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Introduction: Despite the declining public health emergency status, COVID-19 still poses significant risks, especially for immunocompromised individuals. We aimed to evaluate the effectiveness of tixagevimab-cilgavimab (T-C) prophylaxis in preventing severe COVID-19 in patients with hematologic malignancies (HM) treated with anti-CD20 therapy during the early Omicron variant phase of the pandemic., Methods: The European Society of Clinical Microbiology and Infectious Diseases Study Group for Respiratory Viruses (ESGREV) conducted a multicenter retrospective cohort study involving 15 centers from 5 countries. The study included 749 patients with HM treated with anti-CD20 between February 15 and June 30, 2022, comparing 215 who received T-C prophylaxis to 534 who did not., Results: The study revealed a significant reduction in the risk of COVID-19 among patients who received T-C prophylaxis compared to those who did not (11.2% vs 23.4%, p < 0.001), with hazard ratio (HR) of 0.40 (95% CI 0.26-0.63), adjusted for age, sex, vaccination status, baseline HM malignancy and type of anti-CD-20. We also demonstrated a reduction for severe-critical diseases within all study populations, 1.4% vs 5.2%, p = 0.017, HR 0.26 (95% CI 0.08-0.84)., Conclusion: T-C prophylaxis effectively prevented COVID-19 and severe-critical COVID-19 in patients with HM treated with anti-CD20 monoclonal antibodies during the early Omicron variant phase of the pandemic. Even though T-C is ineffective against current variants, these findings highlight the importance of additional protective measures and the continued development of monoclonal antibodies to protect immunocompromised individuals to mitigate the impact of COVID-19 and other respiratory viral diseases., Competing Interests: Declarations. Conflict of Interest: Tal Brosh-Nissimov reports honoraria for lectures and advisory board attendance from AstraZeneca, Gilead, MSD, and Medison; Lior Nesher reports honoraria for educational lectures from Pfizer, MSD, Moderna, AstraZeneca, and participation in advisory boards for MSD, Medison, and AstraZeneca. Roy F Chemaly reportsConsultant/Speaker/Advisor for ADMA Biologics, Janssen, Merck/MSD, Takeda, Shinogi, AiCuris, Roche/Genentech, Astellas, Tether, Oxford Immunotec, Karius, Moderna, InflaRX, and Ansun Pharmaceuticals. He received research grants paid to his institution from Merck/MSD, Karius, AiCuris, Ansun Pharmaceuticals, Takeda, Genentech, Oxford Immunotec, and Eurofins-Viracor. He also serves as a DSMC member for AstraZeneca All other authors (Hovav Azuly, Tali Shafat, Daniel Grupel, Tzvika Porges, Ran Abuhasira, Ana Belkin, Ofir Deri, Yonatan Oster, Shadi Zahran, Ehud Horwitz, Netanel A Horowitz, Hazim Khatib, Marjorie Vieira Batista, Anita Cassoli Cortez, Yafit Segman, Linor Ishay, Regev Cohen, Alaa Atamna, Amy Spallone, Juan Carlos Ramos-Ramos, Michal Chowers, Evgeny Rogozin, Noga Carmi Oren, Şiran Keske and Orit Wolfovitz Barchad) report no COI. Ethical Approval: The Soroka Ethics in Research Committee and each participating site's committee (see supplementary material) approved this study and granted a waiver of informed consent (SOR-22–0198)., (© 2024. The Author(s).)

Safeguarding patients from emerging infectious diseases demands strategies that prioritise patient well-being and protection. Immunobridging is an established trial methodology which has been increasingly employed to ensure patient protection and provide clinicians with swift access to vaccines. It uses immunological markers to infer the effectiveness of a new drug through a surrogate measure of efficacy. Recently, this method has also been employed to authorise novel drugs, such as COVID-19 vaccines, and this article explores the concepts behind immunobridging trials, their advantages, issues, and significance in the context of COVID-19 and other infectious diseases. Our goal is to improve awareness among clinicians, patient groups, regulators, and health leaders of the opportunities and issues of immunobridging, so that fewer patients are left without protection from infectious diseases, particularly from major pathogens that may emerge.

