Azita Leavitt - Academia.edu (original) (raw)
Papers by Azita Leavitt
Antimicrobial Agents and Chemotherapy
The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the wo... more The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the world. We aimed to describe the occurrence and to understand the dissemination of this extendedspectrum b-lactamase family among Enterobacteriaceae strains in our hospital.
Emerging infectious diseases, 2005
A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphyloc... more A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.
JNCI Journal of the National Cancer Institute, 2004
Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia a... more Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer. Methods: We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age-and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided. Results: Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide ؍ 2.7, 95% confidence interval [CI] ؍ 1.2 to 6.2; P trend ؍ .047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile ؍ 3.4, 95% CI ؍ 1.4 to 8.3; P trend ؍ .02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile ؍ 3.4, 95% CI ؍ 1.3 to 8.8; P trend ؍ .03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was
Journal of Clinical Microbiology, 2005
We evaluated a protocol for the accelerated detection of extended-spectrum -lactamases (ESBLs) i... more We evaluated a protocol for the accelerated detection of extended-spectrum -lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.
Journal of Clinical Microbiology, 2006
Forty clinical isolates of Enterobacter spp. were identified as extended-spectrum -lactamase (ES... more Forty clinical isolates of Enterobacter spp. were identified as extended-spectrum -lactamase (ESBL) producers by disk diffusion. The VITEK 2 Advanced Expert System (AES) identified the ESBL phenotype in only 25 isolates (62.5%), and erroneously reported cephalosporin susceptibility in 11 isolates (28%). Refinements in the AES are required in order to improve ESBL detection in Enterobacter.
Journal of Clinical Microbiology, 2009
Ertapenem resistance in Klebsiella pneumoniae is rare. We report on an ertapenem-nonsusceptible p... more Ertapenem resistance in Klebsiella pneumoniae is rare. We report on an ertapenem-nonsusceptible phenotype among 25 out of 663 (3.77%) extended-spectrum--lactamase (ESBL)-producing K. pneumoniae isolates in a multicenter Israeli study. These isolates originated from six different hospitals and were multiclonal, belonging to 12 different genetic clones. Repeat testing using Etest and agar dilution confirmed ertapenem nonsusceptibility in only 15/663 (2.3%) of the isolates. The molecular mechanisms of ertapenem resistance in seven single-clone resistant isolates was due to the presence of ESBL genes (CTX-M-2 in four isolates, CTX-M-10 and OXA-4 in one isolate, SHV-12 in one isolate, and SHV-28 in one isolate) combined with the absence of OMPK36. Seven of 10 isolates initially reported as ertapenem nonsusceptible and subsequently classified as susceptible showed an inoculum effect with ertapenem but not with imipenem or meropenem. Population analysis detected the presence of an ertapenem-resistant subpopulation at a frequency of 10 ؊6 . These rare resistant subpopulations carried multiple ESBL genes, including TEM-30, SHV-44, CTX-M-2, and CTX-M-10, and they lacked OMPK36. The clinical and diagnostic significance of the results should be further studied.
Journal of Antimicrobial Chemotherapy, 2008
The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the wo... more The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the world. We aimed to describe the occurrence and to understand the dissemination of this extendedspectrum b-lactamase family among Enterobacteriaceae strains in our hospital.
Journal of Antimicrobial Chemotherapy, 2010
Objectives: An extremely drug-resistant (XDR) clone of KPC-3-producing Klebsiella pneumoniae emer... more Objectives: An extremely drug-resistant (XDR) clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. We aimed to characterize the local KPC-3encoding plasmid carried by these isolates and study its contribution to antibiotic resistance.
Journal of Antimicrobial Chemotherapy, 2007
Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is increasing in our hospital and w... more Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is increasing in our hospital and worldwide, raising the necessity of finding effective therapies. We aimed to evaluate the in vitro activity of tigecycline against MDR A. baumannii clones isolated before tigecycline was used in our institution.
