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In 1996, public outcry over shortened hospital stays for new mothers and their infants led to the passage of a federal law banning 'drive-through deliveries.' This recent round of brief postpartum stays is not unprecedented. During World War II, a baby boom overwhelmed maternity facilities in American hospitals. Hospital births became more popular and accessible as the Emergency Maternal and Infant Care program subsidized obstetric care for servicemen's wives. Although protocols before the war had called for prolonged bed rest in the puerperium, medical theory was quickly revised as crowded hospitals were forced to discharge mothers after 24 hours. To compensate for short inpatient stays, community-based services such as visiting nursing care, postnatal homes, and prenatal classes evolved to support new mothers. Fueled by rhetoric that identified maternal-child health as a critical factor in military morale, postpartum care during the war years remained comprehensive despite short hospital stays. The wartime experience offers a model of alternatives to legislation for ensuring adequate care of postpartum women. [ABSTRACT FROM AUTHOR]

The purpose of the research is to evaluate the comparative microbiological efficiency of Polykatan in a gel form in combination with lincomicine 1% in inflammatory periodontal disease treatment. A modified gel Polykatan understudy was applied in association with the conventional therapeutic pattern in patients with chronic inflammatory periodontal disease. The medical form of gel provides long-term persistence in oral cavity and has positive action on microorganism's changing of the oral cavity

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are of major clinical concern. We analyzed 85 P . aeruginosa blood isolates non-susceptible to carbapenems collected during 2021-2023 from 15 medical centers in Israel. We aimed to determine the prevalence of high-risk clones, examine clonality, test antibiotic susceptibility, and assess the presence of acquired resistance genes, including carbapenemases. Whole-genome sequencing was performed using Illumina sequencing technology. Susceptibly was determined using the broth microdilution method. In the entire sample, 43.5% were high-risk clones. A main clade (27.1% of isolates) found in multiple hospitals comprised 19 isolates belonging to the high-risk ST654 clone and four closely related isolates. The isolates in this main clade harbored a broad set of resistance genes, including GES-type genes, and 91% had a mutated outer membrane protein (OprD). Isolates in the main clade were uniformly tobramycin (TOB) resistant and 83% were ceftolozane/tazobactam resistant. In the entire sample, we found high resistance to most antipseudomonal agents, including new beta-lactam/beta-lactamase inhibitor combinations. No uniform susceptibility to an antipseudomonal agent was found. Carbapenemases were carried by 9.4% of isolates (5.9% bla GES-5 and 3.5% bla NDM-1 ) and oprD was mutated in 67% of isolates. Thus, the epidemiology of CRPA is explained by a combination of clonal expansion of a dominant high-risk clade and sporadic occurrence of mutated strains. Our findings highlight the importance of susceptibility testing using a wide panel of antibiotics when CRPA is detected. Prevention measures tracking and controlling emerging high-risk clades and clones are crucial to limit the spread of CRPA.

