Stephan Harbarth

University of Geneva, Genève, Geneva, Switzerland

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Publications (300)1736.35 Total impact

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    ABSTRACT: PLEX-ID uses polymerase chain reaction-electrospray ionization/mass spectrometry for rapid identification of infectious agents in clinical samples. We evaluated its concordance with our centre's standard methods (SM) for bacterial and fungal detection in bronchoalveolar lavage (BAL) fluid in a prospective observational cohort study. The primary outcome was concordance (%) between SM and PLEX-ID. Secondary outcomes included concordance when excluding commensal oral flora, detection of resistance genes, and PLEX-ID's potential impact on clinical management, as determined by two independent reviewers. Included were 101 specimens from 94 patients. BALs were performed primarily for suspected pneumonia (76/101, 75%) and lung transplant work-ups (12/101, 12%). Most specimens yielded at least one organism by either method (92/101, 91%). Among all microorganisms detected (n = 218), 83% and 17% were bacterial and fungal, respectively. Overall concordance between SM and PLEX-ID was 45% (45/101). Concordance increased to 66% (67/101) when discordance for commensal flora was excluded. PLEX-ID failed to detect 21% of all 183 SM-identified organisms, while SM did not identify 28% of the 191 PLEX-ID-identified organisms (p <0.001). There was low concordance for mecA detection. Two infectious-disease specialists' analyses concluded that in most of the 31 discordant, non-commensal cases, PLEX-ID results would have had little or no impact on patient management; in eight cases, however, PLEX-ID would have led to ‘wrong decision-making’. The tested version of PLEX-ID concurred weakly with standard methods in the detection of bacteria and fungi in BAL specimens, and is not likely to be useful as a standalone tool for microbiological diagnosis in suspected respiratory infections.
    Clinical Microbiology and Infection 12/2014; · 4.58 Impact Factor
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    ABSTRACT: The objective of this review was to provide an up-to-date account of the interventions used to prevent the introduction of meticillin-resistant Staphylococcus aureus (MRSA) from the expanding community and livestock reservoirs into hospitals in the USA, Denmark, The Netherlands and Western Australia. A review of existing literature and local guidelines for the management of MRSA in hospitals was performed. In Denmark, The Netherlands and Western Australia, where the prevalence of MRSA is relatively low, targeted admission screening and isolation of predefined high-risk populations have been used for several decades to successfully control MRSA in the hospital. Furthermore, in Denmark and The Netherlands, all identified MRSA carriers undergo routine decolonisation, whereas only carriers of particularly transmissible or virulent MRSA clones are subjected to decolonisation in Western Australia. In the USA, which continues to be a high-prevalence MRSA country, policies vary by state and even by hospital, and whilst guidelines from professional organisations provide a framework for infection control practices, these guidelines lack the authority of a legislative mandate. In conclusion, the changing epidemiology of MRSA, exemplified by the recent emergence of MRSA in the community and in food animals, makes it increasingly difficult to accurately identify specific high-risk groups to screen for MRSA carriage. Understanding the changing epidemiology of MRSA in a local as well as global context is fundamental to prevent the introduction of MRSA into hospitals.
    Journal of Global Antimicrobial Resistance. 12/2014;
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    ABSTRACT: The best treatment for Tropheryma whipplei infections is controversial. We report a patient who suffered from T. whipplei aortic native valve endocarditis that relapsed despite surgery and four weeks of intravenous ceftriaxone followed by several months of oral trimethoprim/sulfamethoxazole. Cure was achieved after replacement of the prosthesis with a homograft and 18 months of oral doxycycline-hydroxychloroquine. We discuss the need for a change in treatment guidelines for T. whipplei infections. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
    International Journal of Infectious Diseases 11/2014; 30C:17-19. · 2.33 Impact Factor
  • K Stucki, S Harbarth, M Nendaz
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    ABSTRACT: Enterococci are microorganisms with a remar- kable ability to adapt to their environment. Two species have a significant clinical implication, Enterococcus faecalis and Enterococcus faecium. The risk factors for colonization and infection must be recognized, including prior treatment with antibiotics such as cephalosporins or quinolones. Because of their native resistance to several classes of antibiotics and the increase of acquired resistance to penicillins, the initial empiric treatment of a severe infection in a patient at risk of enterococcal infection often includes a glycopeptide. A restriction in the empirical use of cephalosporins or quinolones and a targeted antibiotic therapy following receipt of the antibiogram are essential to prevent the emergence of enterococcal strains and especially vancomycin-resistant enterococci.