Infection Control and Hospital Epidemiology, 2007
Objectives. To perform a molecular and epidemiologic investigation of multidrug-resistant (MDR) A... more Objectives. To perform a molecular and epidemiologic investigation of multidrug-resistant (MDR) Acinetobacter baumannii in an institution were polyclonal outbreaks have been observed and determine whether these polyclonal outbreaks had an endogenous origin or were caused by in-hospital patient-to-patient transmission.
Genome Research, 2012
In the process of clone-based genome sequencing, initial assemblies frequently contain cloning ga... more In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non-coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions.
European Journal of Clinical Microbiology & Infectious Diseases, 2004
The study presented here was performed to evaluate an accelerated protocol for the early detectio... more The study presented here was performed to evaluate an accelerated protocol for the early detection of organisms producing extended-spectrum beta-lactamase (ESBL). The procedure involved testing isolates directly from positive blood-culture bottles, and a total of 40 clinical isolates (10 ESBL-producing and 10 non-ESBL-producing isolates of both Escherichia coli and Klebsiella pneumoniae) were used. The isolates were inoculated into blood cultures bottles and, upon growth signal, fluid from the bottle was cultured directly onto plates with combination discs containing cefotaxime or ceftazidime with and without clavulanate. Results were compared with those of standard methods for the detection of ESBL. High concordance between the two methods was found, and the direct test showed high sensitivity (95%) and specificity (100%). Use of this accelerated protocol may speed detection of the ESBL phenotype and thereby facilitate the early administration of appropriate antimicrobial therapy.
European Journal of Clinical Microbiology & Infectious Diseases, 2004
European Journal of Clinical Microbiology & Infectious Diseases, 2006
The aims of the study presented here were to determine the prevalence of Staphylococcus aureus ca... more The aims of the study presented here were to determine the prevalence of Staphylococcus aureus carriage and, specifically, community-acquired methicillin-resistant S. aureus (CA-MRSA) carriage in children and their parents in Israel and to determine the genetic relatedness of these isolates. S. aureus was isolated from 580 of 3,373 (17.2%) individuals screened. The predominant type identified by pulsed-field gel electrophoresis was strain ST45-MSSA (25%). Five MRSA isolates were detected, and two of these were classified as CA-MRSA, based on the following criteria: no previous contact with a healthcare facility, absence of a multidrug-resistant (MDR) phenotype, and presence of SCCmec type IV. Isolates were negative for pvl and were classified as ST-45-MRSA. Although CA-MRSA is still rare in Israel, the genetic relatedness of the strains found in this study to a successful MSSA clone warrants close follow up.
Diagnostic Microbiology and Infectious Disease, 2014
We performed comparative sequence analysis of 3 blaKPC-2 encoding plasmids to examine evolution o... more We performed comparative sequence analysis of 3 blaKPC-2 encoding plasmids to examine evolution of these plasmids and their dissemination. We found that all of them have an IncN replicon with a newly determined IncN plasmid sequence type (ST), ST15. The 2 Klebsiella pneumoniae (KPN) plasmids also harbor an IncF2A1-B1- replicon. The blaKPC-2 is located in the Tn4401c transposon with a newly discovered mutation in the P2 promoter. Screening of the 27 additional blaKPC-2 carrying plasmids from Enterobacter cloacae, Escherichia coli (EC), and K. pneumoniae showed that: all KPN and EC plasmids are IncN plasmids belonging to ST15; 4/7 KPN and 1/6 EC plasmids contain an additional IncF2A1-B1- replicon; all Enterobacter plasmids belong to neither IncN nor IncF2A1-B1- replicon plasmids; 6/7 KPN and 2/5 EC plasmids carry the mutated P2 promoter. Study of the blaKPC-2 environment, transposon, pMLST, and Inc group suggests transposon and plasmid inter- and intra-species dissemination and evolution.
