Stephan Harbarth

University of Geneva, Genève, Geneva, Switzerland

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Publications (242)1598.03 Total impact

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    ABSTRACT: Background and purpose - Obesity increases the risk of deep infection after total joint arthroplasty (TJA). Our objective was to determine whether there may be body mass index (BMI) and weight thresholds indicating a higher prosthetic joint infection rate. Patients and methods - We included all 9,061 primary hip and knee arthroplasties (mean age 70 years, 61% women) performed between March 1996 and December 2013 where the patient had received intravenous cefuroxime (1.5 g) perioperatively. The main exposures of interest were BMI (5 categories: < 24.9, 25-29.9, 30-34.9, 35-39.9, and ≥ 40) and weight (5 categories: < 60, 60-79, 80-99, 100-119, and ≥ 120 kg). Numbers of TJAs according to BMI categories (lowest to highest) were as follows: 2,956, 3,350, 1,908, 633, and 214, respectively. The main outcome was prosthetic joint infection. The mean follow-up time was 6.5 years (0.5-18 years). Results - 111 prosthetic joint infections were observed: 68 postoperative, 16 hematogenous, and 27 of undetermined cause. Incidence rates were similar in the first 3 BMI categories (< 35), but they were twice as high with BMI 35-39.9 (adjusted HR = 2.1, 95% CI: 1.1-4.3) and 4 times higher with BMI ≥ 40 (adjusted HR = 4.2, 95% CI: 1.8-9.7). Weight ≥ 100 kg was identified as threshold for a significant increase in infection from the early postoperative period onward (adjusted HR = 2.1, 95% CI: 1.3-3.6). Interpretation - BMI ≥ 35 or weight ≥ 100 kg may serve as a cutoff for higher perioperative dosage of antibiotics.
    Preview · Article · Jan 2016 · Acta Orthopaedica
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    ABSTRACT: Background: Surgical site infections (SSI) due to Staphylococcus aureus are associated with substantial mortality rates and morbidity. Hence, various strategies are being investigated to prevent them. We explore time trends and risk factors associated with S. aureus SSI to identify high risk patients who might benefit the most from these strategies. Methods: This is a retrospective cross-sectional study on a prospectively maintained database. We identified organism specific risk factors for S. aureus SSI as a whole, methicillin-sensitive S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA). We also identified procedure-specific risk factors for S. aureus SSI for colectomy, hip, and knee arthroplasty, herniorrhaphy, and cholecystectomy. Results: We compared 249 patients with S. aureus SSI with 54,988 uninfected control patients. The rate of S. aureus SSI was steady throughout the study period with MSSA being more common than MRSA. Independent risk factors for S. aureus SSI from multivariable analysis were length of hospitalization prior to surgery [odds ratio (OR) 1.01; 95% confidence interval (CI), 1.00-1.02)], colectomy (OR 2.81; 95% CI, 1.94-4.07), hip or knee arthroplasty (OR 1.52; 95% CI, 1.04-2.21), extended duration of surgery (OR 1.61; 95% CI, 1.10-2.37), NNIS score of two or more (OR 2.04; 95% CI, 1.24-3.36), and re-interventions for non-infectious reasons (OR 1.82; 95% CI, 1.16-2.86). Minimally invasive (OR 0.21; 95% CI, 0.13-0.34) and emergency operations (OR 0.61; 95% CI, 0.41-0.92) were protective against S. aureus SSI. Conclusions: Future S.aureus SSI prevention measures should focus on patients with risk profiles identified from this and other similar studies.
    No preview · Article · Dec 2015 · Surgical Infections
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    ABSTRACT: Background: Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP. Methods: We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications. Results: 14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96). Conclusion: Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain.
    Full-text · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: The lack of new antibiotic classes calls for a cautious use of existing agents. Yet, every 10 min, almost two tons of antibiotics are used around the world, all too often without any prescription or control. The use, overuse and misuse of antibiotics select for resistance in numerous species of bacteria which then renders antimicrobial treatment ineffective. Almost all countries face increased antimicrobial resistance (AMR), not only in humans but also in livestock and along the food chain. The spread of AMR is fueled by growing human and animal populations, uncontrolled contamination of fresh water supplies, and increases in international travel, migration and trade. In this context of global concern, 68 international experts attending the fifth edition of the World HAI Resistance Forum in June 2015 shared their successes and failures in the global fight against AMR. They underlined the need for a “One Health” approach requiring research, surveillance, and interventions across human, veterinary, agricultural and environmental sectors. This strategy involves concerted actions on several fronts. Improved education and increased public awareness are a well-understood priority. Surveillance systems monitoring infections need to be expanded to include antimicrobial use, as well as the emergence and spread of AMR within clinical and environmental samples. Adherence to practices to prevent and control the spread of infections is mandatory to reduce the requirement of antimicrobials in general care and agriculture. Antibiotics need to be banned as growth promoters for farm animals in countries where it has not yet been done. Antimicrobial stewardship programmes in animal husbandry have proved to be efficient for minimising AMR, without compromising productivity. Regarding the use of antibiotics in humans, new tools to provide highly specific diagnoses of pathogens can decrease diagnostic uncertainty and improve clinical management. Finally, infection prevention and control measures – some of them as simple as hand hygiene – are essential and should be extended beyond healthcare settings. Aside from regulatory actions, all people can assist in AMR reduction by limiting antibiotic use for minor illnesses. Together, we can all work to reduce the burden of AMR.
