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

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

Hospitalized Patients With Severe Coronavirus Disease 2019 During the Omicron Wave in Israel: Benefits of a Fourth Vaccine Dose.

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.

Dual Oxygenation in the Treatment of Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

BACKGROUND: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation). OBJECTIVES: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula. METHODS: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded. RESULTS: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group. CONCLUSIONS: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.

SARS-CoV-2 and seasonal influenza: similarities and disparities.

This report describes the differences in disease severity and clinical presentation between hospitalized patients with coronavirus disease 2019 (COVID-19) and others with seasonal influenza. A total of 136 influenza and 152 COVID-19 patients were included. Patients with influenza more frequently had dyspnea (p = 0.004), hypoxemia (p < 0.001), underlying diseases (p = 0.046), and elevated liver enzymes (p = 0.028). In contrast, patients with COVID-19 were overweight (p < 0.001), lymphopenic (p < 0.001), had elevated CRP (p = 0.011), and radiological abnormalities (p < 0.001). Patients with influenza were more severely ill on admission (NEWS > 5) (p < 0.001). However, length of hospital stay, ventilatory support, and 30-day-mortality were similar. Despite differences in clinical presentation and disease severity between influenza and COVID-19 patients, both groups had similar clinical outcomes.

Hospitalised patients with breakthrough COVID-19 following vaccination during two distinct waves in Israel, January to August 2021: a multicentre comparative cohort study.

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.

Evaluation of Pediatric Screening for Resistant Pathogens in an Israeli Tertiary Center.

BACKGROUND: Antibiotic resistance is a worldwide problem associated with increased morbidity and mortality. OBJECTIVES: To evaluate multidrug resistant (MDR) bacteria carriage in selected populations. METHODS: Data were collected from all patients under 18 years who met our internal guidelines from 2015-2016. They were screened for carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum beta-actamase (ESBL), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE). Indications for screening were non-resident non-Israeli patients (from the Palestinian Authority, Syria, and foreign patients), internal transfers from intensive care units, admission to high-risk departments, recent carriage of MDR bacteria, transfer from other hospitals, and recent hospitalization. Data were analyzed for MDR bacteria from at least one screening site (rectal, nasal, axillary, groin, throat). All data were analyzed per patient and per sample. RESULTS: During the study period 185/2632 positive screening sets (7%) were obtained from 725 patients. Of these, 165 patients (22.7%) were positive for at least one pathogen. Significantly fewer Israeli residents (120/615, 19.5%) tested positive compared to non-Israeli residents (45/110, 40.9%; P < 0.001). Past MDR bacteria carriage was the only significant screening indication (25/61, 41%; P < 0.001). CRE, VRE, MRSA, and ESBL prevalence rates were 0.6% (5/771), 0.5% (3/560) 0.5%, 4.2% (37/888), and 33.7% (139/413), respectively. Among non-ESBL carriers, MRSA was predominant with 38 positive cultures (n=34). CONCLUSIONS: Non-Israeli non-residents and patients with previous positive MDR screening are at higher risk for MDR bacteria. Indications used to identify high-risk patients for drug resistant pathogens were efficacious. More effort is needed to reduce excessive sampling.

Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses. METHODS: In this prospective cohort study, all consenting eligible CPE carriers received oral capsulized FMT for 2 days. Primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by polymerase chain reaction. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed. RESULTS: Fifteen CPE carriers received FMT, 13 of whom completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants who achieved CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes. CONCLUSIONS: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication. CLINICAL TRIALS REGISTRATION: NCT03167398.

Wall painting following terminal cleaning with a chlorine solution as part of an intervention to control an outbreak of carbapenem-resistant Acinetobacter baumannii in a neurosurgical intensive care unit in Israel.