Clinical Infectious Diseases, 2006
The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterob... more The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterobacteriaceae is increasing worldwide. The influx of these bacteria into hospitals has major implications for infection-control and empirical treatment strategies. Isolates from 2 patient cohorts--patients with gram-negative bacteremia within 2 days after admission and patients screened for fecal colonization at admission--were assessed for ESBL production. ESBL phenotype was confirmed according to Clinical and Laboratory Standards Institute guidelines. Predictors of ESBL phenotype were examined by univariate and multivariate analyses. Of 80 Enterobacteriaceae isolates from blood samples obtained at admission to the hospital, 13.7% produced ESBL. Thirty-eight patients with ESBL-positive isolates and 72 with ESBL-negative isolates were included in a case-control study. Predictors of ESBL production were male sex and nursing home residence (area under receiver operator characteristic curve, 0.7). Of 241 persons screened at admission, 26 (10.8%) had fecal carriage of ESBL-producing Enterobacteriaceae. Predictors of fecal carriage were poor functional status, antibiotic use, chronic renal insufficiency, liver disease, and use of histamine2 blockers (area under receiver operator characteristic curve, 0.8). Four (15.4%) of the 26 individuals with fecal carriage had subsequent bacteremia with ceftazidime-resistant Enterobacteriaceae, compared with 1 (0.5%) noncarrier (odds ratio, 38.9; P<.001). Of 80 ESBL-producing Enterobacteriaceae isolates obtained at admission, 65 were health care associated, and 15 were community acquired. The 15 community-acquired ESBL-producing Enterobacteriaceae belonged to diverse clones. The most prevalent ESBL gene among these isolates was CTX-M-2 (found in 53.3% of the isolates). We report high rates of bacteremia and colonization with ESBL-producing Enterobacteriaceae at admission to our institution, which may undermine infection-control measures and complicate the selection of empirical treatment.
Antimicrobial Agents and Chemotherapy, 2009
A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in ... more A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. This clone was genetically related to outbreak strains from the United States isolated in 2000 but differed in KPC-carrying plasmids. The threat of the global spread of hyperepidemic, extensively drug-resistant bacterial strains should be recognized and confronted.
Antimicrobial Agents and Chemotherapy, 2007
Antimicrobial Agents and Chemotherapy, 2010
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become more common in... more Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become more common in the United States and throughout the world. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to examine the molecular epidemiology of KPC-producing K. pneumoniae isolates sent to the Centers for Disease Control and Prevention (CDC) for reference testing from 1996 to 2008. A dominant strain, sequence type 258 (ST 258), was found and likely accounts for 70% of the CDC's K. pneumoniae PFGE database. Isolates with PFGE patterns related to ST 258 were identified in 10 of the 19 U.S. states currently reporting KPC-producing K. pneumoniae, in addition to one isolate from Israel. KPC subtyping and analysis of the surrounding genetic environment were subsequently performed on 23 representative isolates. Thirteen isolates identified as ST 258 possessed either bla KPC-2 or bla KPC-3 and some variability in the Tn4401 element upstream of the bla KPC gene. Escherichia coli DH10B was successfully transformed by electroporation with KPC-encoding plasmid DNA from 20 of the 23 isolates. Restriction analysis of plasmid DNA prepared from transformants revealed a diversity of band patterns, suggesting the presence of different plasmids harboring the bla KPC gene, even among isolates of the same ST.
Antimicrobial Agents and Chemotherapy
The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the wo... more The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the world. We aimed to describe the occurrence and to understand the dissemination of this extendedspectrum b-lactamase family among Enterobacteriaceae strains in our hospital.
Emerging infectious diseases, 2005
A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphyloc... more A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission.
