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Objective: As a result of high recurrence rates of Candida albicans vaginitis, successful suppressive fluconazole is widely used, and drug resistance is considered rare. We report increased occurrence of secondary fluconazole resistance, analysis of risk factors thereof, and describe management of fluconazole-refractory vaginitis.Methods: Patients referred to the Vaginitis Clinic at Wayne State University with clinically refractory fluconazole-resistant (minimum inhibitory concentration [MIC] 2 micrograms/mL or greater) C albicans vaginitis from 2000 to 2010 were enrolled. Patients completed a questionnaire pertaining to demographics, comorbidities, behavioral characteristics, exposure to antimicrobials and antifungals, fluconazole consumption in defined daily doses in the previous 6 months, management received, and outcomes. With patients not located, data were extracted from charts. Susceptibilities to antifungals were determined by broth microdilution.Results: Twenty-five women with fluconazole-resistant recurrent C albicans vaginitis were identified, and 16 returned filled questionnaires. Study cohort consisted mainly of married, insured white women with more than 12 years of formal education and average or above average socioeconomic status. Median fluconazole MIC was 8 micrograms/mL (range 2-128 micrograms/mL). Risk factors for mycologic failure included increased fluconazole consumption (P=.03) with 16 of 25 women exposed to low-dose weekly fluconazole maintenance therapy. All patients were clinically controlled successfully, although treatment was difficult and often prolonged.Conclusion: Fluconazole-resistant C albicans vaginitis was previously considered rare. We report 25 cases over an 11-year period, indicating an emerging problem. All patients had fluconazole consumption in the previous 6 months. Management of fluconazole refractory disease is extremely difficult with limited options, and new therapeutic modalities are needed. [ABSTRACT FROM AUTHOR]

Background: A beta-lactam antibiotics (BLA) allergy label is common, resulting in disadvantageous outcomes due to the usage of second-line antimicrobial agents. Noncontrolled case-series analyses report low rates of hypersensitivity reactions, following intentional/non-intentional BLA challenges among labeled inpatients. The study aims were to explore predictors and outcomes associated with hypersensitivity reactions following BLA challenge among BLA-allergic labeled inpatients., Methods: Retrospective cohort study (2019-2020) of adult (≥18 years) inpatients (Shamir Medical Center, Israel), labeled as allergic to ≥1 BLA, who received ≥1 dose/s of BLA during their stay. Independent predictors to develop allergic reactions and the independent associations of allergic reactions with clinical outcomes were queried by logistic and Cox regressions., Results: Of 9,670 inpatients (14,088 hospitalizations), 3,570 (37%) were labeled as allergic to ≥1 BLA. Of those, 1,171 (33%) patients received ≥1 BLA. The majority were women (67%), and the mean age was 69.3 ± 19.4 years. Only 30 patients (2.6%) developed a reaction, all mild. Independent predictors to develop an allergic reaction were documented reactions in the past, atopic background, antihistamines administration prior to the BLA challenge, and high risk for cross-reactivity, based on the BLA side chains, between the labeled and the challenged agents. Reaction upon the BLA challenge was not independently associated with any worse outcome., Conclusions: Despite the commonality of allergy labeling, and the commonality of BLA administration to labeled inpatients, hypersensitivity reactions were mild and rare. Interventional stewardship strategies for active BLA de-labeling among low-risk patients should be promoted, to improve patients' and institutional health and fiscal outcomes., Competing Interests: All authors reported no conflicts of interest relevant to this article., (© The Author(s) 2024.)

Stenotrophomonas maltophilia and Achromobacter xylosoxidans are emerging nosocomial, non-glucose fermenting, Gram-negative pathogens. In this nested case-control trial, independent predictors for S. maltophilia infections were hemodialysis and recent antibiotic usage (overall), while recent usage of fluoroquinolones, was independently associated with A. xylosoxidans infections. Infections were independently associated with multiple worse outcomes., Competing Interests: All authors declare no conflict of interest., (© The Author(s) 2024.)

