Risk Factors and Outcomes of Patients Colonized with KPC and NDM Carbapenemase-Producing Enterobacterales.

Carbapenemase-producing enterobacterales (CPE) poses an increasing threat in hospitals worldwide. Recently, the prevalence of different carbapenemases conferring carbapenem resistance in enterobacterales changed in our country, including an increase in New Delhi Metallo-beta-lactamase (NDM)-CPE. We conducted a comparative historical study of adult patients colonized with Klebsiella pneumoniae carbapenemase (KPC)-CPE (July 2016 to June 2018, a historical cohort) vs. NDM-CPE (July 2016 to January 2023). We identified patients retrospectively through the microbiology laboratory and reviewed their files, extracting demographics, underlying diseases, Charlson Comorbidity Index (CCI) scores, treatments, and outcomes. This study included 228 consecutive patients from whom a CPE rectal swab screening was obtained: 136 NDM-CPE positive and 92 KPC-CPE positive. NDM-CPE-colonized patients had a shorter hospitalization length and a significantly lower 30-day post-discharge mortality rate (p = 0.002) than KPC-CPE-colonized patients. Based on multivariate regression, independent risk factors predicting CPE-NDM colonization included admission from home and CCI < 4 (p < 0.001, p = 0.037, respectively). The increase in NDM-CPE prevalence necessitates a modified CPE screening strategy upon hospital admission tailored to the changing local CPE epidemiology. In our region, the screening of younger patients residing at home with fewer comorbidities should be considered, regardless of a prior community healthcare contact or hospital admission.

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.

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.

The yield of total body CT in the workup of fever of unknown origin in hospitalized medical patients.

INTRODUCTION: Total body computerized tomography (TBCT) is frequently used as a diagnostic tool for fever of unknown origin (FUO) workup instead of a recommended fluorodeoxyglucose positron emission tomography FDG-PET/CT. We have assessed the TBCT diagnostic yield on a large, unselected cohort of patients with FUO. METHODS: We performed a single-center retrospective cohort study, examining all patients hospitalized in internal medicine between 2012 and 2019 with a documented fever and three negative blood cultures who subsequently had a total-body CT performed. After manually reviewing, we included 408 who met the criteria of FUO. We defined a positive study as a scan that led to the documented final diagnosis. RESULTS: A total of 164 patients (40.2 %) had a positive TBCT result. The majority of positive CT findings were of infectious etiologies (58.5 %), followed by neoplasms (22.8 %) and inflammatory disorders (14.0 %), with the chest (43.9 %) and abdomen (29.8 %) most affected. Using a logistic regression model, a positive scan results were associated with an elevated CRP (p<0.001). Decision tree analysis showed that 55 % of scans of patients with an elevated CRP (>6 mg/dL), low hemoglobin and high leucocyte count (>18000/ml) were positive. Patients without an elevated CRP had a positive scan in only 26 % of tests, and those with also an elevated albumin (>4 gr/dL) and low CRP had positive scan in only 11 % of cases. CONCLUSIONS: TBCT has a clinically significant yield under specific clinical scenarios in medical patients with FUO- reaching 55 % in patients with an elevated CRP and leukocyte count and low hemoglobin. It is reasonable to proceed to TTBCT when FDG-PET/CT is unavailable and in well-defined clinical situations.

Post-COVID-19 Peripartum Cardiomyopathy: Experience from a Large Tertiary Referral Center.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare but potentially devastating complication of pregnancy. Although the pathophysiology of PPCM is not fully understood, there are known risk factors for developing PPCM, which are maternal and gestation related. In the first wave of the coronavirus disease 2019 (COVID-19) pandemic, we witnessed an elevated incidence of PPCM among COVID-19 survivors. OBJECTIVES: To present a single-center case series of three patients diagnosed with peripartum cardiomyopathy after recovered from COVID-19 during the index pregnancy. METHODS: In this single center case study, all patients diagnosed with PPCM at our institute during the examined time frame were included. Electronic medical records were studied. RESULTS: Three patients previously diagnosed with asymptomatic or mildly symptomatic COVID-19 disease during pregnancy presented with PPCM before or shortly after delivery. Patients underwent testing to rule out residual COVID-19 myocarditis, were treated pharmacologically and with wearable defibrillators as needed, and were examined in follow-up 1-9 months after delivery. CONCLUSIONS: Residual endothelial damage due to COVID-19 disease, even if originally mild in presentation, could predispose pregnant patients to PPCM and should be considered as a risk factor when assessing patients with new onset symptoms of heart failure. Further research is needed to confirm this hypothesis and fully determine the underlying pathophysiology. These preliminary findings warrant a high index of suspicion for PPCM in COVID-19 recoverers.

