The Natural History of Carbapenemase-Producing Enterobacterales: Progression From Carriage of Various Carbapenemases to Bloodstream Infection.

BACKGROUND: Little is known about the risk of progression from carbapenemase-producing Enterobacterales (CPE) carriage to CPE bloodstream infection (BSI) outside of high-risk settings. We aimed to determine the incidence of CPE BSI among CPE carriers and to assess whether the incidence differs by carbapenemase, species, and setting. METHODS: We conducted a nationwide population-based retrospective cohort study using national databases. The cohort consisted of all patients in Israel with CPE detected by screening from 1 January 2020 to 10 October 2022. We calculated the cumulative incidence of CPE BSI within 1 year among CPE carriers. We used a competing-risks model with BSI as the outcome and death as the competing risk. RESULTS: The study included 6828 CPE carriers. The cumulative incidence of CPE BSI was 2.4% (95% confidence interval [CI], 2.1-2.8). Compared with Klebsiella pneumoniae carbapenemase (KPC), the subhazard of BSI was lower for New Delhi metallo-ß-lactamase (NDM) (adjusted subhazard ratio [aSHR], 0.72; 95% CI, .49-1.05) and oxacillinase-48-like (OXA-48-like) (aSHR, 0.60; 95% CI, .32-1.12) but these differences did not reach statistical significance. Compared with K. pneumoniae, the subhazard of BSI was lower for carriers of carbapenemase-producing Escherichia coli (aSHR, 0.33; 95% CI, .21-.52). The subhazard of BSI was higher among patients with CPE carriage first detected in intensive care units (aSHR, 2.10; 95% CI, 1.27-3.49) or oncology/hematology wards (aSHR, 3.95; 95% CI, 2.51-6.22) compared with medical wards. CONCLUSIONS: The risk of CPE BSI among CPE carriers is lower than previously reported in studies that focused on high-risk patients and settings. The risk of BSI differs significantly by bacterial species and setting, but not by carbapenemase.

Use of Fourier-transform infrared spectroscopy for real-time outbreak investigation of OXA-48-producing Escherichia coli.

BACKGROUND: Efficient infection control during carbapenem-resistant Enterobacterales outbreaks demands rapid and simple techniques for outbreak investigations. WGS, the current gold standard for outbreak identification, is expensive, time-consuming and requires a high level of expertise. Fourier-transform infrared (FTIR) spectroscopy (IR Biotyper) is a rapid typing method based on infrared radiation applied to samples, which provides a highly specific absorption spectrum. OBJECTIVES: To investigate an outbreak of OXA-48-producing Escherichia coli in real-time using FTIR and subsequently compare the results with WGS. METHODS: Twenty-one isolates were collected during a nosocomial outbreak, and identification and antibiotic susceptibilities were confirmed by VITEK®2. FTIR was conducted for all isolates, and nine representative isolates were sequenced. RESULTS: FTIR was able to correctly determine the clonal relatedness of the isolates and to identify the outbreak cluster, as confirmed by WGS. By WGS, isolates in the main FTIR cluster belonged to the same MLST type and core-genome MLST type, and they harboured similar plasmids and resistance genes, whereas the singletons external to the FTIR cluster had different genetic content. CONCLUSIONS: FTIR can operate as a rapid, efficient and reliable first-line tool for outbreak investigations during a real-time ongoing E. coli outbreak, which can contribute to limiting the spread of pathogens.

Impact of intensified prevention measures on rates of hospital-acquired bloodstream infection in medical-surgical intensive care units, Israel, 2011 to 2019.

