the following information: type of cardiac lesion, degree of risk of developing IE, history of penicillin allergy, the prophylactic regimen that should be administered, and name and telephone number of the cardiologist [56].
\n\t\t\t\tPROPHYLAXIS RECOMMENDED\n\t\t\t | \n\t\t\t\n\t\t\t\tPROPHYLAXIS NOT RECOMMENDED\n\t\t\t | \n\t\t
HIGH RISK OF IE -Prosthetic heart valves -Previous episodes of IE -Cyanotic congenital heart disease -Transposition of the great vessels -Tetralogy of Fallot -Gerbode’s defect -Surgically constructed systemic-pulmonary shunts or conduits -Mitral valve prolapse with clinical repercussiona\n\t\t\t\t MODERATE RISK OF IE -Acquired valve disease (e.g. due to rheumatic heart disease) -Aortic stenosis -Aortic regurgitation -Mitral regurgitation -Structural heart defectsb\n\t\t\t\t -Hypertrophic obstructive cardiomyopathy -Subaortic membrane | \n\t\t\tLOW RISK OF IE -Pulmonary stenosis -Surgically repaired structural heart defectsc \n\t\t\t\t -Post Fontan or Mustard procedure with no residual murmur or defect -Isolated secundum atrial septal defectd\n\t\t\t\t -Previous coronary artery bypass surgery -Mitral valve prolapse without regurgitation -Innocent heart murmurse\n\t\t\t\t -Cardiac pacemakers or defibrillatorsf\n\t\t\t\t -Coronary artery stent implantation -Heart and/or lung transplantg\n\t\t\t | \n\t\t
Classification of patients at risk of IE: BCS and RCP (London) guideline (2004) [56].
a- Presence of mitral valve regurgitation and/or thickening of the valves; b- Including ventricular septal defects, bicuspid aortic valve, primum atrial septal defects, patent ductus arteriosus, aortic root replacement, coarctation of the aorta, atrial septal aneurysm and patent foramen ovale; c- Including atrial septal defect, ventricular septal defect and patent ductus arteriosus; d- Antibiotic prophylaxis recommended up to 12 months after catheter closure of ASD/PFO; e- If the precise nature of the murmur is not known, the opinion of a cardiologist should be sought; in emergency situations, even if the possible repercussion of the murmur is not known, prophylaxis may be administered for certain dental procedures; f- With the exception of patients considered to have a moderate or high risk of IE, in whom antibiotic prophylaxis is recommended; g- Antibiotic prophylaxis is recommended for the first 6 months after surgery.
In recent years, the updated guidelines published by the BSAC [53], the AHA [48], the NICE [57] and the ESC [58] have limited prophylaxis to high-risk patients, but the cardiac conditions included by each Expert Committee differ (Table 3). For example, according to the latest AHA guideline, IE prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from IE. The conditions included in the list were prosthetic heart valves, previous IE, congenital heart disease (unrepaired defect, repaired defect with residual alterations and the first 6 months after complete repair of a defect) and heart transplant recipients who develop valve disease [48]. Although the AHA guideline recommended prophylaxis in heart transplant recipients who developed valve disease, the ESC stated that such a recommendation was not supported by strong evidence. In addition, although the risk of an adverse outcome was high when IE occurred in transplant patients, the probability of IE of oral origin was extremely low in these patients. Consequently, the ESC did not recommend prophylaxis in such situations [58]. The ESC recommended prophylaxis for cardiac conditions associated with the highest risk of IE (the list is similar to the one proposed by the AHA, except for heart transplant) based on a Class IIa recommendation (weight of evidence/opinion is in favour of usefulness/efficacy) and Level C evidence (consensus of opinion of the experts and/or small studies, retrospective studies, registries)[58]. The NICE also included other cardiac conditions at risk of IE, such as acquired valve disease with stenosis or regurgitation and hypertrophic cardiomyopathy [57].
In our opinion, this lack of consensus could provoke conflicting situations for clinicians at the time of identifying high-risk patients requiring antibiotic prophylaxis, and this could have medico-legal repercussions. However, if a clinician takes into account all the high-risk cardiac conditions defined each of the Expert Committees, there would be no omissions from the group of at-risk patients requiring antibiotic prophylaxis compared with previous IE prophylaxis protocols [59].
\n\t\t\t\tPROPHYLAXIS RECOMMENDED\n\t\t\t | \n\t\t|||
\n\t\t\t\tBSAC, 2006\n\t\t\t | \n\t\t\t\n\t\t\t\tAHA, 2007/ESC, 2009\n\t\t\t | \n\t\t||
-Previous episodes of IE -Prosthetic heart valve -Surgically constructed systemic or pulmonary shunt or conduit | \n\t\t\t-Previous episodes of IE -Prosthetic heart valve -Congenital heart disease (CHD)a\n\t\t\t | \n\t\t||
\n\t\t\t | Unrepaired cyanotic CHD, including palliative shunts and conduits First 6 months after complete repair of a congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter interventionb\n\t\t\t\t Repaired congenital heart defect with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibits endothelialisation) | \n\t\t||
-Heart transplant recipients who develop valve diseasec\n\t\t\t | \n\t\t|||
NICE, 2008 | \n\t\t|||
-Previous episodes of IE -Prosthetic heart valve -Acquired valve disease with stenosis or regurgitation -Structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialised -Hypertrophic cardiomyopathy | \n\t\t
High-risk cardiac conditions requiring antibiotic prophylaxis for IE: guidelines of the BSAC (2006), the AHA (2007), the NICE of the United Kingdom (2008) and the ESC (2009) [48,53,57,58].
a- Except for the conditions listed above, antibiotic prophylaxis is no longer recommended for any other form of CHD; b- Prophylaxis is recommended because endothelialisation of prosthetic material can take up to 6 months after the procedure; c- Although the AHA guideline recommend prophylaxis in heart transplant recipients who develop valve disease, the ESC Task Force does not recommend prophylaxis in such situations.
In 1960, the AHA stated that the dental procedures in which prophylaxis was indicated were dental extractions and gingival treatments, specifying that these procedures frequently caused transient bacteraemia and that the bacteraemia was more intense in patients with oral infections. They also admitted that certain normal activities such as toothbrushing and chewing gave rise to bacteraemia, although of lower intensity [41].
In 1972, a dentist, Dean Millard, was incorporated for the first time onto the AHA panel of experts; this led to recognition of the importance of a good oral health status in minimising the risk of developing IE of oral aetiology. The administration of antibiotic prophylaxis was recommended before performing any dental procedure associated with the potential for causing bacteraemia, the intensity of which depended on the magnitude of the procedure, the degree of the trauma to the gingival tissues and the presence of infection. Prophylaxis was therefore recommended for any dental procedure that caused gingival bleeding [43]. Five years later, the AHA recognised the impossibility of predicting which dental procedures could be responsible for causing IE. Antibiotic prophylaxis was recommended for treatments that can cause gingival bleeding, such as scaling, but not for procedures such as the adjustment of orthodontic appliances and the exfoliation of primary teeth [44].
In the first guideline for the prevention of IE published by the BSAC in 1982, antibiotic prophylaxis was recommended exclusively for dental extractions, scaling and root planing and periodontal surgery [49]. In 1986, the AHA confirmed that certain dental procedures such as dental extractions were associated with a higher frequency of significant bacteraemia than other treatments [50]. In 1990, the AHA reported that bacteraemia secondary to dental procedures did not persist for more than 15 minutes after completion of the procedure. However, their Committee reiterated the importance of maintaining an optimal oral health status in patients considered to be at risk of IE. On this matter, dentists were encouraged to minimise gingival inflammation. Curiously, the AHA also discussed the need to control the fit of dental prostheses in edentulous patients as there was a possibility of developing bacteraemia because of mucosal ulceration due to poorly fitting prostheses [46]. For its part, the BSAC, in 1992, pronounced for the first time against the use of intraligamental local anaesthesia in patients considered to be at risk of IE [52].
In 1995, the ESC declared that dental treatment constituted the principle risk factor for IE and that all procedures should therefore be performed under antibiotic prophylaxis, with the exception of superficial fillings and supragingival prosthetic preparations. However, the ESC recognised that although at-risk dental procedures led to a high prevalence of bacteraemia, this was not predictive of the risk of developing IE. In this context, the duration of the procedure could represent a possible conditioning factor [54].
In its guideline published in 1997, the AHA listed the dental procedures that required antibiotic prophylaxis and those in which this was not necessary (Table 4) [47].
\n\t\t\t\tPROPHYLAXIS RECOMMENDED\n\t\t\t | \n\t\t\t\n\t\t\t\tPROPHYLAXIS NOT RECOMMENDED\n\t\t\t | \n\t\t
-Dental extractions -Periodontal proceduresa \n\t\t\t\t -Placement of implants and reimplantation of avulsed teeth -Endodontal instrumentation or periapical surgery -Placement of subgingival antibiotic fibres or strips -Initial placement of orthodontic bands -Intraligamental anaesthetic injections -Cleaning of teeth or implantsb\n\t\t\t | \n\t\t\t-Restorative dentistry (operative and prosthodontic) with or without retraction cord -Non-intraligamental anaesthetic injections -Intracanal post placement and build-up -Placement of a rubber dam -Removal of sutures -Placement of removable prosthetic or orthodontic appliances -Intra-oral impressions -Fluoride treatments -Intra-oral radiographs -Orthodontic appliance adjustment -Exfoliation of primary teeth | \n\t\t
Dental procedures and antibiotic prophylaxis in patients with a high or moderate risk of IE: AHA guideline (1997) [47].
a- Including surgery, root planing and scaling, probing and maintenance; b- When bleeding is anticipated.
In general, as in previous protocols, antibiotic prophylaxis was recommended for dental procedures associated with gingival bleeding but it was not recommended for restorative dental procedures (with or without gingival retraction), the placement of a rubber dam or the removal of sutures. Although the possibility of developing bacteraemia secondary to traumatic ulcers caused by poorly fitting prostheses had previously been included, the AHA no longer recommended prophylaxis in edentulous patients during the fitting of complete prostheses [47].
In 2004, in agreement with previous guidelines [47,52,54], the ESC once again recommended antibiotic prophylaxis for “dental treatments that caused gingival or mucosal trauma” [55]. In contrast, the BCS and the RCP modified certain aspects concerning bacteraemia of oral origin [56]. First, they excluded the concept of "procedures that cause bleeding" as a criterion for the indication for antibiotic prophylaxis in patients at risk of IE; they also re-evaluated the definition of "significant bacteraemia" which, according to their new interpretation, was defined as "bacteraemia secondary to a dental procedure that was statistically significant with respect to the bacteraemia present under basal conditions (prior to any manipulation)". Considering these new provisions, the indication for prophylaxis included not only surgical procedures such as dental extractions or mucoperiosteal flaps but also other less traumatic procedures such as the placement of a rubber dam, matrices, wedges or retraction cords (Table 5) [56]. Although that Committee recognised the existence of bacteraemia secondary to activities considered to be physiological (such as toothbrushing), it also recognised the impossibility of administering prophylaxis for such practices due to the high risk of potentiating the development of bacterial resistance [56].
\n\t\t\t\tTYPE OF PROCEDURE\n\t\t\t | \n\t\t\t\n\t\t\t\tPROPHYLAXIS RECOMMENDED\n\t\t\t | \n\t\t\t\n\t\t\t\tPROPHYLAXIS NOT RECOMMENDED\n\t\t\t | \n\t\t
ORAL SURGERY | \n\t\t\t-Extraction of a single tooth -Extraction of multiple teeth -Mucoperiosteal flap for access to a tooth or lesion -Dental implants (as for mucoperiosteal flap) | \n\t\t\t-Incision and drainage of an abscess -Biopsy -Insertion of implants (transmucosal approach) -Exfoliation of primary teeth -Suture removal -Removal of surgical packs | \n\t\t
PERIODONTICS | \n\t\t\t-Periodontal surgery -Gingivectomy -Root curettagea -Root planing (similar to curettage) -Placement of antibiotics in the gingival sulcusb -Rubber cup polishing -Oral irrigation with water | \n\t\t\t-Air polishing | \n\t\t
ENDODONTICS | \n\t\t\t-Root canal instrumentation beyond the apex -Reimplantation of avulsed teethc\n\t\t\t | \n\t\t\t-Root canal instrumentation (within the root canal) -Pulpotomy of primary molars -Pulpotomy of permanent molarsd\n\t\t\t | \n\t\t
ORTHODONTICS | \n\t\t\t-Placement of interproximal separators -Exposure of unerupted teeth | \n\t\t\t-Band placement and cementation -Band removal -Adjustment of fixed appliances -Taking alginate impressions | \n\t\t
CONSERVATIVE DENTISTRY | \n\t\t\t-Placement of a rubber dam -Matrix band and wood wedge placement -Placement of a retraction cord | \n\t\t\t-Slow and fast drilling (without a rubber dam) | \n\t\t
PREVENTIVE DENTISTRY | \n\t\t\t\n\t\t\t | -Fossa and fissure sealing -Fluoride application | \n\t\t
ANAESTHETIC TECHNIQUES | \n\t\t\t-Local intraligamental | \n\t\t\t-Local infiltrative -Local nerve block -General with oral intubation -General with nasal intubation -General with laryngeal mask | \n\t\t
EXPLORATION TECHNIQUES | \n\t\t\t-Periodontal probing | \n\t\t\t-Dental examination with mirror and probe | \n\t\t
DIAGNOSTIC TECHNIQUES | \n\t\t\t-Sialography | \n\t\t\t-Intra-oral radiographs -Extra-oral radiographs | \n\t\t
Dental procedures and antibiotic prophylaxis in patients with a high or moderate risk of IE: BCS and RCP (London) guideline (2004) [56].
a- Both supra and subgingival, with manual instrumentation or ultrasound; b- Although there are no studies on this subject, this procedure is very similar to the placement of a retraction cord; c- Antibiotic prophylaxis may be administered up to 2 hours after dental reimplantation; d- Although there are no studies on this subject, this procedure is very similar to pulpotomy of primary molars.