Objectives: To evaluate the effect of COVID-19 during the first trimester on the rate of first- and second-trimester miscarriages. Secondary aims include the effect on stillbirths and the correlation between symptom severity and pregnancy outcomes., Methods: A retrospective matched case-control population-based study extracted data from electronic medical records of a nationwide database of the second largest healthcare organization that provides medical services to over 2 000 000 patients in Israel. Pregnancy outcomes in COVID-19-positive pregnant patients in 2020 were compared with an age- and gestational-week-matched 1:2 case-control cohort of pre-pandemic pregnant patients that received medical care in 2019., Results: Of 68 485 pregnant women treated in 2020, 2333 were COVID-19-positive during pregnancy: 215 during the first trimester, 791 during the second trimester, and 1327 during the third trimester. We compared these data with the control cohort of 4580 pre-pandemic pregnant patients. The rate of spontaneous miscarriage was significantly higher 146/2187 (6.3%) in COVID-19-positive patients versus 214/4580 (4.7%), (P < 0.01, odds ratio 1.34, 95% confidence interval 1.094-1.691). Most miscarriages occurred during the first trimester in both groups, yet the rates were significantly higher in the study group (5.4% vs 3.8%, P < 0.01). There was no association between COVID-19 severity and miscarriage risk., Conclusion: COVID-19 diagnosis during early pregnancy increased the rate of spontaneous miscarriage in our cohort compared with an age- and gestational-week-matched pre-pandemic control group., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Cardiac implantable electronic devices (CIEDs) are associated with risks of device-related infections (DRI) impacting major adverse outcomes. Staphylococcus aureus (SA) is a leading cause of early pocket infection and bacteremia. While studies in other surgical contexts have suggested that nasal mupirocin treatment and chlorhexidine skin washing may reduce colonization and infection risk, limited data exist for CIED interventions., Objectives: To assess the impact of SA decolonization on DRI rates., Methods: We conducted a retrospective, single-center observational study on consecutive patients undergoing CIED interventions (March 2020-March 2022). All patients received pre-procedure antibiotics and chlorhexidine skin washing. Starting in March 2021, additional pre-treatment with mupirocin for SA decolonization was administered. DRI rates within 6 months post-implantation were compared between patients treated according to guidelines (Group 1) and those receiving mupirocin in addition to the recommended guidelines (Group 2)., Results: The study comprised 276 patients (age 77 ± 10 years; 60% male). DRI occurred in five patients (1.8%);80% underwent cardiac resynchronization therapy procedures. In Group 1 (n=177), four patients (2.2%) experienced DRI 11-48 days post-procedure; three with pocket infection (two with negative cultures and one with local Pseudomonas) and one with methicillin-sensitive SA endocarditis necessitating device extraction. In Group 2 (n=99), only one patient (1%) had DRI (Strep. dysgalactiae endocarditis) 135 days post-procedure (P = NS)., Conclusions: The routine decolonization of SA with mupirocin, in addition to guideline-directed protocols, did not significantly affect DRI rates. Larger prospective studies are needed to evaluate the preventive role of routine SA decolonization in CIED procedures.

To gather national level data on Israeli neonatal HSV (NHSV) infection and to evaluate the distinct clinical characteristics of NHSV and neonatal enteroviral meningitis (NEM). Israeli NHSV patients, hospitalized between January 2015 and April 2022 in 22 medical centers were assessed, together with NEM patients, hospitalized at Sheba Medical Center during the same period. NHSV demographic and clinical characteristics were documented and compared to those of NEM. Eighty-five NHSV (73% males) and 130 NEM (62% males) patients were included. The incidence of NHSV was 5.9/100 000 live births, the common phenotype and HSV type were SEM (53%) and HSV1 (91%), respectively. Horizontal transmission was suspected in 50% cases (of which 67% underwent a Jewish ritual circumcision with direct wound sucking, 33% had relatives with highly suspicious herpetic lesions). Compared with NEM, NHSV tends to present with rash (14% vs. 60%, p-value < 0.01) and seizures (0% vs. 6%, p-value 0.02), while fever, irritability and poor feeding appear more frequently in NEM (94% vs. 18%, p-value < 0.01; 37% vs. 1%, p-value < 0.01; 25% vs. 1%, p-value < 0.01 respectively). Of NEM patients, 28% were treated with acyclovir. Our results mark a decrease in the incidence rate of NHSV in Israel and a prominent mode of horizontal infection acquisition. We underscore the unique localized phenotype of NHSV, in contrast to enterovirus, which tends to cause a systemic disease with constitutional symptoms. These findings should be considered when evaluating the need for comprehensive empirical treatment for HSV in the context of neonatal fever, or according to a certain clinical presentation., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes., Methods: A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016-2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients., Results: The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4-5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6-4.2), and chronic renal failure (RR 2.9, 95% CI 2.3-3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23-2.66), neutropenia (RR 2.53, 95% CI 1.19-5.35), neutrophilia (RR 1.66, 95% CI 1.81-2.34), and lymphopenia (RR 2.03, 95% CI 1.37-3.0) were associated with poor outcomes., Conclusions: RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination.

