Calculation of urinary catheter-associated infection rate and urinary catheter utilization ratio.
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"}]},book:{item:{type:"book",id:"6045",leadTitle:null,fullTitle:"The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus",title:"The Rise of Virulence and Antibiotic Resistance in Staphylococcus aureus",subtitle:null,reviewType:"peer-reviewed",abstract:"Staphylococcus aureus (S. aureus) is a growing issue both within hospitals and community because of its virulence determinants and the continuing emergence of new strains resistant to antimicrobiotics. In this book, we present the state of the art of S. aureus virulence mechanisms and antibiotic-resistance profiles, providing an unprecedented and comprehensive collection of up-to-date research about the evolution, dissemination, and mechanisms of different staphylococcal antimicrobial resistance patterns alongside bacterial virulence determinants and their impact in the medical field. We include several review chapters to allow readers to better understand the mechanisms of methicillin resistance, glycopeptide resistance, and horizontal gene transfer and the effects of alterations in S. aureus membranes and cell walls on drug resistance. In addition, we include chapters dedicated to unveiling S. aureus pathogenicity with the most current research available on S. aureus exfoliative toxins, enterotoxins, surface proteins, biofilm, and defensive responses of S. aureus to antibiotic treatment.",isbn:"978-953-51-2984-4",printIsbn:"978-953-51-2983-7",pdfIsbn:"978-953-51-5474-7",doi:"10.5772/67546",price:119,priceEur:129,priceUsd:155,slug:"the-rise-of-virulence-and-antibiotic-resistance-in-staphylococcus-aureus",numberOfPages:224,isOpenForSubmission:!1,isInWos:1,hash:"4f24bfdcb5cd606846da63b96000bed2",bookSignature:"Shymaa Enany and Laura E. 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She received her PhD from School of Medical Sciences, Niigata University, Japan, and spent her postdoc in USA and Japan. She was the first Arab scientist applying bacterial proteomic techniques helping in revealing good markers for microbes spreading in community. She received many awards for her scientific contributions. Recently, she awarded the most prestigious award in Egypt: the state encouragement prize for women in the field of health and pharmaceutical sciences, 2019. Also, she was awarded The World Academy of Sciences (TWAS) Young Arab Scientist Prize 2018 for Scientific Achievement in Medical Sciences. She was selected as a member of Egyptian Young Academy of Science, an evaluator on Academy of Scientific Research and Technology, a reviewer in International Exhibition of Innovation, and an affiliate of The World Academy of Sciences. Dr. Shymaa is also a part of the scientific committee of World Forum for Women in Science, a selected young leader in STS and WSF, a member in the global Open Science Group, and a collaborator in Global Burden of Disease. On Microbiology National Committee, she is working for achieving sustainable development goals for a better future. She was appointed an Egyptian ambassador in Next Einstein Forum (NEF), which showcases the global contribution and potential of scientists from Africa, enabling Africa to get onto the global scientific stage, and she is a selected member in COVID-19 Diagnostics group in Africa, as well as the co-chair of the COVID-19 Clinical Research Coalition platform (Immunology, Virology and Diagnostics Working Group) in low- and middle-income countries. 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Healthcare-associated infections (HAIs) are one of the most common complications in hospitalized patients, leading to increased hospitalization, morbidity and mortality and associated with additional costs (Geffers and Gastmeier, 2011).
\n\t\t\tUrinary tract infection (UTI) is common in hospitalized patients. It has been reported that in U.S. hospitals, among adults and children outside of the intensive care units (ICUs), the urinary tract is the most common site of HAI, accounting for 36% of infections, followed by surgical site infections (20%), bloodstream infections and pneumonia (11%, each) and other infection types (all 22%) (Klevens et al., 2007).
\n\t\t\tAlmost all healthcare-associated UTIs are caused by instrumental urinary tract procedures. In fact, the presence of a foreign body in the urinary tract predisposes the patient to UTI and alters the body’s ability to eradicate bacteria (Gray et al., 2010). It has been estimated that more than 80% of UTIs are associated with an indwelling catheter (Anderson et al., 2007) and notably, catheter-associated UTI (CAUTI) has been related with such complications that prolonged hospital stay, and increased cost, morbidity and mortality (Gould et al., 2009).
\n\t\t\tUrologic patients should be considered at high risk for a healthcare-associated UTI, because they are usually exposed both to urethral catheterization and instrumentation of the urinary tract. In a surveillance study conducted in an urologic clinic of an Italian university hospital the incidence of symptomatic UTIs was 1.4 per 1000 patient-days (Agodi et al., 2007).
\n\t\t\tSince of intrinsic (such as, severity of illness or impaired immunity) and extrinsic (such as, devise exposure: mechanical ventilation, urinary and central line catheterization) risk factors, patients admitted in ICUs are at high risk of HAIs (Lambert et al., 2011). Particularly, in Europe, the Annual Epidemiological Report on Communicable Diseases in Europe of the European Centre for Disease Prevention and Control (ECDC, 2009), show that 3% of patients staying more than two days in ICUs, acquire bloodstream infections, and 6.2% of patients acquire pneumonia.
\n\t\t\t\tUTI is one of the most common infection in ICU. The mean incidence density of UTI in patients admitted in European ICUs is 5.4 UTI episodes per 1000 patient-days. The majority of UTI (96.2%) are associated with the use of a urinary catheter (HELICS, 2005), that is the most important risk factor for development of UTI (Meddings et al., 2010). It has been reported that about 15% - 25% of patients may be exposed to short-term indwelling urinary catheters (Warren JW, 2001) and in several cases, catheters are placed for inappropriate indications. Urinary catheters are used frequently in ICUs for correct monitoring of urinary output, but, once inserted, catheters tend to remain in place until appropriate indications for their use end and thus CAUTI incidence increases as the duration of catheter use increases. Use of urinary catheters in the ICU causes breaches in the mucosa or may provide a surface for colonization, thus, increasing the incidence of CAUTI. The risk for infection is at least 5% per day of catheterization (Tissot et al., 2001; Elpern et al., 2009).
\n\t\t\t\tOther factors have been reported as potential risk factors for CAUTI including constitutional factors such as female gender, pregnancy and older age and potential modifiable factors such as poor nutrition, fecal incontinence, use of systemic antibiotics, severity of illness, impaired immune system function, and elevated creatinine level (Gray, 2010).
\n\t\t\t\tA recent multicenter study was conducted in a cohort of patients from 10 countries (Argentina, Brazil, Colombia, Greece, India, Lebanon, Mexico, Morocco, Peru, and Turkey) to estimate the excess length of stay (LOS) and mortality in ICU due to CAUTI. Results show that CAUTI lead to a small increase LOS in ICU, particularly, prolonging length of ICU stay by an average of 1.59 days, but CAUTI increase the risk of death by 15% (Rosenthal et al., 2011).
\n\t\t\t\tThus, it is necessary to implement every possible preventive measure that have proven useful in the prevention of CAUTI.
\n\t\t\t\tFurthermore, UTIs are often underdiagnosed due the lack of physician requesting systematic laboratory tests and urine cultures (Agodi et al., 2007). Diagnosis, particularly in the ICU setting, is very difficult, as asymptomatic bacteriuria may be hard to be differentiated from symptomatic UTI (Shuman and Chenoweth, 2010).
\n\t\t\t\tThe National Healthcare Safety Network (NHSN) is a system for the surveillance of HAI that aggregates data of surveillance, reported by hospitals participating in the network, into a single national database (Edwards et al., 2007). In the framework of the “Patient Safety component” of the NHSN, data are collected using standardized methods and definitions and are grouped into specific module protocols. Particularly, in the device-associated module infection control professionals collect data on CAUTIs that occur in patients staying in a patient care location such as an ICU, specialty care area, or ward. Indicators are calculated in terms of urinary catheter associated infection rate and urinary catheter utilization ratio (Table 1).
