Stephan Harbarth

University of Geneva, Genève, Geneva, Switzerland

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Publications (282)1591.29 Total impact

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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.
    10/2014; 35(10):1294-1297.
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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; · 5.34 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;
  • 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.
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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;
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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
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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
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    ABSTRACT: Risk factor analyses for nosocomial infections (NIs) are complex. First, due to competing events for NI, the association between risk factors of NI as measured using hazard rates may not coincide with the association using cumulative probability (risk). Second, patients from the same intensive care unit (ICU) who share the same environmental exposure are likely to be more similar with regard to risk factors predisposing to a NI than patients from different ICUs. We aimed to develop an analytical approach to account for both features and to use it to evaluate associations between patient- and ICU-level characteristics with both rates of NI and competing risks and with the cumulative probability of infection. Methods: We considered a multi-center data base of 159 intensive care units containing 10,9216 admissions (71,0221 admission-days) from the Spanish HELICS-ENVIN ICU network. We analysed the data using two models: an etiologic model (rate-based) and a predictive model (risk-based). In both models, random effects (shared frailties) are introduced to assess heterogeneity. Death and discharge without NI are treated as competing events for NI. Results: There was a large heterogeneity across ICUs in NI hazard rates which remained after accounting for multilevel risk factors, meaning that there are remaining unobserved ICU-specific factors which influence NI occurrence. Heterogeneity across ICUs in terms of cumulative probability of NI was even more pronounced. Several risk factors had markedly different associations in the rate-based and risk-based models. For some the associations differed in magnitude. For example high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with modest increases in the rate of NB, but large increases in the risk. Others differed in sign, for example respiratory versus cardiovascular diagnostic categories were associated with reduced rate of NB, but an increased risk. Conclusions: A combination of competing risks and multilevel models is required to understand direct and indirect risk factors for NI and distinguish patient-level from ICU-level factors.
    Critical care (London, England) 04/2014; 18(2):R64. · 4.72 Impact Factor
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    ABSTRACT: Objective. Determine the prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-PE) contamination of food and colonization of food handlers in a hospital kitchen and compare retrieved ESBL-PE strains with patient isolates. Design. Cross-sectional study. Setting. A 2,200-bed tertiary care university hospital in Switzerland. Participants. Food handlers. Methods. Raw and prepared food samples were obtained from the hospital kitchen, with a comparator group from local supermarkets. Fecal samples collected from food handlers and selectively pre-enriched homogenized food samples were inoculated onto selective chromogenic media. Phenotypic confirmation of ESBL production was performed using the double disk method. Representative ESBL-PE were characterized using polymerase chain reaction (PCR) and sequencing for blaCTX-M, blaSHV, and blaTEM genes, and Escherichia coli strains were typed using phylotyping, repetitive element palindromic PCR, and multilocus sequence typing. Meat samples were screened for antibiotic residues using liquid chromatography time-of-flight mass spectrometry. Results. Sixty (92%) of the raw chicken samples were ESBL-PE positive, including 30 (86%) of the hospital samples and all supermarket samples. No egg, beef, rabbit, or cooked chicken samples were ESBL-PE positive. No antibiotic residues were detected. Six (6.5%) of 93 food handlers were ESBL-PE carriers. ESBL-PE strains from chicken meat more commonly possessed blaCTX-M-1 and blaCTX-M-2, whereas blaCTX-M-14 and blaCTX-M-15 were predominant among strains of human origin. There was partial overlap in the sequence type of E. coli strains of chicken and human origin. No E. coli ST131 strains or blaCTX-M-15 genes were isolated from meat. Conclusions. Although there is significant ESBL-PE contamination of delivered chicken meat, current preventive strategies minimize risks to food handlers, hospital staff, and patients.
    Infection Control and Hospital Epidemiology 04/2014; 35(4):375-83. · 4.02 Impact Factor
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    ABSTRACT: There are few reports on the feasibility of conducting successful infection control (IC) interventions in rural community hospitals. Ten small rural community hospitals in Idaho and Utah were recruited to participate in a cluster-randomized trial of multidimensional IC interventions to determine their feasibility in the setting of limited resources. Five hospitals were randomized to develop individualized campaigns to promote HH, isolation compliance, and outbreak control. Five hospitals were randomized to continue with current IC practices. Regular blinded observations of hand hygiene (HH) compliance were conducted in all hospitals as the primary outcome measure. Additionally, periodic prevalence studies of patient colonization with resistant pathogens were performed. The 5-months intervention time period was compared to a 4-months baseline period, using a multi-level logistic regression model. The intervention hospitals implemented a variety of strategies. The estimated average absolute change in "complete HH compliance" in intervention hospitals was 20.1% (range, 7.8% to 35.5%) compared to -3.1% (range -6.3% to 5.9%) in control hospitals (p = 0.001). There was an estimated average absolute change in "any HH compliance" of 28.4% (range 17.8% to 38.2%) in intervention hospitals compared to 0.7% (range -16.7 to 20.7%) in control hospitals (p = 0.010). Active surveillance culturing demonstrated an overall prevalence of MRSA carriage of 9.7%. A replicable intervention significantly improved hand hygiene as a primary outcome measure despite barriers of geographic distance and lack of experience with study protocols. Active surveillance culturing identified unsuspected reservoirs of MRSA colonization and further promoted IC activity.
    Antimicrobial resistance and infection control. 03/2014; 3(1):10.
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    ABSTRACT: Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. In a prospective observational multi-center cohort study in 44 german ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. Median time to AT was 2.1 (IQR 0.8 - 6.0) hours and 3 hours (-0.1 - 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.
    Critical care (London, England) 03/2014; 18(2):R42. · 4.72 Impact Factor