In 2006, the BSAC summarized the indications for antibiotic prophylaxis for high-risk patients stating that it should be given for “all dental procedures involving dento-gingival manipulation or endodontics” [53]. According to the latest AHA and ESC guidelines, prophylaxis was recommended for all dental procedures that involved manipulation of gingival tissues or the periapical region of teeth or perforation of the oral mucosa. This included procedures such as biopsies, suture removal and placement of orthodontics bands, but it did not include routine anaesthetic injections through non-infected tissue, taking dental radiographs, placement of removable prosthodontic or orthodontic appliances, placement of orthodontic brackets, or adjustment of orthodontic appliances [48,58]. The dental procedures with the highest risk of IE and for which prophylaxis was recommended were associated with a Class IIa recommendation (weight of evidence/opinion is in favour of usefulness/efficacy) and Level C evidence (consensus of opinion of the experts and/or small studies, retrospective studies, registries) [58]. There are other events for which prophylaxis was not recommended, such as shedding of deciduous teeth and trauma to the lips or oral mucosa [48].
In the latest guidelines published by the BSAC, the AHA, the NICE of the United Kingdom, and the ESC, the emphasis for the cause of IE shifted from procedure-related bacteraemia to cumulative bacteraemia due to everyday oral activities [48,53,57,58]. The NICE considered that it was biologically implausible that a dental procedure would lead to a greater risk of IE than regular toothbrushing. On the other hand, even some expert committee guidelines concurred with the premise “Maintenance of optimal oral hygiene and periodontal health may reduce the incidence of bacteraemia of oral origin and, in the context of a dental procedure, is more important than prophylactic antibiotics to reduce the risk of IE” [48,58].
The NICE has adopted a drastic stance in this respect, issuing the statement that “antibiotic prophylaxis for IE is not recommended in individuals undergoing dental procedures” [58]. Recently, following the introduction in March 2008 of a clinical guideline from NICE recommending the cessation of antibiotic prophylaxis in the United Kingdom, Thornhill et al [60] quantified the change in the prescription of antibiotic prophylaxis to patients at risk of IE undergoing invasive dental procedures and looked for any concurrent change in the incidence of IE. Despite a 78.6% reduction in the prescription of antibiotic prophylaxis after the introduction of the NICE guideline, that study detected no large increase in the incidence of cases of IE or of IE-related deaths over the following 2 years. Those authors concluded that ongoing data monitoring was needed to confirm this observation supporting the NICE guideline and that further clinical trials should be performed to determine if antibiotic prophylaxis still has a role in protecting some patients at particularly high risk [60].
In 1960, the AHA recommended the administration of antibiotic prophylaxis for any surgical intervention (including those in the orofacial area) performed under general anaesthesia in patients considered to be at risk of IE [41]. However, in subsequent protocols published by the AHA, no specific observations were made with regard to the type of anaesthesia used [42-48].
The BSAC, on the other hand, specified for the first time in 1982 that when dental treatment was performed under general anaesthesia, special prophylactic protocols should be applied, also considering that "If patients due to undergo a general anaesthesia have prosthetic heart valves and/or are allergic to penicillin and/or have received prolonged treatment with penicillin and/or have had previous episodes of IE, their dental problems should be treated in a hospital environment" [49]. The BSAC has maintained that opinion in its protocols on IE prevention published in 1986, 1990 and 1992 [50-52]. In 1995, the ESC also included the anaesthetic technique among the factors to be taken into account when choosing the prophylactic regimen [54]. In the guideline published by the BCS and RCP in 2004, specific prophylaxis regimens were included for dental procedures performed under general anaesthesia [56].
In agreement with the AHA, the latest protocols of the BSAC and ESC on IE prevention recommend antibiotic prophylaxis irrespective of whether the dental procedure is performed under general or local anaesthesia [53,58].
In 1960, the AHA pronounced in favour of administering antibiotic prophylaxis from between 24 and 48 hours before the dental procedure, even in the absence of intraoral infections, in order to reduce the intensity of the post-manipulation bacteraemia [41]. However, in view of the problem of bacterial resistance, it was also suggested that prophylaxis could be administered immediately before the procedure. According to the AHA, the choice of one or other regimen depended on the professional, who should evaluate the probability of infection in order to decide when the prescription of antibiotics was indicated. In contrast to the guideline published in 1955 [39], the exclusively oral protocols were excluded in favour of intramuscular administration, although penicillin continued to be the antibiotic of choice; the prophylactic regimen consisted of several injections of penicillin from 2 days before up to 2 days after the session of dental treatment. A combined intramuscular-oral prophylactic regimen was also elaborated. For patients with a history of penicillin allergy, the AHA was the first to recommended erythromycin at doses of 250 mg orally 4 times a day (for adults and older children); in small children, the dose of erythromycin was of 20 mg/kg body-weight per day, divided into 3 or 4 doses, not exceeding a total dose of 1 g per day [41].
In 1965, the AHA stated that antibiotic prophylaxis should only be administered immediately before the dental procedure and on the subsequent days; this recommendation was based on the argument that penicillin did not sterilise the apical foci, and that its excessive use led to the selection of a resistant oral flora. The AHA also reduced the parenteral regimen to a single injection of several penicillins. In those cases in which the complete collaboration of the patient could be anticipated, an exclusively oral regimen of several doses of penicillin was proposed. Erythromycin was recommended for patients allergic to penicillin [42].
In 1972, the AHA modified its recommendations to include an increase in the initial doses of penicillin and erythromycin administered orally and the use of erythromycin in patients on prolonged treatments with penicillin, as penicillin-resistant Streptococcus viridans could predominate in their oral flora [43]. Five years later, the AHA suggested increasing the initial dose of the antibiotic even further in order to reach higher serum concentrations at the moment at which the microorganism entered the bloodstream [44]. However, they favoured the parenteral regimen, particularly in patients considered to be at high risk of IE. Two regimens were recommended: regimen A, based on the use of penicillin (erythromycin was recommended in patients allergic to penicillin) for parenteral-oral or exclusively oral administration, and regimen B, which combined penicillin and streptomycin (vancomycin and erythromycin for patients allergic to penicillin) for parenteral-oral administration. This latter protocol was reserved for patients with prosthetic heart valves, although patients with a good oral health status could receive the oral prophylaxis regimen for certain non-surgical dental procedures [44].
The BSAC, in its first guideline, suggested a single prophylactic regimen of a single dose of amoxicillin before the dental procedure for all patients considered to be at risk of IE (including patients with prosthetic heart valves) [49]. The BSAC substituted penicillin V, previously recommended by the AHA [44], with amoxicillin due to its more favourable pharmacokinetic and pharmacodynamic characteristics. Erythromycin stearate was the antibiotic of choice in patients allergic to penicillin but because this macrolide has lower activity than amoxicillin against some oral streptococci and showed a lower absorption after a single oral dose, they proposed a second dose 6 hours after completing the dental procedure. One quarter of the adult dose was recommended in children under 5 years of age and a half dose in those of 5 to 10 years of age [49]. In contrast to the AHA [44], the BSAC proposed a combined intramuscular-oral regimen in patients undergoing dental treatment under general anaesthesia. Special prophylactic regimens were proposed for patients being treated in the hospital environment; these regimens were based on the association of amoxicillin and gentamycin or, in patients unable to receive penicillin, a combination of vancomycin and gentamycin; the following doses were used in children under 10 years of age: amoxicillin, half the adult dose; gentamycin, 2 mg/kg body-weight; and vancomycin, 20 mg/kg body-weight [49].
In its protocol published in 1984, the AHA reduced the dose of the antibiotic after completion of the dental treatment, recommending the administration of penicillin V before the dental procedure and a second dose 6 hours after the first. In those patients in whom the oral route was not available, intramuscular penicillin G was proposed before the procedure and 6 hours later [45]. The AHA also showed a clear preference for the parenteral route in patients at high risk of IE and drew up a special regimen for these patients consisting of intramuscular or intravenous ampicillin and gentamycin, together with a second dose of penicillin V orally; intravenous vancomycin was recommended for patients allergic to penicillin, eliminating the second dose of erythromycin [45].
In 1986, the BSAC suggested that vancomycin should be given by slow intravenous infusion over 60 minutes (instead of the previously recommended 30 minutes) to minimise adverse reactions such as episodes of hypotension caused by histamine release (red-man syndrome)[50]. As an alternative to the parenteral regimen proposed earlier, the BSAC proposed 2 oral regimens for patients without prosthetic heart valves undergoing dental treatment under general anaesthesia. The first was based on the administration of amoxicillin before anaesthetic induction followed by a second dose in the immediate postoperative period; the second regimen consisted of the combination of amoxicillin and probenecid administered before anaesthesia [50]. For the first time, the BSAC differentiated between patients with prosthetic heart valves and other patients considered to be at risk of IE, as the AHA [45] had done in its 1984 guideline, proposing specific oral prophylactic regimens for such patients undergoing dental treatment under local anaesthesia [50].
Differing from the BSAC guideline [50], the 1990 AHA guideline continued to favour regimens based on 2 doses. Of particular note amongst the novelties introduced in this protocol was the incorporation of amoxicillin as the antibiotic of choice for all groups at risk of IE [46], an approach that had been adopted by the BSAC in 1982 [49]. According to the AHA, amoxicillin, ampicillin and penicillin showed similar efficacy against α-haemolytic streptococci in vitro but amoxicillin reached higher serum concentrations due to its better gastrointestinal absorption. However, they also defended the use of penicillin V as a suitable alternative for prophylaxis in dental procedures. Erythromycin, in its ethylsuccinate or stearate salt preparations, continued to be the antibiotic of choice in patients allergic to penicillin, being administered 2 hours before the procedure to ensure high serum concentrations. For the first time, the AHA recommended the administration of clindamycin in patients intolerant to penicillin and erythromycin [46]. For patients unable to take oral medication, the AHA drew up a number of regimens for parenteral administration as alternatives to the standard protocol, proposing ampicillin (in patients not allergic to penicillin) and clindamycin (in penicillin-allergic patients) as the antibiotics of choice [46]. In contrast to the previous protocols [45], the AHA recommended the administration of the standard regimen to patients with prosthetic heart valves and other patients considered to be at high risk of IE (patients with a past history of IE and those with surgically constructed systemic-pulmonary shunts). However, recognising that some professionals preferred parenteral prophylaxis, they also drew up a special parenteral regimen for this type of patient [46].
The prophylactic protocol recommended by the BSAC in 1990 included a new option [51]. Due to the high prevalence of undesirable gastrointestinal effects caused by erythromycin, and based on the guideline published in 1984 by the Swiss Expert Committee for the prevention of IE [61], the BSAC proposed the administration of a single oral dose of 600 mg of clindamycin 1 hour before the procedure as an alternative in patients with penicillin allergy; the dose of clindamycin in children under 10 years of age was of 6 mg/kg body-weight [51]. In 1992, the BSAC definitively replaced erythromycin with clindamycin in patients allergic to penicillin, modifying the initial dose in children to 300 mg in those between 5 and 10 years of age and to 150 mg in those under 5 years [52]. Due to the high prevalence of adverse effects associated with vancomycin and its prolonged duration of administration (around 100 minutes), the BSAC drew up 2 alternative regimens for penicillin-allergic patients with a high risk of IE who were being treated in the hospital environment. One was based on the intravenous combination of teicoplanin and gentamycin (in children under 14 years of age the doses were teicoplanin, 6 mg /kg body-weight, and gentamycin, 2 mg/kg body-weight); and the other consisted of an intravenous infusion of clindamycin with a second dose 6 hours after the first. Finally, in patients undergoing dental treatment under general anaesthesia, the BSAC specified that prophylaxis with amoxicillin should be administered intravenously instead of intramuscularly, particularly in children [52].
