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ABSTRACT: SUMMARY Bacterial resistance to antibiotics is a growing clinical problem and public health threat. Antibiotic use is a known risk factor for the emergence of antibiotic resistance, but demonstrating the causal link between antibiotic use and resistance is challenging. This review describes different study designs for assessing the association between antibiotic use and resistance and discusses strengths and limitations of each. Approaches to measuring antibiotic use and antibiotic resistance are presented. Important methodological issues such as confounding, establishing temporality, and control group selection are examined.
Clinical microbiology reviews 04/2013; 26(2):289-307. · 14.69 Impact Factor
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ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization has become a serious emerging condition in equine hospitals. Following the detection of MRSA in asymptomatic hospitalized horses and in two horses with post-operative wound infections, an investigation was conducted. Twelve of 84 horses (14.3%) and 16 of 139 personnel (11.5%) were MRSA carriers. The profile of the dominant MRSA strain common to horses and staff was multi-drug-resistant, spa-type t535, SCCmec type V, pvl-negative. MLST of a representative isolate yielded sequence type (ST) 5. The risk of MRSA carriage among veterinary personnel was greater in equine veterinarians and full-time technicians in comparison to part-time technicians and to other personnel not working with horses. Strict infection control measures were implemented, horses infected or colonized with MRSA were isolated and decolonization of personnel was attempted. Six months after the intervention, the large animal department personnel and hospitalized horses were all MRSA-negative and the decolonization was considered successful. This outbreak, caused by a rare MRSA strain and involving both hospitalized horses and personnel, further demonstrates the ability of MRSA to spread between animals and humans and emphasizes the importance of infection control measures to decrease the risk for MRSA colonization and infection of both horses and personnel.
Veterinary Microbiology 11/2012; · 3.33 Impact Factor
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Amos Adler,
Debby Ben-David, Mitchell J Schwaber,
Samira Masarwa,
David Schwartz,
Nurith Porat,
Tali Kotlovsky,
Maya Shklyar,
Nikolay Polivkin,
Irina Weinberg,
Avraham Lazary,
Nissim Ohana,
Ron Dagan
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ABSTRACT: We aimed to study the prevalence of Streptococcus pneumoniae in respiratory samples from institutionalized patients with chronic tracheostomy. A total of 264 pairs of nasopharyngeal and endotracheal cultures were collected. There was no difference in the proportion of positive cultures between children (21%) and adults (18%). However, the proportion of positive endotracheal cultures was higher than that of nasopharyngeal cultures in adults (18% versus 3%, respectively; P < 0.001) but not in children (17% in both sites).
Journal of clinical microbiology 07/2012; 50(10):3368-70. · 4.16 Impact Factor
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ABSTRACT: In June 2010, a bla(KPC)-negative, ertapenem-resistant ST-258 Klebsiella pneumoniae strain was isolated from a patient in the Laniado Medical Center (LMC). Our aims were (i) to describe its molecular characteristics and resistance mechanisms and (ii) to assess whether the bla(KPC)-negative ST-258 K. pneumoniae clone spreads as efficiently as its KPC-producing isogenic strain. In a prospective study, surveillance of all ertapenem-resistant, carbapenemase-negative K. pneumoniae (ERCNKP) isolates was conducted from June 2010 to May 2011 at LMC (314 beds) and from July 2008 to December 2010 at the Tel Aviv Sourasky Medical Center (TASMC) (1,200 beds). Molecular typing was done by arbitrarily primed PCR, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). A total of 8 of 42 (19%) ERCNKP isolates in LMC and 1 of 32 (3.1%) in TASMC belonged to the ST-258 clone. These strains carried the bla(CTX-M-2) or the bla(CTX-M-25) extended-spectrum β-lactamase (ESBL) gene. Sequencing of the ompK genes showed a frameshift mutation in the ompK35 gene. The fate of the bla(KPC)-carrying plasmid, pKpQIL, was determined by S1 analysis and by PCR of the Tn4401 transposon, repA, and the truncated bla(OXA-9). Plasmid analysis of the ERCNKP ST-258 isolates showed variability in plasmid composition and absence of the Tn4401 transposon and the pKpQIL plasmid. In addition, the ST-258 clone was identified in 35/35 (100%) of KPC-producing K. pneumoniae isolates but in none of 62 ertapenem-susceptible K. pneumoniae isolates collected in the two centers. Our results suggest that ERCNKP ST-258 evolved by loss of the bla(KPC)-carrying plasmid pKpQIL. ERCNKP ST-258 appears to have low epidemic potential.