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.

The Risk of Rectal Temperature Measurement in Neutropenia.

BACKGROUND: Avoiding rectal thermometry is recommended in patients with neutropenic fever. Permeability of the anal mucosa may result in a higher risk of bacteremia in these patients. Still, this recommendation is based on only a few studies. METHODS: This retrospective study included all individuals admitted to our emergency department during 2014-2017 with afebrile (body temperature <38.3°C) neutropenia (neutrophil count <500 cells/microL) who were over the age of 18. Patients were stratified by the presence or absence of a rectal temperature measurement. The primary outcome was bacteremia during the first five days of index hospitalization; the secondary outcome was in-hospital mortality. RESULTS: The study included 40 patients with rectal temperature measurements and 407 patients whose temperatures were only measured orally. Among patients with oral temperature measurements, 10.6% had bacteremia, compared to 5.1% among patients who had rectal temperature measurements. Rectal temperature measurement was not associated with bacteremia, neither in non-matched (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.07-1.77) nor in matched cohort analyses (OR 0.37, 95% CI 0.04-3.29). In-hospital mortality was also similar between the groups. CONCLUSIONS: Patients with neutropenia who had their temperature taken using a rectal thermometer did not experience a higher frequency of events of documented bacteremia or increased in-hospital mortality.

Preventing varicella zoster infection in immunocompromised adults with varicella zoster-specific immunoglobulins.

Background: Varicella zoster virus (VZV) exposure seriously threatens immunocompromised hosts. Postexposure prophylaxis (PEP) using immune globulins is considered the standard of care; however, the available literature is mainly based on its use in pediatric patients. Here, we describe a widespread VZV exposure among immunocompromised adults treated with VZV-specific immunoglobulins (VZVSIG), and we discuss management and outcomes. Methods: We conducted a retrospective study to describe the exposure of immunocompromised patients to a single healthcare worker with primary VZV in 2019. Patients were grouped by their overall risk for infection, and those at risk received a single intramuscular dose of 625 IU of VZVSIG and were followed for 1 year. Results: In total, 83 patients received PEP at <96 hours of exposure: 14 were hospitalized, 68 were outpatients, and 1 was an immunocompromised staff member. The median age was 69 years (range, 21-92), and 49.4% were male. In addition, 30% of the patients were deemed high risk, 42% were intermediate risk, and 28% were considered low risk, although they were given PEP. Varicella infection was not diagnosed in any patient in the first weeks of follow-up. However, during the year of follow-up, 4 patients developed symptoms suspicious of VZV, all >3 months after exposure, thus were probably unrelated to the event. Adverse events related to VZVSIG (pyrexia) were reported in 2 patients (2.4%). Conclusions: Our findings demonstrate the utility of VZVSIG as PEP in one of the largest cohorts of immunocompromised adults to date. No early varicella infection was found following exposure, supporting the current recommendations of the VZVSIG administration.

Beating the clock: Reduced time to first antibiotic dose administration following an audit and feedback intervention.

OBJECTIVE: Quality improvement interventions and policy revisions have been shown to improve clinical practice and patient outcomes. This study evaluated an intervention to shorten the time from the first antibiotic dose ordering to its administration in patients hospitalised with bacterial infections. METHODS: An intervention consisting of a weekly email report to nurse and physician leaders in hospital departments was introduced. The report included the percentage of patients who received their first antibiotic dose within 3 hours and details of those who did not. Interrupted time series analysis was used to compare the delay between the order and administration of antibiotics in various wards (surgical and medical) and daily nursing shifts. RESULTS: The total number of orders pre-intervention and post-intervention was 58 320 and 52 127, respectively. The most protracted delays were observed during the morning shift in the surgical and medical wards (161 and 100 minutes, respectively). Comparing the pre- to post-intervention time to the first antibiotic dose (TTFAD), a reduction in the morning shift was noted both in the surgical wards (87 minutes, 55%) and medical wards (37 minutes, 37%) and with a preserved trend (P < 0.001). The slope's angle before and after the intervention was not affected. CONCLUSION: Using an audit and feedback automatic weekly report significantly reduced TTFAD in hospitalised patients. This intervention proved to be simple and sustainable over time. Raising staff awareness of current medical care practices is an effective way of improving performance.

Detection of extended-spectrum ß-lactamase-producing bacteria isolated directly from urine by infrared spectroscopy and machine learning.

