An international multicenter study comparing COVID-19 omicron outcomes in patients with hematological malignancies treated with obinutuzumab versus rituximab.

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.

Factors Associated with Virological Failure in First-Line Antiretroviral Therapy in Patients Diagnosed with HIV-1 between 2010 and 2018 in Israel.

Despite the progress in contemporary antiretroviral therapy (ART) and the continuous changes in treatment guidelines, virological failure (VF) is still an ongoing concern. The goal of this study was to assess factors related to VF after first-line ART. A longitudinal cohort retrospective study of individuals on first-line ART diagnosed with HIV-1 in 2010-2018 and followed-up for a median of two years was conducted. Demographics, baseline and longitudinal CD4 counts, treatment regimens, adherence and VF were recorded. The Cox proportional hazards regression and mixed models were used. A cohort of 1130 patients were included. Overall, 80% were males and 62% were Israeli-born individuals. Compared to individuals diagnosed in 2010-2014, when treatment was initiated according to CD4 levels, those diagnosed in 2015-2018 were older and had lower baseline CD4 counts. VF was recorded in 66 (5.8%) patients. Diagnosis with CD4 <200 cells/mmᶟ with AIDS-defining conditions (HR = 2.75, 95%CI:1.52-4.97, p < 0.001) and non-integrase strand transfer inhibitor regimens (non-INSTI, HR = 1.80, 95%CI:1.01-3.24, p = 0.047) increased VF risk. No impact of baseline resistance was observed. We concluded that the early detection of HIV-1 infection and usage of INSTI-based regimens are recommended to reduce VF.

Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2.

Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p = 0.008) and four-dose group (HR = 8.14, p = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections.

Bayesian network modeling of patterns of antibiotic cross-resistance by bacterial sample source.

BACKGROUND: Antimicrobial resistance is a major healthcare burden, aggravated when it extends to multiple drugs. While cross-resistance is well-studied experimentally, it is not the case in clinical settings, and especially not while considering confounding. Here, we estimated patterns of cross-resistance from clinical samples, while controlling for multiple clinical confounders and stratifying by sample sources. METHODS: We employed additive Bayesian network (ABN) modelling to examine antibiotic cross- resistance in five major bacterial species, obtained from different sources (urine, wound, blood, and sputum) in a clinical setting, collected in a large hospital in Israel over a 4-year period. Overall, the number of samples available were 3525 for E coli, 1125 for K pneumoniae, 1828 for P aeruginosa, 701 for P mirabilis, and 835 for S aureus. RESULTS: Patterns of cross-resistance differ across sample sources. All identified links between resistance to different antibiotics are positive. However, in 15 of 18 instances, the magnitudes of the links are significantly different between sources. For example, E coli exhibits adjusted odds ratios of gentamicin-ofloxacin cross-resistance ranging from 3.0 (95%CI [2.3,4.0]) in urine samples to 11.0 (95%CI [5.2,26.1]) in blood samples. Furthermore, we found that for P mirabilis, the magnitude of cross-resistance among linked antibiotics is higher in urine than in wound samples, whereas the opposite is true for K pneumoniae and P aeruginosa. CONCLUSIONS: Our results highlight the importance of considering sample sources when assessing likelihood of antibiotic cross-resistance. The information and methods described in our study can refine future estimation of cross-resistance patterns and facilitate determination of antibiotic treatment regimens.

Antibiotics are drugs that kill some bacteria. Antibiotic resistant bacteria are bacteria that continue to grow despite the presence of an antibiotic drug. These bacteria are a major problem in healthcare, particularly if the bacteria are resistant to multiple drugs. Here, we study bacteria that are resistant to several antibiotics that are present in patients in hospital. We find that patterns of cross-resistance differ between the location bacteria were sampled from, such as blood or urine. Our results highlight the importance of considering sample sources when assessing the likelihood that bacteria is resistant to multiple antibiotics. The information and methods described in our study should enable further analysis and prediction of the presence of cross-resistant bacteria, enabling appropriate antibiotic treatments to be used.

Preventing nosocomial bloodstream infections (NBSIs) by implementing hospitalwide, department-level, self-investigations: A NBSIs frontline ownership intervention.

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

Prediction of ciprofloxacin resistance in hospitalized patients using machine learning.