    Revue médicale suisse. 10/2014; 10(446):1918, 1920-3.
  • Benedikt Huttner, Stephan Harbarth, Dilip Nathwani
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    ABSTRACT: It has been increasingly recognized that antimicrobial stewardship (AMS) has to be a key component of any efforts that aim to mitigate the current global antimicrobial resistance (AMR) crisis. It has also become evident that AMR is a problem that cannot be tackled by single institutions or physicians, but needs concerted actions on the regional, national and supranational level. It is, however, easy to become discouraged given the problems that are often encountered when implementing AMS. The aim of this review is to highlight some of the success stories of AMS strategies, to describe the actions that have been taken, the outcomes that have been obtained and the obstacles that have been met. While the best approach to effective AMS remains elusive and may significantly vary among settings, these diverse examples from a range of health care contexts demonstrate that effective AMS is possible. The learning from such examples will inform and encourage others to formally evaluate and share their results with the global stewardship community. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 10/2014; · 4.58 Impact Factor
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    ABSTRACT: IMPORTANCE The clinical benefit of adding a macrolide to a β-lactam for empirical treatment of moderately severe community-acquired pneumonia remains controversial. OBJECTIVE To test noninferiority of a β-lactam alone compared with a β-lactam and macrolide combination in moderately severe community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS Open-label, multicenter, noninferiority, randomized trial conducted from January 13, 2009, through January 31, 2013, in 580 immunocompetent adult patients hospitalized in 6 acute care hospitals in Switzerland for moderately severe community-acquired pneumonia. Follow-up extended to 90 days. Outcome assessors were masked to treatment allocation. INTERVENTIONS Patients were treated with a β-lactam and a macrolide (combination arm) or with a β-lactam alone (monotherapy arm). Legionella pneumophila infection was systematically searched and treated by addition of a macrolide to the monotherapy arm. MAIN OUTCOMES AND MEASURES Proportion of patients not reaching clinical stability (heart rate <100/min, systolic blood pressure >90mmHg, temperature <38.0°C, respiratory rate <24/min, and oxygen saturation >90% on room air) at day 7. RESULTS After 7 days of treatment, 120 of 291 patients (41.2%) in the monotherapy arm vs 97 of 289 (33.6%) in the combination arm had not reached clinical stability (7.6%difference, P = .07). The upper limit of the 1-sided 90% CI was 13.0%, exceeding the predefined noninferiority boundary of 8%. Patients infected with atypical pathogens (hazard ratio [HR], 0.33; 95%CI, 0.13-0.85) or with Pneumonia Severity Index (PSI) category IV pneumonia (HR, 0.81; 95%CI, 0.59-1.10) were less likely to reach clinical stability with monotherapy, whereas patients not infected with atypical pathogens (HR, 0.99; 95%CI, 0.80-1.22) or with PSI category I to III pneumonia (HR, 1.06; 95%CI, 0.82-1.36) had equivalent outcomes in the 2 arms. There were more 30-day readmissions in the monotherapy arm (7.9%vs 3.1%, P = .01). Mortality, intensive care unit admission, complications, length of stay, and recurrence of pneumonia within 90 days did not differ between the 2 arms. CONCLUSIONS AND RELEVANCE We did not find noninferiority of β-lactam monotherapy in patients hospitalized for moderately severe community-acquired pneumonia. Patients infected with atypical pathogens or with PSI category IV pneumonia had delayed clinical stability with monotherapy.
    JAMA Internal Medicine 10/2014; · 13.25 Impact Factor
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    ABSTRACT: We performed a contingent valuation survey to elicit the opportunity cost of bed-days consumed by healthcare-associated infections in 11 European hospitals. The opportunity cost of a bed-day was significantly lower than the accounting cost; median values were €72 and €929, respectively (P < .001). Accounting methods overestimate the opportunity cost of bed-days.