Journal of clinical microbiology 07/2012; 50(10):3180-5. · 4.16 Impact Factor
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ABSTRACT: The carbapenemase OXA-48 has been reported from different Mediterranean countries. It is mostly encoded on a single plasmid in various Enterobacteriaceae species. We characterized the epidemiological and molecular features of OXA-48-producing Enterobacteriaceae (OPE) in Israel.
Epidemiological investigation was conducted by the National Center for Infection Control. Genotyping was performed using multilocus sequence typing. The bla(OXA-48)-carrying plasmids were investigated using S1 endonuclease and restriction fragment length polymorphism (RFLP). Conjugation efficiency of the bla(OXA-48)-carrying plasmids was studied in a filter mating experiment.
Since 2007, four OPE-infected patients were identified, all non-Israeli (two Palestinian, one Jordanian and one Georgian). Three had prior hospitalization; two in Jordan and one in Georgia. The bla(OXA-48) gene was detected in three Escherichia coli strains belonging to different clonal complexes, one Klebsiella oxytoca and one Klebsiella pneumoniae sequence type 101, as previously reported from Tunisia and Spain. In all isolates, the bla(OXA-48) gene was located inside Tn1999.2 and was carried on a 60 kb plasmid with an identical RFLP pattern. The plasmid was able to conjugate from Klebsiella spp. to E. coli, and had a conjugation efficiency up to ~10000 times higher than that of pKpQIL.
OPE, introduced mainly by medical tourism, are an emerging threat to patients from affected Mediterranean countries. The bla(OXA-48)-carrying plasmid demonstrated remarkable conjugation efficiency, which is probably important in the success of its dissemination.
Journal of Antimicrobial Chemotherapy 12/2011; 66(12):2763-6. · 5.07 Impact Factor
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ABSTRACT: Six long-term care facilities were surveyed for methicillin-resistant Staphylcoccus aureus (MRSA). Among 191 residents, 14% were carriers; 1 strain predominated (ST5-SCCmec II). Among 132 staff members, 11% were positive; 2 strains predominated (ST5-SCCmec II, ST8-SCCmec IV). All strains were Panton-Valentine leukocidin-negative. The epidemiology of MRSA among residents and staff involved joint and parallel evolution.
Clinical Infectious Diseases 11/2011; 53(9):910-3. · 9.15 Impact Factor
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ABSTRACT: CRE impede effective therapy of patients with Gram-negative infections. They affect patients with poor functional status,
prolonged hospital stay and multiple exposures to different antibiotic agents. Detecting carbapenemase-mediated carbapenem
resistance is a challenge for many microbiology laboratories using automated susceptibility testing systems. To prevent nosocomial
and community transmission of CRE, we recommend strict infection control measures—including contact isolation, cohorting of
carriers, and dedicated staffing—alongside active surveillance of patients at risk for carriage. Little is known regarding
the added value of antibiotic stewardship interventions to control epidemic or endemic transmission of CRE.
KeywordsAntibiotic resistance-Acinetobacter-Pseudomonas-KPC-Metallo beta-lactamase-OXA
09/2011: pages 105-115;
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Vered Schechner,
Tamar Gottesman,
Orna Schwartz,
Maya Korem,
Yasmin Maor,
Galia Rahav,
Rivka Karplus,
Tsipora Lazarovitch,
Eyal Braun,
Renato Finkelstein, [......],
Rita Bardenstein,
Oren Zimhony,
Alona Paz,
Israel Potasman,
Michael Giladi, Mitchell J Schwaber,
Shiri Klarfeld-Lidji,
Meirav Hochman,
Dror Marchaim,
Yehuda Carmeli
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ABSTRACT: Pseudomonas aeruginosa is an uncommon cause of bacteremia upon hospital admission (UHA) and the chosen empirical antimicrobial therapy may not cover it appropriately. In a multicenter prospective study conducted in Israel, we evaluated risk factors for in-hospital mortality in patients with P. aeruginosa bacteremia UHA and determined the influence of delay in adequate empirical antimicrobial therapy on patients' outcome. Seventy-six adult patients with P. aeruginosa bacteremia within 72 h of hospital admission were included. Demographic, clinical, and treatment data were collected. Microbiological adequacy of empirical therapy was determined. Severe sepsis or septic shock at admission (OR, 21.9; P < 0.001), respiratory or unknown sources of bacteremia (OR, 11.5; P = 0.003), recent hospitalization (OR, 6.2; P = 0.032), and poor functional status (OR, 5.8; P = 0.029) were identified as independent predictors of mortality. Inadequate empirical antimicrobial therapy was marginally associated with increased mortality only among patients who presented with severe sepsis or septic shock (P = 0.051).
