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Carbapenem-resistant Acinetobacter baumannii (CRAB) causes colonization and infection predominantly in hospitalized patients. Distinction between the two is a challenge. When CRAB is isolated from a non-sterile site (soft tissue, respiratory samples, etc.), it probably represents colonization unless clear signs of infection (fever, elevated white blood count, elevated inflammatory markers and abnormal imaging) are present. Treatment is warranted only for true infections. In normally sterile sites (blood, cerebrospinal fluid) the presence of indwelling medical devices (catheters, stents) should be considered when evaluating positive cultures. In the absence of such devices, the isolate represents an infection and should be treated. If an indwelling device is present and there are no signs of active infection, the device should be replaced if possible, and no treatment is required. If there are signs of an active infection the device should be removed or replaced, and treatment should be administered. Current treatments options and clinical data are limited. No agent or combination regimen has been shown to be superior to any other in randomized clinical trials. Ampicillin-sulbactam appears to have the best evidence for initial use. This is probably due to its ability to saturate penicillin-binding proteins 1 and 3 when given in high dose. Tigecycline when used should be given in high dose as well. Polymyxins are a treatment option but are difficult to dose correctly and have significant side effects. Newer treatment options such as eravacycline and cefiderocol have potential; however, currently there are not enough data to support their use as single agents. Combination therapy appears to be the best treatment option and should always include high-dose ampicillin-sulbactam combined with another active agent such as high-dose tigecycline, polymyxins, etc. These infections require a high complexity of skill, and an infectious disease specialist should be involved in the management of these patients.

BackgroundBacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics.ObjectivesWe evaluated the in vitro activity of eravacycline (a recently developed fluorocycline) and comparators against bacterial pathogens isolated from patients with cancer.MethodsAntimicrobial susceptibility testing was performed using CLSI-approved methodology and interpretive criteria for 255 Gram-positive and 310 Gram-negative bacteria. MIC and susceptibility percentage were calculated according to CLSI and FDA breakpoints when available.ResultsEravacycline had potent activity against most Gram-positive bacteria, including MRSA. Of 80 Gram-positive isolates with available breakpoints, 74 (92.5%) were susceptible to eravacycline. Eravacycline had potent activity against most Enterobacterales, including ESBL-producing organisms. Of 230 Gram-negative isolates with available breakpoints, 201 (87.4%) were susceptible to eravacycline. Eravacycline had the best activity among comparators against carbapenem-resistant Enterobacterales, with 83% susceptibility. Eravacycline was also active against many non-fermenting Gram-negative bacteria, with the lowest MIC90 value among comparators.ConclusionsEravacycline was active against many clinically significant bacteria isolated from patients with cancer, including MRSA, carbapenem-resistant Enterobacterales, and non-fermenting Gram-negative bacilli. Eravacycline might play an important role in the treatment of bacterial infections in patients with cancer, and additional clinical evaluation is warranted.

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.

P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years).We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults.Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality.In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

We aimed to review the current state, challenges, and needs of antimicrobial stewardship programs (ASPs) in adult solid organ transplantation (SOT) centers in Israel.We conducted a survey using electronic questionnaires sent during February 2022 to infectious disease (ID) consultants of SOT centers, encompassing general and organ-specific ASP issues.All six centers performing adult SOTs in Israel participated. The institutional ASPs in all centers included SOT recipients, and five centers had specific stewardship activities targeting SOT recipients. ASP activities were performed by ID consultants in all centers, with clinical pharmacists in most. ASP protocols and activity scope were highly variable. Formulary restriction with pre-authorization was used in all centers. Antibiotic allergy was addressed in ASP guidelines in half of the centers. Peri-transplantation antibiotic, antifungal, and antiviral prophylactic regimens varied based on center, transplanted organ, and patient risk group. Approaches to surveillance cultures, diagnosis and treatment of various graft infections were also variable. ASP outcome measurement was not performed in all centers. The main challenges and barriers to successful ASP implementation were difficulty in defining appropriate durations of therapy for certain infections, high rates of antimicrobial resistance (AMR), and lack of dedicated ASP teams.Antimicrobial stewardship in SOT centers in Israel is performed by ID consultants and practices vary. Challenges are related to high AMR rates, insufficient evidence to support practices, lack of dedicated ASP teams, and lack of outcome measurement. There is an urgent need to establish a national collaborative program including all SOT centers.