BACKGROUND: To describe the use of wall painting as part of an intervention to control an outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: An interrupted time-series analysis was performed analyzing an intervention in a neurosurgical intensive care unit (NSICU) and an inpatient hematology department in a tertiary level medical center in Israel. The intervention involved wall painting using a water based acrylic paint following patient discharge and terminal cleaning with sodium troclosene as part of an infection control bundle for an outbreak of CRAB in a NSICU and concurrent outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) colonization/infection in the same NSICU and the hematology department. RESULTS: Between January 2013 and December 2018, 122 patients hospitalized in the NSICU were identified with new CRAB colonization/infection. The median incidence in the periods prior to/post intervention were 2.24/1000 HD (interquartile range [IQR] 0.84-2.90/1000) vs. 0/1000 HD (IQR 0-0.49/1000), respectively. Poisson regression indicated a decrease of 92% in the CRAB incidence following the intervention onset (relative risk [RR] 0.080, 95% confidence interval [CI] 0.037-0.174, p < 0.001). Forty-seven patients in the NSICU and 110 in the hematology department were colonized/infected with CRE in the same time period; a significant change was not observed following the start of the intervention in either department (for NSICU RR 1.236, 95% CI 0.370-4.125, p = 0.731; for hematology RR 0.658, 95% CI 0.314-1.378, p = 0.267). CONCLUSIONS: A. baumannii is able to survive on environmental surfaces despite decontamination efforts; wall-painting as part of a bundle may be a successful infection control measure.

Risk factors for meningitis in neurosurgical patients with cerebrospinal fluid drains: prospective observational cohort study.

BACKGROUND: Cerebrospinal fluid (CSF) drainage or intracranial pressure (ICP) monitoring devices are life-saving devices. We examined the risk factors for infections related to them and assessed the effect of an infection control (IC) intervention. METHODS: A prospective observational study was conducted in the Neurosurgical Department of our hospital between 2014 and 2017. We included all consecutive patients undergoing CSF catheter insertions, including external ventricular drainage (EVD), lumbar drainage (LD), and ICP catheters. An IC intervention was implemented between March and August 2016. We examined risk factors for meningitis or ventriculitis, defined according to Healthcare-associated infections surveillance definitions, on univariate and multivariate analysis. RESULTS: A total of 232 patients with 437 drains (212 EVDs, 92 LDs, and 133 ICPs) were included. On univariate and multivariate analysis, the infection incidence was 13.7 per 1000 drain days (17.3/1000 before IC intervention, 7.9/1000 during, and 9.2/1000 after the intervention). Most episodes were caused by Gram-negative bacteria, and the most common pathogen was Acinetobacter baumanii. Risk factors for infection per patient included diabetes mellitus (p = 0.017), CSF leak (p = 0.032), drain opening (p = 0.027), and the duration of the drain in days (p = 0.035). Risk factors per catheter included drain opening (p < 0.001), drain days (p = 0.001), and the IC intervention period compared to before the intervention period (p = 0.037). When restricting the analysis to EVDs, drain days (p = 0.001) was the only significant risk factor. CONCLUSIONS: Strict adherence to IC, shortening drain duration, and avoiding unnecessary opening and manipulation of the drains are crucial to preventing neurosurgical drain infections.

[THE MORBIDITY AND MORTALITY OF INFLUENZA PATIENTS TREATED AT RAMBAM MEDICAL CENTER INTENSIVE CARE UNIT IN THE YEARS 2009-2014].

INTRODUCTION: Data regarding the characteristics and results of the treatment of patients hospitalized in intensive care units (ICUs) with influenza in Israel are limited. AIMS: We evaluated the characteristics and outcomes of patients treated at Rambam Medical Center at the adult department of critical care medicine for influenza between the years 2009-2014. METHODS: A retrospective cohort study was conducted. Patients were detected by laboratory reports and data were extracted from electronic medical records. RESULTS: The study included 64 patients with laboratory-proven influenza. Median age was 54 years (range 17-83) and symptom duration before admission was 5 days (1-14). The median APACHE-II score at admission was 31.5 and 63.5% were in hemodynamic shock mandating the use of vasopressors. All patients received mechanical ventilation. Inhalation of nitric oxide was needed in a third; 14.3% needed Intra-Pulmonary Percussive Ventilation and steroids were given to 57.1%. ICU mortality was 24/64 (37.5%). Factors significantly associated with mortality were older age, longer length of disease prior to ICU admission, APACHE-II score, septic shock and creatinine. Mortality during the last season was lower than observed during the 2009 pandemia despite increasing severity of illness. CONCLUSIONS: The appearance of a new strain of influenza leads to high morbidity, complications and mortality due to low population immunity. There are no randomized controlled trials evaluating the efficacy of anti-viral drugs and other treatments in severe Influenza with complications. DISCUSSION: The treatment of critically-ill patients with severe influenza is complex, mandates advanced techniques of mechanical ventilation and hemodynamic support. Under intense supportive care most patients with influenza survive.

[REDUCTION OF ANTIBIOTIC CONSUMPTION IN RAMBAM HEALTH CARE CAMPUS - THE ROLE OF AN ANTIBIOTIC STEWARDSHIP PROGRAM].

