Infection Control in Dentistry and Drug-Resistant Infectious Agents: A Burning Issue. Part 1

1. Introduction

Dentistry seems to provide safe procedures for oral health care taking into account all adverse events (AEs). Nevertheless, death, injury, and malfunctions due to dental devices (DDs) increased from the MAUDE report in 2000–2012, and the endosseous implants were at the top of the DDs involved in AEs [1]. In the same period, the number of malpractice payments in dentistry increased by 12%, while those in other health professions fell [2]. Dental AEs, complaints, and claims seem to be relatively common in different countries [3]. About 4–17% of AEs are due to infection [4, 5]. The iatrogenic infectious risk in dentistry has not been quantify closely yet [6, 7], but recently, some outbreaks caused by infective agents, mainly blood-borne viruses and water-borne bacteria, have been documented in dental settings based on molecular biological assays and/or retrospective investigations [8, 9, 10, 11].

Some evidence exists around the hazard due of antibiotic-resistant infectious agents (ARIAs) in dentistry. Fatal adverse events (FAEs) had been reported within 90 days after different instances of dental care [7]. In the last 50 years, FAEs caused by an infection have (a) increased while respiratory complications and bleeding are steady, and those caused by cardiovascular or related to anesthesia have decreased, (b) significant (12%), (c) mainly associated to dental surgery (implant surgery/placement, extractions (>6 erupted teeth or impacted tooth/teeth), surgical extractions, osseous surgery, sinus lift surgery, bone biopsy, orthognathic surgery), and (d) associated with much longer times until death compared with other causes of death [7]. A study on dental malpractice analyzed 4149 legal claims (both in and out of court) from the years of 2000 to 2010 in Spain [12]. About 2.7% of all AEs resulted in death, and 45% of them were caused by infection. In the absence of specific information reported in both papers [7, 12], we do not exclude the possible involvement or nonrecognition of ARIAs or the failure of proper drug treatment in those FAEs. Recently, in an interview, Davies stated that in 20 years time even minor surgeries could be fatal because of infections [13].

We consider that the following two reviews are important and indicative of the limitedness of data published up to 2011–2012 in dentistry [14, 15]. The first review on methicillin-resistant Staphylococcus aureus(MRSA) infection concluded that (1) transmission was ascertained during surgical interventions, particularly in surgical units and among head and neck cancer patients; (2) carriage rates among dental healthcare personnel (DHCP) were lower than those among other healthcare workers (HCWs); (3) carriage rates among adult patients were low, whereas among pedodontic and special care patients rates were higher than those found in the general population; and (4) MRSA had been detected in the environment of emergency, surgical units, and in dental hospitals [14]. In the second review, multi-resistant bacteria infections had been included among the main healthcare viral and bacterial infections in dentistry [15], but the transmission of Enterobacteriaceae and/or their resistant strains did not exist yet. The interest on Enterobacteriaceae is warranted since they are susceptible to only a few (if any) antibacterial drugs.

Here, we think it is important to update these conclusions in the light of the global, wide, and long-term abuse and misuse of antibiotics in dentistry and selective pressure on opportunistic bacteria by favoring potentially pathogenic strains [16, 17]. In addition, the limited awareness on infection prevention guidelines and lapses and errors during infection prevention according to Centers for Disease Control and Prevention (CDC) dental guidelines [6, 8, 9, 10, 11] sustain the evidence of possible reservoirs of ARIAs in humans (patient, dental staff) and in the environment (clinical contact surfaces (CCSs), dental instruments, and dental unit water lines (DUWLs)) and possible hazards in surgical dental setting. Our approach is in line with the CDC recommendation, in which it states that “Preventing infections negates the need for antibiotic use in the first place, and scientific evidence shows that reducing antibiotic use in a single facility can reduce resistance in that facility” [18, 19, 20].

In addition, the cluster of above problems is important for risk management, since it is rationally “harmful” that opportunistic species and/or ARIAs were involved in implant failures [21, 22], periodontitis [23, 24], endodontic failures [25] and oral mucosal and deep infections [26].

