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Objective: To evaluate the impact of Covid‐19 vaccination (Pfizer–BioNTech BNT162b2) during the third trimester of pregnancy on maternal and neonatal outcomes. Design: A multicentre, retrospective computerised database. Population: Women who gave birth at >24 weeks of gestation in Israel, between January and April 2021, with full records of Covid‐19 disease and vaccination status. Methods: Women who received two doses of the vaccine were compared with unvaccinated women. Women who were recorded as having disease or a positive Covid‐19 polymerase chain reaction (PCR) swab during pregnancy or delivery were excluded from both study groups. Univariate analysis was followed by multivariate logistic regression. Main outcome measures: Composite adverse maternal outcomes. Secondary outcomes were vaccination rate and composite adverse neonatal outcomes. Results: The overall uptake of one or both vaccines was 40.2%; 712 women who received two doses of the Covid‐19 vaccine were compared with 1063 unvaccinated women. Maternal composite outcomes were comparable between the groups; however, women who received the vaccine had higher rates of elective caesarean deliveries (CDs) and lower rates of vacuum deliveries. An adjusted multivariable logistic regression analysis demonstrated that Covid‐19 vaccination was not associated with maternal composite adverse outcome (aOR 0.8, 95% CI 0.61–1.03); a significant reduction in the risk for neonatal composite adverse outcomes was observed (aOR 0.5, 95% CI 0.36–0.74). Conclusions: In a motivated population covered by a National Health Insurance Plan, we found a 40.2% rate of vaccination for the Covid‐19 vaccine during the third trimester of pregnancy, which was not associated with adverse maternal outcomes and, moreover, decreased the risk for neonatal adverse outcomes. Covid‐19 vaccine during pregnancy is safe for both mother and fetus. Covid‐19 vaccine during pregnancy is safe for both mother and fetus. [ABSTRACT FROM AUTHOR]

Background: Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus-induced neurologic disease (VZV-ND)., Methods: This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid., Results: We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non-VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25-128) and 82 days (IQR, 36-132) for VZV-ND and non-VZV-ND, respectively, not reaching statistical significance ( P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2)., Conclusions: We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Enterococcal Infective Endocarditis (EIE) is usually treated with the combination of penicillin/ampicillin with gentamicin or ampicillin with ceftriaxone. To enable prolonged outpatient treatment, a combination of benzylpenicillin and ceftriaxone has been suggested. This study aimed to describe the incidence and characteristics of EIE and to determine the outcome of EIE cases treated with benzylpenicillin and ceftriaxone., Methods: This was a retrospective single-center study including all patients diagnosed with infective endocarditis (IE) during 2016-2021, comparing EIE with IE caused by other pathogens. We described the outpatient treatment of patients with EIE, comparing those treated of benzylpenicillin - ceftriaxone with other regimes., Results: Among 222 patients with IE, 44 (20%) were diagnosed with EIE. Those were older, had a male predominance (p = 0.035), and were more disabled (p = 0.004). The incidence of EIE reached 30% towards the last year, becoming the leading etiology. Twenty-six patients received outpatient treatment, five of whom were discharged with benzylpenicillin and ceftriaxone. Adding patients from this cohort to the scarce data available, revealed similar recurrence and mortality rates compared to other treatment regimes., Conclusions: EIE is becoming a more frequent cause of IE, involving older, more disabled patients with male predominance. Our experience and existing literature suggest that the combination of benzylpenicillin and ceftriaxone is as safe as more conventional regimes, although further research is needed., Competing Interests: Declaration of ompeting interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Older adults are at increased risk of severe SARS-CoV-2 infection. In this study we assessed the response to COVID-19 vaccination and infection rates among nursing homes (NH) and assisted-living care home (ALCH) residents., Methods: The study was conducted between August 2021 and January 2022, after widespread population vaccination with the third dose of Pfizer-BioNtech mRNA COVID-19 vaccine in Israel. Three groups were addressed: hospitalized older patients; NH and ALCH residents. Demographic data, COVID-19 serology (anti-spike IgG antibodies) and PCR test results were obtained to assess the dynamics of antibody titers and its correlation to infection rates., Results: Two-hundred eighty-five individuals were evaluated; 92 hospitalized patients; 100 ALCH residents and 93 NH residents. In the latter two groups two serology surveys were conducted three months apart. Hospitalized patients were younger than ALCH and NH residents (mean age 80.4 ± 8 versus 82.6 ± 8 and 83.6 ± 5, respectively, p = 0.01), and had more comorbidities (p = 0.003). The degree of decline in the antibody level overtime was similar in ALCH and NH residents. Infection rates were higher among NH residents than ALCH residents [35/91 (38.4%) versus 11/100 (11%), p < 0.001]. Antibody level was lower among those infected [2113 (1271-3512) Au/ml versus 4113 (3364-5029) Au/ml, p < 0.001]. Adjusted analysis showed that NH residence, but not antibody levels, were significantly associated with infection., Conclusion: Among older adults, infection rates inversely correlated with antibody level. However, only nursing home residence was significantly associated with infection, suggesting that other factors such as crowding considerably contribute to the risk of infection., (© 2024. The Author(s).)