Brucellosis, a systemic infection, can affect various organs, including the genitourinary system, causing epididymo-orchitis in 2%-20 % of cases. This report details a 34-year-old Thai male migrant worker with febrile orchitis. Initial gentamicin treatment failed, but serological tests confirmed brucellosis, likely from raw dairy consumption. The patient was successfully treated with gentamicin, doxycycline, and rifampicin, resulting in complete symptom resolution. Brucella orchitis, though rare, should be considered in patients from endemic areas. Conservative treatment with combined antibiotics is typically effective., Competing Interests: None., (© 2024 The Authors.)

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.)

Resistance of SARS-CoV-2 to antivirals was shown to develop in immunocompromised individuals receiving remdesivir. We describe an immunocompromised patient who was treated with repeated and prolonged courses of nirmatrelvir and developed de-novo E166V/L50F mutations in the Mpro region. These mutations were associated with clinical and virological treatment failure., Competing Interests: Potential conflicts of interest. T. B.-N. reports honoraria and consulting fees from AstraZeneca, MSD, GSK, and Gilead; grants for epidemiological studies on coronavirus disease 2019 from KSM (Maccabi Health Fund); and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Medison. All remaining authors: No reported conflicts of interest. 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) 2023. 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.)

Objectives: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort., Methods: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant., Results: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293)., Conclusions: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

We present a retrospective study on the treatment outcomes of severely immunocompromised patients with persistent COVID-19. The study analyzed data from 14 patients who received a combination of tixegavimab/cilgavimab and antiviral medications. Response was evaluated based on symptom improvement, PCR cycle-threshold values, and C-reactive protein levels. Eleven patients achieved complete clinical and virological resolution, while three showed partial responses. The study suggests a potential association between non-response and tixegavimab/cilgavimab neutralization. The findings underscore the need for tailored treatment approaches and further research on optimal strategies for managing persistent COVID-19, as well as the development of antivirals and variant-specific monoclonal antibodies., Competing Interests: Declaration of competing interest TBN received honoraria and consultation fees from AstraZeneca, MSD, GSK, Gilead, Medison., (Copyright © 2023. Published by Elsevier B.V.)

Background: It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19)., Methods: In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients., Results: A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, -10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9-20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066)., Conclusions: cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19., Trial Registration Number: My Trials MOH&#95;2021-01-14&#95;009667., Competing Interests: Potential conflicts of interest . Y. M. was a primary investigator on a grant received from KAMADA supporting this study. She also received honoraria for participation in advisory boards from KAMADA and MSD and received honoraria for lectures or writing services from MSD, Pfizer, Medison, and Maccabi health services (paid to author); travel grants from Pfizer (paid to institution); unpaid roles on Israeli Ministry of Health's epidemic preparedness committee and infectious disease and vaccine committee, and as Treasurer to Society for Research and Prevention of Sexually Transmitted Diseases. T. B. N. reports consulting fees from AstraZeneca and MSD; honoraria for participation in advisory boards from AstraZeneca and MSD; and honoraria for lectures and travel grants from AstraZeneca, MSD, and Medison. N. A. is an employee of Kamada and holds Kamada stock options. S. C. is an employee of Kamada and holds Kamada stock options. 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) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The Accelerate PhenoTest® BC system (AXDX) is a novel assay for rapid bacterial identification and antimicrobial susceptibility (AST). We report an evaluation of its impact on treatment of patients with Gram-negative bacteremia (GNB) with a high risk of antimicrobial resistance (AMR)., Methods: A prospective single-center evaluation before and after implementation of AXDX in addition to standard-of-care (SOC) microbiology and antimicrobial stewardship program (ASP). Patients with GNB reported during laboratory working hours and prespecified risk factors for AMR were included. The primary outcome was an ASP-oriented beneficial antimicrobial change, defined as either an escalation of an inappropriate empiric treatment or de-escalation of a broad-spectrum treatment of a susceptible organism. Main secondary outcomes were time to an appropriate treatment, antimicrobial treatment duration, length of stay (LOS) and mortality., Results: Included were 46 and 57 patients in the pre- and post-intervention periods, respectively. The median time to an AST-oriented beneficial change was 29.2 h vs. 49.6 h, respectively (p < 0.0001). There were no significant differences in the time to appropriate treatment, LOS or mortality. Antimicrobial treatment duration was longer during the intervention period (10 vs. 8 days, p = 0.007). AXDX failed to correctly identify pathogens in all 6 cases of polymicrobial bacteremia. In two cases patient care was potentially compromised due to inappropriate de-escalation., Conclusions: AXDX implementation resulted in a 20.4-hour shorter time to an ASP-oriented beneficial antimicrobial change. This should be weighed against the higher costs, the lack of other proven clinical benefits and the potential harm from mis-identification of polymicrobial bacteremias., (© 2023. The Author(s).)