There is an urgent need for accurate and fast diagnostic tests to identify carbapenemase-producing bacteria. Here, we evaluated a colorimetric imipenem hydrolysis test, called the CARBA PAcE test, to detect carbapenemase-producing Gram-negative bacteria (GNB). We tested a collection of 270 GNB isolates with a characterized carbapenemase content. Our testing set included 205 carbapenemase-producing, carbapenemase-resistant Enterobacterales ( CP CRE ) with 40 Klebsiella pneumoniae carbapenemase (KPC), 49 New Delhi metallo beta lactamase (NDM), 49 OXA-48-like, 15 Verona integron-mediated metallo-β-lactamase (VIM), three IMP, 43 IMI, six isolates producing more than one carbapenemase, and 65 non-carbapenemase-producing Enterobacterales (20 ESBL producers, 35 non-carbapenemase-producing, carbapenem-resistant [non-CP CRE], and 10 carbapenem-susceptible Enterobacterales [non-CP, non-CSE, third-generation cephalosporin and carbapenem susceptible]). We compared the performances of the CARBA PAcE test, the qualitative colorimetric β-CARBA test, and the modified CarbaNP test to a gold standard of carbapenemase gene detection by PCR. Specificities of all tests were high: 95.4% (62/65) for CARBA PAcE test, 98.5% (64/65) for β-CARBA test, and 100% (65/65) for the modified CarbaNP test. Sensitivity varied by carbapenemase: all three tests had a sensitivity of 100% for NDM, VIM, and IMP and 97.5% for KPC. Sensitivity to detect IMI was 0% for the CARBA PAcE and β-CARBA tests and 11.6% for the modified CarbaNP test. Sensitivity to detect OXA-48-like was 89.7% for the CARBA PAcE test, 87.7% for the β-CARBA test, and 14.2% for the modified CarbaNP test. Reading the results of the CARBA PAcE assay was difficult. The CARBA PAcE assay is highly sensitive for detecting NDM, VIM, IMP, and KPC, but slightly less sensitive for OXA-48-like. It does not detect IMI. It is highly specific, and its overall diagnostic accuracy is similar to that of β-CARBA. Its operational advantages are rapid turnaround time, ease of use, and long shelf life, but reading of results is subjective.IMPORTANCEWe evaluated the ability of the CARBA PAcE test to detect carbapenemases in 274 Gram-negative isolates with a known carbapenemase content. Specificity was high for all carbapenemases tested (96.9%). Sensitivity was high for KPC, NDM, VIM, and IMP (97.5-100%); but lower for OXA-48-like (89.7%). Activity of IMI could not be detected. Taken together, our results indicate that CARBA PAcE is a useful alternative in regions where NDM and KPC are predominant. The limitations of the test are difficulty in reading results and incompatibility with mSuperCARBA.

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-β-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., Competing Interests: Potential conflicts of interest. Y. C. has received grants and personal fees from MSD, Pfizer, Roche, Qpex Pharmaceuticals, and Spero Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Timely detection of carbapenem-resistant Acinetobacter baumannii (CRAB) carriers is essential to direct infection control measures. In this work, we aimed to develop a practical protocol to detect CRAB from screening samples. To choose a selective medium that detects CRAB with high sensitivity and specificity, 111 A . baumannii clinical isolates were inoculated on three types of agar: mSuperCARBA (SC), CHROMagar Acinetobacter (CaA), and modified CHROMagar Acinetobacter (mCaA) containing 4.5 mg/mL meropenem. SC was non-selective, CaA was the most sensitive (100%), but only moderately specific (72%), and mCaA was highly specific (97%) and sensitive (98%). Confirmation of the carbapenem-resistant phenotype using PCR-based detection of bla OXA-23 , bla OXA-24 , and bla OXA-58 genes was specific but not sensitive, detecting only 58% of CRAB isolates. Identification of A. baumannii using either gyrB or bla OXA-51 PCR was excellent. Next, we used the same methodology in routine screening for CRAB carriage. mCaA had the best yield, with high sensitivity but moderate specificity to differentiate between CRAB and other carbapenem-resistant organisms. Skin sampling using sponges and 6 hour enrichment was highly sensitive (98%), while other body sites had poor sensitivity (27%- 41%). Shorter incubation had slightly lower yield, and longer incubation did not improve the detection. Performing PCR for bla OXA-51 and gyrB on colonies growing on modified mCaA differentiated between CRAB and other species with high accuracy (98% and 99%, respectively). Based on our results, we present a procedure for easy and reliable detection of CRAB carriage using skin sampling, short enrichment, selection on mCaA, and PCR-based identification., Importance: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a substantial cause of nosocomial infections, classified among the most significant multidrug-resistant pathogens by the World Health Organization and by the US Centers for Disease Control. Limiting the spread of CRAB is an important goal of infection control, but laboratory methods for identification of CRAB carriers are not standardized. In this work, we compared different selective agar plates, tested the efficiency of A. baumannii identification by PCR for species-specific genes, and used PCR-based detection of common resistance genes to confirm the carbapenem-resistant phenotype. During a prospective study, we also determined the optimal sample enrichment time. Based on our results, we propose a simple and efficient protocol for the detection of CRAB carriage using skin sampling, short enrichment, selection on appropriate agar plates, and PCR-based identification, resulting in a turn-around time of 24 hours., Competing Interests: The authors declare no conflict of interest.