In a multicenter, nationwide, retrospective study of patients hospitalized with spotted fever group rickettsiosis in Israel during 2010-2019, we identified 42 cases, of which 36 were autochthonous. The most prevalent species was the Rickettsia conorii Israeli tick typhus strain (n = 33, 79%); infection with this species necessitated intensive care for 52% of patients and was associated with a 30% fatality rate. A history of tick bite was rare, found for only 5% of patients; eschar was found in 12%; and leukocytosis was more common than leukopenia. Most (72%) patients resided along the Mediterranean shoreline. For 3 patients, a new Rickettsia variant was identified and had been acquired in eastern, mountainous parts of Israel. One patient had prolonged fever before admission and clinical signs resembling tickborne lymphadenopathy. Our findings suggest that a broad range of Rickettsia species cause spotted fever group rickettsiosis in Israel.

Brucellosis has a wide range of clinical severity in humans that remains poorly understood. Whole genome sequencing (WGS) analysis may be able to detect variation in virulence genes. We used Brucella melitensis sequences in the NCBI Sequence Read Archive (SRA) database to assemble 248 whole genomes, and additionally, assembled 27 B. melitensis genomes from samples of human patients in Southern Israel. We searched the 275 assembled genomes for the 43 B. melitensis virulence genes in the Virulence Factors of Pathogenic Bacteria Database (VFDB) and 10 other published putative virulence genes. We explored pan-genome variation across the genomes and in a pilot analysis, explored single nucleotide polymorphism (SNP) variation among the ten putative virulence genes. More than 99% of the genomes had sequences for all Brucella melitensis virulence genes included in the VFDB. The 10 other virulence genes of interest were present across all the genomes, but three of these genes had SNP variation associated with particular Brucella melitensis genotypes. SNP variation was also seen within the Israeli genomes obtained from a small geographic region. While the Brucella genome is highly conserved, this novel and large whole genome study of Brucella demonstrates the ability of whole genome and pan-genome analysis to screen multiple genomes and identify SNP variation in both known and novel virulence genes that could be associated with differential disease virulence. Further development of whole genome techniques and linkage with clinical metadata on disease outcomes could shed light on whether such variation in the Brucella genome plays a role in pathogenesis.

Objective: To assess the impact of changing the reporting threshold policy of positive urine cultures in hospitalized non-pregnant adults from 104 CFU/mL to 105 CFU/mL on the unwarranted use of antibiotics and patient safety. Setting: A 1100-bed tertiary-care hospital in southern Israel. Methods: As an intervention, we changed urine culture reporting policy for patients admitted to general medical wards. If culture grew ≥105 CFU/mL, it was reported with pathogen and antibiotic susceptibility data, if it grew ≤104 CFU/mL, it was reported as “low growth". The withheld information was available upon request. We retrospectively collected data on all patients in a four-month period following the intervention and report using STROBE guidelines. Results: 7808 patients were admitted, in whom 3523 urine cultures were obtained. A total of 496 grew a pathogen, 51 were excluded (candida spp. positive, history of urinary surgery, obtained from catheter). A total of 300 were reported as positive and 145 were reported as low-growth. A higher rate of patients in the low-growth group were not treated with antibiotics 45/145(31%) vs. 56/300(18.7%) in the positive group p = 0.015 and the antibiotic duration of treatment was shorter by day 5 (IQR 0.9) vs. 6 (IQR 0.9) p = 0.015. No between-group difference was observed in recurrent admission rates, pyelonephritis within 30 days, bacteremia or all-cause mortality. Conclusions: Changing the reporting threshold of positive urine culture results from 104 CFU/mL to 105 CFU/mL in hospitalized patients reduced the number of patients who were unnecessarily treated for asymptomatic bacteriuria without negatively impacting patient safety. We urge microbiological laboratories to consider this change in threshold as part of an antimicrobial stewardship program.

Variants of concern (VOC) of SARS-CoV2 and waning immunity pose a serious global problem. Overall, vaccination and prior infection provide significant protection, but some individuals remain susceptible to infection and severe disease. Rigorously identifying correlates of protection (COP) is necessary to identify these susceptible populations. We conducted a multicenter prospective study assessing the association between serological profiles and the risk for SARS-CoV-2 infection, comparing those vaccinated with three to four doses of Pfizer BNT162b2 vaccine. We identified several IgG and IgA binding markers that were COPs. The strongest COP was reduced IgG levels to RBD mutants and IgA levels to VOCs (three-dose-group HR=6.34, p=0.008; four-dose-group HR=8.14, p=0.018). Most importantly, we identified a subset of vaccinated individuals with low antibody levels that generated a significant boost in neutralizing antibody titers after a fourth dose, but were still at significantly increased susceptibility to infection.