    Full-text · Article · Dec 2015
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    ABSTRACT: Predictive models to identify unknown methicillin-resistant Staphylococcus aureus (MRSA) carriage on admission may optimise targeted MRSA screening and efficient use of resources. However, common approaches to model selection can result in overconfident estimates and poor predictive performance. We aimed to compare the performance of various models to predict previously unknown MRSA carriage on admission to surgical wards. The study analysed data collected during a prospective cohort study which enrolled consecutive adult patients admitted to 13 surgical wards in 4 European hospitals. The participating hospitals were located in Athens (Greece), Barcelona (Spain), Cremona (Italy) and Paris (France). Universal admission MRSA screening was performed in the surgical wards. Data regarding demographic characteristics and potential risk factors for MRSA carriage were prospectively collected during the study period. Four logistic regression models were used to predict probabilities of unknown MRSA carriage using risk factor data: "Stepwise" (variables selected by backward elimination); "Best BMA" (model with highest posterior probability using Bayesian model averaging which accounts for uncertainty in model choice); "BMA" (average of all models selected with BMA); and "Simple" (model including variables selected >50% of the time by both Stepwise and BMA approaches applied to repeated random sub-samples of 50% of the data). To assess model performance, cross-validation against data not used for model fitting was conducted and net reclassification improvement (NRI) was calculated. Of 2,901 patients enrolled, 111 (3.8%) were newly identified MRSA carriers. Recent hospitalisation and presence of a wound/ulcer were significantly associated with MRSA carriage in all models. While all models demonstrated limited predictive ability (mean c-statistics <0.7) the Simple model consistently detected more MRSA-positive individuals despite screening fewer patients than the Stepwise model. Moreover, the Simple model improved reclassification of patients into appropriate risk strata compared with the Stepwise model (NRI 6.6%, P = .07). Though commonly used, models developed using stepwise variable selection can have relatively poor predictive value. When developing MRSA risk indices, simpler models, which account for uncertainty in model selection, may better stratify patients' risk of unknown MRSA carriage.
    Full-text · Article · Dec 2015 · BMC Infectious Diseases
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: The increasing emergence and spread of antimicrobial resistance (AMR) is a serious public health issue. Increasing the awareness of the general public about appropriate antibiotic use is a key factor for combating this issue. Several public media campaigns worldwide have been launched; however, such campaigns can be costly and the outcomes are variable and difficult to assess. Social media platforms, including Twitter, Facebook, and YouTube, are now frequently utilized to address health-related issues. In many geographical locations, such as the countries of the Gulf Cooperation Council (GCC) States (Saudi Arabia, United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain), these platforms are becoming increasingly popular. The socioeconomic status of the GCC states and their reliable communication and networking infrastructure has allowed the penetration and scalability of these platforms in the region. This might explain why the Saudi Ministry of Health is using social media platforms alongside various other media platforms in a large-scale public awareness campaign to educate at-risk communities about the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV). This paper discusses the potential for using social media tools as cost-efficient and mass education platforms to raise awareness of appropriate antibiotic use in the general public and in the medical communities of the Arabian Peninsula.
    No preview · Article · Oct 2015 · Journal of Medical Internet Research
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    ABSTRACT: Healthcare-associated infections are common adverse event in acute care medicine causing significant morbidity and mortality. There has been a significant increase in the commitment of infection prevention and control (IPC) among European countries in the past years. However, there is still heterogeneity in training opportunities and IPC qualifications. The European Union promotes the harmonisation of IPC strategies among member states. The European Centre for Disease Prevention and Control (ECDC) commissioned TRICE (Training in Infection Control in Europe) project sets the stage for harmonisation of IPC activities in Europe by issuing a list of core competencies for IPC professionals. European certification of IPC training and professionals would be the next logical step, which must be achieved by close collaboration of different stakeholders in Europe such as the ECDC, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the European Union of Medical Specialities, and the national IPC societies. Therefore, ESCMID has launched the new European Committee on Infection Control (EUCIC) to take the lead in the implementation of a European (board) certificate for IPC professionals.