Background: Klebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage., Methods: We computationally analyzed a large collection of K. pneumoniae ST395 genomes (n = 297) both sequenced in this study and reported previously. By applying multiple bioinformatics tools, we investigated the core-genome phylogeny and evolution of ST395 as well as distribution of accessory genome elements associated with antibiotic resistance and virulence features., Results: Clustering of the core-SNP alignment revealed four major clades with eight smaller subclades. The subclades likely evolved through large chromosomal recombination, which involved different K. pneumoniae donors and affected, inter alia, capsule and lipopolysaccharide antigen biosynthesis regions. Most genomes contained acquired resistance genes to extended-spectrum cephalosporins, carbapenems, and other antibiotic classes carried by multiple plasmid types, and many were positive for hypervirulence markers, including the siderophore aerobactin. The detection of "hybrid" resistance and virulence plasmids suggests the occurrence of the convergent ST395 pathotype., Conclusions: To the best of our knowledge, this is the first study that investigated a large international collection of K. pneumoniae ST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage., (© 2023. The Author(s).)

Background: Older adults frequently experience deconditioning following acute illnesses and require discharge from acute-care facilities to post-acute care facilities, which are limited. Our study aimed to explore predictors and outcomes associated with elongated length of stay (LOS) among older adults awaiting discharge to skilled nursing facility (SNF)., Methods: Retrospective cohort study was conducted at Shamir Medical Center, Israel, among adults (> 65 years) eligible for SNF. ROC curve analysis was used to determine prolonged LOS based on the risk to fall. Logistic and Cox regressions were used to analyze predictors and outcomes., Results: Among 659 older adults awaiting transfer to SNF, 127 patients (24% among survivors of the index hospitalization) had prolonged LOS (> 12 days). The median age of patients was 82 years and 51% were females. The independent predictors for prolonged LOS were lower Norton index, higher MUST score, and admission from home. Prolonged LOS was independently associated with hospital-acquired infections, device related infections, and acquisitions of multidrug-resistant organisms., Conclusion: Prolonged LOS among older adults, awaiting transfer to SNF, should be suspected among non-institutionalized older adults with lower nutritional status and higher risk of pressure ulcers. The burden associated with establishing additional SNF beds, must be outweighed vs. the substantial infectious complications among awaiting older adults., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii , XDR Pseudomonas aeruginosa , and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections., Methods: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii , XDR P. aeruginosa , or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure., Results: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively., Conclusions: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Sepsis is one of the leading causes of hospitalization and death among hemodialysis patients. Infections due to multidrug-resistant organisms (MDROs) are common among these patients, but empiric broad-spectrum coverage for every septic patient is associated with unfavorable outcomes. A retrospective case-control study was conducted at Shamir Medical Center, Israel (July 2016-April 2020), to determine predictors of MDRO infections among septic (per SEPSIS-3) ambulatory adult hemodialysis patients with permanent dialysis access (i.e., fistula, graft, or tunneled Perm-A-Cath). MDROs were determined according to established definitions. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prediction score and determine its performance. Of 509 patients, 225 (44%) had microbiologically confirmed infection, and 79 patients (35% of 225) had MDROs. The eventual independent predictors of MDRO infections were Perm-A-Cath access (vs. fistula or graft, aOR = 3, CI-95% = 2.1-4.2) and recent hospitalization in the previous three months (aOR = 2.3, CI-95% = 1.6-3.3). The score to predict MDRO sepsis with the highest performances contained seven parameters and displayed an area under the receiver operating characteristic curve (ROC AUC) of 0.74. This study could aid in defining a group of hemodialysis patients for which empiric broad-spectrum agents could be safely avoided.

Hospital-acquired urinary tract infection (HAUTI) is one of the most common hospital-acquired infections, and over 80% of HAUTI are catheter-associated (CAUTI). Pseudomonas aeruginosa , as well as other non-glucose fermenting Gram negative organisms (NGFGN, e.g., Acinetobacter baumannii ), are frequently covered empirically with "anti-Pseudomonals" being administered for every HAUTI (and CAUTI). However, this common practice was never trialed in controlled settings in order to quantify its efficacy and its potential impacts on hospitalization outcomes. There were 413 patients with HAUTI that were included in this retrospective cohort study (2017-2018), 239 (57.9%) had CAUTI. There were 75 NGFGN infections (18.2% of HAUTI, 22.3% of CAUTI). P. aeruginosa was the most common NGFGN (82%). Despite multiple associations per univariable analysis, recent (3 months) exposure to antibiotics was the only independent predictor for NGFGN HAUTI (OR = 2.4, CI-95% = 1.2-4.8). Patients who received empiric anti-Pseudomonals suffered from worse outcomes, but in multivariable models (one for each outcome), none were independently associated with the empiric administration of anti-Pseudomonals. To conclude, approximately one of every five HAUTI (and CAUTI) are due to NGFGN, which justifies the practice of empiric anti-Pseudomonals for patients with HAUTI (and CAUTI), particularly patients who recently received antibiotics. The practice is not associated with independent deleterious impacts on outcomes.