BACKGROUND: Ciprofloxacin is a widely used antibiotic that has lost efficiency due to extensive resistance. We developed machine learning (ML) models that predict the probability of ciprofloxacin resistance in hospitalized patients. METHODS: Data were collected from electronic records of hospitalized patients with positive bacterial cultures, during 2016-2019. Susceptibility results to ciprofloxacin (n = 10,053 cultures) were obtained for Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Pseudomonas aeruginosa, Proteus mirabilis and Staphylococcus aureus. An ensemble model, combining several base models, was developed to predict ciprofloxacin resistant cultures, either with (gnostic) or without (agnostic) information on the infecting bacterial species. RESULTS: The ensemble models' predictions are well-calibrated, and yield ROC-AUCs (area under the receiver operating characteristic curve) of 0.737 (95%CI 0.715-0.758) and 0.837 (95%CI 0.821-0.854) on independent test-sets for the agnostic and gnostic datasets, respectively. Shapley additive explanations analysis identifies that influential variables are related to resistance of previous infections, where patients arrived from (hospital, nursing home, etc.), and recent resistance frequencies in the hospital. A decision curve analysis reveals that implementing our models can be beneficial in a wide range of cost-benefits considerations of ciprofloxacin administration. CONCLUSIONS: This study develops ML models to predict ciprofloxacin resistance in hospitalized patients. The models achieve high predictive ability, are well calibrated, have substantial net-benefit across a wide range of conditions, and rely on predictors consistent with the literature. This is a further step on the way to inclusion of ML decision support systems into clinical practice.

Ciprofloxacin is an antibiotic commonly used to treat various infections. Due to the frequent use of ciprofloxacin, bacteria have developed high rates of resistance to it, which means they continue to grow, reducing the effectiveness of treatment. The aim of this study was to develop computer code to predict ciprofloxacin resistance in hospitalized patients. We used data from medical records and tests of whether particular bacteria could be killed by antibiotics from a large hospital in Israel to develop the computer code. The computational model accurately predicted resistance. This model could enable antibiotic treatment to be more appropriately targeted to patients that would benefit from it and reduce the amount of bacteria resistant to ciprofloxacin.

The development and validation of screening tools for semi-automated surveillance of surgical site infection following various surgeries.

Background: Surveillance of surgical site infections (SSIs) is essential for better prevention. We developed a screening method for SSIs in adults. Methods: The training dataset included data from patients who underwent orthopedic surgeries (N = 1,090), colorectal surgeries (N = 817), and abdominal hysterectomies (N = 523) during 2015-2018. The gold standard for the validation of the screening tool was the presence of SSI as determined by a trained infection control practitioner, via manual full medical record review, using the US Center for Disease Control and Prevention criteria. Using multivariable regression models, we identified the correlates of SSI. Patients who had at least one of these correlates were classified as likely to having SSI and those who did not have any of the correlates were classified as unlikely to have SSI. We calculated the sensitivity and specificity of this tool compared to the gold standard and applied the tool to a validation dataset (N = 1,310, years 2019-2020). Results: SSI was diagnosed by an infection control specialist in 8.2, 5.2, and 31.2% of the patients in the training dataset who underwent hysterectomies, orthopedic surgeries and colorectal surgeries, respectively, vs. 6.2, 6.6, and 25.5%, respectively, in the validation dataset. The correlates of SSI after abdominal hysterectomy were prolonged hospitalization, ordering wound or blood culture, emergency room visit and reoperation; in orthopedic surgery, emergency room visit, wound culture, reoperation, and documentation of SSI, and in colorectal surgeries prolonged hospitalization, readmission, and ordering wound or blood cultures. Area under the curve was >90%. The sensitivity and specificity (95% CI) of the screening tool were 98% (88-100) and 58% (53-62), for abdominal hysterectomy, 91% (81-96) and 82% (80-84) in orthopedic surgeries and 96% (90-98) and 62% (58-66) in colorectal surgeries. The corresponding values for the validation dataset were 89% (67-97) and 75% (69-80) in abdominal hysterectomy; 85% (72-93) and 83% (80-86) in orthopedic surgeries and 98% (93-99) and 59% (53-64) in colorectal surgeries. The number of files needed to be fully reviewed declined by 61-66. Conclusion: The presented semi-automated simple screening tool for SSI surveillance had good sensitivity and specificity and it has great potential of reducing workload and improving SSI surveillance.