    No preview · Article · Sep 2015 · Clinical Microbiology and Infection
  • Esther Bettiol · Stephan Harbarth
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    ABSTRACT: Since 2010, awareness of the global threat caused by antimicrobial resistance (AMR) has risen considerably and multiple policy and research initiatives have been implemented. Research and development (R&D) of much-needed new antibiotics active against multiresistant pathogens is a key component of all programmes aiming at fighting AMR, but it has been lagging behind owing to scientific, regulatory and economic challenges. Although a few new antibiotics might be available in Switzerland in the next 5 years, these new agents are not based on new mechanisms of action and are not necessarily active against resistant pathogens for which there is the highest unmet medical need, i.e. multiresistant Gram-negative bacteria. Of the three new antibiotics with pending authorisation in Switzerland for systemic treatment of severe infections, oritavancin and tedizolid target Gram-positive pathogens, while only ceftolozane+tazobactam partially covers multiresistant Gram-negative pathogens. Among six antibiotics currently in phase III of clinical development, delafloxacin and solithromycin will also be useful mostly for Gram-positive infections. Importantly, the four other compounds are active against multiresistant Gram-negative pathogens: ceftazidime+avibactam, meropenem+RPX7009, eravacycline and plazomicin. The three last compounds are also active against carbapenem-resistant Enterobacteriaceae (CRE). A few compounds active against such pathogens are currently in earlier clinical development, but their number may decrease, considering the risk of failure over the course of clinical development. At last, through public and political awareness of pathogens with high public health impact and unmet medical need, development of innovative economic incentives and updated regulatory guidance, R&D of new antibiotics is slowly taking off again.
    No preview · Article · Aug 2015 · Schweizerische medizinische Wochenschrift
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    ABSTRACT: To evaluate the relative efficacy of the World Health Organization 2005 campaign (WHO-5) and other interventions to promote hand hygiene among healthcare workers in hospital settings and to summarize associated information on use of resources. Systematic review and network meta-analysis. Medline, Embase, CINAHL, NHS Economic Evaluation Database, NHS Centre for Reviews and Dissemination, Cochrane Library, and the EPOC register (December 2009 to February 2014); studies selected by the same search terms in previous systematic reviews (1980-2009). Included studies were randomised controlled trials, non-randomised trials, controlled before-after trials, and interrupted time series studies implementing an intervention to improve compliance with hand hygiene among healthcare workers in hospital settings and measuring compliance or appropriate proxies that met predefined quality inclusion criteria. When studies had not used appropriate analytical methods, primary data were re-analysed. Random effects and network meta-analyses were performed on studies reporting directly observed compliance with hand hygiene when they were considered sufficiently homogeneous with regard to interventions and participants. Information on resources required for interventions was extracted and graded into three levels. Of 3639 studies retrieved, 41 met the inclusion criteria (six randomised controlled trials, 32 interrupted time series, one non-randomised trial, and two controlled before-after studies). Meta-analysis of two randomised controlled trials showed the addition of goal setting to WHO-5 was associated with improved compliance (pooled odds ratio 1.35, 95% confidence interval 1.04 to 1.76; I(2)=81%). Of 22 pairwise comparisons from interrupted time series, 18 showed stepwise increases in compliance with hand hygiene, and all but four showed a trend for increasing compliance after the intervention. Network meta-analysis indicated considerable uncertainty in the relative effectiveness of interventions, but nonetheless provided evidence that WHO-5 is effective and that compliance can be further improved by adding interventions including goal setting, reward incentives, and accountability. Nineteen studies reported clinical outcomes; data from these were consistent with clinically important reductions in rates of infection resulting from improved hand hygiene for some but not all important hospital pathogens. Reported costs of interventions ranged from $225 to $4669 (£146-£3035; €204-€4229) per 1000 bed days. Promotion of hand hygiene with WHO-5 is effective at increasing compliance in healthcare workers. Addition of goal setting, reward incentives, and accountability strategies can lead to further improvements. Reporting of resources required for such interventions remains inadequate. © Luangasanatip et al 2015.