JNCI Journal of the National Cancer Institute, 2004
Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia a... more Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer. Methods: We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age-and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided. Results: Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide ؍ 2.7, 95% confidence interval [CI] ؍ 1.2 to 6.2; P trend ؍ .047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile ؍ 3.4, 95% CI ؍ 1.4 to 8.3; P trend ؍ .02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile ؍ 3.4, 95% CI ؍ 1.3 to 8.8; P trend ؍ .03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was
Journal of Clinical Microbiology, 2005
We evaluated a protocol for the accelerated detection of extended-spectrum -lactamases (ESBLs) i... more We evaluated a protocol for the accelerated detection of extended-spectrum -lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.
Journal of Clinical Microbiology, 2006
Forty clinical isolates of Enterobacter spp. were identified as extended-spectrum -lactamase (ES... more Forty clinical isolates of Enterobacter spp. were identified as extended-spectrum -lactamase (ESBL) producers by disk diffusion. The VITEK 2 Advanced Expert System (AES) identified the ESBL phenotype in only 25 isolates (62.5%), and erroneously reported cephalosporin susceptibility in 11 isolates (28%). Refinements in the AES are required in order to improve ESBL detection in Enterobacter.
Journal of Clinical Microbiology, 2009
Ertapenem resistance in Klebsiella pneumoniae is rare. We report on an ertapenem-nonsusceptible p... more Ertapenem resistance in Klebsiella pneumoniae is rare. We report on an ertapenem-nonsusceptible phenotype among 25 out of 663 (3.77%) extended-spectrum--lactamase (ESBL)-producing K. pneumoniae isolates in a multicenter Israeli study. These isolates originated from six different hospitals and were multiclonal, belonging to 12 different genetic clones. Repeat testing using Etest and agar dilution confirmed ertapenem nonsusceptibility in only 15/663 (2.3%) of the isolates. The molecular mechanisms of ertapenem resistance in seven single-clone resistant isolates was due to the presence of ESBL genes (CTX-M-2 in four isolates, CTX-M-10 and OXA-4 in one isolate, SHV-12 in one isolate, and SHV-28 in one isolate) combined with the absence of OMPK36. Seven of 10 isolates initially reported as ertapenem nonsusceptible and subsequently classified as susceptible showed an inoculum effect with ertapenem but not with imipenem or meropenem. Population analysis detected the presence of an ertapenem-resistant subpopulation at a frequency of 10 ؊6 . These rare resistant subpopulations carried multiple ESBL genes, including TEM-30, SHV-44, CTX-M-2, and CTX-M-10, and they lacked OMPK36. The clinical and diagnostic significance of the results should be further studied.
Journal of Antimicrobial Chemotherapy, 2008
The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the wo... more The CTX-M-25 family of b-lactamases is a closely related family of enzymes found rarely in the world. We aimed to describe the occurrence and to understand the dissemination of this extendedspectrum b-lactamase family among Enterobacteriaceae strains in our hospital.
Journal of Antimicrobial Chemotherapy, 2010
Objectives: An extremely drug-resistant (XDR) clone of KPC-3-producing Klebsiella pneumoniae emer... more Objectives: An extremely drug-resistant (XDR) clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. We aimed to characterize the local KPC-3encoding plasmid carried by these isolates and study its contribution to antibiotic resistance.
Journal of Antimicrobial Chemotherapy, 2007
Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is increasing in our hospital and w... more Objectives: Multidrug-resistant (MDR) Acinetobacter baumannii is increasing in our hospital and worldwide, raising the necessity of finding effective therapies. We aimed to evaluate the in vitro activity of tigecycline against MDR A. baumannii clones isolated before tigecycline was used in our institution.
Infection Control and Hospital Epidemiology, 2007
Objectives. To perform a molecular and epidemiologic investigation of multidrug-resistant (MDR) A... more Objectives. To perform a molecular and epidemiologic investigation of multidrug-resistant (MDR) Acinetobacter baumannii in an institution were polyclonal outbreaks have been observed and determine whether these polyclonal outbreaks had an endogenous origin or were caused by in-hospital patient-to-patient transmission.
