Mical Paul

Technion - Israel Institute of Technology, H̱efa, Haifa, Israel

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Publications (199)1231.06 Total impact

  • Leonard Leibovici · Mical Paul

    No preview · Article · Jan 2016 · The Lancet Respiratory Medicine
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    ABSTRACT: Manipulation of the intestinal microbiota has been linked to weight changes and obesity. To explore the influence of specific agents that alter the intestinal flora on weight in different patient groups we conducted a meta-analysis of randomized controlled trials (RCTs) reporting on the effects of probiotics, prebiotics, synbiotics, and antibiotics on weight. We searched the Pubmed and Cochrane Library databases for trials on adults, children, and infants evaluating the effects of these substances on weight. Our primary outcome was weight change from baseline. Standardized mean differences (SMDs) with 95% confidence intervals were calculated.
    No preview · Article · Jan 2016 · Microbial Pathogenesis
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    ABSTRACT: Bloodstream infections (BSIs) are both common and fatal in older patients. We describe data from studies evaluating older patients hospitalized with BSIs. Most older patients with BSIs present "typically" with either fever or leukocytosis. The most common source of BSI in older patients is the urinary tract, and accordingly, Gram-negative organisms predominate. A significant part of these BSIs may thus be preventable by removal of unnecessary urinary catheters. Increased long term mortality is reported following BSIs in older patients, however, data on other long term outcomes, including functional capacity, cognitive decline and others are lacking. Management of BSIs may include less invasive procedures due to the fragility of older patients. This approach may delay the diagnosis and treatment in some cases. Older patients are probably under-represented in clinical trials assessing treatment of bacteremia. Physicians treating older patients should consider the relevance of these studies' outcomes.
    No preview · Article · Dec 2015 · Virulence
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    ABSTRACT: The diagnosis of legionnaire's disease (LD) is based on the isolation of Legionella spp., a fourfold rise in antibodies, a positive urinary antigen or direct immunofluorescence tests. PCR is not accepted as a diagnostic tool for LD. Methods: Systematic review assessing the diagnostic accuracy of PCR in various clinical samples with a direct comparison vs. urinary antigen (UA). We included prospective or retrospective cohort and case-control studies. Studies were included if they used the CDC consensus definition criteria of LD or similar, assessed only patients with clinical pneumonia and reported data for all true positive, false positive, true negative and false negative results. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Results: Thirty-eight studies were included. A total of 653 patients had confirmed LD and 3,593 patients had pneumonia due to other pathogens. The methodological quality of the studies as assessed by the QUADAS-2 tool was poor to fair. The summary sensitivity and specificity values for diagnosis of LD in respiratory samples were 97⋅4% (95% CI 91⋅1-99⋅2%) and 98⋅6% (95% CI 97⋅4-99⋅3%), respectively. These results were mainly unchanged by any covariates tested and subgroup analysis. The diagnostic performance of PCR in respiratory samples was much better than that of UA. Compared to UA, PCR in respiratory samples (especially in sputum or swabs) revealed significant advantage in sensitivity, and additional diagnosis of 18-30% LD cases. Conclusions: The diagnostic performance of PCR in respiratory samples is excellent and preferable to that of the UA. Results were independent on the covariate tested. PCR in respiratory samples should be regarded as a valid tool for the diagnosis of LD.
    No preview · Article · Dec 2015 · Journal of Clinical Microbiology