In 1995, the ESC performed a critical review of the prophylaxis protocols drawn up by the different national committees, noting clear differences between countries, although all included a simple or standard regimen and another more complex regimen for use in special circumstances [54]. In general, the standard guidelines consisted of the oral administration of a single dose of antibiotic which, in the majority of countries, was amoxicillin. Some societies recommended the administration of a second dose, particularly in patients considered to be at high risk of IE. In patients allergic to the beta-lactams, the antibiotic of choice was clindamycin at doses between 300 mg and 600 mg, although some countries, for example, Holland and France, recommended other antibiotics such as erythromycin or pristinamycin [54]. The more complex regimens were based on the synergistic and prolonged effect provided by several doses of different antibiotics with the aim of increasing the safety margin in special situations. In an analysis performed by the ESC, it was found that the majority of protocols recommended ampicillin or amoxicillin by intravenous infusion followed by a second oral dose 6 hours later; there were only minor differences with respect to the doses used. Although some countries did not use the aminoglycosides, these were recommended in other countries in patients considered to be at high risk of IE. The most frequently used antibiotic of choice in patients allergic to penicillin was vancomycin by intravenous infusion; for some scientific societies, teicoplanin and clindamycin were possible antimicrobial alternatives [54]. According to the ESC, the choice of the most suitable prophylactic regimen should be based on the following considerations: the heart condition defined as carrying a risk of IE; the type, magnitude and duration of the dental procedure; and the type of anaesthesia used (local or general). The ESC therefore considered the possibility of individualising the antibiotic prophylaxis regimen in certain situations [54]. The oral regimen proposed by the ESC consisted of the administration of amoxicillin or clindamycin (in penicillin-allergic patients), whilst the combination of amoxicillin or ampicillin with gentamycin and a second dose of amoxicillin orally 6 hours later was recommended in the parenteral regimen. In patients allergic to penicillin, the association of vancomycin and gentamycin was recommended, administering a second dose of vancomycin by intravenous infusion 12 hours after the first dose [54].
The prophylactic protocol recommended by the AHA in 1997 is shown in Table 6 [47]. It is based on a single dose of amoxicillin administered orally 1 hour before the procedure. In this protocol, the dose of amoxicillin was reduced from 3 g to 2 g after confirming that this latter dose provided adequate serum levels of the drug over several hours and caused fewer adverse gastrointestinal effects. Accepting an approach that had been adopted by other societies several years earlier [49-52], the AHA recognised that the administration of a second dose of antibiotic was unnecessary, since the serum levels of the drug exceeded the minimum inhibitory concentrations of many oral Streptococcus spp. and the antimicrobial activity of amoxicillin was prolonged (6 to 14 hours). In patients allergic to penicillin, the antibiotics of choice were clindamycin, cephalosporins (cefalexin or cefadroxil) or macrolides (azithromycin or clarithromycin), although the AHA specified that the cephalosporins should be avoided in patients with type 1 hypersensitivity to penicillin [47]. In patients unable to take oral medication or with problems of gastrointestinal absorption (independently of the IE risk category), the AHA drew up a regimen based on the use of intramuscular or intravenous ampicillin 30 minutes before the procedure. In penicillin-allergic patients in whom parenteral administration of the antibiotic was required, the recommended antibiotic was clindamycin phosphate and, in those patients not presenting type 1 hypersensitivity, was cefazolin. Although erythromycin was abandoned because of its gastrointestinal complications and its particular pharmacokinetic characteristics, the AHA indicated that “Dentists who are used to prescribing this antibiotic successfully for prophylaxis may continue to use it” [47].
\n\t\t\t\tSTANDARD REGIMEN (ORAL)\n\t\t\t | \n\t\t|
\n\t\t\t\tNOT ALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS 2 g of amoxicillin 1 h before tmt | \n\t\t\tCHILDREN 50 mg/kg body-weight of amoxicillin 1 h before tmt | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS A) 600 mg of clindamycin 1 h before tmt B) 2 g of cefalexin or cefadroxil 1 h before tmta\n\t\t\t\t C) 500 mg of azithromycin or clarithromycin 1 h before tmt | \n\t\t\tCHILDREN A) 20 mg/kg body-weight of clindamycin 1 h before tmt B) 50 mg/kg body-weight of cefalexin or cefadroxil 1 h before tmta\n\t\t\t\t C) 15 mg/kg body-weight of azithromycin or clarithromycin 1 h before tmt | \n\t\t
\n\t\t\t\tPARENTERAL REGIMENb\n\t\t\t\t\n\t\t\t | \n\t\t|
\n\t\t\t\tNOT ALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS 2 g of ampicillin (IM or IV) 30 min before tmt | \n\t\t\tCHILDREN 50 mg/kg body-weight of ampicillin (IM or IV) 30 min before tmt | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS A) 600 mg of clindamycin (IV) 30 min before tmt B) 1 g of cefazolin (IM or IV) 30 min before tmt | \n\t\t\tCHILDREN A) 20 mg/kg body-weight of clindamycin (IV) 30 min before tmt B) 25 mg/kg body-weight of cefazolin (IM or IV) 30 min before tmt | \n\t\t
IE prophylaxis protocol for dental procedures: recommendation of the AHA (1997) [47].
tmt= treatment; min= minutes; h= hours; IM= intramuscular; IV=intravenous; mg= milligrams; g= grams; kg= kilograms.
a- The cephalosporins must not be administered to subjects with immediate hypersensitivity reactions to penicillin (urticaria, angioedema or anaphylaxis); b- This protocol is to be applied in patients unable to take the medication orally; the total dose in children should not exceed the adult dose.
In 2004, the ESC published a guideline on IE prophylaxis which were very similar to the 1997 guideline of the AHA [47], except that the use of cephalosporins in patients allergic to penicillin was excluded [55].
In the prophylaxis protocol for IE secondary to dental procedures drawn up by the BSC and RCP (London) in 2004, prophylaxis was reserved for patients with heart diseases included in the categories of high and moderate risk of IE, and the prophylactic regimens varied according to the type of anaesthesia used [56]. Oral prophylaxis regimens were to be administered in procedures performed under local anaesthesia and parenteral regimens for those performed under general anaesthesia (Tables 7 and 8) [56]. In contrast to the 1997 guideline of the AHA [47], the BCS and RCP also provided a special prophylactic regimen for patients with prosthetic heart valves and/or previous episodes of IE (Table 9) [56].
The most recent IE prophylaxis protocols published by the BSAC [53], the AHA [48] and the ESC [58] are very similar and are summarized in Tables 10 and 11. The most recent prophylactic protocol published by the AHA continues to recommend amoxicillin as the antibiotic of choice for oral prophylaxis. For individuals who are allergic to penicillins, the use of cephalexin or another first-generation oral cephalosporin, clindamycin, azithromycin or clarithromycin is recommended [48]. Because of possible cross-reactions, a cephalosporin must not be administered to patients with a history of anaphylaxis, angioedema or urticaria after treatment with any form of penicillin, including ampicillin or amoxicillin. Patients who are unable to tolerate an oral antibiotic may be treated with intramuscular or intravenous ampicillin, ceftriaxone or cefazolin. For penicillin-allergic patients who are unable to tolerate an oral agent, prophylaxis is recommended with parenteral cefazolin, ceftriaxone or clindamycin [48]. According to the ESC, the main aim of antibiotic prophylaxis in patients at risk of IE is to target the oral streptococci. The impact of increasing resistance of these pathogens on the efficacy of antibiotic prophylaxis is unclear. Fluoroquinolones and glycopeptides are not recommended because their efficacy has not been established and because of the potential induction of resistance [58].
It has been estimated that the number of cases of IE that result from dental interventions is very small. The AHA has therefore concluded that only an extremely small number of cases of IE will be prevented by antibiotic prophylaxis for dental procedures even if such prophylactic regimens are 100% effective [48]. According to the ESC, this observation leads to 2 conclusions: (i) IE prophylaxis can at best only protect a small proportion of patients; and (ii) the bacteraemia that causes IE in the majority of patients appears to derive from another source [58]. Finally, the AHA stated the need for prospective placebo-controlled studies of antibiotic prophylaxis for IE to evaluate its efficacy in IE prevention [48].
Reviewing the effect of antibiotic prophylaxis on the intensity and duration of bacteraemia following dental procedures, the NICE recently concluded that “Antibiotic prophylaxis does not eliminate bacteraemia following dental procedures but some studies show that it does reduce the frequency of detection of post-procedure bacteraemia” [57]. This conclusion was reached after analysis of a number of studies on the efficacy of antibiotic prophylaxis for the prevention of post-dental manipulation bacteraemia; those studies presented methodological differences with respect to the type of antibiotic used and the time and route of administration. These important differences make a comparison of the results between the different series inappropriate [59].
\n\t\t\t\tSTANDARD REGIMEN (ORAL)\n\t\t\t | \n\t\t|
\n\t\t\t\tNOT ALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS 3 g of amoxicillin 1 h before tmt | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN BETWEEN 5 AND 10 YEARS OF AGE 1.5 g of amoxicillin 1 h before tmt CHILDREN UNDER 5 YEARS OF AGE 750 mg of amoxicillin 1 h before tmt | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLINa\n\t\t\t\t\n\t\t\t | \n\t\t|
ADULTS 600 mg of clindamycin 1 h before tmt | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN BETWEEN 5 AND 10 YEARS OF AGE 300 mg of clindamycin 1 h before tmt CHILDREN UNDER 5 YEARS OF AGE 150 mg of clindamycin 1 h before tmt | \n\t\t
\n\t\t\t\tUNABLE TO TAKE ORAL MEDICATIONb\n\t\t\t\t\n\t\t\t | \n\t\t|
ADULTS 500 mg of azithromycin 1 h before tmt | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN BETWEEN 5 AND 10 YEARS OF AGE 300 mg of azithromycin 1 h before tmt CHILDREN UNDER 5 YEARS OF AGE 200 mg of azithromycin 1 h before tmt | \n\t\t
IE prophylaxis protocol for dental procedures performed under local anaesthesia: recommendation of the BCS and RCP (London) (2004) [56].
h= hours; tmt= treatment; mg= milligrams; g= grams.
a- This protocol should also be used in patients who have received penicillin or another beta-lactam on more than 1 occasion in the previous month; b- In Great Britain, clindamycin is not available in oral suspension.
\n\t\t\t\tPARENTERAL REGIMEN\n\t\t\t | \n\t\t|
\n\t\t\t\tNOT ALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS 2 g of amoxicillin or ampicillin (IV) during anaesthetic induction | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN BETWEEN 5 AND 10 YEARS OF AGE 500 mg of amoxicillin or ampicillin (IV) during anaesthetic induction CHILDREN UNDER 5 YEARS OF AGE 250 mg of amoxicillin or ampicillin (IV) during anaesthetic induction | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLINa\n\t\t\t\t\n\t\t\t | \n\t\t|
ADULTS 300 mg of clindamycin (IV over 10 min) during anaesthetic induction 150 mg of clindamycin (oral or IV) 6 h after the first dose | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN BETWEEN 5 AND 10 YEARS OF AGE 150 mg of clindamycin (IV over 10 min) during anaesthetic induction CHILDREN UNDER 5 YEARS OF AGE 75 mg of clindamycin (IV over 10 min) during anaesthetic induction | \n\t\t
IE prophylaxis protocol for dental procedures under general anaesthesia: recommendation of the BCS and RCP (London) (2004) [56].
min= minutes; h= hours; IV= intravenous; mg= milligrams; g= grams; kg= kilograms.
a-This protocol should also be used in patients who have received penicillin or another beta-lactam on more than 1 occasion in the previous month.