\n\t\t\t\t\n\t\t\t\t\t\t\t\tIndicator\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t |
Urinary catheter associated infection rate | \n\t\t\t\t\t\t\tNumber of urinary catheter-associated UTI x 1000 Number of urinary catheter-days | \n\t\t\t\t\t\t
Urinary catheter utilization ratio | \n\t\t\t\t\t\t\tNumber of urinary catheter-days Number of patient-days | \n\t\t\t\t\t\t
Calculation of urinary catheter-associated infection rate and urinary catheter utilization ratio.
The NHSN reports that in 2006 pooled mean urinary catheter utilization ratios in ICU and non-ICU wards ranged from 0.23 in inpatient medical/surgical ward to 0.91 in trauma ICU. The pooled mean of CAUTI rates ranged from 3.1 infections per 1000 catheter-days in medical/surgical ICU to 7.5 infections per 1000 catheter-days in burn ICUs.
\n\t\t\t\tIn Europe, the German National Reference Centre for surveillance of nosocomial infections was started in 1997 creating a nationwide surveillance system: the Krankenhaus Infektions Surveillance System (KISS) (Gastmeier et al., 2008). The surveillance methods of the National Nosocomial Infections Surveillance (NNIS) System (Garner et al. 1988; Emori et al., 1991) were used and for diagnosing HAIs the definitions of the CDC were adopted. Surveillance data obtained from January 2005 to December 2009 in German ICUs, report an urinary catheter utilization ratio of 0.81 and a CAUTI rate of 1.97 per 1000 device-days (Geffers and Gastmeier, 2011).
\n\t\t\tMajor challenges in appraising the quality of evidence in the CAUTI literature are represented by the limitations due to heterogeneity of definitions of UTI used in various published studies. Researchers have often used numerous different definitions for UTI, ranging from simple bacteriuria to symptomatic infection defined by combinations of bacteriuria and various signs and symptoms. Furthermore, the heterogeneity of definitions may reduce the quality of evidence for a given intervention and often precludes meta-analyses (Gould et al., 2009).
\n\t\t\t\tCase definition of UTI proposed by the Hospitals in Europe Link for Infection Control through Surveillance (HELICS) system is reported in Table 2 (HELICS-ICU, 2004). Particularly, in the HELICS protocol three different types of UTIs are identified and defined: microbiologically confirmed symptomatic UTI (UTI-A), not microbiologically confirmed symptomatic UTI (UTI-B) and asymptomatic bacteriuria (UTI-C) (HELICS-ICU, 2004). Of note is that UTIs may be added or not, optionally, in the HELICS protocol surveillance.
\n\t\t\t\tThe case definitions of UTI by the HELICS are similar to the case definition by the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN) (NHSN Manual; Horan et al., 2008), where CAUTIs are classified into two groups with specific sets of criteria for each: symptomatic urinary tract infections (SUTI) and asymptomatic bacteriuria (ASB). The only difference is that, in the HELICS, asymptomatic bacteriuria is defined as the subcategory UTI-C, and not as a separate category. Otherwise, the subcategories UTI-A and UTI-B are the same as respectively criterion 1 and 2 of the CDC/NHSN definition of symptomatic urinary tract infection. NHSN in January 2009 has revised the UTI definition criteria. Among the changes are removal of the ASB criterion and refinement of the criteria for defining symptomatic SUTI. The time period for follow-up surveillance after catheter removal also has been shortened from 7 days to 48 hours to align with other device-associated infections (NHSN Manual).
\n\t\t\tMicroorganisms causing CAUTI can be acquired by an endogenous source (such as, via meatal, rectal, or vaginal colonization) or an exogenous one (such as, via contaminated hands of healthcare personnel or devices).
\n\t\t\t\t\n\t\t\t\t\t\t\t\tUTI-A: microbiologically confirmed symptomatic UTI\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\tPatient has at least one of the following signs of symptoms with no other recognized cause: Fever ("/38°C) Urgency Frequency Dysuria Suprapubic tenderness and Patient has a positive urine culture (≥ 105 microorganisms per ml of urine) with no more than two species of microorganisms | \n\t\t\t\t\t\t
UTI-B: not microbiologically confirmed symptomatic UTI | \n\t\t\t\t\t\t\tPatient has at least two of the following with no other recognized cause: Fever ("/38°C) Urgency Frequency Dysuria Suprapubic tenderness and, at least one of the following: Positive dipstick for leukocyte esterase and/or nitrate Pyuria urine specimen with ≥10 WBC/ml or ≥ 3 WBC/high-power field of unspun urine Organisms seen on Gram stain of unspun urine At least two urine cultures with repeated isolation of the same uropathogen (gram-negative bacteria or S. saprophyticus) with ≥ 102 colonies/ml urine in nonvoided specimens ≤105 colonies/ml of a single uropathogen (gram-negative bacteria or S. saprophyticus) in a patient being treated with effective antimicrobial agent for a urinary infection Physician diagnosis of a urinary tract infection Physician institutes appropriate therapy for a urinary infection | \n\t\t\t\t\t\t
UTI-C: asymptomatic bacteriuria | \n\t\t\t\t\t\t\tPatient has no fever ("/38°C), urgency, frequency, dysuria, or suprapubic tenderness and either of the following criteria: Patient has had an indwelling urinary catheter within 7 days before urine is cultured and Patient has a urine culture, that is, ≥105 microorganisms per ml of urine with no more than two species of microorganisms. Patient has not had an indwelling urinary catheter within 7 days before the first positive culture and Patient has had at least two positive urine cultures ≥105 microorganisms per mm3 of urine with repeated isolation of the same microorganism and no more than two species of microorganisms | \n\t\t\t\t\t\t
Case definition of Urinary Tract Infection (HELICS-ICU, 2004).
The NHSN reported that between 2006-2007, the most frequent pathogens associated with CAUTI were Escherichia coli (21.4%) and Candida spp. (21.0%), followed by Enterococcus spp. (14.9%), Pseudomonas aeruginosa (10.0%), Klebsiella pneumoniae (7.7%), and Enterobacter spp. (4.1%). A smaller proportion of CAUTI was caused by other gram-negative bacteria or by Staphylococcus spp. (Hidron et al., 2008).
\n\t\t\t\tFinally, it is important to underline that bacteriuria associated to CAUTI commonly leads to antimicrobial use, that would have been avoidable, as well as to urinary drainage systems that are often reservoirs for multidrug-resistant bacteria and a potential source of transmission to other patients (Gould et al., 2009).
\n\t\t\t\tAs reported in the Annual Epidemiological Report on Communicable Diseases in Europe (ECDC, 2010), the antimicrobial resistance of microorganisms is to be considered the most important disease threat. In 2008 a Europe-wide increase of resistance to all antibiotic classes under surveillance was observed for the most common Gram-negative bacteria – E. coli - responsible for bacteraemia and UTIs.
\n\t\t\tCAUTIs are generally considered an avoidable complication. It has been estimated that between 17% and 69% of all observed CAUTIs may be prevented by implementation of an evidence based prevention program that is particularly important in the ICU setting with a high prevalence of urinary catheterization and a high percentage of patients with comorbidities (Gould et al., 2009).
\n\t\t\t\tThe CDC/Healthcare Infection Control Practices Advisory Committee (HICPAC) published a specific document - Guideline for Prevention of Catheter-associated Urinary Tract Infections – that addresses the prevention of CAUTI for patients with short- or long-term urinary catheterization admitted in any type of healthcare facility and evaluates the evidence for several options of methods of urinary drainage, including intermittent catheterization, external catheters, and suprapubic catheters (Gould et al., 2009). The guideline is based on a specific systematic review of the best available evidence on CAUTI prevention; it uses the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (Atkins et al., 2004; Guyatt et al., 2008a; Guyatt et al. 2008b) in order to provide clear links between the available evidence and the resulting recommendations.
\n\t\t\t\tParticularly, in this document, recommendations include: i) appropriate urinary catheter use; ii) proper techniques for urinary catheter insertion; iii) proper techniques for urinary catheter maintenance; iv) quality improvement programs; v) administrative infrastructure; and vi) surveillance.