    Infection Control and Hospital Epidemiology 10/2014; 35(10):1294-1297. · 3.94 Impact Factor
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    ABSTRACT: Nitrofurantoin has been used for decades for the treatment of urinary tract infections (UTI), however, clinically significant resistance in E. coli is as yet uncommon. Nitrofurantoin concentrations in the gastrointestinal tract tend to be low, which might facilitate selection of nitrofurantoin-resistant (NIT-R) strains in the gut flora. We subjected two nitrofurantoin-susceptible intestinal E. coli strains (ST540-p, ST2747-p) to increasing nitrofurantoin concentrations under aerobic and anaerobic conditions. Whole genome sequencing was performed on both susceptible isolates and on selected mutants that exhibited the highest nitrofurantoin resistance levels aerobically (ST540-a, ST2747-a) and anaerobically (ST540-an, ST2747-an). ST540-a/-an and ST2747-a (aerobic MIC >64 μg/ml) harbored mutations in known nitrofurantoin resistance determinants, nfsA and/or nfsB that encode oxygen-insensitive nitroreductases. ST2747-an showed reduced nitrofurantoin susceptibility (aerobic MIC 32 μg/ml) and exhibited remarkable growth deficits, however, did not harbor nfsA/B mutations. We identified a 12-nucleotide deletion in ribE encoding lumazine synthase, an essential enzyme involved in the biosynthesis of FMN, an important cofactor of NfsA/B. Complementing ST2747-an with a functional wild-type lumazine synthase restored nitrofurantoin susceptibility. Six NIT-R E. coli (NRCI-1 to -6) isolated from stools of UTI patients treated with nitrofurantoin, cefuroxime, or a fluoroquinolone harbored mutations in nfsA and/or nfsB, but not in ribE. Sequencing of the ribE gene in six intestinal and three urinary E. coli strains showing reduced nitrofurantoin-susceptibility (MIC range 16-48 μg/ml) also did not identify any relevant mutations. NRCI-1, -2, -5 exhibited upto four-fold higher anaerobic MICs compared to the in vitro mutants, presumably because of additional mutations in oxygen-sensitive nitroreductases.
    Antimicrobial Agents and Chemotherapy 09/2014; · 4.45 Impact Factor
  • Jean-Francois Timsit, Stephan Harbarth, Jean Carlet
    Intensive Care Medicine 09/2014; · 5.54 Impact Factor
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    ABSTRACT: The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection.
    Journal of Antimicrobial Chemotherapy 09/2014; · 5.44 Impact Factor
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    ABSTRACT: Background Surveillance is an essential element of surgical site infection (SSI) prevention. Few studies have evaluated the long-term effect of these programmes. Aim To present data from a 13-year multicentre SSI surveillance programme from western and southern Switzerland. Methods Surveillance with post-discharge follow-up was performed according to the US National Nosocomial Infections Surveillance (NNIS) system methods. SSI rates were calculated for each surveyed type of surgery, overall and by year of participation in the programme. Risk factors for SSI and the effect of surveillance time on SSI rates were analysed by multiple logistic regression. Findings Overall SSI rates were 18.2% after 7411 colectomies, 6.4% after 6383 appendicectomies, 2.3% after 7411 cholecystectomies, 1.7% after 9933 herniorrhaphies, 1.6% after 6341 hip arthroplasties, and 1.3% after 3667 knee arthroplasties. The frequency of SSI detected after discharge varied between 21% for colectomy and 94% for knee arthroplasty. Independent risk factors for SSI differed between operations. The NNIS risk index was predictive of SSI in gastrointestinal surgery only. Laparoscopic technique was protective overall, but associated with higher rates of organ-space infections after appendicectomy. The duration of participation in the surveillance programme was not associated with a decreased SSI rate for any of the included procedure. Conclusion These data confirm the effect of post-discharge surveillance on SSI rates and the protective effect of laparoscopy. There is a need to establish alternative case-mix adjustment methods. In contrast to other European programmes, no positive impact of surveillance duration on SSI rates was observed.