Here, we discuss briefly main recent evidence and controversy on infections in dedicated dental and mainly in implant surgery, taking into account that many other aspects (i.e. surgery technique, geometry, materials, and surface of dental implants) have already been reviewed extensively [27, 28, 29, 30]. Dental implant (DI) complications are a burning issue, since the current demand of DIs is high (20 DIs in Italy and 4 in the USA per year per million of inhabitants), mainly applied in private offices, and the global DI market size was estimated at 3.77 billion USD in 2016 growing at a compound annual growth rate (CAGR) of 7.7% over 2024 [31]. It is important to underline that the incidence of esthetic, technical and infective complications is still high in implantology, and the 5-year infective complication increased from 7.4 to 9.4% [32]. In general, the expected implant-associated infections and the outbreaks from opportunistic pathogens (Staphylococci, Enterococci, Pseudomonas,etc.) will always be more important. In addition, we have to take into account other factors linked to risk management such as the impact on reputation and finances, the loss of protection of insurance coverings and reimbursements, and shocking advertising rapidly spreading through social networks in the case of outbreaks [8, 9, 10, 11, 33, 34, 35].

Here (Part 1), we focus on the insufficient compliance with infection control (IC) recommendations in oral healthcare and the difficulties and problems of standard precaution implementation also in ambulatory surgical centers [6, 36, 37, 38, 39, 40, 41, 42]. In general, dental surgery and implantology are predominantly done in general dental practice under local anesthesia or sedation [43, 44]. This is a very important aspect since the cross-infection is widespread and more difficult to control compared to surgical rooms. We have divided problems and difficulties for infection prevention into different areas concerning the innovative molecular biology techniques; antibiotic misuse and overuse in dentistry; opportunistic pathogens and antibiotic resistance in dental patients and dental healthcare workers; and surgical infection prevention in dentistry. While in the chapter (Part 2), we have reported infection control implementation, not compliance, lapses and errors during infection prevention according to CDC dental guidelines. We focused on hand hygiene, gloves, environment decontamination, and instrument reconditioning in more detail [6, 43, 44, 45, 46, 47].

2. Approach

The electronic literature search was conducted via the PubMed and Google Scholar databases (from January 2010 up to and including April 2018) using various combinations of the following key indexing terms: (a) patient safety; (b) infection control; (c) implant; (d) endodontia; (e) sterilization; (f) reconditioning; (g) critical items; (h) semicritical items; (i) hand hygiene; (j) DUWL; (k) sharps safety; (l) personal protective equipment (PPE); (m) disinfection; (n) MRSA; (o) VRE; (p) ARIAs; (q) guidelines; and (r) cross-infection. In addition, manual searches were carried out in INTECH books. Then, bibliographic material from the papers has been used in order to find other or older appropriate sources. A total of 179 papers and links were found suitable for inclusion in this chapter (Part 1). Only few papers do not have a DOI or PubMed classification, but the available link by Internet and accessed date have been added.

3. Focus on molecular biology techniques

Expanded Human Oral Microbiome Database (eHOMD) provides the scientific community with broad and up-to-date information on the bacterial species present in the human aero-digestive tract, including the oral cavity. Genomes for 482 taxa (63% of all taxa, 89% of cultivated taxa) are currently available on eHOMD [48]. Fast and very sensitive molecular biological techniques, classified into nucleic acid-based methods [quantitative real-time polymerase chain reaction (PCR), multiplex PCR, microarray, next-generation sequencing technologies, etc.], are available for the screening, detection, and functional activities of pathogens and antibiotic-resistant bacteria, even those not cultivable by classical microbiological methods and by using both patient biological fluids and samples from inanimate objects (surface, air, DUWL colonization, DDs, and instruments) [49, 50, 51, 52]. This is possible because DNA molecules can survive for long time and can be amplified. Current microbiological laboratory approaches based on high-throughput real-time PCR allow quick, easy, and cheap detection of the oral microbiome and the antibiotic resistome, throughout 300 antibiotic resistance genes [53] as far as the rapid diagnosis of virulent slime-producing strains associated with dental caries [54]. The specificity of MRSA plus MSSA carriage detected with Xpert MRSA is better than standard culturing techniques, being 37.9 vs. 23.6%, respectively [55]. Concerning microbiological features of peri-implantitis cases, culture methods were able to detect 81.4% of the targeted species of the cases, whereas “checkerboard DNA–DNA hybridization” method 99.3%. In relation to the limited association between the bacterial contamination and the severity of the peri-implantitis [56], it is decisive the sampling procedure, around DIs and during swabs on dental items, and the use of the proper primer sequence for specific genes in different strains (i.e. ica genes for S. epidermidis and S. aureus) [57]. PCR is more effective in detecting E. faecalisthan other analytical tools, such as culturing. E. faecalishas been found in root-filled teeth associated with periradicular lesions in a range of 0–70% by culture and 0–90% by PCR [58].