    Full-text · Article · Jul 2015 · BMJ (online)
  • Werner C Albrich · Stephan Harbarth
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    ABSTRACT: Patients in the intensive care unit (ICU) frequently receive prolonged or even unnecessary antibiotic therapy, which selects for antibiotic-resistant bacteria. Over the last decade there has been great interest in biomarkers, particularly procalcitonin, to reduce antibiotic exposure. In this narrative review, we discuss the value of biomarkers and provide additional information beyond clinical evaluation in order to be clinically useful and review the literature on sepsis biomarkers outside the neonatal period. Both benefits and limitations of biomarkers for clinical decision-making are reviewed. Several randomized controlled trials (RCTs) have shown the safety and efficacy of procalcitonin to discontinue antibiotic therapy in patients with severe sepsis or septic shock. In contrast, there is limited utility of procalcitonin for treatment initiation or withholding therapy initially. In addition, an algorithm using procalcitonin for treatment escalation has been ineffective and is probably associated with poorer outcomes. Little data from interventional studies are available for other biomarkers for antibiotic stewardship, except for C-reactive protein (CRP), which was recently found to be similarly effective and safe as procalcitonin in a randomized controlled trial. We finally briefly discuss biomarker-unrelated approaches to reduce antibiotic duration in the ICU, which have shown that even without biomarker guidance, most patients with sepsis can be treated with relatively short antibiotic courses of approximately 7 days. In summary, there is an ongoing unmet need for biomarkers which can reliably and early on identify patients who require antibiotic therapy, distinguish between responders and non-responders and help to optimize antibiotic treatment decisions among critically ill patients. Available evidence needs to be better incorporated in clinical decision-making.
    No preview · Article · Jul 2015 · Intensive Care Medicine
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    ABSTRACT: Traditional antibiotic dosing was not designed for today's escalating antibiotic resistance, lack of novel antibiotics and growing complexity in patient populations. Dosing that ensures optimal antibiotic exposures should be considered essential to increase the likelihood of effective patient treatment. Given the variability in these exposures across different patients, a 'one-dose-fits-all' approach is increasingly problematic. Therapeutic drug monitoring (TDM) of the β-lactams, the most widely used antibiotic class, is underutilized in certain populations. Clinical experience with β-lactam TDM remains relatively scarce. Patients most likely to benefit from such an intervention include the critically ill, the obese, the elderly and those with cystic fibrosis. Most centres actively performing β-lactam TDM target a minimum 100% of the time during the dosing interval that the free (unbound) concentration of antibiotic exceeds the MIC of the pathogen (100% fT>MIC), which is higher than a traditional target supported by in vitro data. Ideally, isolated pathogens should undergo MIC testing along with TDM on a regular basis, allowing clinicians to address the triad of bug, drug and patient ('mug') in equal measure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    No preview · Article · Jul 2015 · Journal of Antimicrobial Chemotherapy
  • Stephan Harbarth

    No preview · Article · Jul 2015 · Evidence-based medicine
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    Full-text · Conference Paper · Jun 2015
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    ABSTRACT: Objectives: Nitrofurantoin's use has increased exponentially since recent guidelines repositioned it as first-line therapy for uncomplicated lower urinary tract infection (UTI). We conducted a systematic review and meta-analysis to assess nitrofurantoin's efficacy and toxicity in the treatment of lower UTI. Methods: We performed a systematic review of all human controlled clinical trials published from 1946 to 2014 and assessing short-term (≤14 days) nitrofurantoin for lower UTI. Meta-analyses assessing efficacy and adverse events were conducted on randomized trials. Results: Twenty-seven controlled trials including 4807 patients fulfilled entry criteria; most were conducted between the 1970s and 1990s and were at increased risk for various biases. Nitrofurantoin appears to have good clinical and microbiological efficacy for UTI caused by common uropathogens, with clinical cure rates varying between 79% and 92%. The most methodologically robust studies surveyed indicate overall equivalence between nitrofurantoin when given for 5 or 7 days and trimethoprim/sulfamethoxazole, ciprofloxacin and amoxicillin. Meta-analyses of randomized controlled trials confirmed equivalence in clinical cure, but indicated a slight advantage to comparator drugs in microbiological efficacy (risk ratio 0.93, 95% CI 0.89-0.97). If given for only 3 days, nitrofurantoin's clinical efficacy was diminished (61%-70%). Toxicity was infrequent (5%-16% in the 17 reporting studies), mild, reversible and predominantly gastrointestinal; meta-analyses confirmed no difference between nitrofurantoin and comparators. Hypersensitivity reactions such as pulmonary fibrosis and hepatotoxicity were not observed. Acquisition of resistance to nitrofurantoin is still relatively rare. Conclusions: When given short term for lower UTI, nitrofurantoin has good clinical and microbiological efficacy; toxicity is mild and predominantly gastrointestinal.