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    ABSTRACT: Background: The impact of neuraminidase inhibitors (NAIs) on Influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods: A worldwide meta-analysis of individual participant data (IPD) from 20,634 hospitalised patients with laboratory confirmed A(H1N1)pdm09 (n=20,021) or clinically diagnosed (n=613) 'pandemic influenza'. The primary outcome was radiologically confirmed influenza-related pneumonia (IRP). Odds ratios (OR) were estimated using generalized linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results: Among 20,634 included participants, 5,978 (29.0%) had IRP; conversely, 3,349 (16.2%) had confirmed absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0.83 (95%CI 0.64 - 1.06; p=0.136)]. Among the 5,978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR=0.72 (0.44-1.17; p=0.180)] or likelihood of requiring ventilatory support [adj. OR=1.17 (0.71-1.92; p=0.537)]; but early treatment versus later significantly reduced mortality [adj. OR=0.70 (0.55-0.88; p=0.003)] and likelihood of requiring ventilatory support [adj. OR=0.68 (0.54-0.85; p=0.001)]. Conclusions: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support. This article is protected by copyright. All rights reserved.
    Full-text · Article · Nov 2015 · Influenza and Other Respiratory Viruses
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    ABSTRACT: We assessed the effects of time from hospitalization and culture source on bacterial susceptibility profiles. Increasing resistance correlated with increasing time from hospitalization for all bacterial groups, with 7 days in hospital representing the best time point for dichotomizing susceptibility rates rather than 48 hours. Antibiograms based on isolates from any source best represented susceptibility profiles. Infect. Control Hosp. Epidemiol. 2015;00(0):1–3
    No preview · Article · Nov 2015 · Infection Control and Hospital Epidemiology
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    ABSTRACT: Background: The prognosis of elderly patients with acute myeloid leukemia (AML) is poor, and the best treatment is controversial. Since the majority of AML patients are older than 60 years, identification of those who might benefit from intensive treatment is essential. Methods: Data from electronic charts of consecutive AML patients treated in our center were analyzed. Eligibility criteria included newly diagnosed de novo or secondary AML, an age of 60 years or older, and intensive induction treatment. Results: Sixty-two patients were included in the analysis. Forty-six patients (74%) achieved complete remission (CR) after 1-2 intensive induction courses. Twenty of them received consolidation with conventional chemotherapy, 20 proceeded to allogeneic hematopoietic cell transplantation (allo-HCT), and 6 were ineligible for further treatment. The projected overall survival (OS) at 2 and 3 years was 28 and 23%, respectively. A normal karyotype, CR achievement, and allo-HCT were associated with improved OS, while an Eastern Cooperative Oncology Group performance status of 0-1 was borderline associated. The median survival and disease-free survival at 2 years was 18.7 months and 49%, respectively, for patients who underwent allo-HCT in CR1, compared to 12.8 months and 25%, respectively, for those who did not. Conclusion: Based on our data, selected eligible elderly AML patients might benefit from intensive treatment.
    Full-text · Article · Oct 2015 · Acta Haematologica
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    ABSTRACT: Objectives: To assess the external validity of a pragmatic, investigator-initiated RCT on treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA), we compared patient characteristics and treatment effect estimates for patients included in the RCT versus those excluded. Participants and outcomes: The RCT included hospitalised patients with documented or highly-probable invasive MRSA infections who were randomised to vancomycin versus trimethoprim-sulfamethoxazole (TMP-SMX) treatment, between 2007 and 2014. A concomitant observational study prospectively included all consecutive patients, between 2008 and 2011, who were excluded from the RCT due to no consent, meningitis, left-sided endocarditis, severe neutropaenia, chronic renal dialysis or treatment with study medications for longer than 48 h. The primary outcomes were clinical failure at day 7 and 30-day mortality for both studies. We compared baseline and infection characteristics, outcome rates and treatment effect estimates for included versus excluded patients. Results: The RCT included 252 patients who were compared