Genome Research, 2012
In the process of clone-based genome sequencing, initial assemblies frequently contain cloning ga... more In the process of clone-based genome sequencing, initial assemblies frequently contain cloning gaps that can be resolved using cloning-independent methods, but the reason for their occurrence is largely unknown. By analyzing 9,328,693 sequencing clones from 393 microbial genomes, we systematically mapped more than 15,000 genes residing in cloning gaps and experimentally showed that their expression products are toxic to the Escherichia coli host. A subset of these toxic sequences was further evaluated through a series of functional assays exploring the mechanisms of their toxicity. Among these genes, our assays revealed novel toxins and restriction enzymes, and new classes of small, non-coding toxic RNAs that reproducibly inhibit E. coli growth. Further analyses also revealed abundant, short, toxic DNA fragments that were predicted to suppress E. coli growth by interacting with the replication initiator DnaA. Our results show that cloning gaps, once considered the result of technical problems, actually serve as a rich source for the discovery of biotechnologically valuable functions, and suggest new modes of antimicrobial interventions.
European Journal of Clinical Microbiology & Infectious Diseases, 2004
The study presented here was performed to evaluate an accelerated protocol for the early detectio... more The study presented here was performed to evaluate an accelerated protocol for the early detection of organisms producing extended-spectrum beta-lactamase (ESBL). The procedure involved testing isolates directly from positive blood-culture bottles, and a total of 40 clinical isolates (10 ESBL-producing and 10 non-ESBL-producing isolates of both Escherichia coli and Klebsiella pneumoniae) were used. The isolates were inoculated into blood cultures bottles and, upon growth signal, fluid from the bottle was cultured directly onto plates with combination discs containing cefotaxime or ceftazidime with and without clavulanate. Results were compared with those of standard methods for the detection of ESBL. High concordance between the two methods was found, and the direct test showed high sensitivity (95%) and specificity (100%). Use of this accelerated protocol may speed detection of the ESBL phenotype and thereby facilitate the early administration of appropriate antimicrobial therapy.
European Journal of Clinical Microbiology & Infectious Diseases, 2004
European Journal of Clinical Microbiology & Infectious Diseases, 2006
The aims of the study presented here were to determine the prevalence of Staphylococcus aureus ca... more The aims of the study presented here were to determine the prevalence of Staphylococcus aureus carriage and, specifically, community-acquired methicillin-resistant S. aureus (CA-MRSA) carriage in children and their parents in Israel and to determine the genetic relatedness of these isolates. S. aureus was isolated from 580 of 3,373 (17.2%) individuals screened. The predominant type identified by pulsed-field gel electrophoresis was strain ST45-MSSA (25%). Five MRSA isolates were detected, and two of these were classified as CA-MRSA, based on the following criteria: no previous contact with a healthcare facility, absence of a multidrug-resistant (MDR) phenotype, and presence of SCCmec type IV. Isolates were negative for pvl and were classified as ST-45-MRSA. Although CA-MRSA is still rare in Israel, the genetic relatedness of the strains found in this study to a successful MSSA clone warrants close follow up.
Diagnostic Microbiology and Infectious Disease, 2014
We performed comparative sequence analysis of 3 blaKPC-2 encoding plasmids to examine evolution o... more We performed comparative sequence analysis of 3 blaKPC-2 encoding plasmids to examine evolution of these plasmids and their dissemination. We found that all of them have an IncN replicon with a newly determined IncN plasmid sequence type (ST), ST15. The 2 Klebsiella pneumoniae (KPN) plasmids also harbor an IncF2A1-B1- replicon. The blaKPC-2 is located in the Tn4401c transposon with a newly discovered mutation in the P2 promoter. Screening of the 27 additional blaKPC-2 carrying plasmids from Enterobacter cloacae, Escherichia coli (EC), and K. pneumoniae showed that: all KPN and EC plasmids are IncN plasmids belonging to ST15; 4/7 KPN and 1/6 EC plasmids contain an additional IncF2A1-B1- replicon; all Enterobacter plasmids belong to neither IncN nor IncF2A1-B1- replicon plasmids; 6/7 KPN and 2/5 EC plasmids carry the mutated P2 promoter. Study of the blaKPC-2 environment, transposon, pMLST, and Inc group suggests transposon and plasmid inter- and intra-species dissemination and evolution.