Multidrug-resistant gram-negative bacteria (MDR-GNB) pose one of the greatest challenges to health care today because of their propensity for human-to-human transmission and lack of therapeutic options. Containing the spread of MDR-GNB is challenging, and the application of multifaceted infection control bundles during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article will review the utility of various infection control measures in containing the spread of various MDR-GNB and will provide the supporting evidence for these interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hospital-acquired urinary tract infections (HAUTI) are common and most cases are related to catheters (CAUTI). HAUTI and CAUTI surveillance is mandatory in many countries as a measure to reduce the incidence of infections and appropriately direct the allocation of preventable resources. The surveillance criteria issued by the Israeli Ministry of Health (IMOH), differ somewhat from that of the U.S. Centers for Disease Control and Prevention (CDC). Our study aims were to query and quantify the impact of these differences. In a retrospective cohort study conducted at Shamir Medical Center, for calendar year 2017, the surveillance criteria of both IMOH and CDC were applied on 644 patient-unique adults with "positive" urine cultures (per similar definitions). The incidence of HAUTI per IMOH was significantly higher compared to CDC (1.24/1000 vs. 1.02/1000 patient-days, p = 0.02), with no impact on hospitalization's outcomes. The agreement rate between methods was high for CAUTI (92%), but much lower for all HAUTI (83%). The major error rate, i.e., patients diagnosed with HAUTI per IMOH but had no UTI per CDC, was 31%. To conclude, in order for surveillance to reflect the relative situation and direct allocation of preventable resources based on scientific literature, the process should be uniform worldwide.

Objective: In the era of widespread resistance, there are 2 time points at which most empiric prescription errors occur among hospitalized adults: (1) upon admission (UA) when treating patients at risk of multidrug-resistant organisms (MDROs) and (2) during hospitalization, when treating patients at risk of extensively drug-resistant organisms (XDROs). These errors adversely influence patient outcomes and the hospital's ecology., Design and Setting: Retrospective cohort study, Shamir Medical Center, Israel, 2016., Patients: Adult patients (aged >18 years) hospitalized with sepsis., Methods: Logistic regressions were used to develop predictive models for (1) MDRO UA and (2) nosocomial XDRO. Their performances on the derivation data sets, and on 7 other validation data sets, were assessed using the area under the receiver operating characteristic curve (ROC AUC)., Results: In total, 4,114 patients were included: 2,472 patients with sepsis UA and 1,642 with nosocomial sepsis. The MDRO UA score included 10 parameters, and with a cutoff of ≥22 points, it had an ROC AUC of 0.85. The nosocomial XDRO score included 7 parameters, and with a cutoff of ≥36 points, it had an ROC AUC of 0.87. The range of ROC AUCs for the validation data sets was 0.7-0.88 for the MDRO UA score and was 0.66-0.75 for nosocomial XDRO score. We created a free web calculator (https://assafharofe.azurewebsites.net)., Conclusions: A simple electronic calculator could aid with empiric prescription during an encounter with a septic patient. Future implementation studies are needed to evaluate its utility in improving patient outcomes and in reducing overall resistances.

Objectives: This study aims to examine the prevalence and risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sero-positivity in health care workers (HCWs), a main risk group, and assess the sero-incidence of SARS-CoV-2 infection between the first and second waves of coronavirus disease 2019 (COVID-19) in Israel. Methods: A longitudinal study was conducted among 874 HCWs from nine hospitals. Demographics, health information, and blood samples were obtained at baseline (first wave-April-May 2020) and at follow-up ( n = 373) (second wave-September-November 2020). Sero-positivity was determined based on the detection of total antibodies to the nucleocapsid antigen of SARS-CoV-2, using electro-chemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2, Roche Diagnostics, Rotkreuz, Switzerland). Results: The sero-prevalence of SARS-CoV-2 antibodies was 1.1% [95% confidence intervals (CI) 0.6-2.1] at baseline and 8.3% (95% CI 5.9-11.6) at follow-up. The sero-conversion of SARS-CoV-2 serum antibody was 6.9% (95% CI 4.7-9.9) during the study period. The increase in SARS-CoV-2 sero-prevalence paralleled the rise in PCR-confirmed SARS-CoV-2 infections among the HCWs across the country. The likelihood of SARS-CoV-2 sero-prevalence was higher in males vs. females [odds ratio (OR) 2.52 (95% CI 1.05-6.06)] and in nurses vs. physicians [OR 4.26 (95% CI 1.08-16.77)] and was associated with being quarantined due to exposure to COVID-19 patients [OR 3.54 (95% CI 1.58-7.89)] and having a positive PCR result [OR 109.5 (95% CI 23.88-502.12)]. Conclusions: A significant increase in the risk of SARS-CoV-2 infection was found among HCWs between the first and second waves of COVID-19 in Israel. Nonetheless, the sero-prevalence of SARS-CoV-2 antibodies remains low, similar to the general population. Our findings reinforce the rigorous infection control policy, including quarantine, and utilization of personal protective equipment that should be continued together with COVID-19 immunization in HCWs and the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Muhsen, Schwaber, Bishara, Kassem, Atamna, Na'amnih, Goren, Bialik, Mohsen, Zaide, Hazan, Ariel-Cohen, Cohen, Shitrit, Marchaim, Benenson, Ben-David, Rubinovitch, Gotessman, Nutman, Wiener-Well, Maor, Carmeli and Cohen.)