BackgroundCentral line-associated bloodstream infection (CLABSI) is among the most common preventable infectious complications in patients in intensive care units (ICU). In 2011, the Israel National Center for Infection Control initiated a nationwide CLABSI prevention programme.AimTo evaluate the impact of different components of the programme on CLABSI and non-CLABSI rates in medical-surgical ICUs.MethodsWe included data collected from all 29 medical-surgical ICUs in Israel from November 2011 to December 2019. The study period was divided into three phases: I (baseline, initial CLABSI prevention guidelines introduced, initial feedback on rates provided), II (initial guidelines widely implemented, surveillance undertaken, feedback continued) and III (after implementation of additional prevention measures). Interrupted time series analysis was used to compare CLABSI and non-CLABSI rates during the three phases.ResultsThe pooled mean (SD) incidence of CLABSI per 1,000 central line-days dropped from 7.4 (0.38) in phase I to 2.1 (0.13) in phase III (p < 0.001). The incidence rate ratio (IRR) was 0.63 (95% CI: 0.51-0.79) between phases I and II, and 0.78 (95% CI: 0.59-1.02) between phases II and III. The pooled mean (SD) incidence of non-CLABSI per 1,000 patient-days declined from 5.3 (0.24) in phase I to 3.4 (0.13) in phase III (p < 0.001).ConclusionNational CLABSI prevention guidelines, surveillance and feedback resulted in significant reductions in CLABSI and non-CLABSI rates. In the wake of further interventions, significant reduction was achieved in ICUs reporting improvement in the uptake of additional prevention measures.

Healthcare-associated infection prevention and control practices in Israel: results of a national survey.

BACKGROUND: Healthcare-associated infection (HAI) is a common and largely preventable cause of morbidity and mortality. The COVID-19 pandemic has presented unprecedented challenges to health systems. We conducted a national survey to ascertain hospital characteristics and the use of HAI prevention measures in Israel. METHODS: We e-mailed surveys to infection prevention and control (IPC) leads of acute care hospitals in Israel. The survey included questions about the use of practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), ventilator-associated pneumonia (VAP), and Clostridioides difficile infection (CDI). The survey also assessed COVID-19 impact and healthcare worker well-being. RESULTS: IPC leads from 15 of 24 invited hospitals (63%) completed the survey. Only one-third of respondents reported strong support for IPC from hospital leadership. Although several prevention practices were used by all hospitals (e.g., maximum sterile barrier precautions for CLABSI and real-time assessment of environmental cleaning for CDI), use of other practices was suboptimal-particularly for CAUTI and VAP. COVID-19 had a profound impact on Israeli hospitals, with all hospitals reporting opening of new units to care for COVID patients and most reporting moderate to extreme financial hardship. All hospitals reported highly successful plans to vaccinate all staff and felt confident that the vaccine is safe and effective. CONCLUSION: We provide a status report of the IPC characteristics and practices Israeli hospitals are currently using to prevent HAIs during the COVID-19 era. While many globally accepted IPC practices are widely implemented, opportunities to increase the use of certain IPC practices in Israeli hospitals exist.

National Policy for Carbapenem-Resistant Enterobacteriaceae (CRE) Clearance and Discontinuation of Contact Precautions for CRE Carriers in Post-Acute Care Hospitals in Israel: Impact on Isolation-Days and New Acquisitions.

BACKGROUND: In 2009, the Israeli Ministry of Health implemented in post-acute care hospitals (PACHs) a process of discontinuing carbapenem-resistant Enterobacteriaceae (CRE) carrier status. We evaluated the policy's impact on isolation-days, CRE prevalence among known carriers who had completed clearance testing, and CRE acquisition among noncarriers. METHODS: This retrospective study summarized findings from all 15 PACHs in 2009-2017. CRE carriers were considered cleared and removed from contact isolation after 2 rectal cultures negative for CRE and polymerase chain reaction negative for carbapenemases. Data sources included routine surveillance and 4 point prevalence surveys conducted from 2011 to 2017. RESULTS: During the study period, 887 of 6101 CRE carriers (14.5%) completed clearance testing. From 2013 to 2016, the percentage of patient-days in CRE isolation decreased from 9.4% to 3.9% (P = .008). In all surveys combined, there were 819 known CRE carriers; 411 (50%) had completed clearance testing. Of these, 11.4% (47/411) were CRE positive in the survey. At the ward level, the median percentage of patients with no CRE history who were positive on survey decreased from 11.3% in 2011 to 0% in 2017 (P < .001). We found no ward-level correlation between the proportion of carriers who completed clearance and new acquisitions (ρ = 0.02, P = .86). CONCLUSIONS: A process for discontinuing CRE carrier status in PACHs led to a significant reduction in the percentage of patient-days in contact isolation without increasing CRE acquisitions among noncarriers.