Purpose: To evaluate the impact of Covid-19 (Pfizer-BioNTech BNT162b2) third booster dose vaccination during pregnancy on maternal and neonatal outcomes., Methods: This is a multicenter, retrospective computerized database study. Parturients who delivered in Israel between August and December 2021 with full records of Covid-19 disease and vaccination status were included. Those who received third booster during pregnancy were compared to those who received two doses of vaccine during pregnancy and to unvaccinated parturients. Various adverse maternal and neonatal outcomes were evaluated. Parturients who were previously positive with Covid-19 PCR swabs during pregnancy or before pregnancy were excluded. Univariate analysis was followed by multivariate analysis., Results: A total of 2583 women were included in the analysis; 626 received the third booster dose of the BNT162b2 Covid-19 vaccine, 1094 received two doses of the vaccine, and 863 unvaccinated women. Maternal and neonatal outcomes were comparable between the study groups. An adjusted multivariable logistic regression analysis demonstrated that receiving the third booster was not associated with an increase in neither composite adverse maternal or neonatal outcome (aOR 0.9; 95% CI [0.65-1.22], p = 0.47; aOR 0.7; 95% CI [0.53-1.035], p= 0.09, respectively) when compared to those who received two doses of the vaccine. However, administration of the third booster dose during pregnancy was associated with a reduced composite adverse neonatal outcome when compared to unvaccinated women (aOR 0.6; 95% CI [0.42-0.86], p = 0.01)., Conclusion: Receiving the third booster dose of the BNT162b2 Covid-19 vaccine during pregnancy is not associated with an increased risk of any adverse maternal outcomes and may be beneficial for the neonates., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Vasopressors are frequently utilized for blood pressure stabilization in patients with cardiogenic shock (CS), although with a questionable benefit. Obtaining central venous access is time consuming and may be associated with serious complications. Hence, we thought to evaluate whether the administration of vasopressors through a peripheral venous catheter (PVC) is a safe and effective alternative for the management of patients with CS presenting to the intensive cardiovascular care unit (ICCU)., Methods: A prospective single-center study was conducted to compare the safety and outcomes of vasopressors administered via a PVC vs. a central venous catheter (CVC) in patients presenting with CS over a 12-month period., Results: A total of 1100 patients were included; of them, 139 (12.6%) required a vasopressor treatment due to shock, with 108 (78%) treated via a PVC and 31 (22%) treated via a CVC according to the discretion of the treating physician. The duration of the vasopressor administration was shorter in the PVC group compared with the CVC group (2.5 days vs. 4.2 days, respectively, p < 0.05). Phlebitis and the extravasation of vasopressors occurred at similar rates in the PVC and CVC groups (5.7% vs. 3.3%, respectively, p = 0.33; 0.9% vs. 3.3%, respectively, p = 0.17). Nevertheless, the bleeding rate was higher in the CVC group compared with the PVC group (3% vs. 0%, p = 0.03)., Conclusions: The administration of vasopressor infusions via PVC for the management of patients with CS is feasible and safe in patients with cardiogenic shock. Further studies are needed to establish this method of treatment.