\n\t\t\t\tPARENTERAL REGIMEN\n\t\t\t | \n\t\t|
\n\t\t\t\tNOT ALLERGIC TO PENICILLIN\n\t\t\t | \n\t\t|
ADULTS 2 g of amoxicillin + 1.5 mg/kg body-weight of gentamycin (IV) 30 min before tmt 1 g of amoxicillin (oral or IV) 6 h after the first dose | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN UNDER 10 YEARS OF AGE 1 g of amoxicillin + 1.5 mg/kg body-weight of gentamycin (IV) 30 min before tmt Amoxicillin (oral) 6 h after the first dose | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLINa\n\t\t\t\t\n\t\t\t | \n\t\t|
ADULTS 1 g of vancomycin (IV over 2 h) + 1.5 mg/kg body-weight of gentamycin (IV) before tmt \n\t\t\t | \n\t\t\tCHILDREN OVER 10 YEARS OF AGE Adult dose CHILDREN UNDER 10 YEARS OF AGE 20 mg/kg body-weight of vancomycin (IV over 2 h) + 1.5 mg/kg body-weight of gentamycin (IV) before tmt | \n\t\t
Parenteral IE prophylaxis protocol for patients with prosthetic heart valves and/or previous episodes of IE undergoing dental procedures under local or general anaesthesia: recommendations of the BCS and RCP (London) (2004) [56].
min= minutes; h= hours; tmt= treatment; IV= intravenous; mg= milligrams; g= grams; kg= kilograms.
a- This protocol should also be used in patients who have received penicillin or another beta-lactam on more than 1 occasion in the previous month.
More than half of the studies published on antibiotic prophylaxis and post-dental extraction bacteraemia have investigated the efficacy of the penicillins. The results obtained in the majority of those studies confirmed the efficacy of these antibiotics in prevention, as bacteraemia did not develop in a significant number of patients (compared with the results obtained in patients not receiving antibiotic prophylaxis) [62,63]. However, there are fewer studies on the effect of the prophylactic administration of other antibiotics (clindamycin, azithromycin and cephalosporins) recommended for the prevention of post-dental extraction bacteraemia, and their results have not established whether these antibiotics are effective [62].
\n\t\t\t\tSTANDARD REGIMEN (ORAL)\n\t\t\t | \n\t\t||
\n\t\t\t\tBSAC, 2006\n\t\t\t | \n\t\t\t\n\t\t\t\tNOT ALLERGIC TO PENICILLIN: 3 g of amoxicillin 1 h before tmt \n\t\t\t\tALLERGIC TO PENICILLIN: 600 mg of clindamycin 1 h before tmt \n\t\t\t\tUNABLE TO TAKE ORAL MEDICATIONa\n\t\t\t\t: 500 mg of azithromycin 1 h before tmt | \n\t\t|
\n\t\t\t\tAHA, 2007\n\t\t\t | \n\t\t\t\n\t\t\t\tNOT ALLERGIC TO PENICILLIN: \n\t\t\t\tALLERGIC TO PENICILLIN: | \n\t\t\t2 g of amoxicillin 1 h before tmt 2 g of cephalexin 1 h before tmtb\n\t\t\t\t 600 mg of clindamycin 1 h before tmt 500 mg of azithromycin or clarithromycin 1 h before tmt | \n\t\t
\n\t\t\t\tESC, 2009\n\t\t\t | \n\t\t\t\n\t\t\t\tNOT ALLERGIC TO PENICILLIN: 2 g of amoxicillin 30 min-1 h before tmt \n\t\t\t\tALLERGIC TO PENICILLIN: 600 mg of clindamycin 30 min-1 h before tmt | \n\t\t
IE prophylaxis protocols (oral regimens) for dental procedures: recommendations of the BSAC (2006), the AHA (2007) and the ESC (2009) [48,53,58].
tmt= treatment; min= minutes; h= hours; mg= milligrams; g= grams.
a- In Great Britain, clindamycin is not available in oral suspension; b- Cephalosporins must not be administered to subjects with immediate hypersensitivity reactions to penicillin (urticaria, angioedema or anaphylaxis).
For children, the BSAC recommended amoxicillin (≥10 years, adult dose; ≥5-<10 years, 1.5 g; <5 years, 750 mg), clindamycin (≥10 years, adult dose; ≥5-<10 years, 300 mg; <5 years, 150 mg) or azithromycin (≥10 years, adult dose; ≥5-<10 years, 300 mg; <5 years, 200 mg). For children, the AHA recommended amoxicillin (50 mg/kg body-weight), clindamycin (20 mg/kg body-weight), cefalexin (50 mg/kg body-weight), or azithromycin or clarithromycin (15 mg/kg body-weight). For children, the ESC recommended amoxicillin (50 mg/kg body-weight) or clindamycin (20 mg/kg body-weight).
\n\t\t\t\tPARENTERAL REGIMEN\n\t\t\t | \n\t\t||
\n\t\t\t\tBSAC, 2006\n\t\t\t | \n\t\t\t\n\t\t\t\tNOT ALLERGIC TO PENICILLIN: 1 g of amoxicillin (IV) just before tmt or at induction of anaesthesia \n\t\t\t\tALLERGIC TO PENICILLIN: 300 mg of clindamycin (IV)a just before tmt or at induction of anaesthesia | \n\t\t|
\n\t\t\t\tAHA, 2007\n\t\t\t | \n\t\t\t\n\t\t\t\tNOT ALLERGIC TO PENICILLIN: | \n\t\t\t2 g of ampicillin (IM or IV) 30 min before tmt | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLIN: | \n\t\t\t1 g of cefazolin or ceftriaxone (IM or IV) 30 min before tmtc\n\t\t\t\t 600 mg of clindamycin (IM or IV) 30 min before tmt | \n\t\t|
\n\t\t\t\tESC, 2009\n\t\t\t | \n\t\t\t\n\t\t\t\tNOT ALLERGIC TO PENICILLIN: | \n\t\t\t2 g of ampicillin (IV) 30 min-1 h before tmt | \n\t\t
\n\t\t\t\tALLERGIC TO PENICILLIN: | \n\t\t\t2 g of cephalexin (IV) 30 min-1 h before tmt 1 g of cefazolin or ceftriaxone (IM or IV) 30 min before tmtc\n\t\t\t\t 600 mg of clindamycin (IV) 30 min-1 h before tmt | \n\t\t
IE prophylaxis protocols (parenteral regimens) for dental procedures: recommendations of the BSAC (2006), the AHA (2007) and the ESC (2009) [48,53,58].
tmt= treatment; min= minutes; h= hours; IM= intramuscular; IV= intravenous; mg= milligrams; g= grams.
a- Given over at least 10 min; b- Given over 2 hours; c- Cephalosporins must not be administered to subjects with immediate hypersensitivity reactions to penicillin (urticaria, angioedema or anaphylaxis).
For children, the AHA and ESC recommended ampicillin or amoxicillin (50 mg/kg body-weight), clindamycin (20 mg/kg body-weight), or cephalexin, cefazolin or ceftriaxone (50 mg/kg body-weight).
For children, the BSAC recommended amoxicillin (≥10 years, 1 g; ≥5-<10 years, 500 mg; <5 years, 250 mg) or clindamycin (≥10 years, 300 mg; ≥5-<10 years, 150 mg; <5 years, 75 mg).
A second conclusion reached by the NICE was that “It is not possible to determine the effect of antibiotic prophylaxis on the duration of bacteraemia”. Probably influenced by the idea that bacteraemia secondary to dental procedures is of a transitory nature, few studies have been published on the effect of antibiotic prophylaxis on the duration of post-dental extraction bacteraemia [40]. On this question, the results of our research group have shown that the prophylactic administration of oral amoxicillin (2 g) significantly reduces the prevalence of bacteraemia at 15 minutes and 1 hour after completing dental extractions under general anaesthesia [62]. The conclusions reached by the NICE on the lack of efficacy of antibiotic prophylaxis for the prevention of bacteraemia following dental procedures are based on a small volume of published scientific evidence [59]. Further research should therefore be performed on the recommended antibiotics regimens for IE prophylaxis, analysing the influence of the choice of antibiotic and the time and route of administration, and also on new antibiotic protocols [40].
Antibiotic administration does carry a small risk of anaphylaxis [58]. However, no case of fatal anaphylaxis has been reported in the literature after the oral administration of amoxicillin for IE prophylaxis [63]. Widespread and often inappropriate use of antibiotics may result in the emergence of resistant microorganisms [58], but the extent to which antibiotic use for IE prophylaxis could be implicated in the general problem of resistance is unknown [64].
In 1977, the AHA suggested for the first time performing disinfection of the gingival sulcus as a complement to antibiotic prophylaxis, although they recommended caution in the use of oral irrigators in patients considered to be at risk of IE, particularly in the presence of deficient oral hygiene habits [44]. This approach was also adopted by the BSAC en 1982 [49], when it recommended the application of antiseptics at the gingival margins in addition to the prophylactic administration of antibiotics prior to dental manipulations.
In 1990, the AHA recommended the application of chlorhexidine or other antiseptics (povidone iodine or a combination of iodine and glycerine) for 3 to 5 minutes around the tooth—a proposal also supported by the BSAC at that time [51]—before performing dental extractions in patients considered to be at high risk of IE and/or with deficient oral hygiene [46]. Two years later, the BSAC specified the form of presentation and the concentration of chlorhexidine to be used before starting a dental procedure: 1% gel at the gingival margin or 0.2% mouthwash for 5 minutes [52].
In the European Consensus of 1995, the application of antiseptics was once again recommended as a complementary measure in addition to antibiotic prophylaxis [54]. In its 1997 recommendations, the AHA recognised the need to use antiseptic mouthwashes (chlorhexidine or povidone iodine) prior to a dental manipulation, although they did not favour their application using gingival irrigators and recommended against the continual use of antiseptics in order to avoid the selection of resistant microorganisms [47]. Paradoxically, in their protocols on the prevention of IE secondary to dental manipulations published in 2004, the ESC and the BCS jointly with the RCP made no reference to the use of antiseptics before starting a manipulation [55,56].
In 2006, the BSAC recommended that, when possible, and in addition to the antibiotic prophylaxis, a pre-operative mouthrinse with 0.2% chlorhexidine gluconate should be performed, holding the antiseptic in the mouth for 1 minute [53]. In contrast, in its latest IE guideline, the Expert Committee of the AHA did not recommend the use of antiseptic prophylaxis before at-risk dental procedures [48].
With regard to the effect of chlorhexidine prophylaxis on the intensity and duration of bacteraemia following dental procedures, the NICE concluded that “Chlorhexidine used as an oral rinse does not significantly reduce the level of bacteraemia following dental procedures” [57]. This conclusion was reached after analysis of certain studies on the efficacy of chlorhexidine prophylaxis for the prevention of post-dental manipulation bacteraemia; those studies presented methodological differences with respect to the dental procedure performed, the concentration of chlorhexidine used, and the technique for applying the antiseptic solution (mouthwash and/or irrigation). These important differences make a comparison of the results between the different series inappropriate [59].
Very few studies have been published on the efficacy of mouth rinsing with 0.2% chlorhexidine (recommended by the BSAC in 2006) for the prevention of post-dental extraction bacteraemia [65]. Our research group demonstrated that initial rinsing with 0.2% chlorhexidine significantly reduced the duration of post-dental extraction bacteraemia [66,67]. These results allow us to speculate that the efficacy of antibiotic prophylaxis could be improved by the simultaneous application of chlorhexidine prophylaxis, although there is no scientific evidence to support this hypothesis.
The conclusions reached by the NICE on the lack of efficacy of antiseptic prophylaxis for the prevention of bacteraemia following dental procedures are based on a small volume of published scientific evidence [59]. At the present time, the controversies concerning the risk of developing IE of oral origin, the clinical repercussions of bacteraemia of oral origin, the efficacy of antibiotic prophylaxis and the risk-benefit and cost-benefit relationships of antibiotic prophylaxis could justify the reappraisal of the need for antibiotic prophylaxis for the prevention of IE currently being undertaken by the scientific community. Further research should be encouraged to confirm the efficacy of the recommended chlorhexidine regimens and to investigate new antiseptic protocols [59].
Over the past 50 years, prophylactic regimens for the prevention of IE secondary to dental procedures have been modified but remain consensus based. The indication for prophylaxis is now limited to patients with the highest risk of IE undergoing the highest risk dental procedures. The most recent prophylactic protocols published by the BSAC, the AHA and the ESC continue to recommend amoxicillin as the antibiotic of choice for oral prophylaxis. For individuals who are allergic to penicillins, the use of clindamycin, cephalexin or another first-generation oral cephalosporin, azithromycin or clarithromycin is recommended. However, the NICE has adopted a drastic stance in this respect, recommending the cessation of antibiotic prophylaxis for IE in individuals undergoing dental procedures in the United Kingdom. Further research should be encouraged to determine the impact of this recommendation of the NICE guideline.