\n\t\t\t\tAs suggested by the Authors of this guideline further research in order to prevent CAUTIs should focuse on catheter materials (antimicrobial and antiseptic-impregnated catheters and standard catheters), appropriate urinary catheter use (in incontinent patients and appropriate indications for continued use in postoperative patients), use of antiseptics (for periurethral cleaning prior to catheter insertion and to prevent CAUTI), alternatives to indwelling urethral catheters and bag drainage (suprapubic catheters, urethral catheters, use of catheter valves and other alternative methods of urinary drainage), optimal methods for preventing encrustation in long-term catheterized patients, other prevention measures and prevention of transmission of pathogens colonizing urinary drainage systems.
\n\t\t\t\tA specific recommendation for the appropriate urinary catheter use (category IB) is: “Minimize urinary catheter use and duration of use in all patients, particularly those at higher risk for CAUTI or mortality from catheterization such as women, the elderly, and patients with impaired immunity” (Gould et al., 2009).
\n\t\t\t\tIn this contest, a recent study (Elpern et al., 2009) has been conducted in a medical ICU in order to implement and evaluate the efficacy of an intervention, based on the decreasing use of urinary catheters, to reduce CAUTI. Results of this study report that the implementation of an intervention targeting the appropriate use of indwelling urinary catheters may result in a significant reduction in the duration of catheterization as well as in the occurrences of CAUTIs.
\n\t\t\t\tA systematic literature review and meta-analysis was performed to evaluate the effect of interventions that remind clinicians of the presence of urinary catheters to prompt the timely removal of catheters during hospitalization. Results of the meta-analysis report that the rate of CAUTI was significantly reduced by 52% with the use of a reminder or stop order. Furthermore, the mean duration of catheterization decreased by 37%. Thus, interventions to routinely prompt physicians or nurses to remove unnecessary urinary catheters appear to reduce the rate of CAUTI and should be strongly considered to enhance the safety of hospitalized patients (Medding et al., 2010).
\n\t\t\t\tThe Institute for Health Care Improvement (IHI) developed the model of “bundles” to help health care workers more consistently deliver the best possible care for patients undergoing particular treatments (Institute for Health Care Improvement, 2006). “A bundle is a structured way of improving the processes of care and patient outcomes: a small, straightforward set of evidence-based practices — generally three to five — that, when performed collectively and reliably, have been proven to improve patient outcomes” (Resar et al., 2005).
\n\t\t\t\tA recent observational study (Venkatram et al., 2010) was conducted in order to study the effect of bundle strategies on the device use adjusted rate of HAI in adult medical ICU, to prevent HAIs associated with endovascular catheters, mechanical ventilation, and urinary tract catheters. Particularly, the UTI bundle regards the use of antimicrobial catheters, closed drainage systems, and daily assessment for removal. During the study period, HAIs declined from 47 in 2004 to 3 in 2007. Particularly, CAUTI decreased from 6.23 to 0.63 per 1000 device-days. However, the decline in infection rates cannot be accounted by the decline in device use by itself, in fact, when adjusted to device use, the decrease in HAI rates still showed statistical significance. Therefore, it is not easy to attribute this decline to any one component of the bundle. Results of this study demonstrate that best practices using a multidisciplinary bundle strategy including device use can lead to optimal outcomes with respect to HCAI rates.
\n\t\t\tEpidemiologic surveillance of HAI in ICUs is an important tool of internal quality management in the hospital setting (Zuschneid et al., 2010), and together with appropriate infection control activities, can decrease infection rates significantly (Haley et al., 1985).
\n\t\t\tA specific recommendation, of category II, included in the CDC/HICPAC Guideline for Prevention of Catheter-associated Urinary Tract Infections is: “Consider surveillance for CAUTI when indicated by facility-based risk assessment”. Particularly, it is recommended to identify the patient groups or units on which to conduct surveillance based on frequency of catheter use and potential risk of CAUTI and to use standardized methodology for performing CAUTI surveillance (Category IB). Furthermore, providing regular feedback of CAUTI rates to the staff should be also considered (Gould et al., 2009).
\n\t\t\tIn order to explore the epidemiologic scenario and control of UTIs in intensive care patients, surveillance of HAI was performed on three Sicilian ICUs participating in the first two edition of the SPIN-UTI (Sorveglianza Prospettica delle Infezioni Nosocomiali nelle Unità di Terapia Intensiva) project.
\n\t\t\tThe Italian Nosocomial Infections Surveillance in ICUs, SPIN-UTI project, established in Italy by the Italian Study Group of Hospital Hygiene (GISIO) of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI) (Agodi et al., 2010), started the first edition in 2006 - 2007, the second edition of the project was implemented in 2008 – 2009, and the third, in 2010 – 2011 is in progress.
\n\t\t\t\tThe methodology of surveillance are describes in great details elsewhere (Agodi et al., 2010) and is based on the HELICS-ICU protocol, in order to participate in the European benchmark (HELICS-ICU, 2004; Suetens et al., 2007). The enrollment of patients was prospective, and data regarding ICU stay, patient’s risk factors including exposure to invasive devices (such as intubation, central venous catheter and urinary catheter), were collected using a web-based data collection procedure for each patient staying longer than two days in the ICU (Figure 1).
\n\t\t\t\tThe definitions of HAI used in the SPIN-UTI project are the same proposed by the HELICS-ICU protocol for pneumonia, bloodstream infections (BSIs), central venous catheter-related bloodstream infections (CRIs) and UTIs (HELICS-ICU, 2004; Suetens et al., 2007). UTI data collection was mandatory.
\n\t\t\t\tThe indicators included cumulative incidence and, to adjust for length of stay, incidence density. Furthermore, device-associated infection rates and device utilization ratios were also calculated as the number of infections per 1000 device-days and the number of days with the device divided for the number of patient-days.
\n\t\t\tSurveillance data collection was performed from all patients enrolled in the project using four electronic data forms – designed using SPSS "Data Entry Enterprise Server" - as instruments for data collection. Particularly, the following data forms were used: 1) ‘Characteristics of hospital and of ICU’, 2) ‘Patient’, 3) ‘Infection’ and 4) ‘Microorganism’ (Figure 1). The electronic forms were characterized by functional instruments. Using these electronic forms data are entered via Web and each record is sent to the server, where it is automatically routed to the appropriate database. Cleaning and analyses were performed using SPSS for Windows (version 14.0): univariate analyses and the above reported indicators were calculated. Furthermore, categorical variables were compared using the chi-square-test, and continuous variables by Student’s t-test; p < 0.05 was considered statistical significant.
\n\t\t\tThe study was conducted at three Sicilian ICUs participating in the first two edition of the SPIN-UTI Project. The ICU identified as ICU 1 is a 12-bed interdisciplinary ICU, from a 700-bed acute care hospital; the ICU identified as ICU 2 is a 7-bed interdisciplinary ICU, from a
\n\t\t\t\tMethods of Surveillance and web-based data collection.
830-bed tertiary care hospital; the ICU identified as ICU 3 is a 6-bed interdisciplinary ICU, from a 200-bed tertiary care hospital.
\n\t\t\tA total of 501 patients with length of stay >2 days, for a total of 9681 patient-days, were admitted in the three ICUs during the two edition of the SPIN-UTI project and thus were enrolled in the study. A summary of patient characteristics and urinary catheter use is shown in Table 3.