Background: Blood culture contamination is associated with health care costs and potential patient harm. Diversion of the initial blood specimen reduces blood culture contamination. We report results of the "real-life" clinical implementation of this technique., Methods: Following an educational campaign, use of a dedicated diversion tube was recommended prior to all blood cultures. Blood culture sets taken from adults using a diversion tube were defined as "diversion sets," those without, "non-diversion" sets. Blood culture contamination and true positive rates were compared for diversion and nondiversion sets and to nondiversion historical controls. A secondary analysis investigated efficacy of diversion by patient age., Results: Out of 20,107 blood culture sets drawn, the diversion group included 12,774 (60.5%) and the nondiversion group 8,333 (39.5%) sets. The historical control group included 32,472 sets. Comparing nondiversion to diversion, contamination decreased by 31% (5.5% [461/8333] to 3.8% [489/12744], P < .0001]. Contamination was also 12% lower in diversion than historical controls [3.8% (489/12744) vs 4.3% (1,396/33,174) P = .02)]. The rate of true bacteremia was similar. In older patients, contamination rate was higher, and the relative reduction associated with diversion decreased (54.3% amongst 20-40-year-olds vs 14.5% amongst >80-year-olds)., Conclusions: Use of a diversion tube in the ED reduced blood culture contamination in this large real life observational study. Efficacy decreased with increasing age, which requires further investigation., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: NDM-producing Acinetobacter baumannii (NDMAb) were reported sporadically worldwide but little is known about the transmission, epidemiology and clinical features of NDMAb-infected patients. The goals of this study were to characterize (1) the epidemiology and clinical features of NDMAb-infected patients; (2) the microbiological and molecular features of NDMAb isolates and (3) the transmission networks of NDMAb within healthcare facilities., Methods: The study was conducted at the Tel-Aviv Sourasky, Rambam and Sha'are-Zedek Medical centers (TASMC, RMC and SZMC, respectively) in Israel. All cases detected between January 2018 and July 2019 were included. Phylogenetic analysis was based on core genome SNP distances. Clonal transmission was defined according to molecular (≤ 5 SNP) and epidemiological criteria (overlapping hospital stay). NDMAb cases were compared at a ratio of 1:2 with non-NDM carbapenem-resistant A. baumannii (CRAb) cases., Results: The study included 54 NDMAb-positive out of 857 CRAb patients, including 6/179 (3.3%) in TASMC, 18/441 (4.0%) in SZMC and 30/237 (12.6%) in RMC. Patients infected by NDMAb had similar clinical features and risk factors as patients with non-NDM CRAb. The length-of-stay was higher in NDMAb cases (48.5 days vs. 36 days, respectively, p = 0.097) and the in-hospital mortality was similarly high in both groups. Most isolates (41/54, 76%) were first detected from surveillance culture. The majority of isolates harbored the bla NDM-2 gene allele (n = 33), followed by the bla NDM-1 (n = 20) allele and the bla NDM-4 allele (n = 1). The majority of isolates were related within the ST level to other isolates in SZMC and RMC: 17/18 and 27/30 isolates, respectfully. The common ST's were the bla NDM-1 harboring ST-2 (n = 3) and ST-107 (n = 8) in SZMC and the bla NDM-2 harboring ST-103 in SZMC (n = 6) and in RMC (n = 27). All bla NDM alleles were located within a conserved mobile genetic environment flanked by the ISAb125 and IS91 family transposon. Clonal transmission was identified in most hospital-acquired cases in RMC and SZMC., Conclusion: NDMAb constitutes a minor part of CRAb cases and are clinically similar to non-NDM CRAb. Transmission of NDMAb occurs mostly by clonal spread., (© 2023. The Author(s).)

Background: Maternal CMV infection during pregnancy, either primary or non-primary, may be associated with fetal infection and long-term sequelae. While guidelines recommend against it, screening for CMV in pregnant women is a prevalent clinical practice in Israel. Our aim is to provide updated, local, clinically relevant, epidemiological information about CMV seroprevalence among women at childbearing age, the incidence of maternal CMV infection during pregnancy and the prevalence of congenital CMV (cCMV), as well as to provide information about the yield of CMV serology testing., Methods: We performed a descriptive, retrospective study of women at childbearing age who were members of Clalit Health Services in the district of Jerusalem and had at least one gestation during the study period (2013-2019). We utilized serial serology tests to determine CMV serostatus at baseline and at pre/periconception and identified temporal changes in CMV serostatus. We then conducted a sub-sample analysis integrating inpatient data on newborns of women who gave birth in a single large medical center. cCMV was defined as either positive urine CMV-PCR test in a sample collected during the first 3 weeks of life, neonatal diagnosis of cCMV in the medical records, or prescription of valganciclovir during the neonatal period., Results: The study population Included 45,634 women with 84,110 associated gestational events. Initial CMV serostatus was positive in 89% women, with variation across different ethno-socioeconomic subgroups. Based on consecutive serology tests, the detected incidence rate of CMV infection was 2/1000 women follow-up years, among initially seropositive women, and 80/1000 women follow-up years, among initially seronegative women. CMV infection in pregnancy was identified among 0.2% of women who were seropositive at pre/periconception and among 10% of women who were seronegative. In a subsample, which included 31,191 associated gestational events, we identified 54 newborns with cCMV (1.9/1000 live births). The prevalence of cCMV among newborns of women who were seropositive at pre/periconception was lower than among newborns of women who were seronegative (2.1 vs. 7.1/1000). Frequent serology tests among women who were seronegative at pre/periconception detected most primary CMV infections in pregnancy that resulted in cCMV (21/24). However, among women who were seropositive, serology tests prior to birth detected none of the non-primary infections that resulted in cCMV (0/30)., Conclusions: In this retrospective community-based study among women of childbearing age characterized by multiparity and high seroprevalence of CMV, we find that consecutive CMV serology testing enabled to detect most primary CMV infections in pregnancy that led to cCMV in newborns but failed to detect non-primary CMV infections in pregnancy. Conducting CMV serology tests among seropositive women, despite guidelines' recommendations, has no clinical value, while it is costly and introduces further uncertainties and distress. We thus recommend against routine CMV serology testing among women who were seropositive in a prior serology test. We recommend CMV serology testing prior to pregnancy only among women known to be seronegative or women whose serology status is unknown., (© 2023. The Author(s).)