with 220 excluded patients who were observed. Inability to provide informed consent was the main reason for patient exclusion. Excluded patients' functional and cognitive performance was significantly poorer than that of included patients. Sepsis was more severe among excluded patients (higher rates of mechanical ventilation, indwelling catheters, septic shock and organ failure). Clinical failure occurred in 83/252 (32.9%) versus 175/220 (79.5%) and deaths in 32 (12.7%) versus 64 (29.1%) for included versus excluded patients, p<0.001 for both comparisons. Comparing vancomycin to TMP-SMX, in the RCT mortality, was non-significantly lower with vancomycin (OR 0.76, 95% CIs 0.36 to 1.62), while in the observational analysis of excluded patients, mortality was significantly higher with vancomycin (OR 2.63, 1.04 to 6.65), p=0.04 for the difference. Conclusions: Patient characteristics, outcome event rates and treatment effects differed significantly in the setting of a RCT, despite its pragmatic design, compared to patients treated outside the trial settings.
    Preview · Article · Sep 2015 · BMJ Open
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    ABSTRACT: An antibiogram (ABG) gives the results of in vitro susceptibility tests performed on a pathogen isolated from a culture of a sample taken from blood or other tissues. The institutional cross-ABG consists of the conditional probability of susceptibility for pairs of antimicrobials. This paper explores how interpretative reading of the isolate ABG can be used to replace and improve the prior probabilities stored in the institutional ABG. Probabilities were calculated by both a naïve and semi-naïve Bayesian approaches, both using the ABG for the given isolate and institutional ABGs and cross-ABGs.
    Full-text · Article · Aug 2015 · Artificial intelligence in medicine
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    ABSTRACT: Objective: International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock. Methods: Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled. Results: Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels. Conclusions: Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.
    Full-text · Article · Aug 2015 · PLoS ONE
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    ABSTRACT: Objectives: Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a clinical challenge. We attempted to estimate the mortality burden of CRGNB among haematological cancer patients. Methods: This was a retrospective cohort study. We included adult patients hospitalized in the haemato-oncological/bone marrow transplantation departments for chemotherapy, between 2008 and 2014, with Gram-negative aerobic bacteraemia. We compared patients with CRGNB and carbapenem-susceptible Gram-negative bacteraemia (CSGNB). The primary outcome was 14 day all-cause mortality. In addition, we assessed 1 year survival. Multivariable logistics regression analysis and adjusted Cox regression analysis were conducted. Analyses were adjusted to the propensity for CRGNB bacteraemia. Results: The cohort included mostly young patients (mean age 50.1 years) with acute leukaemia (264/423, 62.4%) and the median absolute neutrophil count at bacteraemia onset was 0 × 10(9)/L. The unadjusted 14 day mortality rate was higher for patients with CRGNB compared with CSGNB [45.6% (47/103) versus 15% (48/320), respectively (P < 0.001)]. Adjusting to baseline prognostic factors, infection characteristics and the propensity score retained a significant association between CRGNB and 14 day mortality (OR 5.14, 95% CI 2.32-11.38). Including only the first bacteraemic episode per patient, 1 year mortality was 74.7% (68/91) for patients with CRGNB versus 49.8% (119/239) for patients with CSGNB (P < 0.001). Adjusting for risk factors associated with 1 year mortality, the HR for mortality with CRGNB was 1.48 (95% CI 1-2.2). CRGNB bacteraemia was associated with several risk factors for mortality, including inappropriate empirical antibiotic treatment and less effective definitive antibiotics. Conclusions: This study demonstrated a significant adjusted association between CRGNB and mortality up to 1 year among haemato-oncological patients receiving chemotherapy.
    No preview · Article · Jul 2015 · Journal of Antimicrobial Chemotherapy
  • Ursula Theuretzbacher · Mical Paul