Diagnostic microbiology and infectious disease 09/2011; 71(1):38-45. · 2.45 Impact Factor
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ABSTRACT: To assess the prevalence of and risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) carriage among patients in post-acute-care facilities (PACFs) in Israel.
A cross-sectional prevalence survey was conducted in 12 PACFs. Rectal swab samples were obtained from 1,144 patients in 33 wards. Risk factors for CRKP carriage were assessed among the cohort. Next, a nested, matched case-control study was conducted to define individual risk factors for colonization. Finally, the cohort of patients with a history of CRKP carriage was characterized to determine risk factors for continuous carriage.
The prevalence of rectal carriage of CRKP among 1,004 patients without a history of CRKP carriage was 12.0%. Independent risk factors for CRKP carriage were prolonged length of stay (odds ratio [OR], 1.001; P < .001), sharing a room with a known carrier (OR, 3.09; P = .02), and increased prevalence of known carriers on the ward (OR, 1.02; P = .013). A policy of screening for carriage on admission was protective (OR, 0.41; P = .03). Risk factors identified in the nested case-control study were antibiotic exposure during the prior 3 months (OR, 1.66; P = .03) and colonization with other resistant pathogens (OR, 1.64; P = .03). Among 140 patients with a history of CRKP carriage, 47% were colonized. Independent risk factors for continued CRKP carriage were antibiotic exposure during the prior 3 months (OR, 3.05; P = .04), receipt of amoxicillin-clavulanate (OR, 4.18; P = .007), and screening within 90 days of the first culture growing CRKP (OR, 2.9; P = .012).
We found a large reservoir of CRKP in PACFs. Infection-control policies and antibiotic exposure were associated with patient colonization.
Infection Control and Hospital Epidemiology 09/2011; 32(9):845-53. · 3.67 Impact Factor
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ABSTRACT: Use of the group 2 carbapenems, imipenem and meropenem, may lead to emergence of Pseudomonas aeruginosa resistance. The group 1 carbapenem ertapenem has limited activity against P. aeruginosa and is not associated with imipenem-resistant P. aeruginosa (IMP-R PA) in vitro. This retrospective, group-level, longitudinal study collected patient, antibiotic use, and resistance data from 2001 to 2005 using a hospital database containing information on 9 medical wards. A longitudinal data time series analysis was done to evaluate the association between carbapenem use (defined daily doses, or DDDs) and IMP-R PA. A total of 139 185 patient admissions were included, with 541 150 antibiotics DDDs prescribed: 4637 DDDs of group 2 carbapenems and 2130 DDDs of ertapenem. A total of 779 IMP-R PA were isolated (5.6 cases/1000 admissions). Univariate analysis found a higher incidence of IMP-R PA with group 2 carbapenems (P < 0.001), aminoglycosides (P = 0.034), and penicillins (P = 0.05), but not with ertapenem. Multivariate analysis showed a yearly increase in incidence of IMP-R-PA (3.8%, P < 0.001). Group 2 carbapenem use was highly associated with IMP-R PA, with a 20% increase in incidence (P = 0.0014) for each 100 DDDs. Group 2 carbapenem use tended to be associated with an increased proportion of IMP-R PA (P = 0.0625) in multivariate analysis. Ertapenem was not associated with IMP-R PA. These data would support preferentially prescribing ertapenem rather than group 2 carbapenems where clinically appropriate.
Diagnostic microbiology and infectious disease 07/2011; 70(3):367-72. · 2.45 Impact Factor
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ABSTRACT: During 2006, Israeli hospitals faced a clonal outbreak of carbapenem-resistant Klebsiella pneumoniae that was not controlled by local measures. A nationwide intervention was launched to contain the outbreak and to introduce a strategy to control future dissemination of antibiotic-resistant bacteria in hospitals.
In March 2007, the Ministry of Health issued guidelines mandating physical separation of hospitalized carriers of carbapenem-resistant Enterobacteriaceae (CRE) and dedicated staffing and appointed a professional task force charged with containment. The task force paid site visits at acute-care hospitals, evaluated infection-control policies and laboratory methods, supervised adherence to the guidelines via daily census reports on carriers and their conditions of isolation, provided daily feedback on performance to hospital directors, and intervened additionally when necessary. The initial intervention period was 1 April 2007-31 May 2008. The primary outcome measure was incidence of clinically diagnosed nosocomial CRE cases.
By 31 March 2007, 1275 patients were affected in 27 hospitals (175 cases per 1 million population). Prior to the intervention, the monthly incidence of nosocomial CRE was 55.5 cases per 100,000 patient-days. With the intervention, the continuous increase in the incidence of CRE acquisition was halted, and by May 2008, the number of new monthly cases was reduced to 11.7 cases per 100,000 patient-days (P<.001). There was a direct correlation between compliance with isolation guidelines and success in containment of transmission (P=.02). Compliance neutralized the effect of carrier prevalence on new incidence (P=.03).