Clinical Infectious Diseases, 2006
The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterob... more The prevalence of infections caused by extended-spectrum beta -lactamase (ESBL)-producing Enterobacteriaceae is increasing worldwide. The influx of these bacteria into hospitals has major implications for infection-control and empirical treatment strategies. Isolates from 2 patient cohorts--patients with gram-negative bacteremia within 2 days after admission and patients screened for fecal colonization at admission--were assessed for ESBL production. ESBL phenotype was confirmed according to Clinical and Laboratory Standards Institute guidelines. Predictors of ESBL phenotype were examined by univariate and multivariate analyses. Of 80 Enterobacteriaceae isolates from blood samples obtained at admission to the hospital, 13.7% produced ESBL. Thirty-eight patients with ESBL-positive isolates and 72 with ESBL-negative isolates were included in a case-control study. Predictors of ESBL production were male sex and nursing home residence (area under receiver operator characteristic curve, 0.7). Of 241 persons screened at admission, 26 (10.8%) had fecal carriage of ESBL-producing Enterobacteriaceae. Predictors of fecal carriage were poor functional status, antibiotic use, chronic renal insufficiency, liver disease, and use of histamine2 blockers (area under receiver operator characteristic curve, 0.8). Four (15.4%) of the 26 individuals with fecal carriage had subsequent bacteremia with ceftazidime-resistant Enterobacteriaceae, compared with 1 (0.5%) noncarrier (odds ratio, 38.9; P<.001). Of 80 ESBL-producing Enterobacteriaceae isolates obtained at admission, 65 were health care associated, and 15 were community acquired. The 15 community-acquired ESBL-producing Enterobacteriaceae belonged to diverse clones. The most prevalent ESBL gene among these isolates was CTX-M-2 (found in 53.3% of the isolates). We report high rates of bacteremia and colonization with ESBL-producing Enterobacteriaceae at admission to our institution, which may undermine infection-control measures and complicate the selection of empirical treatment.
Antimicrobial Agents and Chemotherapy, 2009
A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in ... more A highly epidemic carbapenem-resistant clone of KPC-3-producing Klebsiella pneumoniae emerged in Israel in 2006, causing a nationwide outbreak. This clone was genetically related to outbreak strains from the United States isolated in 2000 but differed in KPC-carrying plasmids. The threat of the global spread of hyperepidemic, extensively drug-resistant bacterial strains should be recognized and confronted.
Antimicrobial Agents and Chemotherapy, 2007
Antimicrobial Agents and Chemotherapy, 2010
Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become more common in... more Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae have become more common in the United States and throughout the world. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to examine the molecular epidemiology of KPC-producing K. pneumoniae isolates sent to the Centers for Disease Control and Prevention (CDC) for reference testing from 1996 to 2008. A dominant strain, sequence type 258 (ST 258), was found and likely accounts for 70% of the CDC's K. pneumoniae PFGE database. Isolates with PFGE patterns related to ST 258 were identified in 10 of the 19 U.S. states currently reporting KPC-producing K. pneumoniae, in addition to one isolate from Israel. KPC subtyping and analysis of the surrounding genetic environment were subsequently performed on 23 representative isolates. Thirteen isolates identified as ST 258 possessed either bla KPC-2 or bla KPC-3 and some variability in the Tn4401 element upstream of the bla KPC gene. Escherichia coli DH10B was successfully transformed by electroporation with KPC-encoding plasmid DNA from 20 of the 23 isolates. Restriction analysis of plasmid DNA prepared from transformants revealed a diversity of band patterns, suggesting the presence of different plasmids harboring the bla KPC gene, even among isolates of the same ST.