The use of mammalian models for in vivo testing of bacterial virulence raises ethical concerns and is expensive and time-consuming. As an alternative, non-mammalian models are sought. Galleria mellonella larvae have been used as a model to study several bacterial pathogens. However, their maintenance is challenging, and commercial supply is low. In this study, we aimed to establish the Zophobas morio larvae as an alternative non-mammalian model for the evaluation of the pathogenicity and antimicrobial susceptibility of Acinetobacter baumannii . We infected Z. morio with Acinetobacter strains and determined the optimal temperature and inoculum. To visualize the bacterial distribution within the larvae, hematoxylin and eosin (H&E) staining was performed. Next, a survival model of infected larvae was established, and virulence was compared between strains. The effect of antimicrobial treatment in relation to antibiotic susceptibility was studied. Our results demonstrate that Z. morio can be used as a model system for in vivo studies of A. baumannii ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rakovitsky, Temkin, Hameir, Lurie-Weinberger, Keren-Paz and Carmeli.)

We aimed to determine whether obtaining two blood cultures (BCs) instead of one improved the detection of bloodstream infections (BSIs) in children. For this descriptive study, we used surveillance data collected in 2019-2021 from all Israeli hospitals serving children. The sample included 178,702 culturing episodes. One BC was taken in 90.1% of all episodes and 98.2% of episodes in the emergency department. A true pathogen was detected in 1687/160,964 (1.0%) of single-culture episodes and 1567/17,738 (8.9%) of two-culture episodes ( p < 0.001). The yield was significantly different even when considering only the first BC in two-culture episodes: 1.0% vs. 7.5%. Among 1576 two-culture episodes that were positive for a true pathogen, the pathogen was detected only in the second culture in 252 (16.0%). We estimated that if a second culture had been taken in all episodes, an additional 343 BSIs by a true pathogen would have been detected. Among 1086 two-culture episodes with commensal bacteria, the second BC was sterile in 530 (48.8%), suggesting contamination. A commensal was isolated in 3094/4781 (64.7%) positive single-culture episodes, which could represent BSI or contamination. The yield of a single BC bottle was low, reflecting both lower sensitivity of a single bottle and the taking of single bottles in patients with a low probability of BSI.

V ibrio c holerae c arbapenemase (VCC-1) is a chromosomal encoded class A carbapenemase thus far reported in environmental Vibrio cholerae isolates. Here, we report the first isolation of a bla VCC-1 -carrying Aeromonas caviae from a clinical sample in Israel. The isolate was resistant to all β-lactam agents, including carbapenems. The bla VCC-1 was located on a large plasmid. GC content suggests that the origin of the bla VCC-1 gene is neither Aeromonas nor Vibrio spp. but an unknown progenitor., Competing Interests: The authors declare no conflict of interest.

The environment surrounding 30 of 31 carriers of carbapenem-resistant Acinetobacter baumannii (CRAB) was contaminated by CRAB. The environmental CRAB loads were similar whether carriers were identified only by surveillance cultures (nonclinical carriers) or also had positive clinical cultures. Screening to detect and isolate nonclinical CRAB carriers may be important to prevent CRAB transmission.

Background: Nosocomial bloodstream infections (NBSIs) are adverse complications of hospitalization. Most interventions focus on intensive care units. Data on interventions involving patients' personal care providers in hospitalwide settings are limited., Objective: To evaluate the impact of department-level NBSI investigations on infection incidence., Methods: Beginning in 2016, positive cultures, classified as suspected of being hospital acquired, were prospectively investigated by patients' unit-based personal healthcare providers using a structured electronic questionnaire. After analyzing the conclusions of the investigation, a summary was sent quarterly to the departments and to hospital management. NBSI rates and clinical data during a 5-year period (2014-2018) were calculated and compared before and after the intervention (2014-2015 versus 2016-2018), using interrupted time-series analysis., Results: Among 4,135 bloodstream infections (BSIs), 1,237 (30%) were nosocomial. The rate of NBSI decreased from 4.58 per 1,000 admissions days in 2014 and 4.82 in 2015, to 3.81 in 2016, 2.94 in 2017 and 2.86 in 2018. Following a 4-month lag after introducing the intervention, the NBSI rate per 1000 admissions dropped significantly by 1.33 ( P = .04; 95% CI, -2.58 to -0.07). The monthly NBSI rate continued to decrease significantly by 0.03 during the intervention period ( P = .03; 95% CI, -0.06 to -0.002)., Conclusions: Detailed department-level investigations of NBSI events performed by healthcare providers, increased staff awareness and frontline ownership and were associated with a decrease in NBSI rates hospitalwide.