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.

The time-varying association between previous antibiotic use and antibiotic resistance.

OBJECTIVES: The objective of the study was to estimate how the time elapsed from previous antibiotic use is associated with antibiotic resistance. METHODS: Data comprised electronic medical records of all patients in an Israeli hospital who had a positive bacterial culture from 2016 to 2019. These included susceptibility testing results and clinical and demographic data. Mixed-effects time-varying logistic models were fitted to estimate the association between the time elapsed since the last use of aminoglycosides and gentamicin resistance (n = 13 095), cephalosporins and ceftazidime resistance (n = 13 051), and fluoroquinolones and ciprofloxacin resistance (n = 15 364) while adjusting for multiple covariates. RESULTS: For all examined antibiotics, previous antibiotic use had a statistically significant association with resistance (p < 0.001). These associations exhibited a clear decreasing pattern over time, which we present as a flexible function of time. Nonetheless, previous antibiotic use remained a significant risk factor for resistance for at least 180 days when the adjusted ORs were 1.94 (95% CI, 1.40-2.69), 1.33 (95% CI, 1.10-1.61), and 2.25 (95% CI, 1.49-3.41) for gentamicin, ceftazidime, and ciprofloxacin, respectively. DISCUSSION: The association between prior antibiotic use and resistance decreases over time. Commonly used cut-offs for prior antibiotic use can either misclassify patients still at higher risk when too recent or provide a diluted estimate of the effects of antibiotic use on future resistance when too distant. Hence, prior antibiotic use should be considered a time-dependent risk factor for resistance in both epidemiological research and clinical practice.

Invasive Fungal Diseases in Hospitalized Patients with COVID-19 in Israel: A Multicenter Cohort Study.

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.

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.

The Effect of Macrolides on Mortality in Bacteremic Pneumococcal Pneumonia: A Retrospective, Nationwide Cohort Study, Israel, 2009-2017.

BACKGROUND: Previous cohort studies of pneumonia patients reported lower mortality with advanced macrolides. Our aim was to characterize antibiotic treatment patterns and assess the role of quinolones or macrolides in empirical therapy. MATERIALS: An historical cohort, 1 July 2009 to 30 June 2017, included, through active surveillance, all culture-confirmed bacteremic pneumococcal pneumonia (BPP) among adults in Israel. Cases without information on antibiotic treatment were excluded. Logistic regression analysis was used to assess independent predictors of in-hospital mortality. RESULTS: A total of 2016 patients with BPP were identified. The median age was 67.2 years (interquartile range [IQR] 53.2-80.6); 55.1% were men. Lobar pneumonia was present in 1440 (71.4%), multi-lobar in 576 (28.6%). Median length of stay was 6 days (IQR 4-11). A total of 1921 cases (95.3%) received empiric antibiotics with anti-pneumococcal coverage: ceftriaxone, in 1267 (62.8%). Coverage for atypical bacteria was given to 1159 (57.5%), 64% of these, with macrolides. A total of 372 (18.5%) required mechanical ventilation, and 397 (19.7%) died. Independent predictors of mortality were age (odds ratio [OR] 1.051, 95% confidence interval [CI] 1.039, 1.063), being at high-risk for pneumococcal disease (OR 2.040, 95% CI 1.351, 3.083), multi-lobar pneumonia (OR 2.356, 95% CI 1.741, 3.189). Female sex and macrolide therapy were predictors of survival: (OR 0.702, 95% CI .516, .955; and OR 0.554, 95% CI .394, .779, respectively). Either azithromycin or roxithromycin treatment for as short as two days was predictor of survival. Quinolone therapy had no effect. CONCLUSIONS: Empirical therapy with macrolides reduced odds for mortality by 45%. This effect was evident with azithromycin and with roxithromycin. The effect did not require a full course of therapy.

Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods.