    No preview · Article · Jun 2015 · Clinical Microbiology and Infection
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    ABSTRACT: In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to 're-develop' these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections. © 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.
    Full-text · Article · Jun 2015 · Journal of Antimicrobial Chemotherapy
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    ABSTRACT: To show non-inferiority of trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of severe infections due to meticillin resistant Staphylococcus aureus (MRSA). Parallel, open label, randomised controlled trial. Four acute care hospitals in Israel. Adults with severe infections caused by MRSA susceptible to trimethoprim-sulfamethoxazole and vancomycin. Patients with left sided endocarditis, meningitis, chronic haemodialysis, and prolonged neutropenia were excluded. Trimethoprim-sulfamethoxazole 320 mg/1600 mg twice daily versus vancomycin 1 g twice daily for a minimum of seven days and then by indication. The primary efficacy outcome was treatment failure assessed at day 7, consisting of death, persistence of haemodynamic instability or fever, stable or worsening Sequential Organ Failure Assessment score, and persistence of bacteraemia. The primary safety outcome was all cause mortality at day 30. Non-inferiority was defined by a difference of less than 15% for treatment failure. 252 patients were included in the trial, of whom 91 (36%) had bacteraemia. No significant difference in treatment failure was seen for trimethoprim-sulfamethoxazole (51/135, 38%) versus vancomycin (32/117, 27%)-risk ratio 1.38 (95% confidence interval 0.96 to 1.99). However, trimethoprim-sulfamethoxazole did not meet the non-inferiority criterion-absolute difference 10.4% (95% confidence interval -1.2% to 21.5%). For patients with bacteraemia, the risk ratio was 1.40 (0.91 to 2.16). In a multivariable logistic regression analysis, trimethoprim-sulfamethoxazole was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93). High dose trimethoprim-sulfamethoxazole did not achieve non-inferiority to vancomycin in the treatment of severe MRSA infections. The difference was particularly marked for patients with bacteraemia.Trial registration Clinical trials NCT00427076. © Paul et al 2015.
    Full-text · Article · May 2015 · BMJ (online)
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    ABSTRACT: BACKGROUND The natural history of carbapenem-resistant Enterobacteriaceae (CRE) carriage and the timing and procedures required to safely presume a CRE-free status are unclear. OBJECTIVE To determine risk factors for recurrence of CRE among presumed CRE-free patients. METHODS Case-control study including CRE carriers in whom CRE carriage presumably ended, following at least 2 negative screening samples on separate days. Recurrence of CRE carriage was identified through clinical samples and repeated rectal screening in subsequent admissions to any healthcare facility in Israel. Patients with CRE recurrence (cases) were compared with recurrence-free patients (controls). The duration of follow-up was 1 year for all surviving patients. RESULTS Included were 276 prior CRE carriers who were declared CRE-free. Thirty-six persons (13%) experienced recurrence of CRE carriage within a year after presumed eradication. Factors significantly associated with CRE recurrence on multivariable analysis were the time in months between the last positive CRE sample and presumed eradication (odds ratio, 0.94 [95% CI, 0.89-0.99] per month), presence of foreign bodies at the time of presumed eradication (4.6 [1.64-12.85]), and recurrent admissions to healthcare facilities during follow-up (3.15 [1.05-9.47]). The rate of CRE recurrence was 25% (11/44) when the carrier status was presumed to be eradicated 6 months after the last known CRE-positive sample, compared with 7.5% (10/134) if presumed to be eradicated after 1 year. CONCLUSIONS We suggest that the CRE-carrier status be maintained for at least 1 year following the last positive sample. Screening of all prior CRE carriers regardless of current carriage status is advised. Infect. Control Hosp. Epidemiol. 2015;00(0):1-6.
    No preview · Article · Apr 2015 · Infection Control and Hospital Epidemiology
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    ABSTRACT: Traditional wisdom suggests that infections in older patients have atypical presentation, including blunted febrile response. Data are scarce. We analyzed data from a prospectively collected database on presentation of infection in 4,308 patients, and compared the presentation of older patients (≥ 75 years) versus adults (< 75 years). Single tertiary medical center. Patients admitted with suspected bacterial infection during 2002-2004 and 2010-2011. We evaluated clinical presentation on day of admission, including vital signs and laboratory parameters. No difference in fever values as a presenting sign of infection was found between older patients and adults (median fever 38.3°C, interquartile range [IQR] 37.4-39.0°C; and 38.4°C, IQR 37.3-39.0°C, respectively, P = 0.08). Median leukocyte count was significantly higher in older patients (median 11.60, IQR 8.30-15.72 in older patients; 10.84, 7.50-15.00 in adults, P < 0.001). Presentation with septic shock, acute renal failure, and reduced consciousness was significantly more common in older patients. These findings were also consistent in the subgroups of bacteremic patients and patients with microbiologically documented infection. Elevated fever and leukocytosis were found to be at least equally common in older patients compared to younger adults as part of the presentation of infection.
    No preview · Article · Apr 2015 · Annals of Medicine
  • Mical Paul · Gilbert Greub