Objectives: NDM-producing Enterobacterales (NDME) account for 34.9% of new carbapenemase-producing Enterobacterales cases in Israeli hospitals. The goals of this study were to characterize the genomic composition of NDME isolates and mobile genetic elements (MGEs) and to identify NDME transmission events (TEs)., Methods: The study was conducted at the Tel-Aviv Sourasky, Rambam and Sha'are-Zedek Medical Centers (TASMC, RMC and SZMC, respectively). All NDME isolates detected between January 2018 and July 2019 were included.Phylogenetic analysis was based on core-genome SNP distances. Core-genome distance of ≤5 SNPs between isolates from patients with overlapping hospitalization periods was suggestive of a potential TE. MGEs were classified by comparison of the blaNDM gene flanking regions., Results: The study included 212 NDME isolates from 203 patients, including 104 isolates from TASMC, 30 isolates from RMC and 78 isolates from SZMC. The majority of isolates (n = 157; 74%) harboured the blaNDM-1 gene, followed by the blaNDM-5 (n = 48) and blaNDM-15 genes (n = 7). The most common NDME species were Klebsiella pneumoniae (n = 67), Escherichia coli (n = 65) and Enterobacter cloacae (n = 45), all showing a highly diverse clonal structure. Most blaNDM-1-harbouring isolates (134/157; 85%) were divided into nine different MGE modules, variably distributed across species and hospitals.The numbers of post-admission acquisition cases (n = 118) that could be linked to other cases by both molecular and epidemiological criteria were 13/58 (24.2%), 3/48 (6.3%) and 4/12 (33.3%) in TASMC, SZMC and RMC, respectively., Conclusions: The study depicted a complex and diverse population structure, suggesting that NDME had not spread via clonal expansion., (© The Author(s) 2023. 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.)

Background: Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19., Methods: In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression., Results: Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P = .72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P < .01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval, .3-.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes., Conclusions: Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses., Competing Interests: Potential conflicts of interest. T. B.-N. reports receiving honoraria from Reckitt Benckiser for lectures. B. C. reports receiving honoraria and/or lecture fees from Pfizer, MSD, Gilead, Tradis Gat, Dexell, AstraZeneca, and Reckitt Benkiser. Y. M. reports receiving a quality grant, unrelated to coronavirus disease 2019 (COVID-19) vaccines, from Pfizer paid to the institution (Wolfson Medical Center); honoraria for lectures unrelated to COVID vaccines from Pfizer and MSD; and consulting fees from MSD for serving on an advisory board. G. R. reports receiving honoraria and/or lecture fees from Pfizer (honoraria for lectures, unrelated to COVID-19 vaccines), MSD (honoraria for lectures, unrelated to COVID-19 vaccines), and Asetllas; consulting fees from MSD and Gilead; and travel fees from MSD; none of these fees are related to the study. T. B. N., K. H., Y. M., and O. Z. are members of the Israeli National Advisory Board on COVID-19 Management and Vaccination. 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) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To prospectively evaluate the incidence of myocardial injury after the administration of the fourth dose BNT162b2 mRNA vaccine (Pfizer-BioNTech) against COVID-19., Methods and Results: Health care workers who received the BNT162b2 vaccine during the fourth dose campaign had blood samples collected for high-sensitivity cardiac troponin (hs-cTn) during vaccine administration and 2-4 days afterward. Vaccine-related myocardial injury was defined as hs-cTn elevation above the 99th percentile upper reference limit and >50% increase from baseline measurement. Participants with evidence of myocardial injury underwent assessment for possible myocarditis. Of 324 participants, 192 (59.2%) were female and the mean age was 51.8 ± 15.0 years. Twenty-one (6.5%) participants had prior COVID-19 infection, the mean number of prior vaccine doses was 2.9 ± 0.4, and the median time from the last dose was 147 (142-157) days. Reported vaccine-related adverse reactions included local pain at injection site in 57 (17.59%), fatigue in 39 (12.04%), myalgia in 32 (9.88%), sore throat in 21 (6.48%), headache in 18 (5.5%), fever ≥38°C in 16 (4.94%), chest pain in 12 (3.7%), palpitations in 7 (2.16%), and shortness of breath in one (0.3%) participant. Vaccine-related myocardial injury was demonstrated in two (0.62%) participants, one had mild symptoms and one was asymptomatic; both had a normal electrocardiogram and echocardiography., Conclusion: In a prospective investigation, an increase in serum troponin levels was documented among 0.62% of healthy health care workers receiving the fourth dose BNT162b2 vaccine. The two cases had mild or no symptoms and no clinical sequela., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05308680., (© 2022 European Society of Cardiology.)