\n\t\t\t\t\n\t\t\t\t\t\t\t\tCharacteristic\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tICU 1\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tICU 2\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tICU 3\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tTotal\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t||||
\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t|
\n\t\t\t\t\t\t\t\tNumber of patients\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t133 | \n\t\t\t\t\t\t\t80 | \n\t\t\t\t\t\t\t103 | \n\t\t\t\t\t\t\t91 | \n\t\t\t\t\t\t\t44 | \n\t\t\t\t\t\t\t50 | \n\t\t\t\t\t\t\t280 | \n\t\t\t\t\t\t\t221 | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tMean age in years (range)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t54.4 (5-94) | \n\t\t\t\t\t\t\t59,3 (22-92) | \n\t\t\t\t\t\t\t65.8 (2-94) | \n\t\t\t\t\t\t\t62,6 (1-97) | \n\t\t\t\t\t\t\t64.7 (19-87) | \n\t\t\t\t\t\t\t62,9 (13-87) | \n\t\t\t\t\t\t\t60.2 (2-94) | \n\t\t\t\t\t\t\t61.5 (1-97) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tMale (%)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t59.8 | \n\t\t\t\t\t\t\t53,8 | \n\t\t\t\t\t\t\t53.5 | \n\t\t\t\t\t\t\t56 | \n\t\t\t\t\t\t\t43.2 | \n\t\t\t\t\t\t\t46 | \n\t\t\t\t\t\t\t54.9 | \n\t\t\t\t\t\t\t52.9 | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tMean SAPS II score (range)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t41.85 (6-98) | \n\t\t\t\t\t\t\t51,58 (16-87) | \n\t\t\t\t\t\t\t31.38 (5-64) | \n\t\t\t\t\t\t\t27,41 (6-62) | \n\t\t\t\t\t\t\t34.06 (9-68) | \n\t\t\t\t\t\t\t43,80 (7-114) | \n\t\t\t\t\t\t\t37.37 (5-98) | \n\t\t\t\t\t\t\t40.84 (6-114) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tMean length of stay in days (range)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t12.92 (3-65) | \n\t\t\t\t\t\t\t30,23 (6-106) | \n\t\t\t\t\t\t\t13.86 (3-79) | \n\t\t\t\t\t\t\t26,71 (3-120) | \n\t\t\t\t\t\t\t10.55 (3-57) | \n\t\t\t\t\t\t\t24,42 (3-84) | \n\t\t\t\t\t\t\t12.9 (3-79) | \n\t\t\t\t\t\t\t27.47 (3-120) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tTotal length of stay in ICU (in days)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t1719 | \n\t\t\t\t\t\t\t1598 | \n\t\t\t\t\t\t\t1428 | \n\t\t\t\t\t\t\t1335 | \n\t\t\t\t\t\t\t464 | \n\t\t\t\t\t\t\t736 | \n\t\t\t\t\t\t\t3611 | \n\t\t\t\t\t\t\t3669 | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tUrinary catheter (%)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t127 (95.5) | \n\t\t\t\t\t\t\t60 (75.0) | \n\t\t\t\t\t\t\t102 (99.0) | \n\t\t\t\t\t\t\t75 (82.4) | \n\t\t\t\t\t\t\t41 (93.2) | \n\t\t\t\t\t\t\t36 (72.0) | \n\t\t\t\t\t\t\t270 (96.4) | \n\t\t\t\t\t\t\t171 (77.4) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tTotal length of urinary catheterization (in days)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t1576 | \n\t\t\t\t\t\t\t1565 | \n\t\t\t\t\t\t\t1269 | \n\t\t\t\t\t\t\t1297 | \n\t\t\t\t\t\t\t412 | \n\t\t\t\t\t\t\t713 | \n\t\t\t\t\t\t\t3257 | \n\t\t\t\t\t\t\t3575 | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tMean length of urinary catheter in days (range\n\t\t\t\t\t\t\t\t)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t12.5 (1-65) | \n\t\t\t\t\t\t\t19.8 (3-106) | \n\t\t\t\t\t\t\t12.6 (1-79) | \n\t\t\t\t\t\t\t14.3 (3-87) | \n\t\t\t\t\t\t\t10.1 (1-58) | \n\t\t\t\t\t\t\t14.9 (3-78) | \n\t\t\t\t\t\t\t12.2 (1-79) | \n\t\t\t\t\t\t\t16.4 (3-106) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tUrinary catheter utilization ratios\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t0.92 | \n\t\t\t\t\t\t\t0.97 | \n\t\t\t\t\t\t\t0.89 | \n\t\t\t\t\t\t\t0.97 | \n\t\t\t\t\t\t\t0.89 | \n\t\t\t\t\t\t\t0.97 | \n\t\t\t\t\t\t\t0.90 | \n\t\t\t\t\t\t\t0.97 | \n\t\t\t\t\t\t
Main characteristics of patients included in the study.
Particularly, in the first edition of the project a total of 280 patients for a total of 3611 patient-days and a total of 221 patients for a total of 3669 patient-days in the second edition, were admitted. During the two edition of the project, a significant reduction of the proportion of patients with urinary catheter was observed (chi-square test, p <0.05). Particularly, in the first edition the overall proportion of patients with urinary catheter was 96.4% (range: 93.2% - 99.0%) and in the second edition was 77.4% (range: 72.0 – 82.4%). Furthermore, in the first edition the total length of urinary catheterization was 3257 days (mean: 12.2 days; range: 1-79) and increased significantly (comparison between means, Student’s t test, p <0.05), in the second edition where was 3575 days (mean 16.4 days; range: 3-106 days).
\n\t\t\t\tConsidering all three ICUs, an increase of urinary catheter utilization ratio, from 0.90 to 0.97, was observed in the second edition of the project.
\n\t\t\t\n\t\t\t\t\tTable 4 reports infection’s indicators. Considering all ICUs, in the first edition of the SPIN-UTI project, the most frequently reported ICU-acquired infection type was pneumonia (38.2%) followed by bloodstream infections (30.9%), urinary tract infections (20.9%) and central venous catheter-related bloodstream infections (10.0%). In the second edition, the most frequently reported ICU-acquired infection type was bloodstream infections (43.7%) followed by urinary tract infections (29.1%), pneumonia (23.2%) and central venous catheter-related bloodstream infections (4.0%). Thus, in the last edition of the SPIN-UTI project an increase of the proportion of infections due to bloodstream infections and to urinary tract infections were registered, both considering all ICUs and each ICU separately. Instead, a decrease of the proportion of infections due to pneumonia infections and to central venous catheter-related bloodstream infections were registered, both considering all ICUs and each ICU separately.
\n\t\t\t\tThe risk of ICU-acquired infections for all sites was estimated by computing the cumulative incidence: 39.3 per 100 patients in the first edition and 68.3 per 100 patients in the second one; and the incidence density: 30.5 per 1000 patient-days in the first edition and 41.2 per 1000 patient-days in the second one. Particularly, the cumulative incidence and the incidence density of UTI were increased in the second edition compared with the first one (Table 4).
\n\t\t\t\tNotably, in the two edition of the project, all UTIs were related to the presence of urinary catheter.
\n\t\t\t\tUrinary catheter-associated UTI rates (i.e. the number of urinary catheter-associated UTI per 1000 urinary catheter-days) was 7.1 per 1000 urinary catheter-days in the first edition and 12.3 per 1000 urinary catheter-days in the second edition.
\n\t\t\tConsidering all infection sites, relative frequencies of the five most common isolated microorganisms in ICU-acquired infections are reported in Table 5.
\n\t\t\t\tDespite difference among ICUs (data not shown), in the first edition of the SPIN-UTI project, the most frequently reported microorganism associated with ICU-acquired infections overall was P. aeruginosa (18.1%), followed by Acinetobacter baumannii (15.5%), S. epidermidis (14.7%), K. pneumoniae (7.8%) and E. coli (6.9%). In the second edition A. baumannii became the most frequently reported microorganism (20.3%), followed by K. pneumoniae (15.8%), P. aeruginosa (12.4%), S. epidermidis (6.8%) and E. coli (4.5%).
\n\t\t\t\tConsidering only UTIs, in the first edition of the SPIN-UTI project, the reported microorganism overall were P. aeruginosa (30.8%), followed by A. baumannii and Escherichia coli (15.4%, each), K. pneumoniae (11.5%), Candida albicans, Candida tropicalis and Enterobacter cloacae (11.5%, each) and Enterococcus spp. (3.8%). In the second edition K. pneumoniae became the most frequently reported microorganism (22.2%), followed by E. coli and P. aeruginosa (13.3%), Enterococcus faecalis (11.1%), A. baumannii and Candida glabrata (8.9%, each) and C. albicans (6.7%) (Table 6).