Background: We sought to determine incidence of common hospital-acquired bacteria among coronavirus disease 2019 (COVID-19) patients in Israeli general hospitals during the first year of the pandemic., Methods: We analyzed routinely collected incidence data to determine hospital acquisition of the following sentinel bacteria: Klebsiella pneumonia e, Escherichia coli , Staphylococcus aureus , Enterococcus faecalis , Enterococcus faecium , Pseudomonas aeruginosa , Acinetobacter baumannii , and Clostridioides difficile . We examined 3 acquisition measures: (1) sentinel bacteria, (2) sentinel bacteremia, and (3) antimicrobial-resistant sentinel bacteremia. The study period was March 1, 2020, through January 31, 2021., Results: Analysis of pooled data from the 26 hospitals surveyed revealed that rates were higher for all 3 acquisition measures among COVID-19 patients than they were among patients on general medical wards in 2019, but lower than those among patients in intensive care units in 2019. The incidence rate was highest during the first COVID-19 wave, despite a lower proportion of severe COVID-19 cases among total hospitalized during this wave. Wide variation in incidence was evident between hospitals., Conclusions: Hospitalized COVID-19 patients experienced nosocomial bacterial infection at rates higher than those of patients on pre-pandemic general medical wards, adding to the complexity of their care. Lower rates of nosocomial infection after the first wave, despite higher proportions of severely ill patients, suggest that healthcare worker practices, rather than patient-related factors, were responsible for most of these infections.

Acinetobacter baumannii (Ab) bloodstream infections (BSIs) are a major public health concern and associated with high mortality. We describe the nationwide incidence, antimicrobial resistance, and mortality of Ab-BSI in Israel using laboratory-based BSI surveillance data from January 2018 to December 2019. During the study period, there were 971 Ab-BSI events (508 in 2018 and 463 in 2019), with an average annual incidence of 8.08/100,000 population. The median age of patients was 72 (IQR 62-83), and 56.4% were males. Two-thirds of Ab-BSI events were hospital-onset (HO), with median day of onset 16 (IQR 9-30). HO-BSI incidence was 0.62/10,000 patient-days (rate per 10,000 patient-days: 2.78, 1.17, and 0.2 for intensive care, medical, and surgical wards, respectively). Carbapenem susceptibility was 23.4%; 41.4% and 14.9% in community and HO events, respectively. The 14-day, 30-day, and 1-year mortality were 51.2%, 59.3%, and 81.4%, respectively. Carbapenem-resistant Ab-BSI were associated with a significantly higher 14-day, 30-day, and 1-year mortality ( p < 0.001 for all). In the multivariable model, age (aHR 1.02) and carbapenem resistance (aHR 3.21) were independent predictors of 30-day mortality. In conclusion, Ab-BSIs pose a significant burden with high mortality, especially associated with antimicrobial resistance. Attention should be focused on prevention and improving treatment.

Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality. IMPORTANCE To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR. We found a high prevalence of HR among clinical carbapenem-resistant A. baumannii isolates; most evolved into a resistant phenotype following colistin exposure and withdrawal. In patients treated with colistin, evolution of HR A. baumannii into full resistance could lead to higher rates of treatment failure and contribute to the reservoir of colistin-resistant pathogens in health care settings., Competing Interests: The authors declare a conflict of interest. E.D.M. reports grants and/or personal fees from Pfizer, M.S.D., Rosh, Anglini, Nordic Pharma, and Sanofi-Aventis. G.L.D. reports grants and/or personal fees from Pfizer, Menarini, and M.S.D. K.S.K. reports grants and/or personal fees from Spero Therapeutics, Q.P.E.X., and MicuRx. M.P. reports grants and/or personal fees from Shionogi and Pfizer. Y.C. reports grants and/or personal fees from Allecra Therapeutics, Genentech, Nabriva Therapeutics, Pfizer, PPD, Q.P.E.X. Biopharma, Roche Pharmaceuticals, Spero Therapeutics, VenatoRX Pharmaceuticals. All other authors have no interests to declare.