Background: Previous cohort studies of pneumonia patients reported lower mortality with advanced macrolides. Our aim was to characterize antibiotic treatment patterns and assess the role of quinolones or macrolides in empirical therapy., Materials: An historical cohort, 1 July 2009 to 30 June 2017, included, through active surveillance, all culture-confirmed bacteremic pneumococcal pneumonia (BPP) among adults in Israel. Cases without information on antibiotic treatment were excluded. Logistic regression analysis was used to assess independent predictors of in-hospital mortality., Results: A total of 2016 patients with BPP were identified. The median age was 67.2 years (interquartile range [IQR] 53.2-80.6); 55.1% were men. Lobar pneumonia was present in 1440 (71.4%), multi-lobar in 576 (28.6%). Median length of stay was 6 days (IQR 4-11). A total of 1921 cases (95.3%) received empiric antibiotics with anti-pneumococcal coverage: ceftriaxone, in 1267 (62.8%). Coverage for atypical bacteria was given to 1159 (57.5%), 64% of these, with macrolides. A total of 372 (18.5%) required mechanical ventilation, and 397 (19.7%) died. Independent predictors of mortality were age (odds ratio [OR] 1.051, 95% confidence interval [CI] 1.039, 1.063), being at high-risk for pneumococcal disease (OR 2.040, 95% CI 1.351, 3.083), multi-lobar pneumonia (OR 2.356, 95% CI 1.741, 3.189). Female sex and macrolide therapy were predictors of survival: (OR 0.702, 95% CI .516, .955; and OR 0.554, 95% CI .394, .779, respectively). Either azithromycin or roxithromycin treatment for as short as two days was predictor of survival. Quinolone therapy had no effect., Conclusions: Empirical therapy with macrolides reduced odds for mortality by 45%. This effect was evident with azithromycin and with roxithromycin. The effect did not require a full course of therapy., Competing Interests: Potential conflicts of interest. R. D. has received grants/research support from Pfizer, MedImmmune/AstraZeneka, and Merck Sharp & Dohme (paid to Ben Gurion University); has been a scientific consultant for MeMed, Merck Sharp & Dohme, and Pfizer (paid to ISRAVAX) and a speaker for GlaxoSmithKline, Merck Sharp & Dohme, Sanofi Pasteur and Pfizer (paid to ISRAVAX); received payment for expert testimony from Pfizer (paid to ISRAVAX); received support for attending meetings and/or travel from Pfizer and MSD; and participated on a DSMB or AB for Pfizer and MSD (paid to ISRAVAX). G. R. has received a research grant from Pfizer and has been a scientific consultant for Teva and Merck; and reports payment or honoraria for lectures from MSD (COVID pandemic, unrelated to the topic of the study); participation on an Advisory Board for Moderna and AstraZeneca. Y. W.-W. reports grants or contracts unrelated to this work from Madaait, Shaare Zedek Medical Center, Jerusalem center of computerized individualized medicine, and Faculty of Medicine, Hebrew University. S. G.-V. reports consulting fees from CytoReason and Photopill. Y. Maor reports a quality grant unrelated to this work from Pfizer; payment or honoraria for lectures from MSD and Pfizer; participation on a DSMB or AB related to COVID-19 for MSD; and leadership or fiduciary role related to COVID-19 and vaccination with the Ministry of Health Israel. 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) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Background: The hepatobiliary system is a sterile micro-environment. Bacterial infection in this system is most commonly associated with anaerobes as well as gram-positive and gram-negative bacteria. Biliary infections with Staphylococcus aureus are poorly characterized., Objectives: To depict the clinical characteristics and outcome of patients with S. aureus infection of the hepatobiliary system., Methods: Medical records of patients with bile cultures positive for S. aureus from January 2006 to November 2020 were extracted from the computerized database of a hospital in Israel., Results: We analyzed the results of 28 cases that were found in the database. The mean age of study patients was 62.2 ± 19 years. Hypertension, dyslipidemia, chronic kidney disease, diabetes, and benign prostatic hypertrophy were the most common co-morbidities (57.1%, 32.1%, 25%, 25%, and 25%, respectively). Fourteen of the methicillin-resistant S. aureus (MRSA) bile cultures (82.3%) were a result of primary S. aureus biliary infections (no other source for S. aureus infection) and the remainder were of a secondary infection. Eight of the MRSA cultures (47.1%) were from hospital acquired infections. Increased hospital mortality in patients with S. aureus hepatobiliary infection was associated with hypertension (P = 0.04), bedridden status (P = 0.01), and nursing home residence (P = 0.003)., Conclusions: Hepatobiliary infection with S. aureus can manifest in a variety of ways. S. aureus should be especially considered in patients who are bedridden, present with hypertension, or live in nursing homes because of their association with in-hospital mortality resulting from this entity.