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

Tuberculous epididymitis is uncommonly encountered and is a very rare complication of Bacillus Calmette-Guérin (BCG) intravesical therapy for the treatment of bladder urothelial cancer. With the increased use of BCG, it is conceivable that practicing urologists will see more patients presenting with this infection. Herein, we describe an unusual presentation of tuberculous epididymitis treated successfully in a conservative fashion with anti-tuberculotic medications and describe current diagnostic, as well as medical and surgical management strategies., Competing Interests: None., (© 2023 The Authors.)

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.)

Recurrent congenital cytomegalovirus infections in consecutive pregnancies are rarely reported. Due to the risk of fetal infection from preconception maternal infection, a 6-month interval after primary maternal infection is generally advised before a new conception. Recently, high-dose valacyclovir treatment was shown to prevent fetal infection in first trimester primary infections. We present a case of first trimester primary infection treated with high-dose valacyclovir but resulting in polymerase chain reaction-confirmed fetal infection. Cytomegalovirus-specific immunoglobulin G titers remained very low during treatment and rose only after cessation of antiviral treatment. Six months after primary seroconversion, in a sequential pregnancy, recurrent fetal infection was diagnosed and resulted in severe fetal sequella. Whole genome sequencing of both amniotic fluid isolates proved them to be identical. Both pregnancies were terminated. We hypothesize that valacyclovir treatment, although unsuccessful in preventing fetal infection, had delayed the adaptive maternal immune response and might have contributed to fetal infection during the sequential pregnancy. We suggest that a longer delay might be warranted after valacyclovir treatment and before a new conception., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Lymphocytic choriomeningitis virus (LCMV) is an often-overlooked cause for viral meningitis but can have severe consequences in certain clinical situations. We present the first documented infection by LCMV in Israel. The epidemiology of LCMV is evolving with a potential for a worldwide endemicity due to the widespread presence of the natural host. Increased awareness and testing are required to identify this virus and screening of certain populations (e.g., organ donors) should be considered., (© 2022 Wiley Periodicals LLC.)

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.

Background: Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults., Methods: A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups., Results: Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs., Conclusions: Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The reduced immune response of maintenance hemodialysis patients to coronavirus disease 2019 (COVID-19) vaccines is a major concern., Objectives: To analyze the late (6 months after full vaccination) antibody response and compare it to early post-vaccination titer., Methods: We conducted a multicenter prospective study of 13 hemodialysis units in Israel., Results: We demonstrated that the low titers observed among ESRD patients 2-3 months after vaccination with the Comirnaty vaccine (median 63.8 AU/ml) declined to critically lower values 6 months after full vaccination. (Mediananti S antibodies, 31 AU/ml). Seropositivity significantly declined among hemodialysis patients from 89% to 74% (P < 0.0001), although it did not significantly change among controls., Conclusions: We recommend all patients on hemodialysis receive a booster COVID-19 vaccine 6 months after the second dose.

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.