    No preview · Article · Mar 2015 · Clinical Microbiology and Infection
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    Full-text · Dataset · Mar 2015
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    ABSTRACT: Objectives To examine how relevant current evidence on antibiotic treatment of pneumonia is for elderly adults.DesignSystematic review.SettingRandomized controlled trials (RCTs; N = 43) comparing different antibiotics and prospective observational studies (N = 182) published since 2005.ParticipantsAdults with community-acquired (CAP), healthcare-associated (HCAP), hospital-acquired (HAP), or ventilator-associated (VAP) pneumonia.MeasurementsExclusion criteria that could preferentially limit participation of elderly adults were examined, subgroup or other adjusted analyses were searched for according to age, and treatment effects in participants younger than 65 in RCTs were compared with those in participants aged 65 and older. Mean participant ages in RCTs and observational studies were compared. Risk ratios (RRs) with 95% confidence intervals (CIs) for differences between older and younger adults were pooled using a fixed effect metaanalysis.ResultsNo RCT reported exclusion based on an upper age limit; 100% of community CAP trials, 90% of hospitalized CAP trials, and 76% of HAP and VAP trials excluded individuals based on comorbidities. None of the RCTs reported a subgroup analysis for mortality according to age. The RR for the pooled difference in treatment failure rates between participants younger than 65 and those aged 65 and older was 1.25 (95% CI = 0.94–1.65, 12 RCTs) and between participants younger than 75 and aged 75 and older was 1.43 (95% CI = 0.98–2.09, 7 RCTs). RCT participants were significantly younger (54.0 ± 9.6) than those in observational studies of CAP (66.2 ± 8.1, P < .001). Age differences were not significant for HCAP, HAP, and VAP.Conclusion Elderly adults are often excluded from RCTs of bacterial pneumonia. No data were found on the comparative efficacy of antibiotic treatment in elderly adults and the general population.
    No preview · Article · Feb 2015 · Journal of the American Geriatrics Society
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    ABSTRACT: Chloramphenicol is an old broad-spectrum antibiotic. We assessed its efficacy and safety. This was a systematic review and meta-analysis. Electronic databases were searched to identify randomized controlled trials (RCTs) that assessed patients, of any age, with systemic bacterial infections that can cause sepsis and compared chloramphenicol alone versus other antibiotics. No restrictions on the date of publication, language or publication status were applied. The primary outcome assessed was overall mortality. Sixty-six RCTs fulfilled the inclusion criteria, and these included 9711 patients. We found a higher mortality with chloramphenicol for respiratory tract infections [risk ratio (RR) 1.40, 95% CI 1.00-1.97] and meningitis (RR 1.27, 95% CI 1.00-1.60), both without heterogeneity. The point estimate was similar for enteric fever, without statistical significance. No statistically significant difference was found between chloramphenicol and other antibiotics regarding treatment failure, except for enteric fever (RR 1.46, 95% CI 1.07-2.00, without heterogeneity). This difference derived mainly from studies comparing chloramphenicol with fluoroquinolones (RR 1.85, 95% CI 1.07-3.2). There were no statistically significant differences between chloramphenicol and other antibiotics in terms of adverse events, including haematological events, except for anaemia, which occurred more frequently with chloramphenicol (RR 2.80, 95% CI 1.65-4.75, I(2) = 0%), and gastrointestinal side effects, which were less frequent with chloramphenicol (RR 0.67, 95% CI 0.46-0.99, I(2) = 0%). Many of the studies included were sponsored by pharmaceutical companies marketing the comparator drug to chloramphenicol, and this might have influenced the results. Chloramphenicol cannot be recommended as a first-line treatment for respiratory tract infections, meningitis or enteric fever as alternatives are probably more effective. Chloramphenicol is as safe as treatment alternatives for short antibiotic courses. RCTs are needed to test this treatment against MDR organisms when better alternatives do not exist. © 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 · Jan 2015 · Journal of Antimicrobial Chemotherapy

Publication Stats

5k Citations
1,231.06 Total Impact Points


  • 2014-2016
    • Technion - Israel Institute of Technology
      • Ruth and Bruce Rappaport Faculty of Medicine
      H̱efa, Haifa, Israel
    • Tel Aviv Sourasky Medical Center
      • Geriatrics
      Tell Afif, Tel Aviv, Israel
  • 2004-2015
    • Rambam Medical Center
      H̱efa, Haifa, Israel
  • 2001-2015
    • Tel Aviv University
      • • Faculty of Medicine
      • • Sackler Faculty of Medicine
      Tell Afif, Tel Aviv, Israel
  • 2003-2012
    • Rabin Medical Center
      • Department of Cardiology
      Tell Afif, Tel Aviv, Israel
  • 2010
    • Johns Hopkins Bloomberg School of Public Health
      • Department of International Health
      Baltimore, Maryland, United States
  • 2006-2007
    • University of Bristol
      • MRC Centre for Causal Analyses in Translational Epidemiology
      Bristol, England, United Kingdom