ESCMID generic competencies in antimicrobial prescribing and stewardship: towards a European consensus.

OBJECTIVE: To develop a consensus-based set of generic competencies in antimicrobial prescribing and stewardship for European prescribers through a structured consensus procedure. METHODS: The RAND-modified Delphi procedure comprised two online questionnaire rounds, a face-to-face meeting between rounds, and a final review. Our departure point was a set of competencies agreed previously by consensus among a UK multi-disciplinary panel, and which had been subsequently revised through consultation with ESCMID Study Group representatives. The 46 draft competency points were reviewed by an expert panel consisting of specialists in infectious diseases and clinical microbiology, and pharmacists. Each proposed competency was assessed using a nine-point Likert scale, for relevance as a minimum standard for all independent prescribers in all European countries. RESULTS: A total of 65 expert panel members participated, from 24 European countries (one to six experts per country). There was very high satisfaction (98%) with the final competencies set, which included 35 competency points, in three sections: core concepts in microbiology, pathogenesis and diagnosing infections (11 points); antimicrobial prescribing (20 points); and antimicrobial stewardship (4 points). CONCLUSIONS: The consensus achieved enabled the production of generic antimicrobial prescribing and stewardship competencies for all European independent prescribers, and of possible global utility. These can be used for training and can be further adapted to the needs of specific professional groups.

Perceptions, attitudes, and practices of French junior physicians regarding antibiotic use and resistance.

OBJECTIVES: To assess the perceptions, attitudes, and practices of French junior physicians regarding antibiotic use and resistance, and then to identify the characteristics of junior physicians associated with appropriate practices of antibiotic use. METHOD: European junior physicians received an email invitation to complete a 49 item web questionnaire between September 2015 and January 2016. We present the French data. Multivariate regression models were used to identify the characteristics of junior physicians associated with appropriate prescription practices and with consideration of the antibiotic prescription consequences. RESULTS: The questionnaire was completed by 641 junior physicians: family medicine (37%), other medical specialties (e.g., pediatrics, internal medicine, neurology: 45%), surgical specialties (11%), and anesthesiology-intensive care specialty (7%). Most respondents (93%) declared being aware of the risk of bacterial resistance and 41% acknowledged prescribing antibiotics more often than necessary. Two factors were independently associated with appropriate prescription practices: a high perceived level of education on antibiotic use (OR=1.51; 95% CI [1.01-2.30]) and a medical specialty (OR=1.69; 95% CI [1.16-2.46]). Factors independently associated with taking into account adverse events of antibiotics were a good perceived knowledge of antibiotics (OR=3.71; 95% CI [2.09-6.61]), and a high perceived education level on antibiotics (OR=1.70; 95% CI [1.11-2.58]). CONCLUSION: Our data can help better define interventions targeting junior physicians in antibiotic stewardship programs.

Comparison of antimicrobial stewardship programmes in acute-care hospitals in four European countries: A cross-sectional survey.

Antimicrobial stewardship programmes (ASPs) are designed to improve antibiotic use. A survey was systematically developed to assess ASP prerequisites, objectives and improvement strategies in hospitals. This study assessed the current state of ASPs in acute-care hospitals throughout Europe. A survey containing 46 questions was disseminated to acute-care hospitals: all Dutch (n = 80) and Slovenian (n = 29), 215 French (25%, random stratified sampling) and 62 Italian (49% of hospitals with an infectious diseases department, convenience sampling) acute-care hospitals, for a Europe-wide assessment. Response rates for the Netherlands (Nl), Slovenia (Slo), France (Fr) and Italy (It) were 80%, 86%, 45% and 66%. There was variation between countries in the prerequisites met and the objectives and improvement strategies chosen. A formal ASP was present mainly in the Netherlands (90%) and France (84%) compared with Slovenia (60%) and Italy (60%). Presence of an antimicrobial stewardship (AMS) team ranged from 42% (Fr) to 94% (Nl). Salary support for AMS teams was provided in 68% (Fr), 51% (Nl), 33% (Slo) and 12% (It) of surveyed hospitals. Quantity of antibiotic use was monitored in the majority of hospitals, ranging from 72% (Nl) to 100% (Slo and Fr) of acute-care hospitals. Participating countries varied substantially in the use of 'prospective monitoring and advice' as a strategy to improve AMS objectives. ASP prerequisites, objectives and improvement activities vary considerably across Europe, with room for improvement. Stimulating appropriate system prerequisites throughout Europe, e.g. by introducing staffing standards and financial support for ASPs, seems a first priority.

Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals.

OBJECTIVES: To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals. METHODS: Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions. RESULTS: Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%-100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence. CONCLUSIONS: Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking.