A case-case-control investigation (216 patients) examined the risk factors and outcomes of carbapenem-resistant Enterobacter (CR-En) acquisition. Recent exposure to fluoroquinolones, intensive care unit (ICU) stay, and rapidly fatal McCabe condition were independent predictors for acquisition. Acquiring CR-En was independently associated with discharge to a long-term care facility after being admitted from home.

The independent association of diabetes and hyperglycemia on the outcomes of sepsis remains unclear. We conducted retrospective cohort analyses of outcomes among patients with community-onset sepsis admitted to Shamir Medical Center, Israel (08-12/2016). Statistical associations were queried by Cox and logistic regressions, controlled for by matched propensity score analyses. Among 1527 patients with community-onset sepsis, 469 (30.7%) were diabetic. Diabetic patients were significantly older, with advanced complexity of comorbidities, and were more often exposed to healthcare environments. Despite statistically significant univariable associations with in-hospital and 90-day mortality, the adjusted Hazard Ratios (aHR) were 1.21 95% CI 0.8-1.71, p = 0.29 and 1.13 95% CI 0.86-1.49, p = 0.37, respectively. However, hyperglycemia at admission (i.e., above 200 mg/dl (was independently associated with: increased in-hospital mortality, aHR 1.48 95% CI 1.02-2.16, p = 0.037, 30-day mortality, aHR 1.8 95% CI 1.12-2.58, p = 0.001), and 90-day mortality, aHR 1.68 95% CI 1.24-2.27, p = 0.001. This association was more robust among diabetic patients than those without diabetes. In this study, diabetes was not associated with worse clinical outcomes in community-onset sepsis. However, high glucose levels at sepsis onset are independently associated with a worse prognosis, particularly among diabetic patients. Future trials should explore whether glycemic control could impact the outcomes and should be part of the management of sepsis, among the general adult septic population.

In human medicine, infections caused by third-generation cephalosporin-resistant Enterobacterales (3GCRE) are associated with detrimental outcomes. In veterinary medicine, controlled epidemiological analyses are lacking. A matched case-case-control investigation (1:1:1 ratio) was conducted in a large veterinary hospital (2017-2019). In total, 29 infected horses and donkeys were matched to 29 animals with third-generation cephalosporin-susceptible Enterobacterales (3GCSE) infections, and 29 uninfected controls (overall n = 87). Despite multiple significant associations per bivariable analyses, the only independent predictor for 3GCRE infection was recent exposure to antibiotics (adjusted odds ratio (aOR) = 104, p < 0.001), but this was also an independent predictor for 3GCSE infection (aOR = 22, p < 0.001), though the correlation with 3GCRE was significantly stronger (aOR = 9.3, p = 0.04). In separated multivariable outcome models, 3GCRE infections were independently associated with reduced clinical cure rates (aOR = 6.84, p = 0.003) and with 90 days mortality (aOR = 3.6, p = 0.003). Klebsiella spp. were the most common 3GCRE (36%), and bla CTX-M-1 was the major β-lactamase (79%). Polyclonality and multiple sequence types were evident among all Enterobacterales (e.g., Klebsiella pneumoniae , Escherichia coli , Enterobacter cloacae ). The study substantiates the significance of 3GCRE infections in equine medicine, and their independent detrimental impact on cure rates and mortality. Multiple Enterobacterales genera, subtypes, clones and mechanisms of resistance are prevalent among horses and donkeys with 3GCRE infections.