It is important to note that microbiological analysis (by culture or DNA-based methods) is rarely used in dentistry mainly because of the difficulties to delay the antibiotic treatment and for the plethora of infective agents involved in inflammatory diseases in dentistry. In addition, specific sampling procedures are needed since the virulence features of microorganisms and problems to sample deep periodontal and peri-implant pocket and abscesses. Sequencing methods that evaluate the entire microbiome are needed to improve identification of microorganisms (pathogen, opportunistic, noncultivable, drug-resistant ones) associated to peri-implant infective diseases and to develop suitable countermeasures with the expertise of clinical oral microbiologists [59]. In addition, emerging approach based on optical nanoprobes, biosensors, and protein biomarkers suitable for peri-implant crevicular fluids has been proposed to identify the severity and progression of the disease and the response to therapy [60, 61].

4. The broad antibiotic misuse or overuse in dentistry

Globally, antibiotic prescription in dental care has continuously increased over the last 17 years, and a lot of evidence has been published on wide antibiotic misuse or overuse, in industrialized, low- and middle-income countries [62, 63, 64, 65, 66, 67, 68, 69, 70]. Dental prescriptions make up 5–11% of all antibiotic prescription among patients in some European countries, Canada, and the USA [19, 20, 65, 71, 72]. The rate of prescription increased the most among dental patients of 60 years or above.

It is important to underline that antibiotic prescription is placed without a microbiological analysis and has mainly prophylactic aim in dentistry. Recently, the prescription of antibiotics in dentistry was reviewed by Holmstrup and Klausen, while the use of antibiotics in odontogenic infections, in addition to the removal of the source of infection, by Martins [73, 74]. A significant percentage (19–37.5%) of microorganisms collected from their patients were penicillin resistant; nevertheless, the relationship between the clinical outcomes and microbial resistance with penicillin is not clear [74].

Recently, to overcome the misuse and abuse of antibiotics in dentistry, different institutions and associations recommended a more restrictive antibiotic policy to improve treatment efficacy and decrease bacterial resistance. Specific guidelines have been published for implantology [17], endodontia [75], oral surgery [17], third molar extraction [76], and medically compromised patients [77] and to prevent infective endocarditis [78, 79] or prosthetic joint infections [80].

5. Focus on opportunistic pathogens and antibiotic resistance in dental patients and dental healthcare workers

Here, based on recent and current knowledge, we focus on two well-known bacterial strains, S. aureusand Enterococcus, and their resistant strains. It is known that S. aureusand Enterococcus faecalishave been implicated in implant-associated infections [21, 23, 24, 81], endodontic infections [22, 25, 82], and recently in an outbreak of Enterococcusendocarditis [11]. We focus on these Gram-positive bacteria for the high innate resistance or ability to become resistant to most antibiotics along with some other virulence factors (hydrophobicity, adherence to abiotic surfaces (including dental implant materials), biofilm formation, ability to growth also in anaerobic conditions) [83]. These features are important in the exploration of standard precaution failures since bacterial adherence on dental implants, collagen-based biomaterials, or many other inanimate objects is known to be linked with the presence of surface components with nonpolar/hydrophobic vs. polar/hydrophilic characteristics. In addition, we focus on Staphylococci and Enterobacteriaceae as markers since they are considered prioritized bacteria according to antibiotic resistance threats, and better knowledge is available on their virulence factors and for dental settings (i.e. contamination on hands and environments, etc.) [6, 43, 45, 46, 47].

6. Surgical infection prevention in dentistry: from gold standard to reality

It is well known that the best choices for dental and implant surgery are a specialized and well-trained dental staff (surgeon, clean nurse, second nurse, anesthetist, etc.) and a specific designed surgical room with proper isolation, clean air system ventilation, instruments for automatic surface decontamination and ISO standards (UNI EN ISO 14644-ISO 5) that allow a very low environmental contamination, and proper antiseptic procedures (including hand washing, wearing, safe instruments passages). Unfortunately, this setting up is used in the case of maxillofacial surgery, and it is commonly present and economically sustainable in hospital surgical dental department. In ambulatory dental offices, there is no isolation and a full separation of the environments used for general dentistry and those used for implant surgery or dental extractions. Only rarely is present a clean air ventilation system according to ISO standards. This difference is very important since in general dental practices the cross-infection is widespread, and the infection prevention is more difficult or less controllable (i.e. absence of the second nurse, environmental contamination) compared to hospital surgical rooms. There are few controls legislated over the operating environment in ambulatory and private dental offices.