Introduction Little is known about the kinetics and different phases of a successful antibiotic stewardship program (ASP) intervention. Methods We analyzed the trends of quarterly antibiotic use measured in defined daily dose (DDD)/100 days hospitalization using the Joinpoint Regression Program and interrupted time series analysis to objectively identify shifts in the trends of antibiotic use. We correlated these changes in trends with the introduction of a hospital-wide ASP intervention. Results The ASP intervention reduced the overall antibiotic use by 33%, from a prior steady state of 76.5 DDD/100 days hospitalization to a post-intervention steady state of 51.2 DDD/100 days hospitalization (p

Viridans group streptococci (VGS) bloodstream infection (BSI) in neutropenic patients can be a severe complication. A higher prevalence of vancomycin use has been reported due to reduced susceptibility to penicillin. We aimed to assess the impact on mortality of both penicillin minimal inhibitory concentration (MIC) and the use of vancomycin. We conducted a retrospective multicenter study including consecutive neutropenic patients with VGS BSI between 2007 and 2019. Univariable and multivariable analyses were conducted to evaluate risk factors for mortality, including penicillin susceptibility as an independent variable. Non-susceptibility to penicillin was defined as MIC ≥ 0.25. We included 125 neutropenic patients with VGS BSI. Mean age was 53 years and ~ 50% were women. Overall, 30-day mortality rate was 25/125 (20%), and 41 patients (33%) had a VGS isolate non-susceptible to penicillin. In univariable analysis, no significant association was demonstrated between penicillin non-susceptibility and mortality (9/25, 26% vs. 32/100, 32%, p = 0.81). Among patients with a non-susceptible strain, the use of vancomycin was not significantly associated with mortality (empirical, p = 0.103, or definitive therapy, p = 0.491). Factors significantly associated with increased mortality in multivariable analysis included functional status (ECOG 1, adjusted odds ratio [aOR] 12.53, 95% CI 3.64-43.14; p 0.0001); allogeneic transplantation (aOR 6.33, 95% CI 1.96-20.46; p = 0.002); and co-pathogen in blood cultures (aOR 3.99, 95% CI 1.34-11.89; p = 0.013). Among neutropenic hemato-oncological patients with VGS BSI, penicillin non-susceptibility and the use of vancomycin were not associated with mortality. Thus, vancomycin should not be used routinely as empirical therapy in neutropenic patients with suspected VGS BSI.

Background Changing patterns of vaccine breakthrough can clarify vaccine effectiveness. Aim To compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave. Methods In 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. Results We 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. Conclusions Vaccination 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.

Diabetic foot infections (DFIs) are associated with major morbidity, reduced quality of life and increased mortality. Osteomyelitis is a leading cause of lower-extremity amputation in diabetic patients. We aimed to examine whether a multifaceted strategy for treating hospitalized patients with a DFI effectively influenced microbiological culture results and outcomes. A retrospective cohort-study in a 1100-bed, tertiary-care university hospital was conducted. Adult patients with a DFI admitted to the orthopedics department between 2015 and 2019 were included. During the pre-intervention period (2015-2016), one general orthopedic department was in operation. In the post-intervention period (2017-2019), a second department was created with a designated “complicated wound unit". The multifaceted strategy included revising local guidelines for DFI culturing emphasizing bone cultures, correct sample handling, and adjusting antibiotic treatment to culture results. Additionally, a weekly multidisciplinary-team grand round was instigated and post-discharge outpatient follow-up was scheduled. 652 patients with DFIs were included; 101 during the pre-intervention period and 551 during the post-intervention period. Compared to the pre-intervention, during the post-intervention period mainly bone or deep-tissue cultures were performed (9.7% vs. 98.2%, P

This case report describes a patient with an unusually large pulmonary hydatid cyst and discusses important management issues.

Background: HBV (hepatitis B virus) vaccination in first year of life is recommended to prevent infection. Observational studies have suggested that vaccination at birth provides protection for 90%...

Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products, is endemic in Southern Israel, mainly among the Bedouin Arab population. However, the genomic epidemiology of

(1) Background: Spontaneous bacterial peritonitis (SBP) is a feared complication of liver cirrhosis. We investigated the prevalence of SBP, positive ascitic fluid cultures, and risk factors for mortality. (2) Methods: A retrospective analysis of all patients with cirrhosis hospitalized or in follow-up in a single center between 1996 and 2020. The clinical data, long-term complications, and mortality of SBP patients were compared with those of non-SBP patients. Ascitic fluid positive culture was compared with those without growth. (3) Results: We included 1035 cirrhotic patients, of which 173 (16.7%) developed SBP. Ascitic fluid culture growth was found in 47.4% of the SBP cases, with Escherichia coli bacteria detected in 38%, 24.4% grew ESBL-producing bacteria, and 14.5% displayed multidrug resistance. In a Cox regression model, SBP, male sex, prolonged INR at diagnosis, and hepatocellular carcinoma were found to be risk factors for mortality in cirrhotic patients. The long-term all-cause mortality was 60% in non-SBP and 90% in SBP patients. (4) Conclusions: Only a minority of cirrhotic patients developed SBP, 47.4% of which had positive ascitic fluid cultures with high antibiotic resistance. Growth of ESBL and multidrug resistant organisms is becoming more frequent in the clinical setting, reaching SBP mortality of 90%.

The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy. This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships. Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died. The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.

Objective:To assess the impact of incorporating early rapid influenza diagnosis on antimicrobial usage, nosocomial influenza transmission, length of stay, and occupancy rates among hospitalized patients.Setting:A 1,100 bed tertiary-care hospital in southern Israel.Methods:We implemented early rapid detection of influenza with immediate communication of results. Using Orion methods, we compared the 2017–2018 influenza season to the prior season in our hospital and to the 2017–2018 occupancy rates at other Israeli hospitals.Results:During the intervention season, 5,006 patients were admitted; 1,824 were tested for influenza, of whom 437 (23.9%) were positive. In the previous season, 4,825 patients were admitted; 1,225 were tested and 288 (23.5%) were positive. Time from admission to test report decreased from 35.5 to 18.4 hours (P < .001). Early discharge rates significantly increased, from 21.5% to 41.6% at 36 hours, from 37.2% to 54.5% at 48 hours, and from 66% to 73.2% at 72 hours. No increase in repeat ER visits, readmission, or mortality rates was observed. Hospital occupancy decreased by 10% compared to the previous year and was 26% lower than the national rate. Hospital-acquired influenza cases were reduced from 37 (11.4%) to 12 (2.7%) (P < .001). Antibiotic usage was reduced both before and after notification of test results by 16% and 12%, respectively.Conclusions:Implementing this intervention led to earlier discharge of patients, lower occupancy in medical wards, reduced antibiotic administration, and fewer hospital-acquired influenza events. This strategy is useful for optimizing hospital resources, and its implementation should be considered for upcoming influenza seasons.

As the prevalence of coronavirus disease 2019 (COVID-19) increased in the local community, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) universal screening was initiated for all adult patients admitted through the emergency departments (EDs) at Soroka University Medical Centre. Of 8518 patients screened, 288 (3.38%) tested positive. One hundred and thirty-three (46%) positive cases were asymptomatic and would have been admitted without necessary precautions. Patients with symptoms that may be attributable to COVID-19 were significantly older and were admitted through the medical ED. Patients of Bedouin Arab ethnicity accounted for half of those who tested positive, which was double their prevalence in the general population. These findings indicate that universal SARS-CoV-2 screening on adult hospital admission is crucial in areas with a high prevalence of COVID-19.

Background Many medical schools and residency programs incorporate research projects into their curriculum, however most remain unpublished. Little is known on the long-term effect of early-career publication, especially in female graduates. Methods We collected data on physicians 15–20 years after graduation (representing a mid-career point), and analysed data on early publication, publication volume and impact according to graduates’ gender and professional characteristics. Physicians were divided into those who never published, early-publishers (EP) who published within 2 years of graduation and late-publishers (LP). We analysed and compared the demographics, publication volume, publication quality as well as current mid-career position. Results Of 532 physicians, 185 were EP (34.8%), 220 were LP (41.3%), 127 (23.9%) never published, 491 (92.2%) became specialists and 122 (22.3%) achieved managerial position. Of the 405 who published, the average number of publications was 20.3 ± 33.0, and median (IQR) 9(19). H-index was significantly higher in EP, males, surgical specialists, and those holding a managerial position. Male gender was associated with higher publication rate (OR = 1.742; 95% CI 1.193–2.544; P = 0.004). Using quantile regression, female gender was negatively associated with the number of publications in Q50-Q95. Surgical specialty and managerial position were positively associated with publications in Q25 to Q75 and early publication in Q25 and Q75. Conclusions We found a strong association between EP and the number, impact, and quality of publications throughout their academic career. This study illuminates the need for further investigations into the causes of gender discrepancies. We should invest in support programs encouraging early high quality research projects for young physicians and female graduates.

