Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents.

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity > 0.9996; Aligned Percentage > 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1Δ33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checkerboard, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.

The Role of an Infectious Diseases Faculty Pharmacist and Pharmacy Students on an Antimicrobial Stewardship Team at a Community Non-teaching Hospital.

Background: Antimicrobial stewardship program implementation at non-teaching community hospitals differs due to staffing and resource disparities. Objective: Demonstrate that an infectious disease (ID) pharmacist faculty with advanced pharmacy practice experience (APPE) students can expand antimicrobial stewardship services at non-teaching community hospitals. Methods: A single-center, retrospective chart review was conducted comparing prospective audit and feedback antimicrobial stewardship interventions by an ID pharmacist faculty with and without APPE students between January 16, 2020 to January 16, 2021. The primary endpoints were intervention rate and the intervention acceptance rate. Secondary endpoints included: the difference in the time from antimicrobial order to intervention and length of stay, as well as comparison of acceptance rates stratified by intervention type or the antimicrobial intervened upon. Results: A total of 739 antimicrobial stewardship interventions were made with an overall acceptance rate of 55.2%. The ID pharmacist faculty with APPE students had a higher number of interventions and intervention rate per working day compared to without students (428 vs 311 and 4.46 vs 2.99, respectively). Conversely, the intervention acceptance rate was lower for the ID pharmacist faculty with APPE students vs without (48.8% vs 64%, P < .001). Both the median time from antimicrobial order to the intervention and length of stay was lower for the ID pharmacist faculty with students vs without (2.50 days [interquartile range (IQR) 1.24 - 4.01] vs 2.99 days [IQR 1.64 - 4.95], P = .003, and 9.20 days [IQR 5.57 - 14.93] vs 11.69 days [IQR 6.89 - 22.31], P < .001, respectively). The acceptance rates by intervention type and the antimicrobial intervened upon were similar between groups. Conclusion: An ID pharmacist faculty with APPE students at a non-teaching community hospital increased the number of stewardship interventions, and was associated with decreased time from antimicrobial order to intervention and length of stay.

Risk factors for readmission in patients discharged with outpatient parenteral antimicrobial therapy: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is a practical and effective way of delivering antimicrobial therapy, but may be associated with significant risk for hospital readmission. This study aimed to elucidate risk factors related to 30-day readmissions in patients who were discharged with OPAT at Mount Sinai Beth Israel (MSBI). METHODS: This IRB approved retrospective cohort study included patients who were at least 18 years or older, admitted to MSBI from August 2015 to March 2016, and discharged to receive OPAT. Patients with intravenous antibiotics prescribed for chronic suppression or planned readmission within 30 days were excluded. The main outcome was readmission to the hospital within 30 days from previous hospital discharge. Univariate and logistic regression analyses were performed to determine predictors of 30-day readmission. RESULTS: There were a total of 200 patients included in the analysis; the median age was 60 years, 65.5% were male, and the median Charlson score was 2. A total of 155 (78%) patients received a peripherally inserted central catheter (PICC); the remainder was discharged with a midline. The most common medications prescribed for OPAT included cephalosporins (41%), vancomycin (31%), carbapenems (23%), and penicillins (16%). A total of 42 patients (21%) were readmitted within 30 days after previous discharge. Discharge to a skilled nursing facility or subacute rehabilitation center was found to be an independent predictor of readmission on logistic regression analyses (p <  0.05). CONCLUSION: Readmissions are common in patients discharged with OPAT. Recognizing predictors of readmission may help determine strategies to optimize care.