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    ABSTRACT: Emerging evidence supports the use of therapeutic drug monitoring (TDM) of β-lactams for intensive care unit (ICU) patients to optimize drug exposure, although limited detail is available on how sites run this service in practice. This multicentre survey study was performed to describe the various approaches used for β-lactam TDM in ICUs. A questionnaire survey was developed to describe various aspects relating to the conduct of β-lactam TDM in an ICU setting. Data sought included: β-lactams chosen for TDM, inclusion criteria for selecting patients, blood sampling strategy, analytical methods, pharmacokinetic (PK)/pharmacodynamic (PD) targets and dose adjustment strategies. Nine ICUs were included in this survey. Respondents were either ICU or infectious disease physicians, pharmacists or clinical pharmacologists. Piperacillin (co-formulated with tazobactam) and meropenem (100% of units surveyed) were the β-lactams most commonly subject to TDM, followed by ceftazidime (78%), ceftriaxone (43%) and cefazolin (43%). Different chromatographic and microbiological methods were used for assay of β-lactam concentrations in blood and other biological fluids (e.g. CSF). There was significant variation in the PK/PD targets (100% fT>MIC up to 100% fT>4×MIC) and dose adjustment strategies used by each of the sites. Large variations were found in the type of β-lactams tested, the patients selected for TDM and drug assay methods. Significant variation observed in the PK/PD targets and dose adjustment strategies used supports the need for further studies that robustly define PK/PD targets for ICU patients to ensure a greater consistency of practice for dose adjustment strategies for optimizing β-lactam dosing with TDM.
    Journal of Antimicrobial Chemotherapy 01/2014; · 5.34 Impact Factor
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    ABSTRACT: Widespread multidrug resistance in Escherichia coli has necessitated the reintroduction of older antibiotics, such as nitrofurantoin. However, mechanisms by which resistance to nitrofurantoin emerges in E. coli are not well elucidated. Toward this aim, we sequenced two nitrofurantoin-sensitive E. coli sequence types (ST540 and ST2747) and their four nitrofurantoin-resistant derivatives generated in vitro under aerobic and anaerobic growth conditions.
    Genome announcements. 01/2014; 2(2).
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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. 01/2014;
  • 01/2014; 19(29).
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    ABSTRACT: Wards cohorting infected orthopaedic patients may be particularly prone to transmitting extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). We analyze their epidemic pattern by performing molecular typing of ESBL-E isolated from patients and healthcare workers (HCW) from our septic ward. Between March 2010 and November 2011, 186 patients were admitted. Among 565 anal swabs, ESBL-E were detected in 204 samples from 45 patients, suggesting prolonged carriage in affected patients. Among 25 cases with identical ESBL-E species and positive epidemiological links, only 9 were really attributable to our service. We also screened 41 healthcare workers (HCW) on 49 occasions during the study period. Six samples (13%) were positive. None of the ESBL-E detected in HCW were related to any of the patient isolates. Among 60 environmental samples taken at the peak of the epidemic none revealed ESBL-E. We conclude that HCW also were anal carriers of ESBL-E, however the ESBL- strains from the HCW were not the same strains isolated from patients in the septic ward. Moreover, the epidemiological attribution of ESBL by simple vicinity, timing, and species identification might grossly overestimate transmission within a given unit.
    SpringerPlus 12/2013; 2(1):91.
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    ABSTRACT: Antimicrobial resistance (AMR) is now a global threat. Its emergence rests on antimicrobial overuse in humans and food-producing animals; globalization and suboptimal infection control facilitate its spread. While aggressive measures in some countries have led to the containment of some resistant gram-positive organisms, extensively resistant gram-negative organisms such as carbapenem-resistant enterobacteriaceae and pan-resistant Acinetobacter spp. continue their rapid spread. Please start the sentence as follows: Antimicrobial conservation/stewardship programs have seen some measure of success in reducing antimicrobial overuse in humans, but their reach is limited to acute-care settings in high-income countries. Outside the European Union, there is scant or no oversight of antimicrobial administration to food-producing animals, while evidence mounts that this administration leads directly to resistant human infections. Both horizontal and vertical infection control measures can interrupt transmission among humans, but many of these are costly and essentially limited to high-income countries as well. Novel antimicrobials are urgently needed; in recent decades pharmaceutical companies have largely abandoned antimicrobial discovery and development given their high costs and low yield. Against this backdrop, international and cross-disciplinary collaboration appears to be taking root in earnest, although specific strategies still need defining. Educational programs targeting both antimicrobial prescribers and consumers must be further developed and supported. The general public must continue to be made aware of the current scale of AMR's threat, and must perceive antimicrobials as they are: a non-renewable and endangered resource.
    Antimicrobial resistance and infection control. 11/2013; 2(1):31.
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    ABSTRACT: OBJECTIVE: To compare the effect of two strategies (enhanced hand hygiene vs meticillin-resistant Staphylococcus aureus (MRSA) screening and decolonisation) alone and in combination on MRSA rates in surgical wards. DESIGN: Prospective, controlled, interventional cohort study, with 6-month baseline, 12-month intervention and 6-month washout phases. SETTING: 33 surgical wards of 10 hospitals in nine countries in Europe and Israel. PARTICIPANTS: All patients admitted to the enrolled wards for more than 24 h. INTERVENTIONS: The two strategies compared were (1) enhanced hand hygiene promotion and (2) universal MRSA screening with contact precautions and decolonisation (intranasal mupirocin and chlorhexidine bathing) of MRSA carriers. Four hospitals were assigned to each intervention and two hospitals combined both strategies, using targeted MRSA screening. OUTCOME MEASURES: Monthly rates of MRSA clinical cultures per 100 susceptible patients (primary outcome) and MRSA infections per 100 admissions (secondary outcome). Planned subgroup analysis for clean surgery wards was performed. RESULTS: After adjusting for clustering and potential confounders, neither strategy when used alone was associated with significant changes in MRSA rates. Combining both strategies was associated with a reduction in the rate of MRSA clinical cultures of 12% per month (adjusted incidence rate ratios (aIRR) 0.88, 95% CI 0.79 to 0.98). In clean surgery wards, strategy 2 (MRSA screening, contact precautions and decolonisation) was associated with decreasing rates of MRSA clinical cultures (15% monthly decrease, aIRR 0.85, 95% CI 0.74 to 0.97) and MRSA infections (17% monthly decrease, aIRR 0.83, 95% CI 0.69 to 0.99). CONCLUSIONS: In surgical wards with relatively low MRSA prevalence, a combination of enhanced standard and MRSA-specific infection control approaches was required to reduce MRSA rates. Implementation of single interventions was not effective, except in clean surgery wards where MRSA screening coupled with contact precautions and decolonisation was associated with significant reductions in MRSA clinical culture and infection rates.
    BMJ Open 09/2013; 3(9). · 1.58 Impact Factor
  • Infection Control and Hospital Epidemiology 09/2013; 34(9):996-7. · 4.02 Impact Factor