INTRODUCTION: Antibiotic stewardship programs (ASP) are designed to optimize antibiotic use in hospitals. Antibiotic consumption is one of the measures assessing the effects of ASPs. AIMS: To evaluate the effect of an ASP on antibiotic consumption in our hospital and compare it to hospitals in Israel and worldwide. METHODS: Between October 2012 and March 2013 an ASP was implemented in Rambam Hospital. The program included educational activities, publication of local guidelines for empirical antibiotic treatment, structured infectious diseases consultations, pre-authorization antibiotic restrictions and stop orders. We compared antibacterial antibiotic consumption in defined daily doses (DDD)/100 hospital days (HD) between the periods before (1/2010-3/2013) and after (4/2013-9/2014) implementing the ASP. The study was conducted in the medical departments, hematology, the intensive care unit (ICU) and all pediatric wards. RESULTS: Total antibiotic consumption before implementing the ASP was 96±11.2 DDD/100 HD in medical departments, 186.4±42.8 in the ICU and 185.5±59 in hematology; all values were higher than the worldwide-reported averages for these departments. Following the ASP, total antibiotic consumption decreased by 12% (p=0.008) in the medical departments and by 26% (p=0.002) in hematology, mostly due to reductions in non-restricted antibiotics. No significant changes were observed overall in the ICU and in pediatric wards. There was a significant reduction in consumption of vancomycin and carbapenems in all settings, the latter was reduced to nearly half. Amikacin use quadrupled in the medical departments. CONCLUSIONS: Implementation of an ASP lead to a reduction in non-restricted and restricted antibiotic consumption, especially carbapenems.

Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis.

BACKGROUND: ESBL-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading worldwide. Their natural reservoir is intestinal. METHODS: We carried out a systematic review and meta-analysis to estimate CRE and ESBL carriage duration and to evaluate the effect of decolonization therapy. We included cohort and comparative studies examining the natural history of CRE/ESBL colonization, examining rates of carriage following decolonization or comparing decolonization and no decolonization conducted in the healthcare setting or in the community. A comprehensive search was conducted until November 2015. We compiled carriage rates at 1, 3, 6 and 12 months with and without decolonization therapy and assessed the effect of decolonization. RESULTS: Thirty-seven studies fulfilled inclusion criteria. In healthcare settings, pooled ESBL/CRE colonization rates decreased without intervention from 76.7% (95% CI = 69.3%-82.8%) at 1 month to 35.2% (95% CI = 28.2%-42.9%) at 12 months of follow-up. Following decolonization, the rate was 37.1% (95% CI = 27.5%-47.7%) at end of therapy and 57.9% (95% CI = 43.1%-71.4%) at 1 month. In two randomized trials, carriage was significantly reduced at end of therapy (risk ratio = 0.42, 95% CI = 0.25-0.65), but the effect was not significant after 1 month (risk ratio = 0.72, 95% CI = 0.48-1.05), with no longer follow-up. Heterogeneity was explained by surveillance methodology, with no differences observed between ESBLs and CREs. Among community dwellers, ESBL colonization decreased from 52.3% (95% CI = 29.5%-74.2%) at 1 month to 19.2% (95% CI = 9.7%-34.4%) at 6 months. CONCLUSIONS: A significant proportion of ESBL and CRE carriers remain colonized up to 1 year in the healthcare setting. While short-term decolonization therapy reduces carriage during therapy, its longer-term effects are unclear.

Treatment of Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia: Retrospective Comparison Between Intravenous Colistin and Intravenous Ampicillin-Sulbactam.