\n\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\tICU 1\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tICU 2\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tICU 3\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tTotal\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t||||
\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t|
Total number of infections | \n\t\t\t\t\t\t\t54 | \n\t\t\t\t\t\t\t86 | \n\t\t\t\t\t\t\t52 | \n\t\t\t\t\t\t\t52 | \n\t\t\t\t\t\t\t4 | \n\t\t\t\t\t\t\t13 | \n\t\t\t\t\t\t\t110 | \n\t\t\t\t\t\t\t151 | \n\t\t\t\t\t\t
Total number of UTI (%) | \n\t\t\t\t\t\t\t10 (18.5) | \n\t\t\t\t\t\t\t18 (20.9) | \n\t\t\t\t\t\t\t13 (25.0) | \n\t\t\t\t\t\t\t22 (42.3) | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t4 (30.8) | \n\t\t\t\t\t\t\t23 (20.9) | \n\t\t\t\t\t\t\t44 (29.1) | \n\t\t\t\t\t\t
Total number of Pneumonia (%) | \n\t\t\t\t\t\t\t24 (44.4) | \n\t\t\t\t\t\t\t29 (33.7) | \n\t\t\t\t\t\t\t16 (30.8) | \n\t\t\t\t\t\t\t5 (9.6) | \n\t\t\t\t\t\t\t2 (50.0) | \n\t\t\t\t\t\t\t1 (7.7) | \n\t\t\t\t\t\t\t42 (38.2) | \n\t\t\t\t\t\t\t35 (23.2) | \n\t\t\t\t\t\t
Total number of CRI (%) | \n\t\t\t\t\t\t\t11 (20.4) | \n\t\t\t\t\t\t\t6 (7.0) | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t11 (10.0) | \n\t\t\t\t\t\t\t6 (4.0) | \n\t\t\t\t\t\t
Total number of BSI (%) | \n\t\t\t\t\t\t\t9 (16.7) | \n\t\t\t\t\t\t\t33 (38.4) | \n\t\t\t\t\t\t\t23 (44.2) | \n\t\t\t\t\t\t\t25 (48.1) | \n\t\t\t\t\t\t\t2 (50.0) | \n\t\t\t\t\t\t\t8 (61.5) | \n\t\t\t\t\t\t\t34 (30.9) | \n\t\t\t\t\t\t\t66 (43.7) | \n\t\t\t\t\t\t
Total length of stay in ICU (in days) | \n\t\t\t\t\t\t\t1719 | \n\t\t\t\t\t\t\t1598 | \n\t\t\t\t\t\t\t1428 | \n\t\t\t\t\t\t\t1335 | \n\t\t\t\t\t\t\t464 | \n\t\t\t\t\t\t\t736 | \n\t\t\t\t\t\t\t3611 | \n\t\t\t\t\t\t\t3669 | \n\t\t\t\t\t\t
Cumulative incidence of infection (all sites) (/100 patients) | \n\t\t\t\t\t\t\t40.6 | \n\t\t\t\t\t\t\t107.5 | \n\t\t\t\t\t\t\t50.5 | \n\t\t\t\t\t\t\t57.1 | \n\t\t\t\t\t\t\t9.1 | \n\t\t\t\t\t\t\t26.0 | \n\t\t\t\t\t\t\t39.3 | \n\t\t\t\t\t\t\t68.3 | \n\t\t\t\t\t\t
Incidence density of infection (all sites) (/1000 patient-days) | \n\t\t\t\t\t\t\t31.4 | \n\t\t\t\t\t\t\t53.8 | \n\t\t\t\t\t\t\t36.4 | \n\t\t\t\t\t\t\t39.0 | \n\t\t\t\t\t\t\t8.6 | \n\t\t\t\t\t\t\t17.7 | \n\t\t\t\t\t\t\t30.5 | \n\t\t\t\t\t\t\t41.2 | \n\t\t\t\t\t\t
Cumulative incidence of UTI (/100 patients) | \n\t\t\t\t\t\t\t7.5 | \n\t\t\t\t\t\t\t22.5 | \n\t\t\t\t\t\t\t12.6 | \n\t\t\t\t\t\t\t24.2 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t8.0 | \n\t\t\t\t\t\t\t8.2 | \n\t\t\t\t\t\t\t19.9 | \n\t\t\t\t\t\t
Incidence density of UTI (/1000 patient-days) | \n\t\t\t\t\t\t\t5.8 | \n\t\t\t\t\t\t\t11.3 | \n\t\t\t\t\t\t\t9.1 | \n\t\t\t\t\t\t\t16.5 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t5.4 | \n\t\t\t\t\t\t\t6.4 | \n\t\t\t\t\t\t\t12.0 | \n\t\t\t\t\t\t
Cumulative incidence of Pneumonia (/100 patients) | \n\t\t\t\t\t\t\t18.0 | \n\t\t\t\t\t\t\t36.3 | \n\t\t\t\t\t\t\t15.5 | \n\t\t\t\t\t\t\t5.5 | \n\t\t\t\t\t\t\t4.5 | \n\t\t\t\t\t\t\t2 | \n\t\t\t\t\t\t\t15.0 | \n\t\t\t\t\t\t\t15.8 | \n\t\t\t\t\t\t
Incidence density of Pneumonia (/1000 patient-days) | \n\t\t\t\t\t\t\t14.0 | \n\t\t\t\t\t\t\t18.1 | \n\t\t\t\t\t\t\t11.2 | \n\t\t\t\t\t\t\t3.7 | \n\t\t\t\t\t\t\t4.3 | \n\t\t\t\t\t\t\t1.4 | \n\t\t\t\t\t\t\t11.6 | \n\t\t\t\t\t\t\t9.5 | \n\t\t\t\t\t\t
Cumulative incidence of CRI (/100 patients) | \n\t\t\t\t\t\t\t8.3 | \n\t\t\t\t\t\t\t7.5 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t3.9 | \n\t\t\t\t\t\t\t2.7 | \n\t\t\t\t\t\t
Incidence density of CRI (/1000 patient-days) | \n\t\t\t\t\t\t\t6.4 | \n\t\t\t\t\t\t\t3.8 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t3.0 | \n\t\t\t\t\t\t\t1.6 | \n\t\t\t\t\t\t
Cumulative incidence of BSI (/100 patients) | \n\t\t\t\t\t\t\t6.8 | \n\t\t\t\t\t\t\t41.2 | \n\t\t\t\t\t\t\t22.3 | \n\t\t\t\t\t\t\t27.5 | \n\t\t\t\t\t\t\t4.5 | \n\t\t\t\t\t\t\t16.0 | \n\t\t\t\t\t\t\t12.1 | \n\t\t\t\t\t\t\t29.9 | \n\t\t\t\t\t\t
Incidence density of BSI (/1000 patient-days) | \n\t\t\t\t\t\t\t5.2 | \n\t\t\t\t\t\t\t20.7 | \n\t\t\t\t\t\t\t16.1 | \n\t\t\t\t\t\t\t18.7 | \n\t\t\t\t\t\t\t4.3 | \n\t\t\t\t\t\t\t10.9 | \n\t\t\t\t\t\t\t9.4 | \n\t\t\t\t\t\t\t18.0 | \n\t\t\t\t\t\t
Infection’s indicators in the three ICUs.
\n\t\t\t\t\t\t\t | All ICUs (all infection types) | \n\t\t\t\t\t\t|
\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t|
\n\t\t\t\t\t\t\t\t1st microorganism (n; %)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tP. aeruginosa (21; 18.1) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tA. baumannii (36; 20.3) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t2nd microorganism (n; %)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tA. baumannii (18; 15.5) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tK. pneumoniae (28; 15.8) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t3rd microorganism (n; %)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tS. epidermidis (17; 14.7) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tP. aeruginosa (22; 12.4) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t4th microorganism (n; %)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tK. pneumoniae (9; 7.8) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tS. epidermidis (12; 6.8) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t5th microorganism (n; %)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tE. coli (8; 6.9) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tE. coli (8; 4.5) | \n\t\t\t\t\t\t
Relative frequencies of the five most common isolated microorganisms in ICU-acquired infections.