A centrally coordinated intervention succeeded in containing a nationwide CRE outbreak after local measures failed. The intervention demonstrates the importance of strategic planning and national oversight in combating antimicrobial resistance.
Clinical Infectious Diseases 02/2011; 52(7):848-55. · 9.15 Impact Factor
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New England Journal of Medicine 12/2010; 363(26):2571-3. · 53.30 Impact Factor
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Dror Marchaim,
Tamar Gottesman,
Orna Schwartz,
Maya Korem,
Yasmin Maor,
Galia Rahav,
Rebekah Karplus,
Tsipora Lazarovitch,
Eyal Braun,
Hana Sprecher, [......],
Michal Chowers,
Pnina Ciobotaro,
Rita Bardenstein,
Alona Paz,
Israel Potasman,
Michael Giladi,
Vered Schechner, Mitchell J Schwaber,
Shiri Klarfeld-Lidji,
Yehuda Carmeli
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ABSTRACT: Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.
Antimicrobial Agents and Chemotherapy 12/2010; 54(12):5099-104. · 4.84 Impact Factor
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ABSTRACT: After the January 12, 2010, earthquake in Haiti, Project Medishare and the University of Miami organized, built, and staffed a 200-bed field hospital (the University of Miami Hospital in Haiti [UMHH]) on the outskirts of Port-au-Prince. We describe the operational challenges of providing a safe environment at the UMHH. Furthermore, we compared how these issues were addressed at this ad hoc hospital with how they were addressed at the field hospital of the Israel Defense Force, a fully deployable hospital with an organization fine-tuned as a result of prior disaster situations, also in Haiti.
Infection Control and Hospital Epidemiology 09/2010; 31(9):951-7. · 3.67 Impact Factor
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ABSTRACT: The spread of carbapenem-resistant Enterobacteriaceae (CRE) or carbapenemase-producing Enterobacteriaceae in healthcare settings is an important medical problem and a major public health threat. Infections with CRE are associated with high rates of morbidity and mortality, and are spreading rapidly across the globe. The medical community can either observe the natural course of this epidemic or act proactively and take adequate preventive measures to contain the spread of these bacteria. The purpose of this review is to highlight the impact of these problematic pathogens and to examine infection control policies needed in order to limit their spread.
The incidence of CRE is on the rise in several parts of the world; however, data regarding proper infection control methods on this issue are scarce. Great variability exists in infection control measures taken to confront CRE in various settings. Recently, two sets of guidelines to control CRE have been issued, one by the US Centers for Disease Control and Prevention and the other by an expert group under the auspices of the European Society of Clinical Microbiology and Infectious Diseases. These guidelines have many similarities but also considerable differences.
Whereas clinical information regarding how to contain infections by CRE pathogens is still limited, it is obvious that it relies on a multifaceted approach and implementation of strict infection control measures. Since it has been observed that lack of adequate and timely reaction is common and associated with great morbidity and mortality, preparation plans should be evaluated and implemented locally, regionally, nationally and even on an international level.
Current Opinion in Infectious Diseases 08/2010; 23(4):327-31. · 4.93 Impact Factor
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Yitshak Kreiss,
Ofer Merin,
Kobi Peleg,
Gad Levy,
Shlomo Vinker,
Ram Sagi,
Avi Abargel,
Carmi Bartal,
Guy Lin,
Ariel Bar,
Elhanan Bar-On, Mitchell J Schwaber,
Nachman Ash
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ABSTRACT: The earthquake that struck Haiti in January 2010 caused an estimated 230,000 deaths and injured approximately 250,000 people. The Israel Defense Forces Medical Corps Field Hospital was fully operational on site only 89 hours after the earthquake struck and was capable of providing sophisticated medical care. During the 10 days the hospital was operational, its staff treated 1111 patients, hospitalized 737 patients, and performed 244 operations on 203 patients. The field hospital also served as a referral center for medical teams from other countries that were deployed in the surrounding areas. The key factor that enabled rapid response during the early phase of the disaster from a distance of 6000 miles was a well-prepared and trained medical unit maintained on continuous alert. The prompt deployment of advanced-capability field hospitals is essential in disaster relief, especially in countries with minimal medical infrastructure. The changing medical requirements of people in an earthquake zone dictate that field hospitals be designed to operate with maximum flexibility and versatility regarding triage, staff positioning, treatment priorities, and hospitalization policies. Early coordination with local administrative bodies is indispensable.