Bearing in mind the higher risk of contamination of ambulatory surgical areas, above all during long surgeries (sinus lift, several implant placing, guided bone regeneration (GBR)) and in medically compromised patients, we cannot exclude that a part of implant failures is the result of a chain of personnel latent errors, including some improper antiseptic measures (not surgical hand hygiene, unsterile gloves, improper use of mask, contamination of operating surface or room air, unsterile barrier covering, lack of surgical guide disinfection and mouth rinses, suture contamination by perioral skin bacteria, among others), as far as untrained professional practice [17, 41, 42, 44, 126].

Maintaining sterile conditions during the surgical procedure is of utmost importance. Saliva, perioral skin, unsterile instruments, contaminated gloves, operating room air, or air expired by the patient, all interfere in the surgical procedure leading to contamination of the implant site [43, 45, 46, 47]. It has been reported that the prevalence rate of MRSA was the highest in samples from dental surgery compared to other dental environments [102]. MRSA’s involvement in surgical infections is in line with the estimated infective dose, which is very low (4 CFU), and surface contamination (<10 CFU/cm²) [127, 128]. In ambulatory surgical centers, the main infection control lapses identified were hand hygiene and use of PPE, injection safety and medication handling, equipment reprocessing, and environmental cleaning [41, 42, 129].

The majority of DIs are predominantly placed in general dental practice under local anesthesia. Concerning local anesthesia, hand contact is the main source of the wide contamination reported on anesthetic syringes and anesthetic tubes used in dentistry [130]. Then, DHCP has to follow scrupulously key recommendations for safe injection reported in CDC guidelines [6]. Taking into account the recent outbreaks, the violations seem very hazardous in dentistry [8, 11]. In addition, it is absolutely forbidden and highly risky in the reuse of whatsoever single use sterile medical devices (i.e. irrigation sets) and the use of the water from DUWLs during implant and piezoelectric surgery, etc. [6]. The use of sterile devices and instruments is a need during surgical cares, but even after reconditioning, the contamination of surgical dental instruments and drills is significant even in hospital settings [131, 132, 133, 134]. Many other specific failures concerning dental instrument reconditioning will be discussed in Part 2. The importance of hand hygiene, sterile gloves, mask, and eye protection during surgery is well known. Violations are frequent and often surgical videos in dentistry show the surgical mask under the nose,that is risky taking into account MRSA nose colonization in dentists and dental nurses. We underline that it is a hazard to touch the barrier membranes during GBR with gloved hands: this is a frequent slip observed in untrained surgeons.

7. Conclusion

Human infectious diseases will be never-ending [174]. After limitation of dental benefits, there was an increase in the volume and severity of odontogenic infections, surgical cares increased 100%, and the related healthcare cost skyrockets [175]. The reported data show that opportunistic species and/or ARIA infections are nearby and expected to increase in dental setting [21, 22, 23, 24, 25, 26, 29, 81, 82, 85, 91, 92, 93, 94, 95, 96, 97, 98, 99, 101, 102, 103, 104, 105, 109, 110, 111, 112, 113, 114, 120, 121, 122, 123, 124, 136, 137, 138, 139, 140, 141, 145, 146, 147, 148, 149, 153, 154, 155, 159, 160, 165] due to the overuse of antibiotics in dentistry and the limited awareness on infection prevention guidelines and the lapses and errors during infection prevention [176]. Moreover, it is considered alarming the genetic connection or similarity between MRSAs isolated in dental clinics and on dentures and the EMRSA-15 or EMRSA-16 clone [97, 102, 119]. In addition, Enterobacteriaceae and some resistant strains are present in oral cavity of dental patients, and recently, the transmission in dental practice has been proven [11, 120, 121, 122, 123, 124]. The incidence rate of enterococcal endocarditis among the total patient population at the oral surgery practice has been reported to be more than 200 times the expected rate among general population [11].

Then, dental teams have to face occupational and clinical hazards due to ARIA infections in dental facilities. In the absence of or limited new effective antibiotic discovery, the sustainable use of antibiotics is essential but have delayed significant effects [177] based on many collective actions (people information, professional dental-care providers, policy-maker and regulators, industry stakeholders). On the contrary, the prevention of cross infection by adopting guidelines is easily applicable and has had early significant effects on infection prevention and cost-saving [178, 179]. Moreover, it is basic to safeguard dental team reputation, insurance coverings, and reimbursements [8, 9, 10, 11, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 176] and to limit the nightmares to get rid of current dental implant infections [149].

Conflict of interest

L.B. had a service agreement with KerrHawe and is a consultant for Dental Trey Il Blog (http://blog.dentaltrey.it/), neither of which gave any input or financial support to the writing of this article. There are no other conflicts of interest to report.

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