Fourier Transform Infrared Spectroscopy Is a New Option for Outbreak Investigation: a Retrospective Analysis of an Extended-Spectrum-Beta-Lactamase-Producing Klebsiella pneumoniae Outbreak in a Neonatal Intensive Care Unit.

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 h. We aimed (i) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole-genome sequencing (WGS) results as the gold standard and (ii) to assess how the cutoff values used to define clusters affect the discriminatory power of the IR Biotyper. The sample consisted of 18 isolates from 14 patients. Specimens were analyzed in the IR Biotyper using the default analysis settings, and spectra were analyzed using OPUS 7.5 software. The software contains a feature that automatically proposes a cutoff value to define clusters; the cutoff value defines up to which distance the spectra are considered to be in the same cluster. Based on FT-IR, the outbreak represented 1 dominant clone, 1 secondary clone, and several unrelated clones. FT-IR results, using the cutoff value generated by the accompanying software after 4 replicates, were concordant with WGS for all but 1 isolate. BOX-PCR was underdiscriminatory compared to the other two methods. Using the cutoff value generated after 12 replicates, the results of FT-IR and WGS were completely concordant. The IR Biotyper can achieve the same typeability and discriminatory power as genome-based methods. However, to attain this high performance requires either previous, strain-dependent knowledge about the optimal technical parameters to be used or validation by a second method.

Linking antimicrobial resistance surveillance to antibiotic policy in healthcare settings: the COMBACTE-Magnet EPI-Net COACH project.

OBJECTIVES: To systematically summarize the evidence on how to collect, analyse and report antimicrobial resistance (AMR) surveillance data to inform antimicrobial stewardship (AMS) teams providing guidance on empirical antibiotic treatment in healthcare settings. METHODS: The research group identified 10 key questions about the link between AMR surveillance and AMS using a checklist of 9 elements for good practice in health research priority settings and a modified 3D combined approach matrix, and conducted a systematic review of published original studies and guidelines on the link between AMR surveillance and AMS. RESULTS: The questions identified focused on AMS team composition; minimum infrastructure requirements for AMR surveillance; organisms, samples and susceptibility patterns to report; data stratification strategies; reporting frequency; resistance thresholds to drive empirical therapy; surveillance in high-risk hospital units, long-term care, outpatient and veterinary settings; and surveillance data from other countries. Twenty guidelines and seven original studies on the implementation of AMR surveillance as part of an AMS programme were included in the literature review. CONCLUSIONS: The evidence summarized in this review provides a useful basis for a more integrated process of developing procedures to report AMR surveillance data to drive AMS interventions. These procedures should be extended to settings outside the acute-care institutions, such as long-term care, outpatient and veterinary. Without proper AMR surveillance, implementation of AMS policies cannot contribute effectively to the fight against MDR pathogens and may even worsen the burden of adverse events from such interventions.

Success of a National Intervention in Controlling Carbapenem-resistant Enterobacteriaceae in Israel's Long-term Care Facilities.

BACKGROUND: Long-term care facilities (LTCFs) are a major reservoir of carbapenem-resistant Enterobacteriaceae (CRE) in healthcare facilities, contributing to rapid regional dissemination of CRE. METHODS: In 2008, The Israeli National Center for Infection Control (NCIC) initiated a coordinated, comprehensive intervention in Israel's LTCFs, encompassing approximately 25000 beds in over 300 institutions. The intervention included implementation of population-tailored contact precautions and early detection of carriers. The NCIC established a real-time repository of all CRE carriers and events of acquisition, supervised information exchange between healthcare facilities and directed intervention at the institutional level during local outbreaks. CRE incidence was determined based on detection of CRE, either during LTFC stay or on admission to another facility. Prevalence was determined by a series of 5 cross-sectional surveys commenced between 2008 and 2015. RESULTS: From January 2009 through December 2015, 5265 patients acquired CRE in LTCFs. During the study period, incidence of acquisition declined in all facility types, to approximately 50% of the baseline (P < .001). The number of skilled nursing facilities and nursing homes experiencing ≥ 5 CRE acquisitions annually decreased from 35 to 11 during this period. The point prevalence of newly detected CRE carriage in post-acute care hospitals decreased from 12.3% in the survey commenced in 2008 to 0.8% in that begun in 2015 (P < .001). CONCLUSIONS: A national, coordinated intervention resulted in a sustained decrease in CRE incidence and prevalence in LTCFs. These results support the assumption that centrally coordinated intervention is an essential public health tool in reducing CRE in healthcare facilities.