Aim: This paper describes the emergency, compassionate use of the COVID-19 vaccination for high-risk adolescents aged 12-15 years prior to approval by the American Food and Drugs Administration in May 2021. The target audience had underlying health conditions associated with severe disease and multisystem inflammatory syndrome in children (MIS-C) or severely immunosuppressed household members., Methods: An orderly approval system was established in Israel for adolescents aged 12-15 years, based on a professional position paper and compassionate treatment regulations. From 12 February 2021, eligible adolescents were referred to the Israeli Ministry of Health for permission to vaccinate, via four health maintenance organisations. Data were collected about adverse events after vaccinations and the incidence of any cases of COVID-19., Results: By 15 March 2021, the vaccine had been approved for 607 adolescents: 333 had received one dose, and 92 had received two doses. The median age was 14.6 years, and the major indication was obesity. Only one child tested positive for the virus, 4 days after vaccination, and no adverse effects were recorded., Conclusion: The emergency use of COVID-19 vaccination for 333 adolescents aged 12-15, 92 of them with 2 doses, based on a position paper and compassionate treatment regulations, did not result in any adverse effects. Since 27 July 2021, the same process was further applied in Israel among younger children, aged 5-11, preceding formal release of the clinical trial., (© 2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Invasive group A Streptococcus (iGAS) infections have increased in Israel since 2016 as successful lineages have emerged. We report the emergence and outbreak of a multidrug-resistant S. pyogenes emm93.0, sequence type 10, among iGAS infections in Israel since 2017. This type has been observed very rarely in other countries. During this period, emm93.0 was the cause of 116 infections in Israel and became the leading type during 2018. Most of the infections were from bacteremia (75%), and most patients were male (76%). We observed infections across Israel, mainly in adults. Of note, we observed multidrug resistance for clindamycin, tetracycline, and trimethoprim/sulfamethoxazole. Whole-genome sequencing confirmed clonality among geographically disseminated isolates. The local emm93.0 sequence type 10 clone contained a novel genomic island harboring the resistance genes lsa(E), lnu(B), and ant (6)-Ia aph(3')-III. Further phenotypic and genomic studies are required to determine the prevalence of this resistance element in other iGAS types.

Aim: To identify clinical and laboratory parameters that can assist in the differential diagnosis of coronavirus disease 2019 (COVID-19), influenza, and respiratory syncytial virus (RSV) infections., Methods: In this retrospective cohort study, we obtained basic demographics and laboratory data from all 685 hospitalized patients confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus, or RSV from 2018 to 2020. A multiple logistic regression was employed to investigate the relationship between COVID-19 and laboratory parameters., Results: SARS-CoV-2 patients were significantly younger than RSV (P=0.001) and influenza virus (P=0.022) patients. SARS-CoV-2 patients also displayed a significant male predominance over influenza virus patients (P=0.047). They also had significantly lower white blood cell count (median 6.3×106 cells/μ) compared with influenza virus (P<0.001) and RSV (P=0.001) patients. Differences were also observed in other laboratory values but were insignificant in a multivariate analysis., Conclusions: Male sex, younger age, and low white blood cell count can assist in the diagnosis of COVID-19 over other viral infections. However, the differences between the groups were not substantial enough and would probably not suffice to distinguish between the viral illnesses in the emergency department.

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.)