All ICUs (only UTIs: n; %) | \n\t\t\t\t\t\t|
\n\t\t\t\t\t\t\t\t(2006-07)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t(2008-09)\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tP. aeruginosa\n\t\t\t\t\t\t\t\t (8; 30.8) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tK. pneumoniae\n\t\t\t\t\t\t\t\t (10; 22.2) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tE. coli and A. baumannii\n\t\t\t\t\t\t\t\t (4; 15.4, each) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tE. coli and P. aeruginosa\n\t\t\t\t\t\t\t\t (6; 13.3, each) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tK. pneumoniae\n\t\t\t\t\t\t\t\t (3; 11.5) | \n\t\t\t\t\t\t\tE. faecalis (5; 11.1) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tC. albicans, C. tropicalis, E. cloacae\n\t\t\t\t\t\t\t\t (2; 7.7, each) | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\tA. baumannii and C. glabrata\n\t\t\t\t\t\t\t\t (4; 8.9, each) | \n\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\tEnterococcus spp. (1; 3.8) | \n\t\t\t\t\t\t\tC. albicans (8; 6.7) | \n\t\t\t\t\t\t
Relative frequencies of the isolated microorganisms in UTIs.
In several high-income countries, device-associated HAI surveillance in the ICU plays a considerable role in hospital infection control and quality assurance (Edwards et al., 2009).
\n\t\t\tA recent study was performed in the framework of the German KISS with the aim of investigating whether surveillance of CAUTI in ICUs leads to reduced infection rates. When comparing the symptomatic CAUTI rates in the third and first years of the surveillance, a significant reduction in CAUTI was shown. However, before-and-after studies are limited by confounding variables such as the difficulties of ICU patients in recognizing and reporting UTI symptoms, that leads to the availability of microbiological reports as a major criterion for diagnosing symptomatic UTI. Thus, in the case of CAUTI diagnosis, microbiological reports may have decreased over time and have influenced reduction of CAUTI rates (Gastmeier et al., 2011).
\n\t\t\tIn the same study, it has been reported that the overall surveillance effect was highest for ventilator-associated pneumonia and central venous catheter bloodstream infection. This could be explained by the perception of the clinicians that ventilator-associated pneumonia and central venous catheter bloodstream infection are more serious infections demanding more effective responses rather than CAUTI. However, CAUTI may also lead to sepsis, and changes in CAUTI rate over time, with consistent microbiology diagnostic procedures, may lead to the introduction of appropriate infection control measures (Gastmeier et al., 2011).
\n\t\t\tThe SPIN-UTI project was implemented to create a HAI surveillance network of Italian ICUs (Agodi et al., 2010). The validation study of the SPIN-UTI project has showed a high sensitivity, specificity, and positive and negative predictive values of surveillance data (Masia et al., 2010).
\n\t\t\tComparison of results of the two editions of the SPIN-UTI project revealed that, the risk of ICU-acquired infections for all sites, estimated by computing the cumulative incidence and the incidence density, increased in the second edition compared to the first one.
\n\t\t\tDifferences were presented considering infection by site. In the second edition of the project a decrease of the proportion of infections due to pneumonia and to CRIs were registered. On the contrary, an increase of the proportion of infections due to BSIs and to UTIs were observed, either considering all ICUs or each ICU separately. Particularly, after comparing results of the two studies, in the second edition a higher proportion of the patients acquired a UTI in ICU than in the first edition. The cumulative incidence of UTI increased from 8.2 per 100 patients to 19.9 per 100 patients. The incidence density also increased from 6.4 per 1000 patient-days to 12.0 per 1000 patient-days.
\n\t\t\tHospital wide prevalence rates for indwelling catheterization vary from 25% to 35% (Haley et al., 1981; Junkin & Selekof, 2007). Prevalence rates in ICU are substantially higher at 67% to 76% (Huang et al., 2004; Gray, 2010). In our study, a high proportion of patients were with urinary catheter (range: 72.0%- 99.0%), and although a significant reduction of the proportion of exposed patients was observed in the second edition of the project an increase of the mean length of urinary catheterization from 12.2 days to 16.4 days was observed. Furthermore, urinary catheter utilization ratio was significantly higher in the second edition compared with the first edition (from 0.90 to 0.97).
\n\t\t\tNotably, in the two edition of the project, all UTIs were related to the presence of urinary catheter. Urinary catheter-associated UTI rates increased from 7.1 per 1000 urinary catheter days in the first edition and 12.3 per 1000 urinary catheter days in the second edition.
\n\t\t\tIt is advised that device-associated infection rates and device utilization ratios should be examined together so that preventive measures may be appropriately targeted. Since urinary catheter use is a significant risk factor for UTI, efforts must be redirected to reducing their use or limiting the duration with which they are used and to addressing the best consensus guidelines and recommendations in their insertion and maintenance (Edwards et al., 2007). In fact, it has been reported that targeted strategies for prevention of UTI include limiting the use and duration of urinary catheterization, using aseptic technique for catheter insertion, and adhering to proper catheter care (Shuman and Chenoweth, 2010).
\n\t\t\tThe most frequently isolated microorganisms causing CAUTI in the ICU setting are enteric Gram-negative bacilli, enterococci, Candida species, and P. aeruginosa (Shuman and Chenoweth, 2010). Microorganisms are often multidrug resistant probably following the increasing use of broad-spectrum antibiotics in hospitals and this is a considerable problem in ICU.
\n\t\t\tIn our surveillance survey, despite difference among ICUs, in the first edition of the project, the most frequently reported microorganism associated to UTI was P. aeruginosa, in the second one, K. pneumoniae (22.2%) was the first species isolated. Notably, in the second edition an increase of K. pneumoniae isolation and a decrease of P. aeruginosa isolation were observed.\n\t\t\t
\n\t\tOur study represents a contribution to improve the quality of care in the ICU setting. A major item was identified for planning future intervention: focusing on the appropriate urinary catheter use. HAIs can be prevented by constant use of “bundles” of simple and effective measures, including the monitoring of device use, recommended by CDC and IHI (Institute for Health Care Improvement, 2006; Gould et al., 2009). To improve patient safety, an integrated, multimodal and comprehensive “bundles” approach is the means to reducing the impact of HAI.
\n\t\tThis work was supported in part by grants from the University of Catania (Progetti di Ricerca di Ateneo to A.A.).
\n\t\t\tThe authors wish to thank all physicians and nurses in the participating ICUs for providing surveillance data and for their co-operation during the development of this surveillance system.
\n\t\tThe use of recombinant technology for antibody selection offers several advantages over conventional antibody selection strategies, such as the selection of antibodies against toxic or non-immunogenic antigens unattainable using conventional methods [1, 2], the ability to select positive clones from vast libraries [3], the realization of in vitro screening [4], and the bypass of animal usage [5]. The selection and production of recombinant monoclonal antibodies require the creation of highly diverse libraries [6] and the subsequent identification of positive clones using a screening technology with low background signals [7]. In particular, the variable domains of the antibody heavy and light chain (VH and VL) are isolated from the lymph tissue of immunized animals and linked together for creating a single-chain variable fragment (scFv) library, and Fab libraries are constructed too. In general, the antibody fragments used for screening are the scFvs. Currently, entirely synthetic libraries [8, 9, 10, 11] and naïve libraries [12] are being used. These antibody gene libraries are incorporated into a phagemid or plasmid and expressed in phage or Escherichia coli (E. coli). Further, panning [13] or colony assays [14] are performed to isolate scFvs possessing affinity to the antigen, thereby establishing monoclonal antibodies. This step, the screening of antibody libraries, is critical for establishing monoclonal antibody fragments with a high affinity and specificity against the antigen. One of the most extensively used methods is the phage display method [15, 16]. The display of the antibody repertoires on the surface of bacteriophages and their selection through panning enables the isolation of monoclonal antibodies [17]. Phage display is also widely used for affinity maturation [18, 19], in which mutations are introduced into the variable domains of an antibody gene mainly into CDRs to produce antibodies with a higher affinity as the original clone [20]. In addition, cell surface panning techniques [1, 21, 22] are being developed to establish antibodies recognizing membrane proteins on living cells that are difficult to produce using the conventional methods. Technologies that enable liquid panning rather than immobilizing the antigens to a solid phase have also been proposed for phage display to establish antibodies that recognize protein conformation [23]. Screening with a colony assay induces the actual expression of the scFvs themselves and involves a direct confirmation of the antigen-antibody binding, lending it the advantage of a low false-positive rate. In addition, the method can be easily used to screen libraries in the order of magnitude larger than those that can be screened with the hybridoma technology. However, this method poses several problems: it requires extensive and complex manipulation of assay steps, the expression of antibody fragments could be at times nonexistent or very low, and the extensive manipulation during the assay can lead to contamination and death of the E. coli cells, potentially preventing gene retrieval. Although this technique is not complete and not widely applied, further development and improvement can render it highly beneficial.