We used Fourier-transform infrared (FTIR) spectroscopy to analyze 4 carbapenem-resistant Acinetobacter baumannii outbreaks. FTIR distinguished between isolates from different hospitals and uncovered the relatedness between isolates from acute-care hospitals and a post-acute-care hospital. Using higher cutoffs reveals more distant relationships and lower cutoffs support analyses of recent events.

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.

Background: The incidence of Escherichia coli bloodstream infections (BSI) is high and increasing. We aimed to describe the effect of season and temperature on the incidence of E. coli BSI and antibiotic-resistant E. coli BSI and to determine differences by place of BSI onset., Methods: All E. coli BSI in adult Israeli residents between January 1, 2018 and December 19, 2019 were included. We used the national database of mandatory BSI reports and outdoor temperature data. Monthly incidence and resistance were studied using multivariable negative binomial regressions with season (July-October vs. other) and temperature as covariates., Results: We included 10,583 events, 9012 (85%) community onset (CO) and 1571 (15%) hospital onset (HO). For CO events, for each average monthly temperature increase of 5.5 °C, the monthly number of events increased by 6.2% (95% CI 1.6-11.1%, p = 0.008) and the monthly number of multidrug-resistant events increased by 4.9% (95% CI 0.3-9.7%, p = 0.04). The effect of season was not significant. For HO events, incidence of BSI and resistant BSI were not associated with temperature or season., Conclusion: Temperature increases the incidence of CO E. coli BSI and CO antibiotic-resistant E. coli BSI. Global warming threatens to increase the incidence of E. coli BSI., (© 2022. The Author(s).)

Importance: Blood culturing is a critical diagnostic procedure affecting patient outcomes and antibiotic stewardship. Although there are standards for blood culturing, the process is not often measured., Objectives: To evaluate processes related to the diagnosis of bloodstream infection and compare them with best practices., Design, Setting, and Participants: A quality improvement study using laboratory data from January 1 to June 30, 2019, was conducted in 28 (96.6%) Israeli acute care hospitals. All blood cultures (BCs) performed on samples from adults and children in a period of 147 hospital-months were analyzed. Data analysis was performed from April 12, 2021, to September 9, 2022., Main Outcomes and Measures: True pathogen detection rate, contamination rate, proportion of adults with blood cultures performed, proportion of adult culturing episodes with only 1 set or bottle used, and median time of steps from sample collection to pathogen identification., Results: The data set consisted of 348 987 BC bottles. Bloodstream infection was detected in a median of 6.7% (IQR, 5.8%-8.2%) of adult culturing episodes and 1.1% (IQR, 0.7%-1.9%) of pediatric episodes. Eleven of 27 hospitals (40.7%) with adult patients met the standard of a contamination rate of less than 3% and only 2 hospitals (7.4%) met the more stringent standard of less than or equal to 1% contamination rate. The percentage of adults with blood cultures ranged from 2.7% to 29.0% (mean [SD], 15.7% [6.0%]). There was an association between sampling rate and pathogen detection until BCs were performed in 17% of adult admissions. The percentage of solitary BCs ranged from 47.8% to 94.4%. An estimated 1745 of 7436 (23.5%) adult bloodstream infections went undetected because solitary BCs were performed, anaerobic bottles were not used, or BCs were not performed. Median processing time was 51.2 (IQR, 33.9-78.0) hours, 3 times the optimal time: 4.4 (IQR, 1.7-12.5) hours for the preanalytical stage, 15.9 (IQR, 10.2-23.6) hours from incubation to growth detection, 4.5 (IQR, 1.5-10.7) hours from detection to Gram stain, and 30.9 (IQR, 22.0-41.9) hours from detection to isolate identification. An 8.6-hour delay was related to off-hours operating of laboratories., Conclusions and Relevance: The findings of this study suggest that the multistep process of blood culturing is not managed comprehensively in Israel, leading to poor clinical practices and delayed results.