All Expert Committees on IE prevention agree on the premise that “Good oral hygiene and regular dental checkups are of particular importance for the prevention of IE of oral origin”.
Over last few decades, crystalline microporous materials, from zeolites, to coordination polymers and its subclass, metal organic frameworks (MOFs) have gained enormous attention in the scientific community due to their structural versatility and tailorable properties like nanoscale porosity, high surface area, and functional density [1, 2]. Metal organic frameworks have evolved in last few years as a revolutionary material that are self-assembled nanostructure [3, 4] built from metal ions and organic ligands. The first MOF, MOF-5 or IRMOF-1 (Zn4O(BDC)3) reported by Omar M. Yaghi was used in gas adsorption applications accounting to its high surface area of 2900 m2/g [5, 6]. To date, 80,000 MOFs [7] have been reported owing to its diverse structure, compositions, tunable porosity, specific surface area, [8] ease of functionalization, unsaturated metal sites [9] and biocompatibility [10] . As a result, MOFs were used in a wide range of applications such as gas storage and separation, drug delivery and storage, chemical separation, sensing, catalysis, and bio-imaging [3, 7, 11, 12, 13]. In terms of structural orientation, the coordination bonding between a metal ion and organic ligand results in the formation of extended networks of one, two, and three-dimensional framework with potential voids [6, 14]. The coordination bonding facilitated through a suitable molecular approach, involving reticular synthesis, provides the flexibility to alter the pore size and transform its structure, targeting specific applications. Thus, utilizing the advantage of various combinations of metal-ligands and interaction of metal-ligands, MOFs are ideal candidates in the field of material science, offering an attractive property of structural tunability, providing a pathway to introduce and tailor intrinsic characteristics, such as optical, electrical, and magnetic properties.
There has been a growing interest exploring MOF as emerging semiconducting materials to meet the current demand in the electronic devices [15]. In particular, the electronic characteristics such as electrical, optical, and magnetic properties of MOFs have become an interesting topic of research attributing to their applications in microelectronic and optical devices. The implementation of MOFs in the electronic industry was first reported by Allendorf and co-workers [16]. MOF-5 with Zn4O metal nodes and orthogonally interconnected six units of terephthalate is the most-studied MOF as a semiconductor. In 2007, Garcia and co-workers reported on the semiconducting behavior of MOF-5 synthesized at room temperature, with a bandgap of 3.4 eV [17]. Since then, intense research has been carried out to develop MOFs with semiconducting properties, opening new research domains for the scientific community in nanoscience.
The presence of narrow band gap structure either direct or indirect and charge mobility contribute to the semiconducting behavior of MOFs. To design MOFs with semiconducting behavior, significant amount of research is ongoing to identify the general structural requirements for enhancing the orbital overlapping between the building components. The main advantage of MOFs is the ability to tune the crystalline structure and functionality through phenomenal conceptual approaches such as rational designing and synthetic flexibility. In reticular chemistry, which is also known as rational designing, the coordination bonding between metal node and organic ligand provides an understanding of atomic positions precisely contributing to determine the fundamental structure–property relationships. Thus, the crystalline structure of MOFs consists of self-assembled ordered nanostructure with defined organized spatial space that is constructed via coordination chemistry between the building components.
Moreover, the sub-angstrom knowledge of atomic positions helps to eliminate any disorder in the structure that contributes to poor mobility in the structure. Considering synthetic flexibility, the electronic properties of MOFs could be tailored, resulting in potential applications such as a photovoltaic device tuned for solar cells, electroluminescent devices, field effect transistors, spintronic devices, and sensors. These developments have led many researchers to explore electrical, magnetic, and optical properties of MOFs [15, 18, 19]. However, the electrical properties of MOFs and integration of them in micro-electronic devices is still at an early stage and remain under research when compared to other types of existing conducting materials [4, 15] due to their insulating character. Although MOFs possess the properties of both organic and inorganic counterparts, they behave as electrical insulators or poor electrical conductors due to the poor overlapping between the π-orbitals of organic ligands and d-orbitals of the metal ion [20]. Yet, MOFs serving as an interface between (inorganic) hard and (organic) soft materials provide an opportunity for adapting various structure–property relationships that is related to wide range of parameters such as choice of metal ion, organic linker, and molecular designing approach. In general, the structure–property relationship in MOFs is a consequence of cooperative mechanism, i.e. the interaction between the metal and ligand, which could be readily identified by taking advantage of the knowledge of their detailed atomic structure, enabling fine tuning of their functionalities [7, 11]. According to the literature, Bastian Hoppe and his co-workers reported Cu-2, 3, 6, 7, 10, 11-hexahydroxytriphenylene (Cu3hhtp2-MOF), a copper-based graphene-like framework with inherent electrical conductivity about 0.045 S cm−1 [21]. MOFs with electrical conductivity higher than 0.1 S cm−1 was achieved by Talin and co-workers [22]. Thus, the designing of MOFs with conducting or semiconducting properties is necessary to enhance the sensitivity of electrical or demonstrate a sensing concept; but rarely have MOFs been an integral part of an actual device [23].
The purpose of this chapter is to provide comprehensive discussion on optoelectronic MOFs developed up to date and identify focus points to bring MOFs with optoelectronic properties for the realization of integrating MOFs into actual devices for electronic device applications. We first provide a MOFs chemistry and isoreticular synthesis advancements to make isoreticular MOFs (IRMOFs) with tailored optical and electronic properties. Then we summarize the current state of MOF research relevant to optoelectronics, particularly discussing the synthesis, electronic structure, and photophysical properties of three selected IRMOFs (IRMOF-1, 8, and 10). Finally, we propose a MOFs-device roadmap, focusing on MOF-based field-effect transistors, photovoltaics, thermoelectric devices, and solid-state electrolytes and lithium ion battery components.
Coordination polymers are organic–inorganic hybrid materials where organic moieties are bonded to metal ion or metal clusters via coordination bonds. The energy of such bonding is usually between 50 and 200 KJ mol−1. Apart from strong coordination bonding, weaker interaction such as hydrogen bonds, van der Waal forces and π-π interactions also influence the formation of coordination polymers. Depending on the geometry, coordination polymers are classified into three subclasses: (1) One-dimensional (1-D) coordination polymers, (2) Two-dimensional (2-D) coordination polymers, and (3) Three-dimensional coordination polymers (Figure 1).
Dimensional structures of coordination polymers.
The coordination polymer assembled from organic ligand and metal ion into three dimensional hierarchical crystalline structures is often regarded as metal organic framework. Since then, the term coordination polymer and metal organic framework have been used interchangeably. The term MOFs was first introduced by Omar Yaghi in 1995 [4, 9]. The framework of MOFs is either porous or non-porous. However, the porosity of MOFs was reported to be reversible due to various environmental factors (temperature, pressure, light intensity) contributing to the weak intermolecular interactions between building components. Thus, efforts have been made to modulate the strong structural rigidity that could incorporate permanent porosity. Based on this, in 1998 Kitagawa classified MOFs into three categories; 1st, 2nd, and 3rd generation coordinated network. Among three generations of coordinated networks, 3rd generation coordinated networks were defined to have permanent porosity with structural flexibility [10]. This led to numerous applications and implementation of coordinated networks in the gas storage community. The intermolecular interaction between organic ligand and metal ions, choice of building units, crystallization, environment, and guest molecules determine the crystal structural rigidity and dimensionality of MOF’s coordination network. This major advance in the field of coordination polymer depicted that coordinated networks of MOFs could be modified and developed in a highly periodic manner, with a defined understanding of the crystalline structure, porosity, and chemical functionality. Thus, the ability to design and control the arrangement of metal ions with extended organic spaces in three-dimensional fashion led to the origin of the term reticular chemistry which was first introduced by Yaghi and coworkers [4].
With the variability of organic and inorganic components and their interaction, the freedom of modulating the structure of MOFs into highly ordered hierarchical structures with tunable pore volume and adjustable surface area has become feasible that made MOFs stand out compared to the other porous materials. Taking advantage of one of these hallmarks of MOFs i.e. designing of topologically diverse structures with desirable properties has been explored extensively attracting wide range of applications in gas storage, separation, catalysis, sensing and drug delivery [5]. Since 1990s, this area of chemistry has experienced tremendous growth in the field of material science and modern chemistry [4]. The flexibility with geometry, size, and functionality led to the “design” of a large number of MOFs. The organic units are generally ditopic or polytopic organic carboxylates, linked to metal-containing units, such as transition metals (e.g., Cu, Zn, Fe, Co, and Ni), alkaline earth elements (e.g. Sr., Ba), p-block elements (e.g. In, Ga), and actinides (e.g. U, Th) [6]. A major advance in the chemistry of MOFs came in 1999 with the invention of two structures i.e. MOF-5 (IRMOF-1) and HKUST-1 [11] reported by Omar et al. and Chui et al., respectively. Subsequently, in the coming years around 2002, the flexible and non-flexible structures of MIL-88/53 [12] was reported by Ferey et al.
The demand for the synthesis of new materials to perform highly specific and cooperative functions has been increasing rapidly in parallel with advanced technology [13, 14]. Recently, the field of metal organic framework has evolved significantly due to its practical and conceptual approach to design and develop the target material. Intrinsically, the reticular chemistry is described as the process of assembly of molecular building blocks held together by strong bonding that pattern into periodic arrays of the ordered net like structures [13, 14, 15, 16]. Some of the advantages of this approach are: (1) Molecular approach, which provides the ability to design and control the structure of frameworks [17]; (2) Bonding in which the strong bonding between the building blocks could impart superior functionalities like thermal and chemical stability into the framework; and (3) Engineered crystallinity, which is based on the type of the interactions (intermolecular or intramolecular) design and synthesis with controlled and desired properties.
After the introduction of the parent MOF, MOF-5, taking advantage of reticular chemistry that includes reticulating metal ions and organic carboxylate, the group of Omar M. Yaghi synthesized a new class of materials called IRMOFs. Thus, the theory of isoreticular chemistry was established in the year 2002 with the development of IRMOFs. These class of materials were developed to improve the surface area and pore volume by incorporation of different topological linkers. In IRMOF, IR stands for isoreticular, which means it is a series of MOFs with the same topology, but different pore size [14, 20, 22, 23]. A series of different IRMOFs share similar pcu topology of IRMOF-n (n = 1–16). As shown in the Figure 2, the pore volume and porosity vary with the variation in the organic linker. Applying the concept of isoreticular chemistry, various kinds of MOFs were developed.
Crystal structures of IRMOFs-n series [n = 1–16]. The non-interpenetrated structures from (n = 1,2,3,4,5,6,7,8,10,12,14,16). The yellow sphere represents the pore volume. Zn atoms are in green, O in red, C in gray, Br atoms in Orange, and amino groups in blue [17].
The conceptual approach of designing and assembling a metal–organic framework follows reticular synthesis and is based upon identification of how building blocks come together to form a net, or reticulate. The synthesis of MOFs is often regarded as “design” which implies to construct, built, execute, or create according to the target material. The synthesis approach for a new MOF should follow several factors asides from the geometric principles that are considered during its design. Among such factors, by far the most important is the maintenance of the integrity of the building blocks. A great deal of research effort has been demonstrated on the synthesis of a novel organic link and synthesis conditions that are mild enough to maintain the functionality and conformation of organic ligand, yet reactive enough to establish the metal–organic bonds. In situ generation of a desired secondary subunit (SBU) is required carful design of synthetic conditions and must be compatible with the mobilization and preservation of the linking units [24]. Typically, this is achieved by precipitation of the product from a solution of the precursors where solubility is a necessary attribute of the building blocks but is quite often circumvented by using solvothermal techniques [24].
Traditional goal of MOF synthesis is to obtain high quality single crystal for deducing the structure and understand the crystal packing, geometry, and pore volume with respect to the organic ligand’s length. Thus, prior to begin elucidating the concept of reticular synthesis, most early studies were exploratory and early stage synthesis has mainly involved simple, highly soluble precursors, and labile metal ions of the late transition series. The polymerization that leads to make 3D-network of MOFs needs an assembly process where an insoluble entity is quickly formed that precludes recrystallization. Fortunately, it differs in the degree of reversibility of the bond formation event, allowing detachment of incoherently matched monomers followed by reattachment with continued defect free crystal growth. The framework assembly occurs as a single synthetic step, where all of the desired attributes of the target material constructs by the building blocks. This often requires a combinatorial approach, which involves subtle changes in concentration, solvent polarity, pH, or temperature. Any subtle changes in these parameters leads to poorer quality crystals, reduced yields, or the formation of entirely new phases [24].