    Journal of Hospital Infection 09/2014; · 2.78 Impact Factor
  • Gerd Fätkenheuer, Bernard Hirschel, Stephan Harbarth
    The Lancet 08/2014; · 39.21 Impact Factor
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    ABSTRACT: Topical mupirocin is widely used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers. We evaluated the capacity of various MRSA clonotypes to develop mutations in the ileS gene associated with low-level mupirocin resistance. Twenty-four mupirocin-sensitive MRSA isolates from a variety of genotypes (determined by multilocus variable number of tandem repeats assay) were selected. Mupirocin MICs were determined by Etest. The isolates were then incubated in sub-inhibitory concentrations of mupirocin for 7-14 days. Repeat MIC determination and sequencing of the ileS gene were then performed. Doubling times of isolates exposed and unexposed to mupirocin were compared. We found that exposure to mupirocin led to rapid induction of low-level resistance (MICs 8-24 μg/ml) in 11 of 24 (46%) MRSA isolates. This phenomenon was observed in strains with diverse genetic backgrounds. Various mutations were detected in 18 of 24 (75%) MRSA isolates. Acquisition of mutations appeared to be a stepwise process during prolonged incubation with the drug. Among five low-level resistant isolates with the highest MICs, four tested sensitive after incubation in the absence of mupirocin but there was no reversion to the susceptible wild-type primary sequence. Resistance was not associated with significant fitness cost, suggesting that low-level mupirocin-resistant MRSA strains may have a selective advantage in facilities where mupirocin is commonly used. Our findings emphasize the importance of the judicious use of this topical agent and the need to closely monitor for the emergence of resistance.
    Journal of Clinical Microbiology 08/2014; · 4.23 Impact Factor
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    ABSTRACT: Background Given the breadth and depth of antiseptic use, it is surprising how few large-scale studies have been undertaken into the consequences of their use, particularly in clinical practice. Depending on your point of view, this may either reflect an assurance that reduced susceptibility to antiseptics, and notably whether this confers cross-resistance to systemically administered antimicrobial agents, is not an issue of concern, or relative ignorance about the potential threat. Aim This point/counterpoint review offers a differentiated perspective and possible answers to the question, ‘Should we be worried about reduced susceptibility to disinfectants and antiseptics in healthcare settings?’. Methods This topic was the subject of a debate by MHW (point) and SH (counterpoint) during the SHEA Spring Conference 2013: Advancing healthcare epidemiology and the role of the environment, held in Atlanta, GA, USA on 4th May 2013. This review is a general representation of the main themes presented during the debate, rather than a systematic review of the literature. Findings There are examples of reduced susceptibility to antiseptics in clinical practice; however, to date, there is no strong evidence that reduced susceptibility to antiseptics is a major clinical problem. Given the growing number of potential indications for use of biocidal active ingredients, the potential for emergence of reduced susceptibility remains a concern. Conclusions Changes in the clinical use of antiseptics should be matched with surveillance studies to understand whether there are unintended microbiological or clinical consequences, including the selection of bacterial strains that can survive exposure to antiseptics.
    Journal of Hospital Infection 08/2014; · 2.78 Impact Factor
  • Kalisvar Marimuthu, Stephan Harbarth
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    ABSTRACT: To describe the latest evidence for methicillin-resistant Staphylococcus aureus (MRSA) infection control strategies, with particular emphasis on active surveillance cultures with contact precautions and targeted decolonization, and their impact.
    Current Opinion in Infectious Diseases 08/2014; 27(4):356-362. · 5.03 Impact Factor
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    Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 07/2014; 19(29). · 4.66 Impact Factor
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    ABSTRACT: The prevalence of multidrug-resistant organisms (MDROs) in ICUs is increasing worldwide. This review assesses the role of infection control measures, excluding antibiotic stewardship programs, in reducing the burden of resistance in ICUs.