Background: Limited data exist on long-term consequences of bloodstream infections (BSIs). We aimed to examine incidence, 1-year mortality, and years of potential life lost (YPLL) following BSI. We estimated the relative contribution of hospital-onset BSI (HO-BSI) and antibiotic-resistant BSI to incidence, mortality and YPLL., Methods: We used data from Israel's national BSI surveillance system (covering eight sentinel bacteria, comprising 70% of all BSIs) and the national death registry. Adults with BSI between January 2018 and December 2019 were included. The outcomes were all-cause 30-day and 1-year mortality, with no adjustment for co-morbidities. We calculated the age-standardized mortality rate and YPLL using the Global Burden of Disease reference population and life expectancy tables., Findings: In total, 25,376 BSIs occurred over 2 years (mean adult population: 6,068,580). The annual incidence was 209·1 BSIs (95% CI 206·5-211·7) per 100,000 population. The case fatality rate was 25·6% (95% CI 25·0-26·2) at 30 days and 46·4% (95% CI 45·5-47·2) at 1 year. The hazard of death increased by 30% for each decade of age (HR=1·3 [95% CI 1·2-1·3]). The annual age-standardized mortality rate and YPLL per 100,000 were 50·8 (95% CI 49·7-51·9) and 1,012·6 (95% CI 986·9-1,038·3), respectively. HO-BSI (6,962 events) represented 27·4% (95% CI 26·9-28·0) of BSIs, 33·9% (95% CI 32·6-35·0) of deaths and 39·9% (95% CI 39·5-40·2) of YPLL. HO-BSI by drug-resistant bacteria (3,072 events) represented 12·1% (95% CI 11·7-12·5) of BSIs, 15·6% (95% CI 14·7-16·5) of deaths, and 18·4% (95% CI 18·1-18·7) of YPLL., Interpretation: One-year mortality following BSI is high. The burden of BSI is similar to that of ischemic stroke. HO-BSI and drug-resistant BSI contribute disproportionately to BSI mortality and YPLL., Funding: None., Competing Interests: Y.C. has received grants and personal fees from MSD, Pfizer, Roche, Qpex Pharmaceuticals, and Spero Therapeutics. All other authors report no potential conflicts of interest., (© 2022 The Author(s).)

Objectives: Escherichia coli is the leading cause of bloodstream infection (BSI). The incidence of E. coli BSI caused by antibiotic-resistant strains is increasing. We aimed to describe the nationwide incidence and resistance profile of E. coli BSI in Israel and its impact on mortality, to compare E. coli BSI mortality with all-cause mortality, and community-onset with hospital-onset E. coli BSIs., Methods: We used mandatory BSI surveillance reports submitted by all Israeli hospitals to the Ministry of Health and the national death registry. All E. coli BSIs from 1 January 2018 to 31 December 31 2019 in patients aged 18 and over were included., Results: A total of 11 113 E. coli BSIs occurred in 10 218 patients; 85% (9012/10 583) were community onset. Median age was 76 (IQR 65-85), and 57% (6304/11 113) of cases occurred in women. The annual incidence was 92.5 per 100 000 population. Antibiotic resistance was frequent and significantly more common in hospital-onset than in community-onset BSI; 65% (1021/1571) vs. 45% (4049/9012) were multidrug-resistant (MDR) (p < 0.001). The case fatality rate (CFR) was higher following hospital-onset BSI than community-onset: 23% (276/1214) vs. 12% (926/7620) at 14 days, 31% (378/1214) vs. 16% (1244/7620) at 30 days, and 55% (418/766) vs. 34% (1645/4903) at 1 year (p < 0.001 for all comparisons). The 1-year CFR was 47% (1258/2707) for MDR vs. 28% (928/3281) for non-MDR (p < 0.001). The annual mortality rate was 31.0 per 100 000 population, comprising 4.2% (31.0/734.8) of all causes of deaths., Discussion: E. coli BSI carries a high burden, with a large proportion of MDR isolates, which are associated with increased incidence and CFR., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the effect of 2 regulations issued by the Israel Ministry of Health on coronavirus disease 2019 (COVID-19) infections and quarantine among healthcare workers (HCWs) in general hospitals., Design: Before-and-after intervention study without a control group (interrupted time-series analysis)., Setting: All 29 Israeli general hospitals., Participants: All HCWs., Interventions: Two national regulations were issued on March 25, 2020: one required universal masking of HCWs, patients, and visitors in general hospitals and the second defined what constitutes HCW exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and when quarantine is required., Results: Overall, 283 HCWs were infected at work or from an unknown source. Before the intervention, the number of HCWs infected at work increased by 0.5 per day (95% confidence interval [CI], 0.2-0.7; P < .001), peaking at 16. After the intervention, new infections declined by 0.2 per day (95% CI, -0.3 to -0.1; P < .001). Before the intervention, the number of HCWs in quarantine or isolation increased by 97 per day (95% CI, 90-104; P < .001), peaking at 2,444. After the intervention, prevalence decreased by 59 per day (95% CI, -72 to -46; P < .001). Epidemiological investigations determined that the most common source of HCW infection (58%) was a coworker., Conclusions: Universal masking in general hospitals reduced the risk of hospital-acquired COVID-19 among HCWs. Universal masking combined with uniform definitions of HCW exposure and criteria for quarantine limited the absence of HCWs from the workforce.