Augmenting simple crystal growth processes used to grow simple inorganic salts, early efforts of producing highly crystalline MOFs involved the slow introduction of the building blocks to reduce the rate of crystallite nucleation. Methods included slow evaporation of a solution of the precursors, layering of solutions, or slow diffusion of one component solution into another through a membrane or an immobilizing gel [24]. During the nucleation stage, the ligand deprotonation prior to the coordination onto metal ion is catalyzed introducing a volatile amine gradually via vapor diffusion. Just as for many of the polar solvents used, suitable choice of base is necessary to avoid competitive coordination with the organic links for the available metal sites. While in some cases, blocking of metal coordination sites is necessary for the formation of a particular SBU. However, this approach has generally been regarded as leading to low-dimensional structures that are less likely to define an open framework.
With the need for more robust frameworks, having larger pore volumes and higher surface area, introducing bulker, longer length organic linkers are necessary, but greater difficulties in crystal growth were encountered. Thus, later, solvothermal techniques were found to be a convenient solution to overcome this challenge and have largely benefit over often time-consuming methods involving slow coupling of the coordinating species. The typical solvothermal method combines the precursors as dilute solutions in polar solvents such as water, alcohols, acetone or acetonitrile and heated in sealed vessels such as Teflon-lined stainless-steel bombs or glass tubes, generating autogenous pressure. The crystal growth process is enhanced by using mixed solvent systems where the solution polarity and the kinetics of solvent-ligand exchange can tune to achieve rapid crystal growth. It has found that, exposing the growing framework to a variety of space-filling solvent molecules may also be an effective way to stabilize its defect-free construction as they efficiently pack within the defined channels [24]. For deprotonation of the linking molecule alkyl formamides and pyrrolidinones have been particularly useful, as they are also excellent solubilizing agents.
In recent years, modifying the solvothermal method, there are several rapid synthesis methods were proposed by researchers to develop MOF crystals within a short duration of time. Some of the external parameters implemented to develop MOFs include the use of Microwave energy (Microwave synthesis), [25] Ultrasonic waves (Sonochemical synthesis), Mechanical energy (Mechano-chemical synthesis) and electrical energy (Electrochemical synthesis). The synthetic strategies developed up to date to make different type of MOFs are summarized in the Table 1 along with reaction conditions [26]. Additionally, a surfactant driven-templating method, [22] a CO2-expanded liquid route, [27] a post-synthetic method, [28] and an ionic liquid-based method [29] are developed to create hierarchical mesoporous microstructures and thin films of MOFs [25, 27, 28, 29].
Synthesis method | Reaction time | Temperature (K) |
---|---|---|
Slow evaporation | 7 days to 7 months | 298 |
Sonochemical method | 30–180 mins | 272–313 |
Solvothermal method | 48–96 hours | 353–453 |
Mechano-chemical method | 30 min to 2 hours | 298 |
Electrochemical method | 10–30 mins | 273–303 |
Microwave Synthesis | 4 mins to 4 hours | 303–373 |
Synthesis methods developed up to date to make MOFs.
In the area of MOFs, the main desire is to design MOFs with optoelectronic properties and to optimize the charge transport mechanism suitable for developing electronic devices. Although numerous applications of MOFs with different types of synthesis methods are being investigated, a versatile and scalable synthesis approach for the preparation of MOFs with semiconducting properties for optoelectronic devices are still in the early stage and a little research work so far done towards tailoring MOFs structure–property relationship to use as active materials in optoelectronic devices, such as solar cells, field-effect transistors, and photoluminescence devices.
To introduce MOFs as semiconducting materials, tuning of band gap such as lowering the bandgap or increasing the charge mobility is required. This tunability is again dependent upon the type of interaction i.e. Intermolecular interaction: metal ion and the organic ligand or Intramolecular interaction - π stacking [18]. The two key factors responsible for poor electrical conductivity in MOFs are: (1) the insulating character of organic ligand and (2) due to poor overlapping between the π-orbitals of organic ligand and d-orbitals of metal ions [16]. The common strategies for constructing MOFs with electrical conductivity involves three possible charge pathways.
Pathway 1: A long range of charge transport in this pathway is facilitated through bonds. This mechanism is promoted by interaction between ligand π and metal d orbital [16]. This mechanism is based on the tunneling of electron between the donor and acceptor portions of the framework. Typically, the electrical conductivity in the range 10−7 to 10−10 S cm−1 is considered as insulator. This is caused due to poor overlapping between the metal ion and organic linker as the electronegative nature of oxygen atom in the carboxylate group of the linker is so high that it requires high voltage for tunneling of the electrons [30]. Various MOFs that exhibit conductivity through this mechanism have been reported, of which [[Cu2(6-Hmna) (6-mn)]·NH4]n, a copper-sulfur based MOF constructed from 1,6-Hmna = 6-mercaptonicotinic acid, 6-mn = 6-mercaptonicotinate shows highest electrical conductivity of 10.96 S/cm (Table 2).
Materials | Mechanism | Conductivity (Scm−1) | Charge carrier | Mobility (cm2V−1 S−1) | Ref. |
---|---|---|---|---|---|
Metals Cu Au Fe | Tunneling | 6.5 x105 4.1x105 1.0 x 105 | e | 46 | [31] |
Organic polymers Polyacetylene Polythiophenes Rubrene | Charge transfer (electron hopping) | 10–9 1975 | h | 1–10 4 | [31] |
TTF-TCNQ Ni3 (HITP)2 Zn2 (TTFTB) | Through-space | 700 40 4.0x10–6 | h or e | 48.6 0.2 | [16, 31, 32] |
Cu3(BTC)2- TCNQ NU-901-C60 | Guest molecule | 0.07 1x10–3 | h | [33, 34] | |
Fe2(DSBDC) {[Cu2(6-Hmna) (6-mn)] ·NH4]n Cu [Ni(pdt)2] | Through-bond | 1x10–6 10.96 1x10–4 | [18, 35, 36, 37] |
Significant progress in the last few years made towards developing electrically conductive MOFs and their conductive properties compared with conventional metals.
Pathway 2: In this pathway, the charge transport is facilitated through space via π stacked aromatic ligands which was proposed as an alternative to through bond strategy. This mechanism typically promotes electron hopping mechanism by employing electroactive molecules [16, 30]. TTF-TCNQ i.e. tetrathiafulvalene- tetracyano quinomethane is one of the MOFs that demonstrate metallic conductivity (shown in the Table 2) through-space (π-π stacking) mechanism [38]. Recently, TTF-based ligand consisting of benzoate spacers is used to develop Zn based MOF reported by Dincă et al. These MOFs shows columnar stacks of TTF (3.8 Å) with the charge mobility of a magnitude that resembles some best conductive organic polymers [35, 36].
Pathway 3: The other alternative strategy to increase the conductivity of MOFs is via incorporating an appropriate guest molecule within the MOF. These molecules can activate long range delocalization either through bonds or through space or that can inject mobile charge carriers by oxidizing or reducing the organic ligand and metal ions [16, 30] NU-901, a MOF consisting of Zr6 (μ3-O)4 (μ3-OH)4 (H2O)4 (OH)4 nodes and tetratopic 1,3,6,8-tetrakis (p- benzoate) pyrene (TBAPy4-) linkers. These materials were chosen for the encapsulation of C60. After installation of C60, the NU-901-C60 shows electrical conductivity higher than that of NU-901 (shown in the Table 2). As per reports, the donor-acceptor interactions between TBAPy4-/C60 contribute to the electrical conductivity of the framework [32, 38].
IRMOF-1, which is commonly known as MOF-5, invented by Yaghi and co-workers [39] in 1996, has become one of mostly studied MOF with promising application in high capacity hydrogen storage [40, 41]. MOF-5, consists of Zn4O units connected by linear 1,4-benzenedicarboxylate units to form a cubic network, having the primitive cubic unit cell. Syntheses demonstrated for MOF-5 in which the starting materials are mixed in solution at ambient temperature. Subsequent addition of triethylamine promotes the deprotonation of the organic linker to precipitate MOF-5. Depending on the addition of base either slowly by diffusion as described in the original synthesis method [39] or rapidly as an aliquot [42] the product can be either single crystal mixtures, which must be mechanically separated, or microcrystalline powders. The ambient temperature synthesis method described above following the fast addition of base, is easy to scale up. However, metal precursor, zinc nitrate poses potential safety concerns, especially for large-scale production. Furthermore, reports of such synthetic conditions have been largely limited to MOF-5 and IRMOF-8 [42, 43, 44].
Later, a rapid, simple, room-temperature high yielding synthesis method was introduced by Yaghi and co-workers that can apply to make a wide range of new MOFs, including IRMOF-0, which uses acetylenedicarboxylate as the linker [45]. This synthesis method follows a room temperature synthesis, wherein separate N,N-dimethylformamide (DMF) solutions of terephthalic acid (BDC) with triethylamine and zinc acetate dihydrate are prepared, then the zinc salt solution is added to the organic solution with rapid stirring at ambient temperature. Upon immediately of the formation of a white powder followed by 2.5 hours of reaction time, pure MOF-5 is collected and confirmed by powder XRD. The same synthesis without a base (triethylamine) has also yielded pure MOF-5, confirming that addition of a base is unnecessary when zinc acetate is used as a source of Zn (II) in the MOF-5 synthesis [45].
This synthesis method has later modified by Rathnayake et.al to make IRMOFs (IRMOF-1, 8, and 10) by cutting down the reaction time from 2.5 hours to 7–9 minutes [23]. As depicted in Figure 3, our group is able to make a wide range of hierarchical microstructures of highly crystalline MOFs, including IRMOF-1. Microstructures of IRMOF-1 prepared from the modified solvothermal method (Figure 3), are visualized using scanning electron microscope and are depicted in Figure 4(a). Crystal structure of IRMOF-1, retrieved by matching its simulated XRD with experimental powder XRD is depicted in Figure 4(b), and follows cubic lattice cell, which belongs to Fm3m cubic space groups. The electron density potential distribution modeled from VESTA (Figure 4(c)) evidences that the electron potential is localized on Zn4O clusters and there is no electron delocalization with the organic linkers, confirming no orbital overlap for energy transfer through metal–ligand charge transfer processes.
Reaction scheme for synthesis of Isoreticular MOFs using modified solvothermal method followed by solvent driven self-assembly.
(a) A SEM image of IRMOF-1 microstructures, (b) crystal structure of IRMOF-1 retrieved from crystallographic open database, and (c) electron density potential distribution of IRMOF-1 modeled from VESTA.
As a first member of isoreticular series, IRMOF-1 has explored for luminescence due to ZnO quantum dots behavior, which has been believed, contributing to luminescence. The ZnO QD absorption and emission spectra from electronic transitions have been investigated, suggesting that that the luminescent behavior of IRMOF-1 arises from a O2 − Zn+ → O − Zn+ charge-transfer transition within each tetrahedral Zn4O metal cluster, which has been described as a ZnO-like QD [46]. The photoluminescence emissions of IRMOF-1 with intensity peak maximum at 525 nm, was ascribed to energy harvesting and LMCT from 1,4-benzenedicarboxylate (BDC) linked to the Zn4O cluster. The nature of the luminescence transitions in IRMOF-1 nanoparticles has been investigated by Tachikawa et al. where the transition responsible for the green emission of IRMOF-1 is similar to that of ZnO [47]. Therefore, the emission observed in IRMOF-1 has been speculated to originate from the ZnO QD not from the ligand. However, Further investigations demonstrated that ZnO impurities in the material gave rise to the emission assigned to the quantum dot like luminescence and that pure MOF-5 displays a luminescence behavior that is more closely relevant to that of the ligand. [9] However, the exact nature of the luminescence of MOF-5 is still under dispute with ligand− ligand charge transfer, [10] ligand-centered, [9] and ligand–metal charge transfer [11] mechanisms as primary suggestions.
In an on-going study, our group has been investigating optoelectronic behavior of IRMOF-1. As depicted in Figure 5, UV–vis absorption spectrum shows absorption vibrionic features similar to the linker with two absorptions peaks at 208 nm and 240 nm along with a shoulder peak at 285 nm. The emission spectrum collected by exciting at 240 nm exhibits linker-based emission with three well-resolved vibrionic transitions at 328 nm, 364 nm, and 377 nm. We observed a small high energy shoulder peak at 464 nm, which corresponds to an excitonic transition of Zn4O nodes. However, we have no observed a longer wavelength emission peak at 525 nm, which has claimed in prior studies to energy harvesting and LMCT from 1,4-benzenedicarboxylate (BDC) linked to the Zn4O cluster. Therefore, our findings support that IRMOF-1’s luminescence comes from linker emission rather than the charge transfer processes. This further excludes the emission originating from the ZnO quantum dots like clusters of Zn4O. The optical band gap calculated from the UV–visible spectrum on-set is found to be 3.97 eV. There are no experimental band gaps reported for IRMOF-1 up to date.