    No preview · Article · Jun 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: Estimates of the excess length of stay (LOS) attributable to healthcare-associated infections (HAIs) in which total LOS of patients with and without HAIs are biased because of failure to account for the timing of infection. Alternate methods that appropriately treat HAI as a time-varying exposure are multistate models and cohort studies, which match regarding the time of infection. We examined the magnitude of this time-dependent bias in published studies that compared different methodological approaches. METHODS We conducted a systematic review of the published literature to identify studies that report attributable LOS estimates using both total LOS (time-fixed) methods and either multistate models or matching patients with and without HAIs using the timing of infection. RESULTS Of the 7 studies that compared time-fixed methods to multistate models, conventional methods resulted in estimates of the LOS to HAIs that were, on average, 9.4 days longer or 238% greater than those generated using multistate models. Of the 5 studies that compared time-fixed methods to matching on timing of infection, conventional methods resulted in estimates of the LOS to HAIs that were, on average, 12.6 days longer or 139% greater than those generated by matching on timing of infection. CONCLUSION Our results suggest that estimates of the attributable LOS due to HAIs depend heavily on the methods used to generate those estimates. Overestimation of this effect can lead to incorrect assumptions of the likely cost savings from HAI prevention measures.
    No preview · Article · Jun 2015 · Infection Control and Hospital Epidemiology
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    ABSTRACT: Background: Previous investigations of community-associated (CA)-MRSA isolates have revealed a wide diversity of genetic backgrounds with only sporadic occurrence of ST8-USA300 in Geneva. We conducted an epidemiologic and molecular analysis to identify the origin of a sudden increase of ST8 PVL-positive isolates in Geneva during the year 2013. Methods: Based on prospective CA-MRSA surveillance we collected isolates from colonized and infected cases with ST8-USA300 and compared them with non-ST8 CA-MRSA cases. Whole-genome sequencing (WGS) was performed for each isolate of this collection and discriminating molecular features were linked to patient data. Results: In 2013, 22 isolates with ST8-USA300 profile were identified among 46 cases of CA-MRSA. WGS revealed two groups of strains that differed by the type of the SCCmec IV element encoded and whether they harbored an ACME locus. ACME-negative strains were mainly isolated from patients traveling in or originating from South America. SNP positions in isolate groups were used to infer their common ancestor, determine their geographical origin and trace their relatedness. Conclusions: WGS allowed the identification of transmission events and revealed that the increased prevalence of USA300 CA-MRSA isolates resulted from multiple importation events from the Americas but not from local clonal expansion of a successful clone.
    Preview · Article · Jun 2015
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    Benedikt D Huttner · Stephan Harbarth
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    ABSTRACT: Non-manual techniques for terminal disinfection of hospital rooms have gained increasing interest in recent years as means to reduce transmission of multidrug-resistant organisms (MDROs). A prospective crossover study by Blazejewski and colleagues in five ICUs of a French academic hospital with a high prevalence of MDRO carriers showed that two different hydrogen peroxide (H2O2)-based non-touch disinfection techniques reduced environmental contamination with MDROs after routine cleaning. This study provides further evidence of the ‘in use’ bioburden reduction offered by these techniques. Before H2O2-based non-touch disinfection can be recommended for routine clinical use outside specific outbreak situations, further studies need to show whether the environmental contamination reduction provided by these techniques is clinically relevant and results in reduced cross-infections with MDROs.
    Preview · Article · May 2015 · Critical Care

Publication Stats

11k Citations
1,598.03 Total Impact Points

Institutions

  • 1998-2016
    • University of Geneva
      • • Division of Infectious Diseases
      • • Department of Internal Medicine
      Genève, Geneva, Switzerland
  • 1998-2014
    • Hôpitaux Universitaires de Genève
      • Service de médecine interne générale (SMIG)
      Genève, Geneva, Switzerland
  • 2011
    • University of Pennsylvania
      Philadelphia, Pennsylvania, United States
    • Royal Prince Alfred Hospital
      • Division of Infectious Diseases & Microbiology
      Camperdown, New South Wales, Australia
  • 2006
    • Universitätsspital Basel
      • Klinik für Infektiologie & Spitalhygiene
      Bâle, Basel-City, Switzerland
  • 2002
    • University Hospital of Lausanne
      • Institute of Microbiology (IMUL)
      Lausanne, Vaud, Switzerland
  • 2001-2002
    • Boston Children's Hospital
      • Division of Infectious Diseases
      Boston, Massachusetts, United States
  • 2000-2001
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1999-2000
    • Harvard University
      • Department of Epidemiology
      Cambridge, Massachusetts, United States