Highly variable estimates of COVID-19-associated fungal diseases (IFDs) have been reported. We aimed to determine the incidence of clinically important fungal diseases in hospitalized COVID-19 patients during the first year of the pandemic. We performed a multicenter survey of IFDs among patients hospitalized with COVID-19 in 13 hospitals in Israel between February 2020 and May 2021. COVID-19-associated pulmonary mold disease (PMD) and invasive candidiasis (IC) were defined using ECMM/ISHAM and EORTC/MSG criteria, respectively. Overall rates of IC and PMD among patients with critical COVID-19 were 10.86 and 10.20 per 1000 admissions, respectively, with significant variability among medical centers. PMD rates were significantly lower in centers where galactomannan was a send-out test versus centers with on-site testing ( p = 0.035). The 30-day mortality rate was 67.5% for IC and 57.5% for PMD. Treatment with an echinocandin for IC or an extended-spectrum azole for PMD was associated with significantly lower mortality rates (adjusted hazard ratio [95% confidence interval], 0.26 [0.07-0.91] and 0.23 [0.093-0.57], respectively). In this multicenter national survey, variable rates of PMD were associated with on-site galactomannan testing, suggesting under-detection in sites lacking this capacity. COVID-19-related IFDs were associated with high mortality rates, which were reduced with appropriate antifungal therapy.

BackgroundChanging patterns of vaccine breakthrough can clarify vaccine effectiveness.AimTo compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave.MethodsIn an observational multicentre cohort study in Israel, hospitalised COVID-19 patients were divided into three cohorts: breakthrough infections in Comirnaty-vaccinated patients (VD; Jun-Aug 2021) and unvaccinated cases during the Delta wave (ND) and breakthrough infections during an earlier Alpha wave (VA; Jan-Apr 2021). Primary outcome was death or ventilation.ResultsWe included 343 VD, 162 ND and 172 VA patients. VD were more likely older (OR: 1.06; 95% CI: 1.05-1.08), men (OR: 1.6; 95% CI: 1.0-2.5) and immunosuppressed (OR: 2.5; 95% CI: 1.1-5.5) vs ND. Median time between second vaccine dose and admission was 179 days (IQR: 166-187) in VD vs 41 days (IQR: 28-57.5) in VA. VD patients were less likely to be men (OR: 0.6; 95% CI: 0.4-0.9), immunosuppressed (OR: 0.3; 95% CI: 0.2-0.5) or have congestive heart failure (OR: 0.6; 95% CI: 0.3-0.9) vs VA. The outcome was similar between all cohorts and affected by age and immunosuppression and not by vaccination, variant or time from vaccination.ConclusionsVaccination was protective during the Delta variant wave, as suggested by older age and greater immunosuppression in vaccinated breakthrough vs unvaccinated inpatients. Nevertheless, compared with an earlier post-vaccination period, breakthrough infections 6 months post-vaccination occurred in healthier patients. Thus, waning immunity increased vulnerability during the Delta wave, which suggests boosters as a countermeasure.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important cause of nosocomial infections. Active surveillance for CRAB carriage to identify and isolate colonized patients is used to reduce transmission., Objectives: To assess the rate and risks of clinical infection among CRAB-carrier and non-carrier patients., Methods: Hospitalized patients from whom CRAB screening-cultures were obtained between January and June 2018 were identified retrospectively. All CRAB-carriers were compared to a convenient sample of non-carriers and were followed to detect development of CRAB clinical infection during admission., Results: We compared 115 CRAB carriers to 166 non-carriers. The median age in the study group was 76 years (IQR 71-87) vs. 65 years (55-79) in the non-carriers group (P < 0.001). Residence in a nursing facility, debilitated state, and admission to medical wards vs. intensive care units were more frequent among CRAB-carriers (P < 0.001). Mechanically ventilated patients included 51 CRAB carriers (44%) and 102 non-carriers (61%). Clinical infection developed in 49 patients (17%), primarily CRAB pneumonia. Of the CRAB-carriers and non-carriers, 26/115 (23%) and 23/166 (14%), respectively, developed a clinical infection (P = 0.05). One-third of the ventilated patients were infected. Debilitated state and antibiotic treatment during hospitalization were linked to higher infection rates (P = 0.01). Adjusted analysis showed that mechanical ventilation and CRAB colonization were strongly associated with clinical infection (P < 0.05)., Conclusions: The rate of CRAB infection among carriers was high. Mechanical ventilation and CRAB colonization were associated with CRAB clinical infection, primarily pneumonia.