IntroductionThe optimal treatment for extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae bloodstream infections has yet to be defined. Retrospective studies have shown conflicting results, with most data suggesting the non-inferiority of beta-lactam–beta-lactamase inhibitor combinations compared with carbapenems. However, the recently published MERINO trial failed to demonstrate the non-inferiority of piperacillin–tazobactam to meropenem. The potential implications of the MERINO trial are profound, as widespread adoption of carbapenem treatment will have detrimental effects on antimicrobial stewardship in areas endemic for ESBL and carbapenem-resistant bacteria. Therefore, we believe that it is justified to re-examine the comparison in a second randomised controlled trial prior to changing clinical practice.Methods and analysisPeterPen is a multicentre, investigator-initiated, open-label, randomised controlled non-inferiority trial, comparing piperacillin–tazobactam with meropenem for third-generation cephalosporin-resistant Escherichia coli and Klebsiella bloodstream infections. The study is currently being conducted in six centres in Israel and one in Canada with other centres from Israel, Italy and Canada expected to join. The two primary outcomes are all-cause mortality at day 30 from enrolment and treatment failure at day seven (death, fever above 38°C in the last 48 hours, continuous symptoms, increasing Sequential Organ Failure Assessment Score or persistent blood cultures with the index pathogen). A sample size of 1084 patients was calculated for the mortality endpoint assuming a 12.5% mortality rate in the control group with a 5% non-inferiority margin and assuming 100% follow-up for this outcome.Ethics and disseminationThe study is approved by local and national ethics committees as required. Results will be published, and trial data will be made available.Trial registration numbersClinicalTrials.gov Registry (NCT03671967); Israeli Ministry of Health Trials Registry (MOH_2018-12-25_004857).

[Background] Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality., [Methods] This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009–15. We evaluated the association between β-lactam plus aminoglycoside or quinolone combination therapy versus β-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy., [Results] Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64–1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens., [Conclusions] In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

Objective:To determine whether a multifaceted approach effectively influenced antibiotic use in an orthopedics department.Design:Retrospective cohort study comparing the readmission rate and antibiotic use before and after an intervention.Setting:A 1,000-bed, tertiary-care, university hospital.Patients:Adult patients admitted to the orthopedics department between January 2015 and December 2018.Methods:During the preintervention period (2015–2016), 1 general orthopedic department was in operation. In the postintervention period (2017–2018), 2 separate departments were created: one designated for elective “clean” surgeries and another that included a “complicated wound” unit. A multifaceted strategy including infection prevention measures and introducing antibiotic stewardship practices was implemented. Admission rates, hand hygiene practice compliance, surgical site infections, and antibiotic treatment before versus after the intervention were analyzed.Results:The number of admissions and hospitalization days in the 2 periods did not change. Seven-day readmissions per annual quarter decreased significantly from the preintervention period (median, 7 days; interquartile range [IQR], 6–9) to the postintervention period (median, 4 days; IQR, 2–7; P = .038). Hand hygiene compliance increased and surgical site infections decreased in the postintervention period. Although total antibiotic use was not reduced, there was a significant change in the breakdown of the different antibiotic classes used before and after the intervention: increased use of narrow-spectrum β-lactams (P < .001) and decreased use of β-lactamase inhibitors (P < .001), third-generation cephalosporins (P = .044), and clindamycin (P < .001).Conclusions:Restructuring the orthopedics department facilitated better infection prevention measures accompanied by antibiotic stewardship implementation, resulting in a decreased use of broad-spectrum antibiotics and a significant reduction in readmission rates.

Single-stage group testing uses compressed sensing for efficient high-throughput SARS-CoV-2 testing., Recent reports suggest that 10 to 30% of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infected patients are asymptomatic and that viral shedding may occur before symptom onset. Therefore, there is an urgent need to increase diagnostic testing capabilities to prevent disease spread. We developed P-BEST, a method for Pooling-Based Efficient SARS-CoV-2 Testing, which identifies all positive subjects within a set of samples using a single round of testing. Each sample is assigned into multiple pools using a combinatorial pooling strategy based on compressed sensing. We pooled sets of 384 samples into 48 pools, providing both an eightfold increase in testing efficiency and an eightfold reduction in test costs, while identifying up to five positive carriers. We then used P-BEST to screen 1115 health care workers using 144 tests. P- BEST provides an efficient and easy-to-implement solution for increasing testing capacity that can be easily integrated into diagnostic laboratories.