\nA critical step in the establishment of antigen-specific monoclonal antibody fragment clones is the screening of the recombinant-antibody libraries [6, 7]. Methods for screening the antibody libraries can be largely divided into two strategies [24]: the display and repertoire cloning strategies (Figure 1).
\nStrategies for antibody library screening. (A) Display strategy: scheme of the phage display panning process. (B) Repertoire cloning strategy: scheme of the cloning and assay process. (C) Detection of antigen-specific antibody fragments released from a bacterial colony by a colony assay.
In the display strategy [25], the antibody fragment and its gene, i.e., the antigen recognition function and information, are joined, and antibody fragments with an affinity against the antigen are screened. Phage display systems in which an scFv joined to the filamentous phage coat protein, g3p, is displayed on the phage are extensively used [15, 16]. Other display systems include yeast display systems in which scFvs are displayed on the surface of yeast [26]; mRNA display [27]; ribosome display in which a ribosome, mRNA, and an scFv are integrated [28]; bacterial surface display [29]; and mammalian cell surface display [30, 31] for human antibody discovery. In these display systems, panning is applied for screening [13]. The antigen is immobilized on the surface of a microtiter plate, and the scFv library can be screened with phage display and with ribosome/mRNA display. Weakly bound clones are removed by washing, retaining the specific clones bound to the antigen (Figure 1A). This panning method is characterized by repeated selection, proliferation, and the enrichment of positive clones for enabling the processing of large libraries. For yeast, bacterial and mammalian cell surface display FACS with the cells displaying the recombinant antibody fragments using labeled antigen is applied.
\nIn contrast, in repertoire cloning strategies, the antibody library is transformed into E. coli; the scFvs are expressed and secreted from a single clone, and scFvs are screened by ELISA (Figure 1B). Clones are selected based on assays, using scFv characteristics such as the affinity; thereby, this method offers advantages such as low false-positive rates and the ability to reliably identify clones with a high affinity. However, an assay must be performed for each individual E. coli clone, and only the positive clones are selected. There is no enrichment process in the screening method, and only limited libraries can be used for antibody selection.
\nParticularly, antibody repertoires from immunized animals with a clone number of approximately 106 are suitable for the repertoire cloning but not naïve and synthetic antibody repertoires with high clone numbers (109–1012 clones). During the assay, a clone from an E. coli library is cultured, and its expression is induced. The reactivity of the expressed scFv against the antigen is measured. Clones exhibiting high reactivity are selected as the positive clones. In this method, only a few thousands of clones can be examined simultaneously, even if a multi-well microtiter plate is used. Although this number is higher than the clones obtained by the hybridoma technique, positive clones cannot be efficiently obtained, when the positive ratio is low.
\nColony assay in which periplasmic expression and E. coli colony formation lifted onto filters are used provides a method for handling large libraries (Figure 1C). In colony assay, the clones do not need to be picked up individually before screening; all the colonies on the plate can be assayed simultaneously. Thus, numerous clones can be assayed from a single plate. Antibody fragments released by bacteria were detected by a phage plaque assay in earlier experiments [32, 33]. Libraries of the antibody fragments were expressed in E. coli using phage λ vectors [34, 35]. Then, the active fragments secreted from the viable E. coli colonies were detected by colony-lift immunoassay [36]. With the colony assay, considerably larger libraries can be dealt with because the number of colonies screened can be easily increased.
\nIn a phage display system, panning is used to isolate phages that display the antibody fragments exhibiting affinity to the antigen (Figure 1A). Positive clones are established by selecting only the phages that displays antibody fragments (primarily scFvs) fused to the g3p coat proteins on the surface of the filamentous phage, which have affinity to the antigen. This method has the advantage of processing large libraries (~1011) [3, 37]. The antigen is immobilized, and the recombinant phage bound to the antigen is left intact; weakly bound recombinant phages are washed away. The remaining recombinant phages, which possess a binding capacity are detached from the antigen by acid treatment and infected into E. coli. Further, E. coli cells are cultured to propagate positive clones. The E. coli clones expressing the phagemids are then infected with a helper phage, and the phages displaying scFvs with binding capacities are collected. Panning is performed repeatedly for the selected group of phages. The repeated selection and propagation of positive clones enrich clones with antibodies comprising binding capacities to the antigen. Then, single clones are isolated at the final step with high binding capacities [38]. This method renders it possible to handle large libraries.
\nOne limitation of this method is that the high background during panning selection often results in false-positive clones. A specific antigen-binding activity is typically not the only driving force exploited during the panning process [39, 40]. Multiple rounds of panning have been documented to frequently cause a strong bias for antibodies directed against immunodominant epitopes and abundant proteins [41], resulting in the loss of the library’s diversity and of valuable antibody clones. Several factors influence the selection of the antigen-specific clones and produce undesired effects; these factors include a high efficiency of expression and folding despite poor antigen-binding activity, the nonspecific hydrophobic binding properties of the phage particle itself, and a superior compatibility with the host cells, not related to the antibody fragment affinity.
\nHowever, as several antibody fragments are themselves toxic to E. coli, these clones will be lost during panning, even if they possess a high affinity. Conversely, repeated panning may result in the relatively preferential propagation of clones with reduced E. coli toxicity, even if the clones do not possess a high binding capacity. Toxicity to E. coli can increase the background, resulting in several false-positive clones being obtained. This situation renders panning extremely difficult; it is not easy to establish single positive clones only through several rounds of panning [14]. Although the phage display is a powerful tool for establishing monoclonal antibodies, it is used less frequently than expected [39].
\nAs an alternative antibody-screening tool, the colony assay can be used which is sometimes superior to the phage display method [42]. The advantage of this method is that the antibody-antigen binding can be directly observed during the screening process, reducing the selection of false-negative clones [24]. Thus, the colony assay presents notable advantages over the phage display and biopanning method.
\nIn the colony assay (Figure 2), antibody libraries are expressed in E. coli for the selection of clones with a favorable affinity to the antigen. An scFv library is transformed into E. coli cells, and afterward transformed E. coli cells are plated on appropriate agar plates. After growing of the colonies, they are lifted onto a filter. Further, an expression-inducing reagent such as isopropyl-β-D-thiogalactopyranoside (IPTG) is applied, inducing the expression and secretion of scFvs from the E. coli cells (Figure 2A). scFvs with the desired affinity will diffuse out and bind the antigen coated on the membrane beneath the colonies. However, scFvs without affinity will not bind the antigen (Figure 2B), and the unbound scFvs are washed away. Then, the bound scFvs with an affinity against the antigen are detected using an enzymatic method. The His-tags attached to the scFvs are detected with anti-His antibodies (Figure 2C). Positive clones are identified as the colonies corresponding to positive signals (Figure 2D).