Publication Stats

9k Citations
1,591.29 Total Impact Points


  • 1997–2014
    • University of Geneva
      • • Faculty of Medicine
      • • Division of Infectious Diseases
      Genève, Geneva, Switzerland
  • 2013
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2012
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 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
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Royal Prince Alfred Hospital
      • Division of Infectious Diseases & Microbiology
      Camperdown, New South Wales, Australia
    • 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
    • Hospital Universitari Mutua de Terrassa
      Terrassa, Catalonia, Spain
  • 1998–2011
    • Hôpitaux Universitaires de Genève
      Genève, Geneva, Switzerland
  • 2008
    • Chris Hani Baragwanath Hospital
      Johannesburg, Gauteng, South Africa
  • 2005–2006
    • Universitätsspital Basel
      Bâle, Basel-City, Switzerland
    • Erasmus Universiteit Rotterdam
      • Department of Medical Microbiology and Infectious Diseases
      Rotterdam, South Holland, Netherlands
    • Hospital of Saint Raphael
      New Haven, Connecticut, United States
    • Johns Hopkins Medicine
      • Division of Infectious Diseases
      Baltimore, MD, United States
  • 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
    • Beth Israel Deaconess Medical Center
      • Division of Infectious Diseases
      Boston, MA, United States
  • 1998–2001
    • Harvard Medical School
      Boston, Massachusetts, United States