Photophysical properties of IRMOF-1 – (a) UV–visible spectrum and (b) photoluminescence spectrum in solution (ethanol).
Significant research efforts have demonstrated successful synthesis of a variety of isoreticular MOFs (IRMOFs) with the formula of Zn4O(L)3 (where L is a rigid linear dicarboxylates) using traditional solvothermal method, which uses zinc nitrate as metal precursor and the respective organic ligands in an amide-based solvent system. These IRMOFs follow the same cubic topology as the prototypical MOF-5, a framework with octahedral Zn4O(CO2)6 clusters, which are linked along orthogonal axes by phenylene rings. [3, 26, 48, 49] This family of IRMOFs-n (n = 1–16) gained significant attention in gas storage community due to its high pore volume and surface area. Among the IRMOFs series, IRMOF-1 and 8 have been extensively studied for gas adsorption and photoluminescence properties [39, 50, 51] but have not explored their optoelectronic properties until recently.
IRMOF-8 is constructed from the linkage of basic zinc acetate clusters and naphthalene-2,6-dicarboxylic acid units (NDC). Originally reported IRMOF-8 with non-interpenetrated cubic crystal lattice has only been extensively studied for gas sorption and storage applications [50, 51]. Later, a number of interpenetrated phases of Zn4O(ndc)3-based systems have been discovered [52, 53, 54]. Although the synthesis of interpenetrated IRMOF-8 (INT-IRMOF-8) are similar to that of IRMOF-8, the possibility that typical solvothermally synthesized IRMOF-8 contains at least a significant amount of an interpenetrated phase. There are modified synthesis methods have been introduced to make fully non-interpenetrated IRMOF-8 [55] and INT-IRMOF-8 [23, 55]. The crystal structures of non-interpenetrated IRMOF-8 and INT-IRMOF-8 along with their space filling structures, acquired from the Crystallographic Open Database (COD) and generated using VESTA are depicted in Figure 6.
Crystal structures of: (a) non-interpenetrated IRMOF-8 and (b) its space filling view, (c) INT-IRMOF-8 and (d) its space filling view.
Recently, our group has introduced a modified solvothermal synthesis method, which involves a solvent polarity driven self-assembly process to make hierarchical microstructures of INT- IRMOF-8, exhibiting promising optoelectronic properties for the first time [23]. Instead using zinc nitrate as the metal precursor, the synthesis we developed utilizes zinc(II)acetate as the metal precursor. Hierarchical microstructures of INT-IRMOF-8 nanocrystals can be prepared in high yield in the presence of minimum volume of dimethyl formamide by mixing zinc(II) precursor with naphthalene-2,6-dicarboxylic acid at room temperature followed by subjecting to solvothermal annealing at 260°C for 7 minutes [23]. Microstructures visualized under TEM (Figure 7(b)) reveal that they are hierarchical layers of self-assembled nanocrystals with randomly arranged voids among the nanocrystals. The wide-angel X-ray scattering (WAXS) pattern along with the selective area electron diffraction (SAED) pattern have shown that the microstructures are made from self-assembled nanocrystals of INT-IRMOF-8, which exhibits lamella packing pattern (Figure 7(c) and (d)), benefiting for optoelectronic behavior.
(a) Interpenetrated view of INT-IRMOF-8’s crystal structure; (b) a TEM image of a microstructure; (c) the SAED pattern of a microstructure taken from the TEM under dark field diffraction mode along with (d) a TEM image of the respective microstructure. [Figure 7 is re-created from the original data].
The photophysical properties of INT-IRMOF-8 exhibit mainly linker based optical properties. The presence of high intensity absorption peak set from 220 nm to 360 nm, which corresponds to vibronic π-π* absorption transitions of naphthalene core, evidencing the linker-based absorption, resulting from the lack of favorable spatial and energetic overlap of the metal and the ligand orbitals [21, 49]. Typically, MOFs’ photoluminescence behavior arises as a result of different types of charge transfer processes, which include metal-to-ligand charge transfer (MLCT), ligand-to-metal charge transfer (LMCT), ligand–ligand charge transfer (LLCT), ligand-centered luminescence, and metal-to-metal charge transfer (MMCT) processes [56]. However, this metal-centered luminescence depends on the metal type, ligand type, and their spatial orientations. The emission spectrum of INT-IRMOF-8 microstructures exhibits three emission bands, in which vibrionic transitions corresponds to only linker-based emission with no indication of additional emissions due to any charge transfer processes. The optical band gap reported for INT-IRMOF-8 is 2.82 eV [23] and the theoretical band gap reported in the past for non-interpenetrated IRMOF-8 was ranged from 2.83 eV to 3.27 eV [57]. There are no experimental band gaps reported for IRMOF-8 up to date.
The charge transfer ability of IRMOF-8 for the first time is evaluated by our group. The average electrical conductivity of INT-IRMOF-8 microstructures was ranged from 3.98 x 10−2 to 2.16 x 10−2 S cm−1, which is higher than the electrical conductivities reported for most MOFs (<10−10 S/cm). The interpenetrated structure, high crystallinity, and narrow band gap contribute to the to the electrical conductivity of hierarchical structures of INT-IRMOF-8 nanocrystals.
Among the series of IRMOFs (IRMOF 1–16) introduced by Yaghi and coworkers [58, 59, 60], several IRMOFs have shown effective selective preconcentration properties, including IRMOF-10 [61, 62, 63, 64].
Compared to IRMOF-1, physicochemical, optical, and electronic properties of IRMOF-10 with its 4,4′-biphenyldicarboxylate linkers has received much less attention. IRMOF-10 was first synthesized by Yaghi and coworkers [50, 58, 59, 60], Owing to its higher surface area and larger pore sizes, use of IRMOF-10 for gas absorption and separation and hydrogen storage have been widely investigated, but scarce attention has been paid to other properties of IRMOF-10, such as structural stability, optical and electrical properties, electronic structure, and chemical bonding. The first publication about biphenyl MOFs already anticipated the major challenges related to Zn-biphenyl MOFs: the growth of single-crystals and interpenetration. A structure from single-crystal XRD of non-functionalized IRMOF-10 is not yet available. A single-crystal X-ray structure analysis of a non-interpenetrated IRMOF-10 derivative was not reported until the breakthrough of the group of Telfer, which showed how interpenetration can be effectively suppressed by using thermolabile protecting groups in the synthesis of amino-MOFs [65]. Following the modified solvothermal synthesis method introduced by Rathnayake et al., microstructures of non-interpenetrated IRMOF-10 was successfully synthesized, and crystal structure was confirmed by matching the powder XRD traces with the simulated XRD pattern. The microstructures morphology is depicted in Figure 8(a) and crystal structure retrieved from the Crystallographic Open Database is depicted in Figure 8(b). IRMOF-10’s single crystal structure reveals three-dimensional coordination framework, formed by periodic arrangement of Zn(II) atoms, which is tetrahedrally coordinated by four oxygen atoms from four biphenyl linker units, following the unit formula of Zn4O(L)3 with cubic topology as IRMOF-1.
(a) A SEM image of IRMOF-10 microstructures, (b) crystal structure of IRMOF-10 retrieved from crystallographic open database, and (c) electron density potential distribution of IRMOF-10 modeled from VESTA.
The electron potential density localization surrounding the metal oxide nodes and organic linker units in IRMOF-10’s unit cell reveals the electron density distribution with respect to the biphenyl conjugation length. As shown in Figure 8(c), the electron potential is delocalized within metal oxide nodes and bi-phenyl units, and partial distribution of charges has increased around bi-phenyl units compared to naphthalene units of IRMOF-8. Thus, the findings suggest that linker length has more pronounced effect on the individual material’s electronic band structure and density of state, providing clear visualization on the localization of electronic potential within the crystal lattice. The delocalization of electron density potential through biphenyl linkers evidences its potential to be used as optoelectronic materials. Thus, exploring its electronic structure, band gap, optical, and electrical properties is a major interest to the materials science community. However, despite computational investigations on theoretical prediction of optoelectronic properties, [66] there are no experimental investigations on IRMOF-10’s optoelectronic behavior has been conducted up to date.
The equilibrium solid-state structure, electronic structure, formation enthalpy, chemical bonding, and optical properties of IRMOF-10 have investigated with density functional calculations. Electronic density of states and band structures study have shown that the band gap for the IRMOF-10 is ranged from 2.9 eV to 3.0 eV, resulting in a nonmetallic character [66]. Until now, there are no experimental studies available to verify theoretical predictions on IRMOF-10’s electronic structure. The calculated optical properties of IRMOF-10 provide useful information for future experimental exploration. The optical properties (dielectric function, refractive index, absorption coefficient, optical conductivity s(v), reflectivity, and electron energy-loss spectrum of the IRMOF-10 have computed in the past, [66] but there is no experimental investigation conducted up to date.
Recently, our group has studied optoelectronic behavior of non-interpenetrated IRMOF-10. As shown in Figure 9, we explored the photophysical properties of non-interpenetrated IRMOF-10 and calculated its optical band gap. IRMOF-10 exhibits linker-based absorption with absorption maximum at 282 nm along with a shoulder peak at 222 nm. IRMOF-10 shown blue luminescence with broader emission ranged from 310 nm to 450 nm along with the emission maximum at 353 nm. The optical band gap calculated from the UV–visible spectrum on-set is 3.80 eV, which is narrower than the optical band gap of IRMOF-1 and larger than the theoretical band gap predicted from computational analysis.
Photophysical properties of IRMOF-10 – (a) UV–visible spectrum and (b) photoluminescence spectrum in solution (ethanol).
In summary, the conjugation length of the organic linker in IRMOFs contributes to the semiconducting properties rather than the periodic pattern or the distances between the Zn4O clusters. The conjugation length of organic linkers of IRMOF-1, 8, and 10 described here differs from one aromatic unit (benzene) to one and half aromatic unit (naphthalene) to two aromatic units (biphenyl). The resonance effect arises due to the conjugation speaks directly to the photophysical behavior and optical band structure characteristics, reflecting a clear trend in narrowing the band gap with gradual increase in the conjugation length of the ligand. The dramatic change in the optical band gap upon changing the organic linker in the MOF structure has also been reported in the past [66]. Thus, these studies evidences that the semiconducting properties of MOFs strongly depends on the resonance effects from the organic linker [67].
With a growing demand for continuous miniaturization and functional scaling, the complementary metal-oxide semiconductor (CMOS) platform continues to drive advances in integrated circuits (IC), nanoelectronics and information processing technologies. While it is now possible to produce an amazing array of nanoscale materials and morphologies, the assembly and integration of these nanostructures into ordered arrays, with other materials, remain key challenges. Moore’s Second Law projects a need for new, high throughput fabrication approaches that can produce useful and defect free nanostructures for future silicon-based CMOS related technologies. Recent advances in nanomaterial synthesis enable new families of emerging research materials (ERMs) that show potential for extending and augmenting existing CMOS technology, with respect to wafer level manufacturability, uniformity, reliability, performance and cost, and they warrant additional research focus and verification. The integration of More-than-Moore, application specific, materials and structures on a CMOS platform leverages the best of both technologies, though this added complexity also challenges the extensibility of conventional fabrication and patterning methods. Consequently, there remains a need for simple fabrication methods that can create two- and three-dimensional ordered functional nanostructures, which can adapt to a wide variety of materials, patterning, and application needs.
Highly crystalline microstructures of MOFs have been paving the path, addressing the current challenges in fabrication needs that create two- and three-dimensional ordered structures and which are adaptable to a wide variety of materials specific applications. These nanoscale building blocks, and their assemblies combine the flexibility, conductivity, transparency, and ease of processability of soft matter (organic) with electrical, thermal, and mechanical properties of hard matter (inorganic). They offer a new window for fine-tuning structural nodes with known geometries and coordination environments. With respect to the fabrication of ordered nanoscale structures, MOFs have several advantages. First, since they are themselves a highly ordered self-assembled nanostructure, as a result of their crystallinity, their pore dimensions are completely defined, making knowledge of atomic positions possible. Second, the nanoporosity of their structure results from geometric factors associated with the bonding between their inorganic and organic components, enabling rational template design [68]. Third, unlike the conventional template materials, MOFs possess a high degree of synthetic flexibility with potentially widely tunable electrical, optical, and mechanical properties. Surely, the development of simple, versatile low-cost methodologies for the design, production, and nanoscale manipulation of innovative functional organic–inorganic hybrid building blocks will provide a powerful new capability for designing, integrating, and patterning new nanoscale materials with tunable properties onto a CMOS platform. Recent milestones of MOFs in photovoltaic, optical and chemical sensing, and field effect transistors highlight the potential of these materials for future electronic devices, heterogeneous platforms, non-traditional patterning opportunities [16, 69, 70, 71].