Background: Humoral responses to coronavirus disease 2019 (COVID-19) vaccines in hemodialysis (HD) patients can direct vaccination policy., Methods: We compared 409 COVID-19-naïve HD patients from 13 HD units in Israel to 148 non-dialysis-dependent COVID-19-naïve controls. Twenty-four previously infected (antinucleocapsid positive) HD patients were analysed separately. Blood samples were obtained ≥14 days post-vaccination (BNT162b2, Pfizer/BioNTech) to assess seroconversion rates and titers of anti-spike (anti-S) and neutralizing antibodies., Results: The median time from vaccination to blood sample collection was 82 days [interquartile range (IAR) 64-87] and 89 days (IQR 68-96) for HD patients and controls, respectively. Seroconversion rates were lower in HD patients compared with controls for both anti-S and neutralizing antibodies (89% and 77% versus 99.3%, respectively; P < 0.0001). Antibody titers were also significantly lower in HD patients compared with controls {median 69.6 [IQR 33.2-120] versus 196.5 [IQR 118.5-246], P < 0.0001; geometric mean titer [GMT] 23.3 [95% confidence interval (CI) 18.7-29.1] versus 222.7 [95% CI 174-284], P < 0.0001, for anti-S and neutralizing antibodies, respectively}. Multivariate analysis demonstrated dialysis dependence to be strongly associated with lower antibody responses and antibody titers waning with time. Age, low serum albumin and low lymphocyte count were also associated with lower seroconversion rates and antibody titers. HD patients previously infected with sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had no difference in their seroconversion rates or antibody titers compared with COVID-19-naïve patients., Conclusion: This study demonstrates diminished and waning humoral responses following COVID-19 vaccination in a large and diverse cohort of HD patients, including those previously infected with SARS-CoV-2. Considering these results and reduced vaccine effectiveness against variants of concern, in addition to continued social distancing precautions, a third booster dose should be considered in this population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Introduction: Concerns were raised over an increase in Bell's palsy, herpes simplex and herpes zoster after BNT162b2 vaccination, all are manifestations of herpesviruses reactivation. As herpesviruses commonly reactivate in the oropharynx, we have hypothesized that oropharyngeal shedding of herpesviruses will increase after vaccination., Methods: Immune-competent Adults, excluding those using topical steroids or manifesting symptomatic herpesvirus infection, were sampled before BNT162b2 vaccination and one week after. Herpesviruses 1-7 shedding was tested with a multiplexed PCR., Results: In 103 paired samples the prevalence of herpesviruses was similar before and after vaccination: HSV1, 3.9% vs. 5.8% (p = 0.75); HSV2, 0% vs. 1% (p = not applicable, NA); VZV, 0% vs. 0% (p = NA); EBV, 14.6% vs. 17.5% (p = 0.63); CMV, 0% vs. 0% (p = NA); HHV6, 4.9% vs. 7.8% (p = 0.55); HHV7, 71.8% vs. 72.8% (p = 1); any herpesvirus, 73.8% vs. 74.8% (p = 1)., Discussion: We did not find evidence for increased oropharyngeal reactivation of herpesviruses one week after BNT162b2., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tal Brosh-Nissimov reports a relationship with Pfizer Inc that includes: travel reimbursement, with no relevence to COVID-19 vaccines. Tal Brosh-Nissimov is a co-chairman of the Israeli COVID-19 vaccine advisory committee., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Following low incidence of respiratory syncytial virus (RSV) infections in 2020 during the COVID-19 pandemic, we noted a resurgence in hospitalised children in spring/summer 2021 following relaxation of public health measures. We compared this outbreak to previous autumn/winter seasons. We found higher weekly case numbers and incidence rates, more cases from urban neighbourhoods with lower socioeconomic status, and similar clinical presentation and severity. Public health implications include the re-evaluation of palivizumab administration and the need for surge capacity planning.

The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The coronavirus disease 2019 global pandemic is reshaping our understanding of medicine, including the diagnostic approach to common medical presentations. We describe a novel case of a 3-year-old male with a clinical diagnosis of Henoch-Schonlein Purpura vasculitis with concurrent SARS-CoV-2 infection. This case highlights a potentially newly described presentation of coronavirus disease 2019 infection., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Environmental surfaces have been suggested as likely contributors in the transmission of COVID-19. This study assessed the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contaminating surfaces and objects in two hospital isolation units and a quarantine hotel., Methods: SARS-CoV-2 virus stability and infectivity on non-porous surfaces was tested under controlled laboratory conditions. Surface and air sampling were conducted at two COVID-19 isolation units and in a quarantine hotel. Viral RNA was detected by RT-PCR and infectivity was assessed by VERO E6 CPE test., Results: In laboratory-controlled conditions, SARS-CoV-2 gradually lost its infectivity completely by day 4 at ambient temperature, and the decay rate of viral viability on surfaces directly correlated with increase in temperature. Viral RNA was detected in 29/55 surface samples (52.7%) and 16/42 surface samples (38%) from the surroundings of symptomatic COVID-19 patients in isolation units of two hospitals and in a quarantine hotel for asymptomatic and very mild COVID-19 patients. None of the surface and air samples from the three sites (0/97) were found to contain infectious titres of SARS-Cov-2 on tissue culture assay., Conclusions: Despite prolonged viability of SARS-CoV-2 under laboratory-controlled conditions, uncultivable viral contamination of inanimate surfaces might suggest low feasibility for indirect fomite transmission., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Various respiratory viral infections in general and seasonal influenza in particular may increase the susceptibility to bacterial infections. Plague caused by Yersinia pestis endangers large populations during outbreaks or bioterrorism attacks. Recommended antibiotic countermeasures include well-established protocols based on animal studies and corroborated by effective treatment of human cases. Until now, prior exposure to viral respiratory infections was not taken into consideration when selecting the appropriate treatment for plague. Here, we show that as late as 25 days after exposure to influenza virus, convalescent mice still exhibited an increased susceptibility to sublethal doses of Y. pestis, presented with aberrant cytokine expression, and impaired neutrophil infiltration in the lungs. Increased levels of M2 alveolar macrophages and type II epithelial cells, as well as induction in metalloproteases expression and collagen and laminin degradation, suggested that the previous viral infection was under resolution, correlating with enhanced susceptibility to plague. Surprisingly, postexposure prophylaxis treatment with the recommended drugs revealed that ciprofloxacin was superior to doxycycline in mice recovering from influenza infection. These results suggest that after an influenza infection, the consequences, such as impaired immunity and lung tissue remodeling and damage, should be considered when treating subsequent Y. pestis exposure.