Antimicrobial use trends, Israel, 2012 to 2017.

BackgroundIn 2012, Israel's National Center for Infection Control initiated a national stewardship programme that included mandatory annual reporting of antimicrobial use. Here we present nationwide Israeli data for the period 2012 to 2017.AimThe goal of this study was to detect trends in antimicrobial use in Israel following the introduction of the stewardship programme, as part of an assessment of the programme's impact.MethodsIn this retrospective observational study, data were collected from Israel's health maintenance organisations (HMOs), acute care hospitals and post-acute care hospitals (PACHs). Acute care hospital data were collected for general medical and surgical wards, and medical/surgical intensive care units (ICUs). Data were converted into defined daily doses (DDD), with use rates presented as DDD per 1,000 insured/day in the community and DDD per 100 patient-days in hospitals and PACHs. Trends were analysed using linear regression.ResultsAntimicrobial use decreased across sectors between 2012 and 2017. In the community, the decrease was modest, from 22.8 to 21.8 DDD per 1,000 insured per day (4.4%, p = 0.004). In acute care hospitals, antibiotic DDDs per 100 patient-days decreased from 100.0 to 84.0 (16.0%, p = 0.002) in medical wards, from 112.8 to 94.2 (16.5%, p = 0.004) in surgical wards and from 154.4 to 137.2 (11.1%, p = 0.04) in ICUs. Antimicrobial use decreased most markedly in PACHs, from 29.1 to 18.1 DDD per 100 patient-days (37.8%, p = 0.005).ConclusionBetween 2012 and 2017, antimicrobial use decreased significantly in all types of healthcare institutions in Israel, following the introduction of the nationwide antimicrobial stewardship programme.

The Impact of a Carbapenem-Resistant Enterobacteriaceae Outbreak on Facilitating Development of a National Infrastructure for Infection Control in Israel.

In 2006 the Israeli healthcare system faced an unprecedented outbreak of carbapenem-resistant Enterobacteriaceae, primarily involving KPC-producing Klebsiella pneumoniae clonal complex CC258. This public health crisis exposed major gaps in infection control. In response, Israel established a national infection control infrastructure. The steps taken to build this infrastructure and benefits realized from its creation are described here.

Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae: Results From the INCREMENT Cohort.

BACKGROUND: There is little information about the efficacy of active alternative drugs to carbapenems except ß-lactam/ß-lactamase inhibitors for the treatment of bloodstream infections (BSIs) due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E). The objective of this study was to assess the outcomes of patients with BSI due to ESBL-E who received empiric therapy with such drugs (other active drugs [OADs]) or carbapenems. METHODS: A multinational retrospective cohort study of patients with BSI due to ESBL-E who received empiric treatment with OADs or carbapenems was performed. Cox regression including a propensity score for receiving OADs was performed to analyze 30-day all-cause mortality as main outcome. Clinical failure and length of stay were also analyzed. RESULTS: Overall, 335 patients were included; 249 received empiric carbapenems and 86 OADs. The most frequent OADs were aminoglycosides (43 patients) and fluoroquinolones (20 patients). Empiric therapy with OADs was not associated with mortality (hazard ratio [HR], 0.75; 95% confidence interval [CI], .38-1.48) in the Cox regression analysis. Propensity score-matched pairs, subgroups, and sensitivity analyses did not show different trends; specifically, the adjusted HR for aminoglycosides was 1.05 (95% CI, .51-2.16). OADs were neither associated with 14-day clinical failure (adjusted odds ratio, 0.62; 95% CI, .29-1.36) nor length of hospital stay. CONCLUSIONS: We were unable to show that empiric treatment with OAD was associated with a worse outcome compared with carbapenems. This information allows more options to be considered for empiric therapy, at least for some patients, depending on local susceptibility patterns of ESBL-E.