Background: Infected diabetic foot ulcers (IDFU) are a major complication of diabetes mellitus. These potentially limb-threatening ulcers are challenging to treat due to impaired wound healing characterizing diabetic patients and the complex microbial environment of these ulcers. Aim: To analyze the microbiome of IDFU in association with clinical outcomes. Methods: Wound biopsies from IDFU were obtained from hospitalized patients and were analyzed using traditional microbiology cultures, 16S rRNA sequencing and metagenomic sequencing. Patients' characteristics, culture-based results and sequencing data were analyzed in association with clinical outcomes. Results: A total of 31 patients were enrolled. Gram-negative bacteria dominated the IDFU samples (79%, 59% and 54% of metagenomics, 16S rRNA and cultures results, respectively, p<0.001). 16S rRNA and metagenomic sequencing detected significantly more anaerobic bacteria, as compared to conventional cultures (59% and 76%, respectively vs. 26% in cultures, p=0.001). Culture-based results showed that Staphylococcus aureus was more prevalent among patients who were treated conservatively (p=0.048). In metagenomic analysis, the Bacteroides genus was more prevalent among patients who underwent amputation (p<0.001). Analysis of metagenomic-based functional data showed that antibiotic resistance genes and genes related to biofilm production and to bacterial virulent factors were more prevalent in IDFU that resulted in amputation (p<0.001). Conclusion: Sequencing tools uncover the complex biodiversity of IDFU and emphasize the high prevalence of anaerobes and Gram-negative bacteria in these ulcers. Furthermore, sequencing results highlight possible associations among certain genera, species, and bacterial functional genes to clinical outcomes.

Estimating the impact of cefuroxime versus cefazolin and amoxicillin/clavulanate use on future collateral resistance: a retrospective comparison.

BACKGROUND: Quantitative estimates of collateral resistance induced by antibiotic use are scarce. OBJECTIVES: To estimate the effects of treatment with amoxicillin/clavulanate or cefazolin, compared with cefuroxime, on future resistance to ceftazidime among hospitalized patients. METHODS: A retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-19 was conducted. Patients were restricted to those treated with amoxicillin/clavulanate, cefazolin or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. Matching was performed using exact, Mahalanobis and propensity score matching. Each patient in the amoxicillin/clavulanate and cefazolin groups was matched to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and the g-formula (standardization) were used to estimate the OR, risk difference (RD) and number needed to harm (NNH). RESULTS: Cefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin; the marginal OR was 1.76 (95% CI = 1.16-2.83) compared with amoxicillin/clavulanate and 1.98 (95% CI = 1.41-2.8) compared with cefazolin and the RD was 0.118 (95% CI = 0.031-0.215) compared with amoxicillin/clavulanate and 0.131 (95% CI = 0.058-0.197) compared with cefazolin. We also estimated the NNH; replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime resistance in 1 more patient for every 8.5 (95% CI = 4.66-32.14) or 7.6 (95% CI = 5.1-17.3) patients re-hospitalized in the following year, respectively. CONCLUSIONS: Our results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.

Community antibiotic prescriptions during COVID-19 era: a population-based cohort study among adults.

OBJECTIVES: This study investigated the association between the COVID-19 pandemic and antibiotic prescription ratios and the determinants of antibiotic prescription in the community. METHODS: The study was based on a retrospective population cohort of adults in a community setting. Antibiotic prescription ratios from March 1, 2020 to February 28, 2021 (COVID-19 period) were compared to similar months in previous years. Differences in visit type, infectious disease-related visit, and antibiotic prescription ratios during these visits were compared. A logistic regression model was used to identify independent determinants of antibiotic prescription during the study period. RESULTS: The cohort included almost 3 million individuals with more than 33 million community medical encounters per year. In the COVID-19 period, the antibiotic prescription ratio decreased 45% (from 34.2 prescriptions/100 patients to 19.1/100) compared to the previous year. Visits due to an infectious disease etiology decreased by 10% and prescriptions per visit decreased by 39% (from 1 034 425 prescriptions/3 764 235 infectious disease visits to 587 379/3 426 451 respectively). This decrease was observed in both sexes and all age groups. Telemedicine visits were characterized by a 10% lower prescription ratio compared to in-person visits. Thus, a threefold increase in telemedicine visits resulted in a further decrease in prescription ratios. The COVID-19 period was independently associated with a decrease in antibiotic prescription, with an OR of 0.852 (95% CI 0.848-0.857). DISCUSSION: We describe a significant decrease in antibiotic prescription ratios during the COVID-19 periods that was likely related to a decrease in the incidence of certain infectious diseases, the transfer to telemedicine, and a change in prescription practices among community-based physicians.