Objective: Administration of antimicrobials to patients with asymptomatic bacteriuria (ASB) is a common error that can lead to worse outcomes. However, controlled analyses quantifying the commonality and impact of this practice are lacking. We analyzed the independent predictors for antimicrobials misuse in ASB and quantified the impact of this practice on clinical outcomes., Design: Retrospective case-control and cohort analyses for calendar year 2017., Setting: Tertiary-care, university-affiliated medical center., Patients: The study included adult (>18 years) patients with positive urine culture. Pregnant women, renal transplant recipients, and patients who underwent urologic procedures were excluded., Methods: ASB was determined according to US Centers for Disease Control and Prevention (CDC) criteria. Multivariable logistic regression models were constructed to analyze predictors and outcomes associated with antimicrobial use for patients with ASB., Results: The study included 1,530 patient-unique positive urine cultures. Among these patients, 610 patients (40%) were determined to have ASB. Of the 696 isolates, 219 (36%) were multidrug-resistant organisms (MDROs). Also, 178 (29%) patients received antimicrobials specifically due to the ASB. Independent predictors for improper administration of antimicrobials were dependent functional status (adjusted odds ratio [aOR], 2.3; 95% CI, 1.4-3.6) and male sex (aOR, 2; 95% CI, 1.25-2.6). Use of antimicrobials was independently associated with re-hospitalizations (aOR, 1.7; 95% CI, 1.1-2.6) and later, acute Clostridioides difficile infections (CDI) in the following 90 days (aOR, 4.5; 95% CI, 2-10.6)., Conclusions: ASB is a common condition, frequently resulting from an MDRO. Male sex and poor functional status were independent predictors for mistreatment, and this practice was independently associated with rehospitalizations and CDI in the following 90 days.

Antimicrobial resistance is a common iatrogenic complication of modern life and medical care. One of the most demonstrative examples is the exponential increase in the incidence of extended-spectrum β-lactamases (ESBLs) production among Enterobacteriaceae, that is, the most common human pathogens outside of the hospital setting. Infections resulting from ESBL-producing bacteria are associated with devastating outcomes, now affecting even previously healthy individuals. This poses an enormous burden and threat to public health. This article aims to narrate the evolving epidemiology of ESBL infections and highlights current challenges in terms of management and prevention of these common infections., Competing Interests: Conflicts of interest No potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli infections have become endemic worldwide. We aimed to describe the molecular and clinical epidemiology of ESBL-producing E. coli infections during a period of rising global prevalence., Methods: Three hundred sixty-nine consecutive ESBL-producing E. coli infections in Detroit from 2010-2011 were analyzed. Sequence typing (ST) and CH typing were performed. Clinical characteristics and outcomes were compared between patients infected with ST131 and non-ST131 isolates., Results: Ninety-six percent of isolates were ST 131, and 78.6% of ST 131 isolates produced bla CTX-M-15 . Median time to effective therapy was 48 h vs. 35 h (P = 0.38) in the ST131 vs. non-ST131 groups. Ninety-day mortality rates (8% vs. 8%, P = 1.0) were similar between the two groups., Conclusion: bla CTX-M-15 ST131 E. coli predominated in Detroit during an early period of global ST131 dissemination. Patients with ST131 E. coli infections had similar clinical outcomes to those with non-ST131 E. coli infections.