    Current Opinion in Critical Care 07/2014; · 3.18 Impact Factor
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    ABSTRACT: Given the current bacterial resistance crisis, antimicrobial stewardship programmes are of utmost importance. We present here a narrative review of the impact of infectious diseases specialists (IDS) on the quality and quantity of antibiotic use in acute care hospitals, and discuss the main factors that could limit the efficacy of IDS recommendations. A total of 31 studies were included in this review, with a wide range of infections, hospital settings and types of antibiotic prescriptions. Seven of 31 studies were randomised controlled trials, before/after controlled studies or before/after uncontrolled studies with interrupted time-series analysis. In almost all studies, IDS intervention was associated with a significant improvement of the appropriateness of antibiotic prescribing compared with prescriptions without any IDS input, and with decreased antibiotic consumption. Variability in the antibiotic prescribing practices of IDS, informal (curbside) consultations, involvement of junior IDS are among the factors that could have an impact on the efficacy of IDS recommendations and on compliance rates, and deserve further investigation. We also discuss possible drawbacks of IDS in acute care hospitals that are rarely reported in the published literature. Overall, IDS are valuable to antimicrobial stewardship programmes in hospitals, but their impact depends on many human and organisational factors.This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 07/2014; · 4.58 Impact Factor
  • Future Microbiology 06/2014; 9:757-771. · 4.02 Impact Factor
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    ABSTRACT: Objective. To test the hypothesis that methicillin-susceptible Staphylococcus aureus (MSSA) carriage may protect against nosocomial methicillin-resistant S. aureus (MRSA) acquisition by competing for colonization of the anterior nares. Design. Prospective cohort and nested case-control study. Setting. Swiss university hospital. Patients. All adult patients admitted to 14 wards of the general medicine division between April 1 and October 31, 2007. Methods. Patients were screened for MRSA and MSSA carriage at admission to and discharge from the division. Associations between nosocomial MRSA acquisition and MSSA colonization at admission and other confounders were analyzed by univariable and multivariable analysis. Results. Of 898 patients included, 183 (20%) were treated with antibiotics. Nosocomial MRSA acquisition occurred in 70 (8%) of the patients (case patients); 828 (92%) of the patients (control subjects) were free of MRSA colonization at discharge. MSSA carriage at admission was 20% and 21% for case patients and control subjects, respectively. After adjustment by multivariate logistic regression, no association was observed between MSSA colonization at admission and nosocomial MRSA acquisition (adjusted odds ratio [aOR], 1.2 [95% confidence interval (CI), 0.6-2.3]). By contrast, 4 independent predictors of nosocomial MRSA acquisition were identified: older age (aOR per 1-year increment, 1.05 [95% CI, 1.02-1.08]); increased length of stay (aOR per 1-day increment, 1.05 [95% CI, 1.02-1.09]); increased nursing workload index (aOR per 1-point increment, 1.02 [95% CI, 1.01-1.04]); and previous treatment with macrolides (aOR, 5.6 [95% CI, 1.8-17.7]). Conclusions. Endogenous MSSA colonization does not appear to protect against nosocomial MRSA acquisition in a population of medical patients without frequent antibiotic exposure.
    Infection Control and Hospital Epidemiology 05/2014; 35(5):527-33. · 4.02 Impact Factor

Publication Stats

10k Citations
1,736.35 Total Impact Points


  • 1998–2014
    • University of Geneva
      • • Faculty of Medicine
      • • Division of Infectious Diseases
      • • Department of Internal Medicine
      Genève, Geneva, Switzerland
  • 2002–2012
    • University of Utah
      • • Division of Epidemiology
      • • Department of Internal Medicine
      • • Division of Infectious Diseases
      Salt Lake City, Utah, United States
  • 2011
    • Queensland University of Technology
      • Institute of Health and Biomedical Innovation
      Brisbane, Queensland, Australia
    • Royal Prince Alfred Hospital
      • Division of Infectious Diseases & Microbiology
      Camperdown, New South Wales, Australia
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • University of Pennsylvania
      Philadelphia, Pennsylvania, United States
    • Catholic University of the Sacred Heart
      • School of Infectious Diseases
      Roma, Latium, Italy
    • University of Buenos Aires
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2009–2011
    • Ospedale Centrale di Bolzano
      Bozen, Trentino-Alto Adige, Italy
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 1998–2011
    • Hôpitaux Universitaires de Genève
      Genève, Geneva, Switzerland
  • 2008
    • Chris Hani Baragwanath Hospital
      Johannesburg, Gauteng, South Africa
  • 2006
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
  • 2005
    • Hospital of Saint Raphael
      New Haven, Connecticut, United States
    • Erasmus Universiteit Rotterdam
      • Department of Medical Microbiology and Infectious Diseases
      Rotterdam, South Holland, Netherlands
  • 2004
    • Emory University
      Atlanta, Georgia, United States
  • 1999–2003
    • Harvard University
      • Department of Epidemiology
      Cambridge, Massachusetts, United States
  • 2000–2002
    • Boston Children's Hospital
      • Division of Infectious Diseases
      Boston, Massachusetts, United States
  • 2000–2001
    • Beth Israel Deaconess Medical Center
      • Division of Infectious Diseases
      Boston, MA, United States
  • 1998–2001
    • Harvard Medical School
      Boston, Massachusetts, United States