How do physicians cope with controversial topics in existing guidelines for the management of infective endocarditis? Results of an international survey.

International guidelines are available to help physicians prescribe appropriate antibiotic regimens to patients with infective endocarditis (IE). However some topics of these guidelines are controversial. We conducted an international survey to assess physicians' adherence to these guidelines, focusing on these controversial items. An invitation to participate to a 15-question online survey was sent in 2012-2013 to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members, scientific societies and corresponding authors of publications on IE mentioned in PubMed from 1990 to 2012, inclusive. Eight hundred thirty-seven physicians participated in the survey, and 625 (74.7%) completed it over the first question. The results showed great heterogeneity of practices. Claiming to follow guidelines was marginally associated with more guideline-based strategies. Gentamicin use depended on causative pathogens (p <0.001) and physician specialty (p 0.02). Eighty-six per cent of the physicians favoured vancomycin alone or in combination with gentamicin or rifampicin as a first-line treatment for left-sided native valve methicillin-resistant Staphylococcus aureus IE, 31% considered switching to oral therapy as a therapeutic option and 33% used the ampicillin and ceftriaxone combination for enterococcal IE as a first-line therapy. Physician specialty significantly affected the choice of a therapeutic strategy, while practicing in a university hospital or the number of years of practice had virtually no impact. Our survey, the largest on IE treatment, underscores important heterogeneity in practices for treatment of IE. Nonetheless, physicians who do not follow guidelines can have rational strategies that are based on the literature. These results could inform the revision of future guidelines and identify unmet needs for future studies.

Staffing for infectious diseases, clinical microbiology and infection control in hospitals in 2015: results of an ESCMID member survey.

We aimed to assess the current status of infectious diseases (ID), clinical microbiology (CM) and infection control (IC) staffing in hospitals and to analyse modifiers of staffing levels. We conducted an Internet-based survey of European Society of Clinical Microbiology and Infectious Diseases members and affiliates, collecting data on hospital characteristics, ID management infrastructure, ID/IC-related activities and the ratio of physicians per 100 hospital beds. Regression analyses were conducted to examine factors associated with the physician-bed ratio. Five hundred sixty-seven hospital responses were collected between April and June 2015 from 61 countries, 81.2% (384/473) from Europe. A specialized inpatient ward for ID patients was reported in 58.4% (317/543) of hospitals. Rates of antibiotic stewardship programmes (ASP) and surveillance activities in survey hospitals were high, ranging from 88% to 90% for local antibiotic guidelines and 70% to 82% for programmes monitoring hospital-acquired infections. The median ID/CM/IC physician per 100 hospital beds ratio was 1.12 (interquartile range 0.56-2.13). In hospitals performing basic ASP and IC (including local antibiotic guidelines and monitoring device-related or surgical site infections), the ratio was 1.21 (interquartile range 0.57-2.14). Factors independently associated with higher ratios included compliance with European Union of Medical Specialists standards, smaller hospital size, tertiary-care institution, presence of a travel clinic, beds dedicated to ID and a CM unit. More than half of respondents estimated that additional staffing is needed for appropriate IC or ID management. No standard of physician staffing for ID/CM/IC in hospitals is available. A ratio of 1.21/100 beds will serve as an informed point of reference enabling ASP and infection surveillance.

Meningococcal disease in Slovenia (1993-1999): serogroups and susceptibility to antibiotics. Slovenian Meningitis Study Group.

The epidemiology of meningococcal disease was studied prospectively in Slovenia from 1993 to 1999 in children and from 1995 to 1999 in adults. Patients with meningococci isolated from normally sterile body sites were included in the study. Altogether 75 patients (57 children, 18 adults) were found with meningococcal diseases. The overall yearly incidence was 0.43 per 100000 inhabitants. The highest annual incidence (18.5/100000) was found in children between 1 month and 1 year of age. The case to fatality ratio was 4.1%. Group B meningococci were isolated most frequently (84.7%), followed by group C (11.1%). In six patients (8.3%) isolates were less susceptible to penicillin. Four of these were successfully treated with penicillin alone.

Influence of fever on the pharmacokinetics of ciprofloxacin.

The influence of fever on the pharmacokinetics of ciprofloxacin was investigated in seven patients with acute febrile diseases. Antibiotic serum concentrations were determined using high-performance liquid chromatograpy (HPLC). The analog computer and the Simulink software package were used to identify the pharmacokinetic model and Penoclin software package to obtain the secondary parameters. During fever, higher maximum serum concentrations (Cmax) of ciprofloxacin were observed in six out of seven patients. The result suggests that the influence of fever on the pharmacodynamics of ciprofloxacin is favorable.

Influence of fever on cefazolin pharmacokinetics.