Carbapenem-resistant Acinetobacter baumannii has been increasingly reported as the causative agent of ventilator-associated pneumonia (VAP) among patients in the intensive care units. However, there are insufficient data to guide the appropriate treatment for such infection. Our aim was to compare the outcome of carbapenem-resistant A. baumannii VAP treated with colistin or with ampicillin-sulbactam. We conducted a retrospective study of patients diagnosed with carbapenem-resistant A. baumannii VAP during 2008 and 2009. Clinical and microbiologic cure rates, 30-day mortality, and change in renal function were compared between patients treated with colistin versus those treated with ampicillin-sulbactam. The association between treatment and mortality was examined through multivariable logistic regression analysis. Of the 98 patients diagnosed with carbapenem-resistant A. baumannii VAP, 66 were treated with colistin and 32 with ampicillin-sulbactam. Baseline characteristics of patients were similar, except for a longer intensive care unit stay and lower creatinine clearance test before VAP diagnosis among patients treated with colistin. Clinical cure rates were similar in the 2 groups. In the colistin group, microbiologic failure rates were higher at 7 days [16/33 (48%) vs. 3/17 (18%); P = 0.03]; patients had a more significant elevation in creatinine (+0.2 ± 1.0 mg/dL vs. -0.3 ± 1.1 mg/dL; P = 0.021), and treatment was associated with an increased 30-day mortality (adjusted-odds ratio, 6.5; 95% confidence interval, 1.348-31.342; P = 0.02). In conclusion, patients treated with colistin or ampicillin-sulbactam had similar clinical cure rates. However, colistin was associated with higher rates of microbiologic failure, reduction in renal function, and an increased 30-day mortality. A prospective study comparing high-dose colistin and ampicillin-sulbactam for the treatment of carbapenem-resistant A. baumannii VAP is warranted.

Is Leclercia adecarboxylata a new and unfamiliar marine pathogen?

Leclercia adecarboxylata infection is rarely reported in the context of human infections. In the scant cases reported in the literature, it usually involves individuals who are immunocompromised with infections of a polymicrobial nature. Recently, data have begun to accumulate suggesting that L. adecarboxylata is a pathogen associated with water environments. We review the literature regarding L. adecarboxylata infections and present a case of cellulitis and soft-tissue infection in the foot of a healthy surfer.

Persistent COVID-19 in immunocompromised patients-Israeli society of infectious diseases consensus statement on diagnosis and management.

BACKGROUND: Immunocompromised patients with impaired humoral immunity are at risk for persistent COVID-19 (pCOVID), a protracted symptomatic disease with active viral replication. OBJECTIVES: To establish a national consensus statement on the diagnosis, treatment, management, isolation, and prevention of pCOVID in adults. SOURCES: We base our suggestions on the available literature, our own experience, and clinical reasoning. CONTENT: Literature on the treatment of pCOVID is scarce and consists of few case reports and case series. The available studies provide low-quality evidence for monoclonal antibodies, convalescent plasma, antiviral drugs, and immunomodulators. Different combination therapies are described. Continuous viral replication and antiviral treatment may lead to the development of mutations that confer resistance to therapy. IMPLICATIONS: To reduce the risk of resistance and improve outcomes, we suggest treating pCOVID with a combination of antibody-based therapy and two antiviral drugs for duration of 5-10 days. Immunomodulatory therapy can be added in patients with an inflammatory clinical picture. In cases of treatment failure or relapse, prolonged antiviral treatment can be considered. For the prevention of pCOVID, we suggest active and passive vaccination and early initiation of treatment for acute COVID-19. Additional research on pCOVID treatment is urgently needed.

Knowledge of the Serological Response to the Third BNT162b2 Vaccination May Influence Compliance of Healthcare Workers to Booster Dose.

BACKGROUND: Previous studies showed that the fourth SARS-CoV-2 vaccine dose has a protective effect against infection, as well as against severe disease and death. This study aimed to examine whether knowledge of a high-level antibody after the third dose may reduce compliance to the fourth booster dose among healthcare workers (HCWs). METHODS: We conducted a prospective cohort study among HCWs vaccinated with the first three doses at Rambam Healthcare Campus, a tertiary hospital in northern Israel. Participants underwent a serological test before the fourth booster vaccine was offered to all of them, with results provided to participants. The population was divided into two groups, namely those with antibodies below 955 AU/mL and those with 955 AU/mL and higher, a cutoff found protective in a previous study. Multiple logistic regression was carried out to compare the compliance to the fourth booster between the two groups, adjusted for demographic and clinical variables. RESULTS: After adjusting for the confounding variables, the compliance was higher in those with antibody levels below 955 AU/mL (OR = 1.41, p = 0.05, 95% CI 1.10-1.96). In addition, male sex and age of 60 years and above were also associated with higher vaccination rates (OR = 2.28, p < 0.001, 95% CI 1.64-3.17), (OR = 1.14, p = 0.043, 95% CI 1.06-1.75), respectively. CONCLUSIONS: Knowledge of the antibody status may affect compliance with the booster dose. Considering waning immunity over time, reduced compliance may affect the protection of HCWs who declined the fourth dose.

Clinical outcomes of immunomodulation therapy in immunocompromised patients with severe Covid-19 and high oxygen requirement.

Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease.However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce.We aimed to assess clinical outcomes of bar/toc treatment in immunocompromised patients. A multi-center registry of consecutive immunocompromised patients hospitalized due to severe Covid-19 during the Omicron variant dominance period. After excluding patients who did not require high oxygen supply, patients treated with bar/toc were compared to patients treated by standard of care (SOC). Primary outcome was in hospital mortality. Secondary outcomes were 30 and 60 day mortality, super-infection and thromboembolic events. Among an overall 228 immunocompromised patients hospitalized in six Israeli hospitals with severe Covid-19, 112 patients required high oxygen support, of whom 48 (43%) were treated with bar/toc. In-hospital mortality rates were exceptionally high and did not significantly differ between bar/toc and SOC treated patients (62.5% vs. 64.1%, p = 1.0). A logistic regression analysis revealed that advanced age and incomplete vaccination were predictors of in-hospital mortality. Patients treated with bar/toc had no excess of suspected super-infection (62.8% vs. 60.7%, p = 0.84) or thromboembolic events (8.3% vs 3.1%, p = 0.39). In immunocompromised patients with severe Covid-19 and a high oxygen demand, bar/toc therapy was not associated with reduced mortality or with a higher rate of associated complications, compared to SOC. Larger prospective studies should better address efficacy and safety.

Six-Year Surveillance of Acquired Bloodstream Infection in a Pediatric Intensive Care Unit in Israel.

OBJECTIVES: We studied profile of the bloodstream infections (BSI) in the pediatric intensive care unit (PICU) and identified predictors of mortality. METHODS: The study collected data from hospital records for children younger than 18-years who developed BSI during their PICU stay between 2014 and 2019. RESULTS: In 114 patients, 136 PICU-acquired BSIs with 152 pathogens were documented. The incidence of BSI was 47.12/1,000 PICU admissions and 7.95/1000 PICU hospital days. Gram-negative rods accounted for 75% of isolates, Gram-positive cocci accounted for 21.7% of isolates, and fungi accounted for 3.3% of isolated pathogens. ICU mortality was observed in 25 (21.9%) patients with a BSI compared to 94 (3.1%) patients without a BSI (P<0.001). Hemodynamic instability (P=0.014, OR 4.10, CI 1.33-12.66), higher blood urea nitrogen (BUN) (P=0.044), and lower albumin levels (P=0.029) were associated with increased risk of ICU mortality. CONCLUSION: BSI in the PICU is associated with increased mortality. Early identification and management of risk factors independently associated with poor clinical outcomes in these patients should be aimed to ensure improved survival.

Risk factors for acquisition of carbapenemase-producing versus non-carbapenemase-producing enterobacterales: a case-control study.

OBJECTIVES: We aimed to assess the association between carbapenem-resistant Enterobacterales (CRE) colonization pressure and carbapenem exposure and acquisition of carbapenemase-producing Enterobacterales (CPE) and non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE). METHODS: We conducted a parallel 1:2 matched case-control study at Rambam Health Care Campus, Israel, from January 2014 to June 2017. The cases included all adults who acquired CPE or non-CP-CRE in hospital. The controls were hospitalized patients who were negative for CRE on screening and matched by age, hospitalization division and the number of hospitalization days 90 days prior to CRE screening. The exposures of interest were high CRE colonization pressure, defined as a higher-than-median proportion of CRE carriers in the concurrent patient's department before acquisition, and carbapenem exposure, assessed as days of treatment. Conditional logistic regression was used for analyses of CPE and non-CP-CRE. RESULTS: In total, 1058 patients were included: 278 CPE and 75 non-CP-CRE cases, matched to 556 and 149 controls, respectively. High CRE colonization pressure was associated with CPE acquisition (adjusted odds ratio [aOR], 2.6; 95% CI, 1.69-4.02); however, the duration of carbapenem treatment was not (aOR, 1.004; 95% CI, 0.98-1.03; 1-day increment). The duration of carbapenem treatment was significantly associated with non-CP-CRE acquisition (aOR per day, 1.07; 95% CI, 1.03-1.11). A source patient was identified significantly more frequently in epidemiological acquisition investigations of CPE than in those of non-CP-CRE (107/240, 44.6% vs. 18/64, 28.1%, respectively; p 0.017). CONCLUSIONS: CPE acquisition was associated with horizontal transmission, whereas non-CP-CRE was associated with carbapenem exposure. Differences in the drivers of acquisition mandate tailored infection prevention efforts.