Evolution and dissemination of the Klebsiella pneumoniae clonal group 258 throughout Israeli post-acute care hospitals, 2008-13.

Objectives: The KPC-producing Klebsiella pneumoniae (KPC-KP) clonal group (CG) 258 has disseminated throughout Israeli post-acute care hospitals (PACHs). The objectives of the study were (i) to describe the evolution and (ii) to understand the dissemination modes of CG 258 in the PACH system in Israel. Methods: KPC-KP surveillance cultures isolates were collected in Israeli PACHs in three national point-prevalence surveys: 2008, 2011 and 2013. CG 258 was identified by pilv-l PCR. WGS was performed for CG 258 isolates from 9 of 14 PACHs and data extracted for core-genome MLST (cgMLST) and for capsule polysaccharide gene cluster analysis. Results: The proportional representation of CG 258 among the KPC-KP isolates increased from 72 of 104 isolates (69.2%) in 2008 to 113 of 133 isolates (85%) in 2011 ( P = 0.004 for 2008 versus 2011) and remained high in 2013 [56 of 67 isolates (83.6%)]. All isolates were related to CG 258 clade 2. cgMLST phylogenetic analysis showed relative convergence in the 2008 survey, with increasing diversification in the subsequent surveys. A predominantly institutional dissemination pattern was observed only in centre F from southern Israel. A predominantly regional dissemination pattern was observed in the two PACHs in Jerusalem. The other PACHs were characterized by a combined institutional and generalized pattern, with the majority of isolates clustering within the same PACH and survey. Conclusions: CG 258 clade 2 has retained its predominance despite increased diversification. Although interchanging of CG 258 strains occurred between most PACHs, local spread is the leading cause of its dissemination.

Development and validation of the INCREMENT-ESBL predictive score for mortality in patients with bloodstream infections due to extended-spectrum-ß-lactamase-producing Enterobacteriaceae.

Background: Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30 day mortality. Methods: A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30 day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC. Results: The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR = 2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR = 2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR = 3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR = 3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR = 3.04; 95 CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR = 4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR = 2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of < 11 and ≥11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC. Conclusions: We developed and validated an easy-to-collect predictive scoring model for all-cause 30 day mortality useful for identifying patients at high and low risk of mortality.

A Multinational, Preregistered Cohort Study of ß-Lactam/ß-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae.

The spread of extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether ß-lactam/ß-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.).

Ertapenem for the treatment of bloodstream infections due to ESBL-producing Enterobacteriaceae: a multinational pre-registered cohort study.

OBJECTIVES: Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E. METHODS: A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality. RESULTS: The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P = 0.06) in the ETC and 89.8% and 82.6% (P = 0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P = 0.01) in the ETC and 9.3% and 17.1% (P = 0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P = 0.58) and 1.04 (0.44-2.50; P = 0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P = 0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P = 0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P = 0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems. CONCLUSIONS: Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock.

Methicillin-Resistant Staphylococcus aureus spa Type t002 Outbreak in Horses and Staff at a Veterinary Teaching Hospital after Its Presumed Introduction by a Veterinarian.

Methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization, involving MRSA strains which differ from common human health care-associated clones, have become serious emerging conditions in equine veterinary hospitals. In 2010, MRSA spa type t535 caused an outbreak involving both horses and personnel in a veterinary teaching hospital in Israel. Since then, surveillance continued, and occasional MRSA isolation occurred. Two years later, MRSA of another spa type, t002, was isolated from a veterinarian and, 3 weeks later, from a horse. The appearance of spa type t002, a common clone in human medicine in Israel, among both personnel and horses, prompted a point-prevalence survey of hospital personnel and hospitalized horses. Fifty-nine staff members (n = 16 equine; n = 43, other) and 14 horses were screened. Ten of 59 staff members (16.9%) and 7 of 14 horses (50%) were MRSA carriers. Among the staff, 44% of large animal department (LAD) personnel, compared with only 7% of non-LAD personnel, were carriers. Isolates from all horses and from 9 of 10 personnel were found to be of MRSA spa type t002. This clone was later isolated from an infected postoperative wound in a hospitalized horse. Measures were taken to contain transmission between horses and personnel, as was done in the previous outbreak, resulting in reduction of transmission and, finally, cessation of cross-transmission between horses and personnel.