Resistant bacteria have become one of the leading health threats in the last decades. Extended-spectrum ß-lactamase (ESBL) producing bacteria, including Escherichia (E.) coli and Klebsiella (K.) pneumoniae (the most frequent ones), are a significant class out of all resistant infecting bacteria. Due to the widespread and ongoing development of ESBL-producing (ESBL+) resistant bacteria, many routinely used antibiotics are no longer effective against them. However, an early and reliable ESBL+ bacteria detection method will improve the efficiency of treatment and limit their spread. In this work, we investigated the capability of infrared (IR) spectroscopy based machine learning tools [principal component analysis (PCA) and Random Forest (RF) classifier] for the rapid detection of ESBL+ bacteria isolated directly from patients' urine. For that, we examined 1881 E. coli samples (416 ESBL+ and 1465 ESBL-) and 609 K. pneumoniae samples (237 ESBL+ and 372 ESBL-). All samples were isolated directly from the urine of midstream patients. This study revealed that within 40 min of receiving the patient urine it is possible to determine the infecting bacterium as E. coli or K. pneumoniae with 95% success rate while it was possible to determine the ESBL+E. coli and ESBL+K. pneumoniae with 83% and 78% accuracy rates, respectively.

In vitro activity of eravacycline and comparator agents against bacterial pathogens isolated from patients with cancer.

Background: Bacterial infections are common in patients with cancer, and many bacteria have developed resistance to currently used antibiotics. Objectives: We evaluated the in vitro activity of eravacycline (a recently developed fluorocycline) and comparators against bacterial pathogens isolated from patients with cancer. Methods: Antimicrobial 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. Results: Eravacycline 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. Conclusions: Eravacycline 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.

Outcomes of neutropenic hemato-oncological patients with viridans group streptococci (VGS) bloodstream infection based on penicillin susceptibility.

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.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Characterization of community-acquired Clostridioides difficile strains in Israel, 2020-2022.

Background: The prevalence of community-acquired Clostridioides difficile infection (CA-CDI) has been rising, due to changes in antibiotics prescribing practices, emergence of hypervirulent strains and improved diagnostics. This study explored CA-CDI epidemiology by examining strain diversity and virulence factors of CA-CDI isolates collected across several geographical regions in Israel. Methods: Stool samples of 126 CA-CDI patients were subjected to PCR and an immunoassay to identify toxin genes and proteins, respectively. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Biofilm production was assessed by crystal violet-based assay. Minimum inhibitory concentration was determined using the Etest technique or agar dilution. WGS and multi-locus sequence typing (MLST) were used to classify strains and investigate genetic diversity. Results: Sequence types (ST) 2 (17, 13.5%), ST42 (13, 10.3%), ST104 (10, 8%) and ST11 (9, 7.1%) were the most common. All (117, 92.8%) but ST11 belonged to Clade 1. No associations were found between ST and gender, geographic area or antibiotic susceptibility. Although all strains harbored toxins genes, 34 (27%) produced toxin A only, and 54 (42.9%) strains produced toxin B only; 38 (30.2%) produced both toxins. Most isolates were biofilm-producers (118, 93.6%), primarily weak producers (83/118, 70.3%). ST was significantly associated with both biofilm and toxin production. Conclusion: C. difficile isolates in Israel community exhibit high ST diversity, with no dominant strain. Other factors may influence the clinical outcomes of CDI such as toxin production, antibiotic resistance and biofilm production. Further studies are needed to better understand the dynamics and influence of these factors on CA-CDI.

The Effect of Nonpharmaceutical Interventions Implemented in Response to the COVID-19 Pandemic on Seasonal Respiratory Syncytial Virus: Analysis of Google Trends Data.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infection in children. Despite usually following a consistent seasonal pattern, the 2020-2021 RSV season in many countries was delayed and changed in magnitude. OBJECTIVE: This study aimed to test if these changes can be attributed to nonpharmaceutical interventions (NPIs) instituted around the world to combat SARS-CoV-2. METHODS: We used the internet search volume for RSV, as obtained from Google Trends, as a proxy to investigate these abnormalities. RESULTS: Our analysis shows a breakdown of the usual correlation between peak latency and magnitude during the year of the pandemic. Analyzing latency and magnitude separately, we found that the changes therein are associated with implemented NPIs. Among several important interventions, NPIs affecting population mobility are shown to be particularly relevant to RSV incidence. CONCLUSIONS: The 2020-2021 RSV season served as a natural experiment to test NPIs that are likely to restrict RSV spread, and our findings can be used to guide health authorities to possible interventions.

The Safety and Impact of Raising the Urine Culture Reporting Threshold in Hospitalized Patients.

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.

Current state of antimicrobial stewardship in solid organ transplantation in Israel.

BACKGROUND: We aimed to review the current state, challenges, and needs of antimicrobial stewardship programs (ASPs) in adult solid organ transplantation (SOT) centers in Israel. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.