Nationwide studies on hospital-onset bloodstream infections (HO-BSIs) are scarce. To describe incidence, mortality and antimicrobial resistance (AMR) of HO-BSI caused by eight sentinel bacteria in Israel, we used laboratory-based BSI surveillance data from 1 January 2018 to 31 December 2019. All hospitals reported positive blood cultures growing Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Acinetobacter baumannii , Streptococcus pneumoniae , Staphylococcus aureus , Enterococcus faecalis and Enterococcus faecium . We calculated HO-BSI incidence and 14-day, 30-day and 1-year mortality in adults. We performed multivariable logistic regression to identify predictors of 30-day mortality. The study included 6752 HO-BSI events: K. pneumoniae (1659, 22.1%), E. coli (1491, 19.8%), S. aureus (1315, 17.5%), P. aeruginosa (1175, 15.6%), E. faecalis (778, 10.4%), A. baumannii (654, 8.7%), E. faecium (405, 5.4%) and S. pneumoniae (43, 0.6%). Overall incidence was 2.84/1000 admissions (95% CI: 2.77-2.91) and 6.88/10,000 patient-days (95% CI: 6.72-7.05). AMR isolates accounted for 44.2% of events. Fourteen-day, thirty-day and one-year mortality were 30.6% (95% CI: 28.5%-32.8%), 40.2% (95% CI: 38.2%-42.1%) and 66.5% (95% CI: 64.7%-68.3%), respectively. Organisms with highest risk for 30-day mortality (compared with E. coli ) were A. baumannii (OR 2.85; 95% CI: 2.3-3.55), E. faecium (OR 2.16; 95% CI: 1.66-2.79) and S. pneumoniae (OR 2.36; 95% CI: 1.21-4.59). Mortality was higher in AMR isolates (OR 1.57; 95% CI: 1.4-1.77). This study highlights the incidence, associated high mortality and important role of antibiotic resistance in HO-BSI.

Objectives: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries., Methods: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed., Results: In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily blaOXA-23. The chromosomal oxaAb (blaOXA-51-like) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1α., Conclusions: The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade's/ST's success., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections., Methods: Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 10 5  CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes., Results: The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04-2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03-2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95-2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09-3.25)., Conclusions: In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Colistin dependent (CD) isolates are dependent on colistin for optimal growth. Here we aimed to systematically determine the emergence of CD among colistin-heteroresistant carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We also examined the phenotypic characteristics of CD and the evolution of CD strains to overt resistance. Additionally, we examined whether detection of growth in blood cultures was impaired by CD. Heteroresistant isolates, as determined by population analysis profiling, were exposed to colistin; when the colony count with colistin was significantly higher than without, isolates were suspected to be CD. CD was confirmed by Etest and growth curves. CD strains with colistin minimum inhibitory concentrations > 2 mg/L after growth in colistin-free media were considered colistin-resistant. Of the 65 heteroresistant strains tested, eight became CD after colistin exposure. These strains attained higher colony counts and growth rates with colistin vs. without, and grew adjacent to the colistin Etest strip. CD strains exhibited increased susceptibilities to multiple antibiotics compared to their parent heteroresistant strains. All CD strains tested became colistin-resistant following growth without colistin. CD strains were detected in blood culture bottles, but time to detection was significantly prolonged compared with parent strains, suggesting that CD may lead to delay in detection of CRAB bacteremia.