The influence of fever on the pharmacokinetics of cefazolin was investigated in patients with acute febrile diseases. Nine patients were included in the study. Antibiotic serum concentrations were determined using high performance liquid chromatograpy (HPLC). An analog computer and the SIMULINK software package were used to identify the pharmacokinetic model and PCNONLIN software package to obtain the secondary parameters. In 6 patients a two-compartment pharmacokinetic model of cefazolin was observed during fever and after defervescence. In 2 patients a two-compartment model changed to a one-compartment after defervescence, and a one-compartment model was observed in one patient during both periods. Cefazolin-treated patients with a two-compartment model (6/9) had higher Cmax, mean steady state serum concentrations (Css), and area under the plasma concentration-time curve (AUC(0-->infinity)), smaller central compartment volume (V1), and lower clearance (Cl) during fever. The varying distribution of antibiotics during fever probably reflects different hemodynamic responses to fever.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study.

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Does ertepenem alter the susceptibility of Pseudomonas aeruginosa to carbapenems?

We investigated the effect of ertapenem on carbapenem susceptibility of Pseudomonas aeruginosa. Antibiotic consumption was recorded monthly in defined daily doses (DDD)/100 patient-days in the infectious diseases (ID), abdominal surgery (AS), and surgical intensive care units (SICU) of a teaching hospital from January 2005 to December 2008. Trends of decreased susceptibility of P. aeruginosa were observed in all three units. After the introduction of ertapenem, the number of P. aeruginosa isolates/ 1000 patients-days per month increased in AS and in SICU (p=0.05). The increase in carbapenem non-susceptible isolates/1000 patients-days in the same units was less significant (p=0.07 and p=0.054). Correlations between ertapenem and the carbapenem non-susceptibility for the lagtime of 1 to 6 months ahead gave no significant result. In the SICU, 30% of variability of carbapenem non-susceptibility could be predicted by the consumption of ertapenem. There is no evidence that ertapenem alters the P. aeruginosa susceptibility to carbapenems, but the relationship deserves further observation.

Clinical characteristics of adult patients with influenza-like illness hospitalized in general ward during Influenza A H1N1 pandemic 2009/2010.

OBJECTIVE: To investigate clinical and laboratory features of patients with Influenza A H1N1 virus infection hospitalized during 2009/2010 pandemic. METHODS: Prospective observational study comparing clinical and laboratory characteristics of Influenza A H1N1 positive and negative patients with influenza-like illness (ILI). RESULTS: From October 21, 2009 to February 14, 2010 196 ILI patients were admitted, of which 66 tested positive for Influenza A H1N1. The patients with H1N1 infection were younger (43 years vs. 65 years; P < 0.01), more patients were pregnant (P < 0.01), had allergies (P < 0.05) or, asthma (P < 0.01). H1N1 positive patients were more often febrile (91% vs. 72.9%; P < 0.01) and had a higher prevalence of headache (31.8% vs. 18.5%; P < 0.05). Lower values of C-reactive protein (88 pg/dl vs. 126 pg/dl; P < 0.01), procalcitonine (0.42 µg/l vs. 3.98 µg/l; P < 0.05), leukocyte count (7.4*10(9)/l vs. 11.7*10(9)/l; P < 0.01) and higher values of troponin (0.162 µ/l vs. 0.146 µg/l; P < 0.01) were found in H1N1 positive patients. More bacterial infections were found in H1N1 negative group (68.8% vs. 89.2%; P < 0.05). CONCLUSIONS: In this study patients infected with Influenza A H1N1 differed from H1N1 negative ILI patients in several clinical and laboratory characteristics. The same was observed also by other investigators. The results of the study suggest some other specific features, such as a higher incidence of headache and higher values of troponin in Influenza A H1N1 infected patients.

The impact of total control of antibiotic prescribing by infectious disease specialist on antibiotic consumption and cost.

We analyzed the impact on antimicrobial consumption of antimicrobial therapy totally guided by an infectious disease specialist (iD). in a teaching hospital antibiotic consumption was recorded yearly from 1998 to 2005 in three units. Antibiotic policy was introduced in 1999. in Unit A, restricted antimicrobials were prescribed after approval by the head of the unit. the iD was involved as a consultant upon request. in unit b, restricted antimicrobials were approved by an iD. All other antimicrobials were prescribed by the physicians on the ward. in unit C, all antimicrobials were prescribed by an iD. A significant decreasing trend in antibiotic consumption in defined daily doses (DDD) per patient day and per admission, and cost of antimicrobials per patient was observed in unit C, a decreasing trend in antibiotic consumption per patient was observed in unit b as well. totally iD guided antimicrobial therapy is an efficient method of antimicrobial policy.