Diabetes and peripheral vascular diseases are accompanied frequently by lower limb ischemia and in minority, need for amputation, as a treatment of last resort. Even after a decision has been made regarding amputation, the procedures are often repeatedly postponed due to more urgent surgeries and lack of operating room availability. This study assessed the possible relationship between the duration of time inpatients wait for semiurgent amputations and the incidence of postamputation complications. A retrospective cohort, including all 360 adult patients who underwent nontraumatic limb amputation due to an ischemic/gangrenous/infected foot in a single center during an 11-year period (2007-2017). Most (96%) of the procedures were major amputations. The mean waiting time until amputation was 3 ± 5 days. Mortality during hospitalization occurred in 101 (28%) patients and re-amputation in 38 (11%). The duration of antibiotic treatment was 11 ± 14 days. The rate of sepsis was 30% (107/360). There was no significant difference between the duration of time until amputation and mortality during hospitalization: among those who waited ≤48 hours, the mortality rate was 27% (60/224) and among those who waited >48 hours 30% (41/136) (p = .5). Patients waiting ≤48 hours had higher re-amputation rates than those waiting >48 (31/223 (14%) vs 7/136 (5%), p = .009). Mortality was associated significantly to patients' age and renal function. Correlation was found between the waiting time until amputation (≤48 or >48 hours) and the rates of in-hospital mortality, sepsis, duration of antibiotic treatment and overall duration of hospitalization. Re-amputation rate was higher in group with the shorter waiting time. This correlation may be explained by the fact that patients who needed urgent amputation had a more extensive and severe disease, and thus tended to require more re-amputation operations., (Copyright © 2021 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of Covid-19 vaccination (Pfizer-BioNTech BNT162b2) during the third trimester of pregnancy on maternal and neonatal outcomes., Design: A multicentre, retrospective computerised database., Population: Women who gave birth at >24 weeks of gestation in Israel, between January and April 2021, with full records of Covid-19 disease and vaccination status., Methods: Women who received two doses of the vaccine were compared with unvaccinated women. Women who were recorded as having disease or a positive Covid-19 polymerase chain reaction (PCR) swab during pregnancy or delivery were excluded from both study groups. Univariate analysis was followed by multivariate logistic regression., Main Outcome Measures: Composite adverse maternal outcomes. Secondary outcomes were vaccination rate and composite adverse neonatal outcomes., Results: The overall uptake of one or both vaccines was 40.2%; 712 women who received two doses of the Covid-19 vaccine were compared with 1063 unvaccinated women. Maternal composite outcomes were comparable between the groups; however, women who received the vaccine had higher rates of elective caesarean deliveries (CDs) and lower rates of vacuum deliveries. An adjusted multivariable logistic regression analysis demonstrated that Covid-19 vaccination was not associated with maternal composite adverse outcome (aOR 0.8, 95% CI 0.61-1.03); a significant reduction in the risk for neonatal composite adverse outcomes was observed (aOR 0.5, 95% CI 0.36-0.74)., Conclusions: In a motivated population covered by a National Health Insurance Plan, we found a 40.2% rate of vaccination for the Covid-19 vaccine during the third trimester of pregnancy, which was not associated with adverse maternal outcomes and, moreover, decreased the risk for neonatal adverse outcomes., Tweetable Abstract: Covid-19 vaccine during pregnancy is safe for both mother and fetus., (© 2021 John Wiley & Sons Ltd.)