\nScheme of the colony assay principle. (A) scFvs are expressed and secreted from E. coli. (B) scFvs with the desired affinity bind the antigen beneath the colonies. (C) Bound scFvs with an affinity against the antigen are detected using an enzymatic method. (D) Positive clones are identified as the colonies corresponding to positive signals.
Dreher et al. [43, 44] improved the colony assay by developing the filter-sandwich colony-screening assay (hereafter, the filter-sandwich assay) for selecting positive clones; E. coli colonies are grown directly on a hydrophilic filter, which is then transferred to an antigen-coated membrane soaked with IPTG solution and placed on an agar plate containing IPTG to induce antibody fragment production. The antibody fragments produced by the colonies diffuse out and bind to the antigen on the membrane. The presence of antibody fragments bound to the membrane is then detected, and the spot is superimposed on the colony. This method circumvents the difficult technique of lifting the colony [14, 36]. In addition, the filter-sandwich assay was further optimized. The procedure can now be performed by a single step [45] under tightly controlled IPTG concentration for expression of the scFvs.
\nThe procedure used in the filter-sandwich colony assay is depicted schematically in Figure 3.
\nProcedure for filter-sandwich colony assay.
In particular, the RNAs are isolated from the lymph tissue of immunized animals, and the corresponding cDNA is synthesized; this cDNA is used as the template for the polymerase chain reaction (PCR) amplification of the VL and VH domains. Further, the variable domains are assembled to an scFv and cloned into an expression vector to create the scFv libraries [46]. As expression vector, for example, pET22b (+), containing a pelB signal sequence for periplasm expression and a His-tag sequence for the detection of the scFv expression driven by the T7 promoter, is used. The antibody repertoire is transformed into E. coli, and the filter sandwich assay is performed as described in Figure 3.
\nThe hydrophilic PVDF filter is placed on an agar plate. Transformed E. coli with the scFv libraries is spread onto the filter and incubated. After the formation of the bacterial colonies on the filter surface, the filter harboring the colonies is transferred to an antigen-coated nitrocellulose membrane on the agar plate containing IPTG and incubated to induce scFv expression. Then, the filter harboring the colonies is removed, placed on a fresh plate, and stored for the later recovery of the bacteria. Subsequently, antigen-bound scFvs on the nitrocellulose membrane are detected with chemiluminescence from a horseradish peroxidase (HRP)-conjugated anti-His antibody. The filter harboring the colonies and the image presenting the chemiluminescence data are superimposed, and positive colonies corresponding to the chemiluminescence signals are identified. These positive clones are transferred to a medium and incubated. The plasmid encoding the scFv gene with an affinity against the antigen is purified, and the antibody coding sequence is determined.
\nA colony assay is used for screening the antibody fragments against a variety of antigens, with optimizations for each specific purpose. The recombinant antibody fragments against EspA and the intimin of E. coli O157:H7 were established by colony filter screening [47]. Colony-lift assay was combined with phage display, using cell-coated filters to screen the phage libraries for cell-binding clones [48]. Robert et al. developed subtractive colony filter screening to select scFvs that recognize atherosclerotic but not the normal aorta [49]. Giovannoni et al. isolated antiangiogenesis antibodies from combinatorial libraries by iterative colony filter screening: colonies located around the positive signals were selected, and the screening step was repeated; monoclonal scFvs were established after several rounds of the assay [50]. Neumann-Schaal et al. developed a colony-screening method in which E. coli colonies producing the required scFv were selected in the presence of ampicillin conjugated to the antigen of interest; this method relies on the neutralization of the conjugate by the produced scFv. The scFvs were identified against biotin by the growth of the scFv library-expressing E. coli in the presence of a biotin-ampicillin conjugate [51]. Kumada et al. improved the sensitivity of the colony assay utilizing antibody-coupled liposome encapsulating HRP [52].
\nIt is possible to screen 3–5 × 103 clones on a 10-cm diameter plate in a filter-sandwich assay, whereas in the hybridoma method, dozens of 96-well microtiter plates are required for screening these clones. Further, the filter-sandwich assay can be readily upscaled by increasing the number of plates. Therefore, the number of positive clones from the filter-sandwich assay can be higher than that from the hybridoma method. This would increase the chance of obtaining monoclonal antibody fragments with the desired affinity, specificity, and function.
\nHowever, the filter-sandwich assay needs to be improved further for the selection of positive clones, particularly with respect to the reliability of the antibody fragment expression and the handling of the colonies during the assay. For the colony assay, the control of the expression level is critical. Because the scFv expression by itself is considerably toxic to E. coli, an excess induction of expression, namely, exposure to an excess of the expression-inducing reagent (IPTG), leads to cell death and prevents the selection of antigen-specific scFvs. Conversely, exposure to insufficient IPTG induces inadequate antibody expression for the detection of signals from positive clones. In the filter-sandwich assay, expression induction is not stringently controlled because the concentration of the IPTG added to the cells cannot be precisely controlled. IPTG reaches the colonies by diffusing through the filter from the antigen-coated membrane and the agar plate. Quantitative control of the expression level is required for superior screening. This uncertainty in the IPTG concentration in the filter-sandwich assay also causes a problem in the induction timing. For appropriate induction, the colony size is a critical factor [14, 44]; however, the colony continues to grow during the assay. Hence, the timing of the expression induction is crucial for proper expression. If the ITPG diffusion is delayed, an initially small colony would grow too large for proper induction to occur; however, if the colonies are too small, the signal from each colony is inadequate for detecting the antigen binding. The induction strength cannot be accurately determined, particularly during the step, when the filter is transferred to the IPTG-containing plate to initiate the induction of expression. These induction-related uncertainties in the filter-sandwich assay lead to unstable expression and failure in isolating the antibody-encoding genes. Stringent control of the expression level is critical. Various factors related to the expression vector, such as the promoter, strength of the ribosomal binding site, fusion tags, and the copy number, must be optimized [53, 54, 55, 56, 57]. The incubation temperature is also an important factor in controlling the expression strength [58]. For inducing expression, additional methods such as the cold-shock system [59] should be examined. Expression-inducing reagents that are less toxic than IPTG to E. coli, such as rhamnose [60], should also be tested.
\nIn the filter-sandwich assay, before the induction of antibody expression, the filter harboring the colonies must be transferred without disturbance. This transfer requires delicate manipulation of the filter and frequently produces unwanted stress on the filter, occasionally disturbing the colonies themselves. A method that does not require the transfer of the filter should be developed for more efficient antibody establishment. Recently, a single-step colony assay was established by us using a tightly controlled IPTG concentration for scFv expression [45]. One advantage is also that no transfer of the filter on which the colonies are grown to the antigen-coated membrane is necessary.
\nThe establishment of a high-quality antibody library and efficient screening are the most important factors for successful recombinant antibody selection and production. Improvements in the screening technology are critical for quickly and reliably establishment of high-performance antibodies. Phage display screening is a powerful tool for this purpose; however, it has certain disadvantages such as the frequent selection of false-positive clones, but it can easily deal with a vast library. On the other hand, screening with a colony assay could identify the positive clones reliably; however, it cannot deal with a large complex library. Thus, screening methods using a display panning system and a colony assay have certain advantages and disadvantages, respectively. They should be utilized cooperatively, depending on the purpose of the experiments. Hence, condensing the library by phage display and then cloning the positive clones by colony assay would be advantageous. To efficiently establish high-quality antibodies, the adequate choice of these technologies and their combination would be crucial.
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',metaTitle:"Horizon 2020 Compliance",metaDescription:"General requirements for Open Access to Horizon 2020 research project outputs are found within Guidelines on Open Access to Scientific Publication and Research Data in Horizon 2020. The guidelines, in their simplest form, state that if you are a Horizon 2020 recipient, you must ensure open access to your scientific publications by enabling them to be downloaded, printed and read online. Additionally, said publications must be peer reviewed. ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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\n\nMetadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
\n\nIn other words, publishing with IntechOpen guarantees compliance.
\n\nRead more about Open Access in Horizon 2020 here.
\n\nWhich scientific publication to choose?
\n\nWhen choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
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