Outcomes by Candida spp. in the ReSTORE Phase 3 trial of rezafungin versus caspofungin for candidemia and/or invasive candidiasis.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Impact of Clinical Decision Support System Implementation at a Community Hospital With an Existing Tele-Antimicrobial Stewardship Program.

Background: Lack of on-site antimicrobial stewardship expertise is a barrier to establishing successful programs. Tele-antimicrobial stewardship programs (TASPs) utilizing a clinical decision support system (CDSS) can address these challenges. Methods: This interrupted time series study reports the impact of CDSS implementation (February 2020) within an existing TASP on antimicrobial usage in a community hospital. Segmented regression analysis was used to assess differences in antimicrobial usage from January 2018 through December 2021. Pre- and post-CDSS frequencies of intravenous vs oral antimicrobials, time to optimal therapy (TTOT), pharmacist efficiency (number of documented interventions per month), and percentage of hospitalized patients receiving antimicrobials were compared with descriptive statistics. Results: Implementation of a CDSS into an existing TASP was associated with an immediate 11% reduction in antimicrobial usage (level change, P < .0001). Antimicrobial usage was already trending down by 0.25% per month (pre-CDSS slope, P < .0001) and continued to trend down at a similar rate after implementation (post-CDSS slope, P = .0129). Frequency of use of select oral agents increased from 38% to 57%. Median TTOT was 1 day faster (2.9 days pre-CDSS vs 1.9 days post-CDSS). On average, pharmacists documented 2.2-fold more interventions per month (198 vs 90) and patients received 1.03 fewer days of antimicrobials per admission post-CDSS. Conclusions: Implementation of a CDSS within an established TASP at a community hospital resulted in decreased antimicrobial usage, higher rates of oral usage, faster TTOT, and improved pharmacist efficiency.

Defining the incidence and risk factors of colistin-induced acute kidney injury by KDIGO criteria.

BACKGROUND: Acute kidney injury (AKI) remains a treatment-limiting toxicity of colistin. Recently developed clinical practice guidelines from the Kidney Disease: Improving Global Outcomes (KDIGO) group have harmonized definitions of AKI, but have not been widely applied to patients receiving colistin. METHODS: We retrospectively defined AKI by KDIGO definitions among adult patients receiving intravenous colistin for ≥ 3 days. Risk factors for AKI within 48 hours and 7 days of initiating colistin were determined by multivariable logistic regression. RESULTS: Among 249 patients treated with colistin, rates of AKI were 12% and 29% at 48 hours and 7 days, respectively. At 48 hours, patients in the intensive care unit were at increased risk for AKI. Within 7 days, colistin daily doses >5mg/kg, chronic liver disease, and concomitant vancomycin were independent predictors. Seven percent of patients required renal replacement therapy at a median of 5 days (range: 3-7) following colistin initiation. CONCLUSION: Safe use of colistin is promoted by early detection of AKI with KDIGO criteria, avoiding nephrotoxins, and limiting duration of therapy.