Objectives: Compared to cephalosporin-based prophylaxis, ertapenem prophylaxis lowers the risk of surgical site infection among carriers of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PEs) undergoing colorectal surgery. We aimed to determine whether ertapenem prophylaxis leads to increased postoperative colonization with carbapenem-resistant Enterobacterales (CREs) and third-generation-cephalosporin-resistant Enterobacterales (3GCR-Es)., Methods: This study was nested within a quality improvement study of prophylaxis for ESBL-PE carriers undergoing colorectal surgery. Patients were screened 4-6 days after surgery for carriage of ESBL-PEs or other 3GCR-Es and CREs. When CREs were detected, pre- and postsurgical clones were compared using Fourier-transform infrared (FT-IR) spectroscopy., Results: The sample consisted of 56 patients who carried ESBL-PEs before surgery and received cefuroxime/metronidazole prophylaxis (Group 1), 66 who carried ESBL-PEs before surgery and received ertapenem (Group 2), and 103 ESBL-PE non-carriers who received cefuroxime/metronidazole prophylaxis (Group 3). CRE carriage was detected postoperatively in one patient (1.5%) in Group 2 versus eight patients (14.3%) in Group 1 (RD -12.8%; 95%CI -22.4% to -3.1%). For seven out of nine patients, preoperative ESBL-PE and postoperative CRE isolates were compared; in five of them, the pre- and postoperative clones were identical. Postoperative 3GCR-E carriage was detected in 37 patients (56.1%) in Group 2 versus 46 patients in Group 1 (82.1%) (aRD -20.7%, 95%CI -37.3% to -4.1%)., Conclusions: Among ESBL-PE carriers undergoing colorectal surgery, detection of short-term postsurgical colonization by CREs and 3GCR-Es was significantly lower among patients who received ertapenem prophylaxis than those who received cephalosporin-metronidazole prophylaxis. Resistance development in a colonizing bacterial clone, rather than carbapenemase acquisition, was the major mechanism of carbapenem resistance., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We characterized 57 isolates from a 2-phase clonal outbreak of New Delhi metallo-β-lactamase-producing Eschericha coli, involving 9 Israeli hospitals; all but 1 isolate belonged to sequence-type (ST) 410. Most isolates in the second phase harbored blaKPC-2 in addition to blaNDM-5. Genetic sequencing revealed most dual-carbapenemase-producing isolates to be monophyletically derived from a common ancestor.

Background: Acinetobacter baumannii is a successful nosocomial pathogen, causing severe, life-threatening infections in hospitalized patients, including pneumonia and bloodstream infections. The spread of carbapenem-resistant Acinetobacter baumannii (CRAB) strains is a major health threat worldwide. The successful spread of CRAB is mostly due to its highly plastic genome. Although some virulence factors associated with CRAB have been uncovered, many mechanisms contributing to its success are not fully understood., Methods: Here we describe strains of CRAB that were isolated from fulminant cases in 2 hospitals in Israel. These isolates show a rare hypermucoid (HM) phenotype and were investigated using phenotypic assays, comparative genomics, and an in vivo Galleria mellonella model., Results: The 3 isolates belonged to the ST3 international clonal type and were closely related to each other, as shown by Fourier-transform infrared spectroscopy and phylogenetic analyses. These isolates possessed thickened capsules and a dense filamentous extracellular polysaccharides matrix as shown by transmission electron microscopy (TEM), and overexpressed the capsule polysaccharide synthesis pathway-related wzc gene., Conclusions: The HM isolates possessed a unique combination of virulence genes involved in iron metabolism, protein secretion, adherence, and membrane glycosylation. HM strains were more virulent than control strains in 2 G. mellonella infection models. In conclusion, our findings demonstrated several virulence factors, all present in 3 CRAB isolates with rare hypermucoid phenotypes., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)