Background: Many septic patients are receiving empirical antipseudomonal (or Gram-negative non-glucose fermenting [GNNGF]) coverage on admission to acute care hospitals, despite the fact that the indications are not scientifically established. Overuse of antipseudomonals might contribute to the burden of resistance., Materials and Methods: Retrospective observational analyses of the characteristics of septic adult patients who received empirical antipseudomonals, along with its impact on outcomes, were executed at Shamir Medical Center, Zerifin, Israel (08-12/2016). Proper empirical antipseudomonal usage was defined by the following: (1) if the patient received the agents as per Infectious Disease Society of America (IDSA) guidelines; (2) if the patient had a positive multidrug-resistant organism (MDRO) test on his or her admission score (https://assafharofe.azurewebsites.net); or (3) if a GNNGF was the eventual causative pathogen. Risk factors and outcomes were queried by logistic and Cox regression., Results: GNNGF was the causative pathogen in only 57 (3.7%) of 1536 patients with acute sepsis. There were 192 (13%) who received empirical antipseudomonals, of whom 161 (84%) were defined as proper. Patients who received empirical antipseudomonals were significantly older (P < 0.001), with higher indices of chronic and acute conditions, and higher rates of past MDRO carriage; 24 patients received empirical antipseudomonals only because of IDSA guidelines (15%), and that was an independent predictor for later acquisition (up to 90 days) of carbapenem-resistant A. baumannii (CRAB; odds ratio [aOR] = 7.1; P = 0.03)., Conclusions: Improper empirical usage of antipseudomonals in acute care hospitals is common. Instituting empirical antipseudomonals solely due to IDSA guidelines was independently associated with later acquisition of CRAB. Empirical antipseudomonal usage should be based on scientifically established prediction tools and not on IDSA guidelines., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Background: Risk factors and outcomes associated with carbapenem-resistant Enterobacteriaceae (CRE) acquisitions are derived primarily from cohorts consisting of carbapenemase-producing (CP) strains. Worldwide epidemiology of non-CP-CRE is evolving, but controlled epidemiological analyses are lacking., Methods: A matched case-case-control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, on November 2014-December 2016. Noncarbapenemase-producing CRE (as defined by the US Clinical and Laboratory Standards Institute Standards) carriers were matched to patients with non-CRE Enterobacterales and to uninfected controls (1:1:1 ratio). Matched and nonmatched multivariable regression models were constructed to analyze predictors for acquisition and the independent impact of carriage on multiple outcomes, respectively. Representative isolates were whole genome sequenced and analyzed for resistome and phylogeny., Results: Noncarbapenemase-producing CRE carriers (n = 109) were matched to the 2 comparative groups (overall n = 327). Recent exposure to antibiotics (but not specifically to carbapenems), prior intensive care unit admission, and chronic skin ulcers were all independent predictors for non-CP-CRE acquisition. Acquisitions were almost exclusively associated with asymptomatic carriage (n = 104), and despite strong associations per univariable analyses, none were independently associated with worse outcomes. Genomic analyses of 13 representative isolates revealed polyclonality, confirmed the absence of carbapenemases, but confirmed the coexistence of multiple other genes contributing to carbapenem-resistance phenotype (multiple beta-lactamases and efflux pumps)., Conclusions: Noncarbapenemase-producing CRE acquisitions are primarily associated with asymptomatic carriage, specifically among prone populations with extensive recent exposures to antibiotics. The prevalent mode of acquisition is "emergence of resistance" (not "patient-to-patient transmission"), and therefore the role of stewardship interventions in reducing the spread of these therapeutically challenging pathogens should be further explored., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: Recent guidelines recommended removing metronidazole as a therapeutic option for Clostridioides difficile infections (CDI). However, superiority of vancomycin over metronidazole in mild CDI is not established and use of vancomycin might lead to emergence of vancomycin-resistant enterococci (VRE). Patients & methods: A retrospective cohort study and efficacy analyses were conducted at Shamir Medical Center, Israel (2010-2015), among adults with acute CDI. Results:  A total of 409 patients were enrolled. In multivariable analyses, metronidazole was noninferior to vancomycin for mild CDI, but vancomycin was an independent predictor for post-CDI VRE acquisition. Conclusion: A significant independent association was evident between treatment with vancomycin and, later, acquisition of VRE. In first episodes of mild acute CDI, metronidazole should be considered a valid therapeutic option.

Due to lack of better therapeutic options, colistin use for extensively drug-resistant Gram-negative organisms was revived in the past two decades, including in patients in intensive-care units (ICU). There are multiple knowledge gaps pertaining to the clinical use and utility of colistin in critically-ill patients, but due to lack of options, it is used in these high risk patients. In this chapter, we critically review the various topics pertaining to colistin use in critically-ill patients, while highlighting the (lack of) controlled evidence supporting common current practices pertaining to colistin use by clinicians.

A case-case-control investigation (N = 255 patients) explored the epidemiology of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Recent exposure to carbapenems and a rapidly fatal condition should prompt practitioners to shorten delays in initiating appropriate therapy, which can adversely impact CRPA outcomes, as opposed to the isolated impact of the carbapenem resistance determinant.

