Stefan P. Kuster

Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis.

Objective To evaluate risk factors for severe outcomes in patients with seasonal and pandemic influenza. Design Systematic review. Study selection Observational studies reporting on risk factor-outcome combinations of interest in participants with influenza. Outcomes included death, ventilator support, admission to hospital, admission to an intensive care unit, pneumonia, and composite outcomes. Data sources Medline, Embase, CINAHL, Global Health, and the Cochrane Central Register of Controlled Trials to March 2011. Risk of bias assessment Newcastle-Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality of evidence. Results 63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence supporting risk factors for severe outcomes of influenza ranged from being limited to absent. This was particularly relevant for the relative lack of data for non-2009 H1N1 pandemics and for seasonal influenza studies. Limitations in the published literature included lack of power and lack of adjustment for confounders was widespread: adjusted risk estimates were provided for only 5% of risk factor-outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for “any risk factor” (odds ratio for mortality 2.77, 95% confidence interval 1.90 to 4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza), obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68, 1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all other risk factors. Some well accepted risk factors such as pregnancy and belonging to an ethnic minority group could not be identified as risk factors. In contrast, women who were less than four weeks post partum had a significantly increased risk of death from pandemic influenza (4.43, 1.24 to 15.81). Conclusion The level of evidence to support risk factors for influenza related complications is low and some well accepted risk factors, including pregnancy and ethnicity, could not be confirmed as risks. Rigorous and adequately powered studies are needed.

Prolonged Outbreak of Mycobacterium chimaera Infection After Open-Chest Heart Surgery

BACKGROUND Invasive Mycobacterium chimaera infections were diagnosed in 2012 in 2 heart surgery patients on extracorporeal circulation. We launched an outbreak investigation to identify the source and extent of the potential outbreak and to implement preventive measures. METHODS We collected water samples from operating theaters, intensive care units, and wards, including air samples from operating theaters. Mycobacterium chimaera strains were characterized by randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Case detection was performed based on archived histopathology samples and M. chimaera isolates since 2006, and the patient population at risk was prospectively surveyed. RESULTS We identified 6 male patients aged between 49 and 64 years with prosthetic valve endocarditis or vascular graft infection due to M. chimaera, which became clinically manifest with a latency of between 1.5 and 3.6 years after surgery. Mycobacterium chimaera was isolated from cardiac tissue specimens, blood cultures, or other biopsy specimens. We were able also to culture M. chimaera from water circuits of heater-cooler units connected to the cardiopulmonary bypass, and air samples collected when the units were in use. RAPD-PCR demonstrated identical patterns among M. chimaera strains from heater-cooler unit water circuits and air samples, and strains in 2 patient clusters. CONCLUSIONS The epidemiological and microbiological features of this prolonged outbreak provided evidence for the airborne transmission of M. chimaera from contaminated heater-cooler unit water tanks to patients during open-heart surgery.

Transmission of Mycobacterium chimaera from Heater-Cooler Units during Cardiac Surgery despite an Ultraclean Air Ventilation System.

All such units should be separated from air that can gain access to sterile areas.

Prosthetic Valve Endocarditis and Bloodstream Infection Due to Mycobacterium chimaera

ABSTRACT Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected.

Different patterns of inappropriate antimicrobial use in surgical and medical units at a tertiary care hospital in Switzerland: a prevalence survey.

Background Unnecessary or inappropriate use of antimicrobials is associated with the emergence of antimicrobial resistance, drug toxicity, increased morbidity and health care costs. Antimicrobial use has been reported to be incorrect or not indicated in 9–64% of inpatients. We studied the quality of antimicrobial therapy and prophylaxis in hospitalized patients at a tertiary care hospital to plan interventions to improve the quality of antimicrobial prescription. Methodology/Principal Findings Experienced infectious diseases (ID) fellows performed audits of antimicrobial use at regular intervals among all patients—with or without antimicrobials—hospitalized in predefined surgical, medical, haemato-oncological, or intensive care units. Data were collected from medical and nursing patient charts with a standardized questionnaire. Appropriateness of antimicrobial use was evaluated using a modified algorithm developed by Gyssens et al.; the assessment was double-checked by a senior ID specialist. We evaluated 1577 patients of whom 700 (44.4%) had antimicrobials, receiving a total of 1270 prescriptions. 958 (75.4%) prescriptions were for therapy and 312 (24.6%) for prophylaxis. 37.0% of therapeutic and 16.6% of prophylactic prescriptions were found to be inappropriate. Most frequent characteristics of inappropriate treatments included: No indication (17.5%); incorrect choice of antimicrobials (7.6%); incorrect application of drugs (9.3%); and divergence from institutional guidelines (8%). Characteristics of inappropriate prophylaxes were: No indication (9%); incorrect choice of antimicrobials (1%); duration too long or other inappropriate use (6.7%). Patterns of inappropriate antimicrobial varied widely in the different hospital units; empirical prescriptions were more frequently incorrect than prescriptions based on available microbiological results. Conclusions/Significance Audits of individual patient care provide important data to identify local problems in antimicrobial prescription practice. In our study, antimicrobial prescriptions without indication, and divergence from institutional guidelines were frequent errors. Based on these results, we will tailor education, amend institutional guidelines and further develop the infectious diseases consultation service.

Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators: the NORDIC ICD randomized clinical trial

Aims This trial was designed to test the hypothesis that shock efficacy during follow-up is not impaired in patients implanted without defibrillation (DF) testing during first implantable cardioverter-defibrillator (ICD) implantation. Methods and results Between February 2011 and July 2013, 1077 patients were randomly assigned (1 : 1) to first time ICD implantation with (n = 540) or without (n = 537) DF testing. The intra-operative DF testing was standardized across all participating centres, and all ICD shocks were programmed to 40 J irrespective of DF test results. The primary end point was the average first shock efficacy (FSE) for all true ventricular tachycardia and fibrillation (VT/VF) episodes during follow-up. The secondary end points included procedural data, serious adverse events, and mortality. During a median follow-up of 22.8 months, the model-based FSE was found to be non-inferior in patients with an ICD implanted without a DF test, with a difference in FSE of 3.0% in favour of the no DF test [confidence interval (CI) −3.0 to 9.0%, Pnon-inferiority <0.001 for the pre-defined non-inferiority margin of −10%). A total of 112 procedure-related serious adverse events occurred within 30 days in 94 patients (17.6%) tested compared with 89 events in 74 patients (13.9%) not tested (P = 0.095). Conclusion Defibrillation efficacy during follow-up is not inferior in patients with a 40 J ICD implanted without DF testing. Defibrillation testing during first time ICD implantation should no longer be recommended for routine left-sided ICD implantation.

Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: systematic review and meta-analysis

OBJECTIVES Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant. METHODS OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers. RESULTS Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n=13), skin and soft tissue infections (n=8), intra-abdominal infections (n=4) and others (n=8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P=0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P=0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P=0.01); tigecycline displayed a close to significant association with increased mortality (P=0.05) if compared with other bacteriostatic agents. CONCLUSIONS The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn.

Reemergence of Mycobacterium chimaera in Heater–Cooler Units despite Intensified Cleaning and Disinfection Protocol

Invasive Mycobacterium chimaera infections after open-heart surgery have been reported internationally. These devastating infections result from aerosols generated by contaminated heater–cooler units used with extracorporeal circulation during surgery. Despite intensified cleaning and disinfection, surveillance samples from factory-new units acquired during 2014 grew nontuberculous mycobacteria after a median of 174 days.

Previous Antibiotic Exposure and Antimicrobial Resistance in Invasive Pneumococcal Disease: Results From Prospective Surveillance

BACKGROUND Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD). METHODS We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers. RESULTS Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses. CONCLUSIONS Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes.

Change of antibiotic susceptibility testing guidelines from CLSI to EUCAST: influence on cumulative hospital antibiograms.

Objective We studied whether the change in antibiotic susceptibility testing (AST) guidelines from CLSI to EUCAST influenced cumulative antibiograms in a tertiary care hospital in Switzerland. Methods Antibiotic susceptibilities of non-duplicate isolates collected within a one-year period before (period A) and after (period B) changing AST interpretation from CLSI 2009 to EUCAST 1.3 (2011) guidelines were analysed. In addition, period B isolates were reinterpreted according to the CLSI 2009, CLSI 2013 and EUCAST 3.1 (2013) guidelines. Results The majority of species/drug combinations showed no differences in susceptibility rates comparing periods A and B. However, in some gram-negative bacilli, decreased susceptibility rates were observed when comparing CLSI 2009 with EUCAST 1.3 within period B: Escherichia coli / cefepime, 95.8% (CLSI 2009) vs. 93.1% (EUCAST 1.3), P=0.005; Enterobacter cloacae / cefepime, 97.0 (CLSI 2009) vs. 90.5% (EUCAST 1.3), P=0.012; Pseudomonas aeruginosa / meropenem, 88.1% (CLSI 2009) vs. 78.3% (EUCAST 1.3), P=0.002. These differences were still evident when comparing susceptibility rates according to the CLSI 2013 guideline with EUCAST 3.1 guideline. For P. aeruginosa and imipenem, a trend towards a lower antibiotic susceptibility rate in ICUs compared to general wards turned into a significant difference after the change to EUCAST: 87.9% vs. 79.8%, P=0.08 (CLSI 2009) and 86.3% vs. 76.8%, P=0.048 (EUCAST 1.3). Conclusions The change of AST guidelines from CLSI to EUCAST led to a clinically relevant decrease of susceptibility rates in cumulative antibiograms for defined species/drug combinations, particularly in those with considerable differences in clinical susceptibility breakpoints between the two guidelines.