Background: We assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP., Methods: A prospective cohort study. Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (≤4.0 versus >4.0)., Findings: Of 49 patients, 11 (22.4%) had moderate, 38 (77.6%) had severe disease, 28 were ventilated. At day 14, 24 (49.0%) patients improved, 9 (18.4%) died, and 13 (26.5%) were ventilated. In 14/98 (14.3%) CP units IgG was < 1.1 (cutoff calibration) and in 60 (61.2%) ≤4.0. IgG level and neutralizing antibody titer were correlated (0.85 p  < 0.001). In patients receiving ≤4.0 antibody levels, 11/30 improved (36.7%) versus 13/19 (68.4%) in patients receiving >4.0 odds ratio (OR) 0.267 [95% confidence interval (CI) 0.079-0.905], P  = 0.030. In patients diagnosed >10 days prior to treatment, 4/14 (22.4%) improved in the ≤4.0 antibody group, versus 6/7 (85.7%) in the >4.0 antibody group, OR 0.048 (95% CI, 0.004-0.520), P  = 0.007. No serious adverse events were reported., Interpretation: Treatment with CP with higher levels of IgG against S1 may benefit patients with moderate and severe COVID-19. IgG against S1 level in CP predicts neutralization antibodies titers., Competing Interests: The authors have declared that they have nothing to disclose., (© 2020 The Authors.)

Background: One Health is a biomedical approach that aims to optimize the health of humans, animals, and the environment through interdisciplinary collaboration. Cellulitis is an infection of the dermis and subcutaneous fat that may be caused by zoonotic streptococci species., Case Report: We report a case of cellulitis caused by Streptococcus canis in a woman who was taking Etanercept. We frame the presentation within a One Health approach and urge emergency physicians to collaborate with veterinarians in the management of patients with zoonotic diseases who are discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pets are a source for zoonotic diseases, including resistant bacteria, that pose particular risk to immunocompromised patients. Emergency physicians often discharge patients with potential zoonotic infections such as cellulitis home without a long-term, holistic care plan, according to a One Health approach. Physicians should then collaborate with veterinarians in caring for humans and animals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A previously healthy young man presented with a chronic cavitary pulmonary infection that began while in Goa, India. Burkholderia pseudomallei was cultured from sputum samples. The infection fully resolved after prolonged antibiotic treatment. Other than traveling during the monsoon season, extensive use of well-water for water-pipe smoking of cannabis was identified as a possible risk factor for infection. This is one of the first reports of travel-associated melioidosis from India. Genomic and immunological characterization suggested that the B. pseudomallei isolate collected from the reported case exhibited limited similarity to other B. pseudomallei strains.

We report here the draft genome sequence of Burkholderia pseudomallei MAA2018. This highly virulent strain was isolated in 2018 from the first melioidosis case in Israel associated with recreational travel to Goa, India., (Copyright © 2019 Israeli et al.)