A significant proportion of patients with acute myocardial infarction (AMI) also present with clinical manifestations of inflammatory response, which may be confused with a concomitant infection. This leads to a dilemma regarding the empiric use of antibiotics. We explored if serum procalcitonin (PCT), which is known to be elevated in bacterial infections, may be utilized to rule-out bacterial infection in AMI patients. In this prospective, single center study, PCT was collected within 48 hours from AMI patients. Patients' demographic, clinical, and laboratory data were collected prospectively. Two experienced infectious diseases specialists blinded to the PCT results independently determined the presence of infection in every patient. Sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve were calculated to determine the accuracy of PCT, fever, white blood cell (WBC) count, and C-reactive protein (CRP) levels for the diagnosis of the infection. The analysis included 230 AMI patients (age 63.0 ± 13.0 years) of whom 36 (15.6%) had coexisting infections. The best cutoff for PCT as a differentiating marker between patients with and without coexisting infection was 0.09 ng/dl (sensitivity 94.4%, specificity 85.1%, area under the curve 0.94). PCT outperformed CRP, WBC, and fever for diagnosing infection. In conclusion, compared with CRP, fever, and WBC, serum PCT had a better performance in differentiating infected from noninfected AMI patients and thus should be considered as an adjunct test when facing the dilemma of initiating empiric antibiotic in AMI patient demonstrating inflammatory signs., (Copyright © 2018. Published by Elsevier Inc.)

Background: Health care-associated infection (HcAI) is a term frequently used to describe community-onset infections likely to be caused by multidrug-resistant organisms (MDROs). The most frequently used definition was developed at Duke University Medical Center in 2002 (Duke-2002). Although some professional societies have based management recommendations on Duke-2002 (or modifications thereof), neither Duke-2002 nor other variations have had their performance measured., Methods: A case-control study was conducted at Assaf Harofeh Medical Center (AHMC) of consecutive adult bloodstream infections (BSIs). A multivariable model was used to develop a prediction score for HcAI, measured by the presence of MDRO infection on admission. The performances of this new score and previously developed definitions at predicting MDRO infection on admission were measured., Results: Of the 504 BSI patients enrolled, 315 had a BSI on admission and 189 had a nosocomial BSI. Patients with MDRO-BSI on admission (n = 100) resembled patients with nosocomial infections (n = 189) in terms of epidemiological characteristics, illness acuity, and outcomes more than patients with non-MDRO-BSI on admission (n = 215). The performances of both the newly developed score and the Duke-2002 definition to predict MDRO infection on admission were suboptimal (area under the receiver operating characteric curve, 0.76 and 0.68, respectively)., Conclusions: Although the term HcAI is frequently used, its definition does not perform well at predicting MDRO infection present on admission to the hospital. A validated score that calculates the risk of MDRO infection on admission is still needed to guide daily practice and improve patient outcomes.

Background: The epidemiology of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI. However, controlled comparative data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent vancomycin-resistant Enterococcus (VRE) isolation remains unknown., Methods: A retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, from 2013 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs. metronidazole among patients with mild CDI, and the independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation, was analyzed by logistic regression., Results: A total of 260 patients with CDI were enrolled. The majority were elderly (75%), and 56% had moderate to severe disease. Among 75 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a "vancomycin case". In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=74, p=0.004)., Conclusions: Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis.

It is unknown as to whether other beta-lactams can be used for bloodstream infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non-susceptible to one or more carbapenem. We conducted a retrospective cohort study at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014. Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but susceptible to ceftazidime or piperacillin (with or without tazobactam), were enrolled. We compared the outcomes of patients who received an appropriate beta-lactam antibiotic ("cases") to those who received an appropriate non-beta-lactam antibiotic ("controls"). Whole genome sequencing was performed for one of the isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and one colistin and an aminoglycoside). All clinical outcomes were similar between the groups. There were large variations in the phenotypic susceptibilities of the strains. A detailed molecular investigation of one isolate revealed a strain that belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene was intact. Non-carbapenem-β-lactams may still be effective alternatives for short duration therapy (up to 14 days) for BSI caused by a carbapenem non-susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin-tazobactam) PA strain. This observation requires further confirmatory analyses. Future molecular investigations should be performed, in order to further analyze additional potential mechanisms for this prevalent phenotype., Competing Interests: The authors declare no conflict of interest.