Prevalence, Risk Factors, and Transmission Dynamics of Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae: a National Survey of Cattle Farms in Israel in 2013.

Our objectives were to study the prevalence, risk factors for carriage, and transmission dynamics of extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae (ESBLPE) in a national survey of cattle. This was a point prevalence study conducted from July to October 2013 in Israel. Stool samples were collected from 1,226 cows in 123 sections on 40 farms of all production types. ESBLPE were identified in 291 samples (23.7%): 287 contained Escherichia coli and 4 contained Klebsiella pneumoniae. The number of ESBLPE-positive cows was the highest in quarantine stations and on fattening farms and was the lowest on pasture farms (P = 0.03). The number of ESBLPE-positive cows was the lowest in sections containing adult cows (age, >25 months) and highest in sections containing calves (age, <4 months) (P < 0.001). Infrastructure variables that were significant risk factors for ESBLPE carriage included crowding, a lack of manure cleaning, and a lack of a cooling (P < 0.001 for each), all of which were more common in sections containing calves. Antimicrobial prophylaxis was given almost exclusively to calves and was associated with a high number of ESBLPE carriers (P < 0.001). The 287 E. coli isolates were typed into 106 repetitive extragenic palindromic (REP)-PCR types and mostly harbored blaCTX-M-1 or blaCTX-M-9 group genes. The isolates on the six farms with ≥15 isolates of ESBLPE were of 4 to 7 different REP-PCR types, with one dominant type being harbored by about half of the isolates. Fourteen types were identified on more than one farm, with only six of the farms being adjacent to each other. The prevalence of ESBLPE carriage is high in calves in cowsheds where the use of antimicrobial prophylaxis is common. ESBLPE disseminate within cowsheds mainly by clonal spread, with limited intercowshed transmission occurring.

Persistence of Klebsiella pneumoniae ST258 as the predominant clone of carbapenemase-producing Enterobacteriaceae in post-acute-care hospitals in Israel, 2008-13.

OBJECTIVES: To study the molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) in post-acute-care hospitals (PACHs) in Israel and to analyse the temporal changes between 2008 and 2013. METHODS: CPE isolates were obtained during two cross-sectional, point prevalence national surveys of PACHs in Israel performed in 2008 and 2013. Surveillance cultures were collected by streaking rectal swabs onto selective media. Isolates were identified to species level and tested for blaKPC, blaNDM and blaOXA-48 by PCR and by the Carba NP test. Molecular typing was done by PCR for the pilv-l gene, designed for the ST258 KPC-producing Klebsiella pneumoniae (KPC-KP) clone, BOX-PCR and MLST. RESULTS: The prevalence of CPE carriage in the first survey was 184/1147 (16%); all of the isolates were KPC-KP. The prevalence of CPE carriage in the second survey was 127/1287 (9.9%); of these isolates, 113 (89%) were KPC-KP, 9 (7%) were other KPC-producing species and 5 (4%) were NDM- and OXA-48-producing CPE (n = 1 and 4, respectively). The proportion of the KPC-KP population represented by the ST258 clone increased from 120/184 (65%) in 2008 to 91/113 (80%) in 2013. In 58% (71/122) of the KPC-CPE carriers identified in the 2013 survey, the source of acquisition was determined to be the PACH itself. All four OXA-48 CPE were acquired either directly or indirectly from patients arriving from the Palestinian Authority or Syria. CONCLUSIONS: Despite the decreased prevalence of CPE in Israeli PACHs, and the emergence of new types of CPE, the KPC-KP ST258 clone remains the predominant clone represented.

Epidemiological interpretation of studies examining the effect of antibiotic usage on resistance.

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.