Annals of internal medicine 06/2010; 153(1):45-8. · 16.73 Impact Factor
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ABSTRACT: Klebsiella pneumoniae carbapenemase (KPC) 3-producing Escherichia coli was isolated from a carrier of KPC-3-producing K. pneumoniae. The KPC-3 plasmid was identical in isolates of both species. The patient's gut flora contained a carbapenem-susceptible E. coli strain isogenic with the KPC-3-producing isolate, which suggests horizontal interspecies plasmid transfer.
Emerging Infectious Diseases 06/2010; 16(6):1014-7. · 6.79 Impact Factor
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New England Journal of Medicine 03/2010; 362(11):e38. · 53.30 Impact Factor
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ABSTRACT: The spread of carbapenem-resistant members of the Enterobacteriaceae family (CRE) harboring carbapenemases is an emerging public health threat. As KPC-producing Klebsiella species are endemic in our tertiary care hospital, we aimed to evaluate a PCR-based surveillance test for identification of rectal carriage of KPC-producing CRE. We conducted a surveillance study between May and December 2007. Rectal swabs were collected from patients known to harbor CRE and from contacts of newly discovered patients harboring CRE. Specimens were evaluated by culture and by PCR analysis for blaKPC and were defined as positive if CRE was cultured and blaKPC was identified. Discrepant results between the culture and PCR analysis were resolved by subculturing, repeating the PCR, and performing a hydrolysis assay. Positive CRE cultures prior or subsequent to the time of sampling for the study were also taken into consideration. Sensitivity, specificity, and time to result were calculated. A total of 755 swabs were included. Concordant results were documented for 735 specimens; 51 were positive as determined by both PCR and culture. Discrepancies existed for 20 swabs; 9 were blaKPC negative and CRE culture positive, and 11 were blaKPC positive and CRE culture negative. After repeat testing, a total of 64 samples were classified as blaKPC-positive CRE. The sensitivity and specificity of the PCR analysis were 92.2% and 99.6%, respectively, and those of the culture were 87.5% and 99.4%, respectively. Over the last 3 months of the study, the sensitivity of the PCR improved to 96.3%, versus 77.8% for culture. Time to result was 30 h for the PCR and 60 h (negative) and 75 h (positive) for the CRE culture. blaKPC PCR-based testing is a useful method for the surveillance of KPC-producing CRE. Its main advantage over culturing is a shorter time to result, and it may prove to be more sensitive.
Journal of clinical microbiology 09/2009; 47(10):3261-5. · 4.16 Impact Factor
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Vered Schechner,
Vandack Nobre,
Keith S Kaye,
Moshe Leshno,
Michael Giladi,
Peter Rohner,
Stephan Harbarth,
Deverick J Anderson,
Adolf W Karchmer, Mitchell J Schwaber,
Yehuda Carmeli
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ABSTRACT: Pseudomonas aeruginosa is an uncommon cause of community-acquired bacteremia among patients without severe immunodeficiency. Because tension exists between the need to limit unnecessary use of anti-pseudomonal agents and the need to avoid a delay in appropriate therapy, clinicians require better guidance regarding when to cover empirically for P. aeruginosa. We sought to determine the occurrence of and construct a model to predict P. aeruginosa bacteremia upon hospital admission.
A retrospective study was conducted in 4 tertiary care hospitals. Microbiology databases were searched to find all episodes of bacteremia caused by gram-negative rods (GNRs) <or= 48 h after hospital admission. Patient data were extracted from the medical records of 151 patients with P. aeruginosa bacteremia and of 152 randomly selected patients with bacteremia due to Enterobacteriaceae. Discriminative parameters were identified using logistic regression, and the probabilities of having P. aeruginosa bacteremia were calculated.
P. aeruginosa caused 6.8% of 4114 unique patient episodes of GNR bacteremia upon hospital admission (incidence ratio, 5 cases per 10,000 hospital admissions). Independent predictors of P. aeruginosa bacteremia were severe immunodeficiency, age >90 years, receipt of antimicrobial therapy within past 30 days, and presence of a central venous catheter or a urinary device. Among 250 patients without severe immunodeficiency, if no predictor variables existed, the likelihood of having P. aeruginosa bacteremia was 1:42. If >or= 2 predictors existed, the risk increased to nearly 1:3.
P. aeruginosa bacteremia upon hospital admission in patients without severe immunodeficiency is rare. Among immunocompetent patients with suspected GNR bacteremia who have >or= 2 predictors, empirical anti-pseudomonal treatment is warranted.
Clinical Infectious Diseases 03/2009; 48(5):580-6. · 9.15 Impact Factor