Validation of a semiautomated system for surveillance of surgical site infection after cesarean section.

Surveillance of surgical site infection after cesarean section is challenging due to the high volume of these surgeries. A manual chart review of women undergoing cesarean section between January and June 2017 (675 charts, 40 infections) was compared to charts identified via an algorithm (141 charts, 39 infections). The algorithm achieved 97.5% sensitivity and 83.9% specificity and reduced the workload of infection control personnel.

Early effectiveness of BNT162b2 Covid-19 vaccine in preventing SARS-CoV-2 infection in healthcare personnel in six Israeli hospitals (CoVEHPI).

BACKGROUND: Methodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate early real-world VE in a closely monitored population. METHODS: We conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples - at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher's exact test. RESULTS: Of the 1567 HCP enrolled between December 27, 2020 and February 15, 2021, 1250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR-confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant. CONCLUSIONS: Our prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 infection in recently vaccinated HCP during a period of predominant alpha variant circulation. FUNDING: Clalit Health Services.

Long term dual antiretroviral therapy: A real life retrospective countrywide Israeli study.

AIM: Combined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines. PURPOSE: Characterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey. METHODS: A cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment. RESULTS: 176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment in 2019. 2DR that included INSTI and PI were more commonly used in cases of drug resistance, while a combination of INSTI and NNRTI was used in all other 2DR indications. A switch to 2DR induced a mean CD4 T cell increase from 599 cells/µl at treatment initiation to 680 cells/µl at 96 weeks of treatment p<0.001 and viral suppression improvement from 73.9% at initiation to 87.0% at 48 weeks of treatment (p = 0.004). PI and INSTI 2DR was inferior in suppressing viral levels compared to other 2DRs but used for subset of more complex patients. CONCLUSIONS: 2DR in a large-scale real-life nation-wide survey proved to be safe and effective. Most 2DRs, other than PI and INSTI, were similarly effective in suppressing HIV viremia and in elevating CD4 T cell counts.

Risk factors for surgical site infections following open versus laparoscopic colectomies: a cohort study.

BACKGROUND: Surgical site infections (SSIs) are among the most common healthcare-associated infections. Evaluating risk factors for SSIs among patients undergoing laparoscopic and open colorectal resections can aid in selecting appropriate candidates for each modality. METHODS: A cohort of all consecutive patients undergoing elective colorectal resections during 2008-2017 in a single center was analyzed. SSIs were prospectively assessed by infection control personnel. Patient data were collected from electronic medical records. Risk factors for SSIs were compared between patients who underwent laparoscopic and open surgeries. A multivariate analysis was performed for significant variables. RESULTS: During the study period, 865 patients underwent elective colorectal resection: 596 laparoscopic and 269 open surgeries. Mean age was 68.2 ± 15.1 years, weight 72.5 ± 18.3 kg and 441 (51%) were men. The most common indication for surgery was malignancy, in 767 patients (88.7%) with inflammatory bowel diseases and diverticulitis following (4.5% and 3.9%, respectively). Patients undergoing laparoscopic surgery were younger, had fewer comorbidities, shorter pre-operative hospitalizations, lower risk index scores, and lower rates of SSI, compared with open surgery. Independent risk factors for SSI following laparoscopic surgery were chronic obstructive pulmonary disease [odds ratio (OR) 2.655 95% CI (1.267, 5.565)], risk index ≥ 2 [OR 2.079, 95% CI (1.041,4.153)] and conversion of laparoscopic to open surgery [OR 2.056 95%CI (1.212, 3.486)]. Independent risk factors for SSI following open surgery were immunosuppression [OR 3.378 95% CI (1.071, 10.655)], chronic kidney disease [OR 2.643 95% CI (1.008, 6.933)], and need for a second dose of prophylactic antibiotics [OR 2.519 95%CI (1.074, 5.905)]. CONCLUSIONS: Risk factors for SSIs differ between laparoscopic and open colorectal resections. Knowledge of specific risk factors may inform patient selection for these modalities.