Objectives: Most studies addressing community-acquired urinary tract infections (UTIs) pertain to mixed cohorts, in which young healthy adults are under-represented. We aimed to dissect the intricate interrelation between exposures and subsequent antimicrobial resistance (AMR) patterns in a unique setting of young healthy adults, allowing further guidance in this group., Methods: We carried out a retrospective cross-sectional study of all Enterobacteriaceae-associated outpatient UTIs during 2014-16 in soldiers, representing the young fit population in Israel. Electronic medical records were reviewed for demographic and clinical data, antimicrobial exposures and prescriptions. Risk factors for AMR were analysed by multivariate logistic regression., Results: Of 1207 cases, 1144 (94.8%) were females, with a median age of 20.2 years. Escherichia coli was the predominant species (83.2%). Only 686 (56.8%) isolates were fully susceptible. AMR rates were as follows: trimethoprim/sulfamethoxazole, 19.6%; oral cephalosporins, 9.7%-16.7%; amoxicillin/clavulanate, 12.1%; ciprofloxacin, 11.1%; and nitrofurantoin, 12.6%. Predictors of AMR were recurrent UTIs, past-year hospitalization, male gender and non E. coli strains. Antimicrobials prescribed >6 months preceding the culprit infection were not related to AMR. Fluoroquinolone and cephalosporin exposures were highly predictive of further AMR, yet nitrofurantoin and, to a lesser extent, amoxicillin/clavulanate had fewer associations with AMR induction and resistance to these antimicrobials was less associated with any exposure., Conclusions: This nationwide study of community-related UTIs shows significant AMR rates for commonly used oral antimicrobials even in young fit adults. Nitrofurantoin proved once more to be an adequate empirical choice regardless of previous exposures, having a less detrimental effect on future AMR. Conversely, both resistance to fluoroquinolones following previous exposures and the associated heavy ecological burden should deter their common use as first-line agents for UTIs.

Background Data regarding sexually transmissible infections (STI) often originate from STI clinics, screening programs or laboratory-based studies, thus are biased for specific risk groups or lack clinical details. This real-life observational study presents sample data of most young adult Israeli population by exploiting the centralised diagnostic and documentation platforms resulting from a mandatory military service at the age of 18 years for both genders., Methods: All STI diagnoses of Israeli Defence Forces soldiers during a 6-month period were reviewed. Patients with Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) (major-STI) and Ureaplasma urealyticum (UU), Ureaplasma parvum (UP) and Mycoplasma hominis (MH) (equivocal STI) were compared with STI-negative controls., Results: Sexually transmissible infection positivity rates (n=2816) were as follows: CT 6.6%; MG 1.9%; NG 0.7%; TV 0.5%; UU 15.7%; UP 28.2%; and MH 6.2%. The CT+MG coinfection rate was 4.1%, yet CT+NG coinfections were rare (≈0.5%). More than half of the patients with ureaplasmas and/or MH were treated; 40% of them were recommended partner treatment. Most antibiotics were prescribed to patients with equivocal infections. Classic STI symptoms in males were linked to major-STI and UU, while females were asymptomatic or presented non-specific symptoms., Conclusions: The judicious use of antibiotics in the era of antimicrobial resistance necessitates re-evaluating the significance of equivocal pathogen detection and reporting (MH, UU, UP). Likewise, universal empiric treatment for NG should be reconsidered in light of its low rates in non-high-risk groups. Conversely, a high MG rate, a pathogen with potential resistance to common STI protocols, requires evaluation of guidelines adequacy.

Tinea corporis caused by Microsporum canis is usually associated with exposure to animals, but outbreaks with anthropophilic transmission were described. A large outbreak in a military base was investigated. We investigated the outbreak's source and risk factors for infection in order to contain and eliminate it. All staff-members at the base were interviewed and examined. A case-control analysis of symptomatic patients was used to elucidate risk factors. Stray cats were captured and sampled. M. canis isolated from skin and fur specimens of patients and cats were genotyped by microsatellite sequencing. Fifty-three of 502 staff-members were symptomatic. Logistic regression showed risk associated with female gender, cat contact at base and performance of guarding duty. Multiple stray cats were found at the base. M. canis isolates from 4 cats and 4 patients had an identical genotype, while 2 patients had different genotypes. We describe the largest M. canis outbreak reported until now. Epidemiological and phylogenetic tools were used to investigate the source of the outbreak. Multiple exposures to stray cats caused infection of mainly young female soldiers performing guarding duty. Other persons were infected by person-to-person transmission. These findings aided in the termination of the outbreak., (© 2018 Blackwell Verlag GmbH.)