Interest in using these materials in fields such as gas storage [72], separations [73], [sensing [21], and catalysis [74] is rapidly accelerating. The advantages of MOFs for above applications are promising due to the wide range of possibilities of the rational design inherited in these materials. Thus, superior properties and new understanding with respect to the interaction of small molecules with nanoporous materials are being achieved. Although most MOFs are found to be dielectrics, a few semiconducting frameworks are known [23, 37, 75, 76]. The theoretical predictions conduced up to date on variety of MOFs suggest that there are possible MOFs with semiconducting properties [77, 78, 79] . MOFs that are magnetic [80], ferroelectric [81, 82], proton-conducting [83, 84, 85, 86], and luminescent [87, 88] are also known. Additionally, their porosity creates the potential to introduce non-native functionality to a given structure by infusing the accessible volume with a second molecule or material. Moreover, because the chemical environment within the pore can be modified, it is possible to tailor the interface between the MOF and a templated material to stabilize specific materials or nanostructures. Consequently, MOFs and the coordination polymers of crystalline nanoporous frameworks possess many of the properties of an ideal template.
Despite the endless possibilities for how MOFs could be used for device applications, when using MOFs for semiconductor microelectronic devices such as sensors, field-effect transistors, light harvesting and absorbing, light-emitting diodes, thermoelectric devices, energy storages and lithium ion batteries, and scintillators, it is necessary to understand how these materials function within the device and how they will interface with other functional and structural elements. Therefore, this section focuses on providing a future prospective for advances that must be made for their realization in electronic devices. A possible MOF-device roadmap, which identifies MOFs applications in electronic devices along with machine learning for new MOFs developments and MOFs database screening for novel properties is depicted in Figure 10. Our intention of providing this roadmap is to stimulate future endeavors of MOFs roadmap for electronic industry by translating current MOFs basic research agenda into applied research in the future. The roadmap that we identified here is created by combining the prospective previously provided by Allendorf et al., focusing five major fields pertinent to device fabrication [89]. These previously proposed areas include: (1) Fundamental Properties, (2) Thin film growth and processing, (3) MOFs hybrid and multilevel structures, (4) Device integration, and (5) Manufacturing issues. Our prospective for the proposed potential MOF-device roadmap particularly concentrated on member-specific applications in electronic industry, where functional density of MOFs can be utilized in subcategories of a wide variety of electronic devices. As the MOF-based optoelectronic field is fairly new and fall within the basic research stage, our roadmap is structured based on MOFs relative progress made so far and build upon the future road map comparing with the progress made in the field of organic electronics.
A possible MOF-device roadmap for electronic industry proposed by Rathnayake.
Exploring electronic properties, such as electronic structure, band gap, conductivity, electron, and hole mobilities, and dielectric constants of MOFs need to be one of the priority areas in the next decades and must be understood. Additionally, understanding lattice defects and their relationship to electronic properties must be explored combining theoretical and experimental approaches as they likely will limit the ultimate performance of a device. The field-effect transistor (FETs), which is the basic device building block for modern electronics, dictates the materials properties relevant to electronic applications. The FET performance is determined by the carrier mobility, source and drain contact resistance, and the capacitance of the gate electrode. Si is the preeminent materials for FET fabrication because of its bandgap of 1.1 eV, high carrier mobility, availability of multiple n- and p-type dopants, environmental stability, stable oxide, and high terrestrial abundance. However, Si based device fabrication requires enormous capital investment and Si is not compatible with a variety of low cost, flexible, transparent, and low melting temperature substrates. For these reasons, alternative materials including polymers, organic molecules, and more recently nanotubes and nanowires have been gaining a lot of attention for various emerging applications. The long-range crystalline order of MOFs implies that charge transport through delocalized conduction and valence bands typical of crystalline inorganic semiconductors is possible. Emergence of delocalized bands in MOFs will require that the π orbitals in the linker groups overlap effectively with the metal d orbitals. Such overlap is absent in the majority of synthetically known MOFs where carboxylate oxygen atoms are coordinated to the metal center through σ bonds. Therefore, most MOFs are electrical insulators. This barrier needs to be overcome in next decades, perhaps by synthesizing novel MOFs using higher order conjugated linkers and increasing the functional density of the MOFs. Modifying the linker structure could lead to better charge transfer between linker and the metal cations of the framework. One possible route has suggested replacing the carboxylate terminating linkers with isocyanide groups [89]. It has been shown that, Prussian Blue, a mixed valence crystalline compound with Fe(II) and Fe(III) ions coordinated with isocyanide ligands, is electrically conducting [90]. Another approach, suggested by Allendorf et al., is to introduce conducting phases into the MOF channels [89]. Some other approaches have been taken place to enhance electronic transport properties of MOFs by introducing other conductive nanomaterials, inorganic oxides, polymers, and carbon nanotubes into MOFs framework [91, 92, 93] .
Atomic level fundamental understanding that cannot be obtained readily from experimental methods, is necessary to address MOFs electronic band structure, density of state, band gap, and electron and hole mobilities. There has been increasing accuracy of predictive results using molecular dynamics (MD) force fields (FF) and DFT approximations for various MOFs’ property studies [94, 95, 96, 97, 98, 99, 100]. Density Functional Theory (DFT) methods using periodic boundary conditions have been popular for predicting the electronic structure of MOFs [57, 67, 101, 102]. However, DFT-based computational calculations are underestimate excited state energies by about a factor of two. Adapting high-accuracy methods, such as Quantum Monte Carlo (QMC), DFT + U, and GW are not feasible for systems with large numbers of electrons. For example, practical QMC calculations currently could not apply to the systems that exceed 1000 electrons. One formula unit of IRMOF-1 has 760 electrons and 106 atoms. Owing to these limitations in current computational approaches, MOFs are much more challenging than traditional electronic materials with much smaller unit cells. The computational methods for predicting properties of MOFs are at an early stage of development, in particularly for predicting electronic properties of MOFs [57, 101]. Developing simple and rapid analytical approaches are not only a necessary tool to experimental investigations but also can be used as an accelerate investigation and predictive tool by themselves to screen semiconducting MOFs from the database of synthetically known MOFs. Such analytical approaches combined with computational studies will eventually enable the design of machine learning approaches for large-scale screening of existing and hypothetical MOF structures for specific applications [103, 104, 105].
MOFs are also showing promise in their use as electrolytes due to their low electronic conductivity, tunable polarity, and high porosity [106]. There are many ways that MOFs have been employed to elevate the downfalls of current electrolytes. For example, they have been using as hosts for liquid electrolyte solutions or ionic liquids [107, 108]. However, the drying of the electrolyte solution within the MOFs presents an issue since the ion transport is mostly achieved by the solvent molecules within the electrolyte rather than by the MOF itself. Furthermore, MOFs is used as a filler to reduce the crystallinity of SPEs [107, 108]. However, up to date MOFs have not been explored to be used as a solid electrolyte excepts in a composite form [109]. One way to achieve this is designing lithium-based metal organic frameworks (Li MOF) where excess lithium is transferred through the defects in the MOF structure. However, research regarding Li MOFs as solid electrolytes is currently lacking. The majority of MOF/electrolyte studies are only focused on employing MOFs as a host of ionically conductive materials rather than utilizing MOFs as solid-state electrolytes. Therefore, we identified this area of research in the proposed roadmap to stimulate investigating the potential of Li-based MOFs as solid electrolytes. There are different types of Li-MOFs already developed [110, 111, 112], but many of them are designed for applications other than battery electrolytes. We believe that Li- MOF structures can be tuned for lithium transport. Overall, Li MOFs show potential for the use as solid ionic conductors and much research should be performed to explore their possibility for solid state electrolytes and battery components.
Exploring thermoelectric properties of MOFs emerges five years ago along with exploring the electronic properties of MOFs by systematic structural modifications and introducing guest molecules onto MOFs. The first thermoelectric property measurements on MOFs has introduced by Erikson in 2015 [113]. then, up to date, there have been less than ten publications in thermoelectric MOFs, thus this field of research is relatively new. Highly nanoporous MOFs are promising since porosity can reduce the lattice thermal conductivity. The effect the conjugation length of the organic linker that tailors the pore dimension for lattice thermal conductivity must be investigated. The thermoelectric figure of merit that measures the efficiency of a thermoelectric device can be improved by decreasing the lattice thermal conductivity. It is believed that changing the conjugation length or the complexity of the organic linker changes phonon scattering, thereby changing the lattice thermal conductivity [77, 114]. The ligand modifications can be successfully achieved by isoreticular synthesis approaches. Also, increasing the porosity of MOFs increases phonon scattering that also reduces thermal conductivity [114]. Therefore, in order to utilize MOFs as active materials in thermoelectric devices, understanding the contribution of phonon vibrations to lattice thermal conductivity is essential and must be investigated. Directing future research on thermoelectric MOFs towards experimentally investigating thermoelectric properties of MOF based thin films to find ways of decreasing thermal conductivity by structural modifications to the organic ligand is beneficial.
In order to use MOFs as photoactive layer for energy harvesting and conversion, MOFs should possess decent light harvesting capability in the region from visible light to near-infrared (NIR). As the material’s light-harvesting window is primarily determined by its band gap, synthesizing a MOF with a semiconducting band gap that can absorb light in the solar spectrum should be a requirement for it to serve as the photoactive material. Given that the electronic configuration of MOFs is contributed by both the constituent metal ion and the organic linker, the resultant bandgap and semiconducting properties of MOFs can thus be tailored by their structural design and engineering. Since most MOFs possess large band gap due to lack of overlap between metal ion and the organic linker and low degree of conjugation, they cannot effectively absorb light in the solar spectrum. The ligand center of MOFs plays a dominant role in its resulting light harvesting behavior [77, 114]. Tailoring the structure and its composition, MOFs charge transfer processes can be improved to enable the photocurrent of MOFs and fulfilling the photoactive functions.
To effectively reduce the band gap of MOFs and enrich their semiconducting properties for photovoltaic applications, three strategies can be implemented and have been identified [115]. These strategies are: (1) selecting electron rich metal nodes and conjugated-based organic molecules, (2) enhancing the conjugation of the organic linker, and (3) functionalizing the organic linker with electron-donating groups, such as hydroxyl, nitro, and amino groups. Additionally, facilitating electron delocalization through guest-mediated p-donor/acceptor stacks can also effectively diminish the band gaps of the materials [115]. Besides narrowing the band gap, electronic structure that contributes the semiconducting properties of MOFs also play a vital role as sufficient dissociation of the photoexcitons generated in the MOFs is required to produce a reasonable photocurrent. In this regard, MOFs exhibit critical barriers to use as the photoactive materials directly and impedes its progress in photovoltaic applications to date. However, up to date, besides acting as the photoactive materials, the MOFs has been contributing to the photovoltaic community by serving as functional additives or interlayers to improve the performance and stability of the derived solar cell devices. In order to utilize MOFs for photoactive layer in photovoltaics, it is necessary to design electrically conductive MOFs. The research efforts developing more functional conducting MOFs are required in the coming decade.
Owing to synthetic processability using reticular chemistry, MOFs offer unusual properties paving the path for many opportunities and their use in optoelectronic devices. Their use in devices so far is limited to sensors and gas storage. However, MOFs field is moving towards exploring their optical and electrical properties to use in electronic devices. There are many MOFs with tunable bandgap, both ultralow-k and high-k dielectric constants, varied magnetic properties, luminescence, and a few with semiconducting behavior, suggesting MOFs as emerging material with unique properties exceeding any other class of materials. Combining the solvothermal synthesis method with self-assembly processes, we can achieve highly ordered nanoporous structures with precise dimensionality that creates the potential for electronics and self-assembly with atomic-scale resolution and precision. In order to become MOFs for electronic devices, many challenges must be solved, and electronic structures of MOFs should be revealed. The MOFs-device roadmap should be one meaningful way to reach MOFs milestones for optoelectronic devices and will enable MOFs to be performed in their best, as well as allowing the necessary integration with other materials to fabricate fully functional devices.
Authors acknowledge the Joint School of Nanoscience and Nanoengineering, a member of the South-eastern Nanotechnology Infrastructure Corridor (SENIC) and National Nanotechnology Coordinated Infrastructure (NNCI), supported by the NSF (Grant ECCS-1542174).
There is no conflict of interest to declare.
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