Objectives: The mRNA coronavirus disease 2019 (COVID-19) vaccines have shown high effectiveness in the prevention of symptomatic COVID-19, hospitalization, severe disease and death. Nevertheless, a minority of vaccinated individuals might become infected and experience significant morbidity. Characteristics of vaccine breakthrough infections have not been studied. We sought to portray the population of Israeli patients, who were hospitalized with COVID-19 despite full vaccination., Methods: A retrospective multicentre cohort study of 17 hospitals included patients fully vaccinated with Pfizer/BioNTech's BNT162b2 vaccine who developed COVID-19 more than 7 days after the second vaccine dose and required hospitalization. The risk for poor outcome, defined as a composite of mechanical ventilation or death, was assessed., Results: A total of 152 patients were included, accounting for half of hospitalized fully vaccinated patients in Israel. Poor outcome was noted in 38 patients and mortality rate reached 22% (34/152). Notably, the cohort was characterized by a high rate of co-morbidities predisposing to severe COVID-19, including hypertension (108; 71%), diabetes (73; 48%), congestive heart failure (41; 27%), chronic kidney and lung diseases (37; 24% each), dementia (29; 19%) and cancer (36; 24%), and only six (4%) had no co-morbidities. Sixty (40%) of the patients were immunocompromised. Higher viral load was associated with a significant risk for poor outcome. Risk also appeared higher in patients receiving anti-CD20 treatment and in patients with low titres of anti-Spike IgG, but these differences did not reach statistical significance., Conclusions: We found that severe COVID-19 infection, associated with a high mortality rate, might develop in a minority of fully vaccinated individuals with multiple co-morbidities. Our patients had a higher rate of co-morbidities and immunosuppression compared with previously reported non-vaccinated hospitalized individuals with COVID-19. Further characterization of this vulnerable population may help to develop guidance to augment their protection, either by continued social distancing, or by additional active or passive vaccinations., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Official guidelines recommend tuberculosis (TB) screening programmes for all healthcare workers (HCWs), along with offering treatment when latent TB infection (LTBI) is diagnosed. However, adherence to treatment among HCWs is lower compared with non-HCWs. The aim of the present study was to examine the rate of LTBI treatment acceptance among HCWs and to characterise the factors associated with non-acceptance., Design and Setting: This was a retrospective cohort study. All HCWs diagnosed with LTBI, who had tuberculin skin test (TST) conversion during their work, between 2000 and 2015, in a single tertiary academic medical centre, and who consented to answer a questionnaire, were enrolled., Results: Overall, 147 of 219 (67%) with TST conversion agreed to participate. Acceptance rate for LTBI treatment was only 16%. The overall completion rate among those who accepted treatment was 87%. HCWs' recall of discussing the importance of LTBI treatment with their caregiver had the strongest association with LTBI treatment acceptance: 23 of 52 HCWs (44%) who recalled this discussion accepted treatment (adjusted OR=10.2, 95% CI: 2.2 to 47.6, p=0.003). Knowing the risk of developing TB was associated with 3.7 increased odds to accept treatment (95% CI: 1.2 to 11.8, p=0.02)., Conclusions: LTBI acceptance rate was very low among our HCWs. Focusing on educating HCWs is potentially the key step towards an increased rate of LTBI treatment acceptance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aims to examine the prevalence and risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sero-positivity in health care workers (HCWs), a main risk group, and assess the sero-incidence of SARS-CoV-2 infection between the first and second waves of coronavirus disease 2019 (COVID-19) in Israel. Methods: A longitudinal study was conducted among 874 HCWs from nine hospitals. Demographics, health information, and blood samples were obtained at baseline (first wave-April-May 2020) and at follow-up ( n = 373) (second wave-September-November 2020). Sero-positivity was determined based on the detection of total antibodies to the nucleocapsid antigen of SARS-CoV-2, using electro-chemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2, Roche Diagnostics, Rotkreuz, Switzerland). Results: The sero-prevalence of SARS-CoV-2 antibodies was 1.1% [95% confidence intervals (CI) 0.6-2.1] at baseline and 8.3% (95% CI 5.9-11.6) at follow-up. The sero-conversion of SARS-CoV-2 serum antibody was 6.9% (95% CI 4.7-9.9) during the study period. The increase in SARS-CoV-2 sero-prevalence paralleled the rise in PCR-confirmed SARS-CoV-2 infections among the HCWs across the country. The likelihood of SARS-CoV-2 sero-prevalence was higher in males vs. females [odds ratio (OR) 2.52 (95% CI 1.05-6.06)] and in nurses vs. physicians [OR 4.26 (95% CI 1.08-16.77)] and was associated with being quarantined due to exposure to COVID-19 patients [OR 3.54 (95% CI 1.58-7.89)] and having a positive PCR result [OR 109.5 (95% CI 23.88-502.12)]. Conclusions: A significant increase in the risk of SARS-CoV-2 infection was found among HCWs between the first and second waves of COVID-19 in Israel. Nonetheless, the sero-prevalence of SARS-CoV-2 antibodies remains low, similar to the general population. Our findings reinforce the rigorous infection control policy, including quarantine, and utilization of personal protective equipment that should be continued together with COVID-19 immunization in HCWs and the general population., 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 © 2021 Muhsen, Schwaber, Bishara, Kassem, Atamna, Na'amnih, Goren, Bialik, Mohsen, Zaide, Hazan, Ariel-Cohen, Cohen, Shitrit, Marchaim, Benenson, Ben-David, Rubinovitch, Gotessman, Nutman, Wiener-Well, Maor, Carmeli and Cohen.)

Objectives: Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients., Methods: All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed., Results: Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52-76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD., Conclusions: Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp ., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.