Background: Basins used for patient bathing have been shown to be contaminated with multidrug-resistant organisms (MDROs) and have prompted the evaluation of alternatives to soap and water bathing methods., Methods: We conducted a prospective, randomized, open-label interventional crossover study to assess the impact of replacing traditional bath basins with prepackaged washcloths on the incidence of hospital-associated infections (HAIs), MDROs, and secondarily, rates of skin deterioration. Unit-wide use of disposable washcloths over an 8-month period was compared with an 8-month period of standard care using basins., Results: A total of 2,637 patients were included from 2 medical-surgical units at a single tertiary medical center, contributing 16,034 patient days. During the study period, there were a total of 33 unit-acquired infections, the rates of which were not statistically different between study phases (incidence rate ratio, 1.05; 95% confidence interval [CI], 0.50-2.23; P = .88). However, occurrence of skin integrity deterioration was significantly less in the intervention group (odds ratio, 0.44; 95% CI, 0.22-0.88; P = .02)., Conclusions: Although we were unable to demonstrate a significant reduction in HAI or MDRO acquisition, we found a decrease in skin deterioration with the use of disposable washcloths and confirmed earlier findings of MDRO contamination of wash basins., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The global spread of carbapenem-resistant Enterobacteriaceae (CRE) has been fostered by the lack of preemptive screening of patients in healthcare facilities that could prevent patient-to-patient transmission. Outbreaks of CRE infections have led some institutions to implement rigorous screening programs, although controlled comparative data are frequently lacking. Resource limitations and uncertainty regarding the optimal approach has kept many facilities from enacting more active routine surveillance policies that could reduce the prevalence of CRE. The ideal population to target for screening, the frequency of testing, and the preferred test method are components of surveillance programs that remain open to debate. This review discusses the rationale for different screening policies in use and the performance characteristics of laboratory methods available to detect CRE carriage.

Aim: The transmission dynamics of Acinetobacter baumannii in endemic settings, and the relation between microbial properties and patients' clinical outcomes, are yet obscure and hampered by insufficient metadata., Methods & Results: Of 20 consecutive patients with A. baumannii bloodstream infection that were thoroughly analyzed at a single center, at least one transmission opportunity was evident for 85% of patients. This implies that patient-to-patient transmission is the major mode of A. baumannii acquisitions in health facilities. Moreover, all patients who died immediately (<24 h of admission) were infected with a single clone (ST457; relative risk = 1.6; p = 0.05)., Conclusion: This preliminary analysis should prompt further investigation by mapping genomic virulence determinants among A. baumannii ST457 lineage compared with other strains.

Molecular typing using repetitive sequenced-based PCR (rep-PCR) and hsp60 sequencing were applied to a collection of diverse Enterobacter cloacae complex isolates. To determine the most practical method for reference laboratories, we analyzed 71 E. cloacae complex isolates from sporadic and outbreak occurrences originating from 4 geographic areas. While rep-PCR was more discriminating, hsp60 sequencing provided a broader and a more objective geographical tracking method similar to multilocus sequence typing (MLST). In addition, we suggest that MLST may have higher discriminative power compared to hsp60 sequencing, although rep-PCR remains the most discriminative method for local outbreak investigations. In addition, rep-PCR can be an effective and inexpensive method for local outbreak investigation.

Background: Intra-abdominal infections (IAI) constitute a common reason for hospitalization. However, there is lack of standardization in empiric management of (1) anaerobes, (2) enterococci, (3) fungi, and (4) multidrug-resistant organisms (MDRO). The recommendation is to institute empiric coverage for some of these organisms in "high-risk community-acquired" or in "healthcare-associated" infections (HCAI), but exact definitions are not provided., Methods: Epidemiological study of IAI was conducted at Assaf Harofeh Medical Center (May-November 2013). Logistic and Cox regressions were used to analyze predictors and outcomes of IAI, respectively. The performances of established HCAI definitions to predict MDRO-IAI upon admission were calculated by receiver operating characteristic (ROC) curve analyses., Results: After reviewing 8219 discharge notes, 253 consecutive patients were enrolled (43 [17%] children). There were 116 patients with appendicitis, 93 biliary infections, and 17 with diverticulitis. Cultures were obtained from 88 patients (35%), and 44 of them (50%) yielded a microbiologically confirmed IAI: 9% fungal, 11% enterococcal, 25% anaerobic, and 34% MDRO. Eighty percent of MDRO-IAIs were present upon admission, but the area under the ROC curve of predicting MDRO-IAI upon admission by the commonly used HCAI definitions were low (0.73 and 0.69). Independent predictors for MDRO-IAI were advanced age and active malignancy., Conclusions: Multidrug-resistant organism-IAIs are common, and empiric broad-spectrum coverage is important among elderly patients with active malignancy, even if the infection onset was outside the hospital setting, regardless of current HCAI definitions. Outcomes analyses suggest that empiric regimens should routinely contain antianaerobes (except for biliary IAI); however, empiric antienterococcal or antifungals regimens are seldom needed., (© The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)