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Introduction: It is unknown whether infectious diseases consultation improves outcomes for enterococcal bacteraemia in a multicentre healthcare system., Methods: This retrospective multicentre observational cohort study included 250 adult patients with enterococcal bacteraemia between July 2016 and December 2020. The primary endpoint was a composite of clinical failure, including persistent bacteraemia, persistent fever, and in-hospital mortality. Secondary endpoints included adherence to a treatment bundle (appropriate empiric and definitive antibiotics, appropriate planned treatment duration, obtaining repeat blood cultures and an echocardiogram)., Results: Clinical failure occurred in 35 of 155 patients (22.6%) with an infectious diseases consultation and 16 of 95 patients (16.8%) without an infectious diseases consultation (P = 0.274). Multivariate analysis identified vasopressors as the only independent predictor of the primary outcome. Infectious diseases consultation resulted in higher adherence to a treatment bundle, including echocardiogram (75.5% vs. 34.7%; P < 0.0001), repeat blood cultures (85.2% vs. 68.4%; P = 0.002), appropriate definitive antibiotics (70.5% vs. 91.6%; P < 0.0001) and appropriate planned durations of therapy (81.1% vs. 94.2%; P = 0.001). More patients in the consult group were treated with ampicillin (47.1% vs. 22.1%; P < 0.0001) and fewer were treated with vancomycin (17.4% vs. 24.2%; P = 0.068)., Conclusion: Despite finding no difference in clinical failure between groups, this study highlights important benefits of infectious diseases consultation in enterococcal bacteraemia., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The Infectious Diseases Society of America (IDSA) recommends numerous antibiotics for the treatment of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing bacteria. The purpose of this study was to evaluate clinical outcomes of oral step-down antibiotics compared with continued intravenous therapy in UTIs without bacteraemia. This multicentre, retrospective, cohort study was conducted in hospitalised patients with ESBL-producing UTIs between July 2016 and March 2020. The primary outcome was a composite all-cause clinical failure, defined as 30-day re-admission, 30-day hospital mortality or a change in oral antibiotics during hospitalisation. Secondary outcomes included individual primary outcome components, re-admission due to a recurrent UTI, change in antibiotic during hospitalisation, hospital length of stay (LOS), antibiotic costs and adverse events. The study included 153 patients. The primary outcome occurred in 28% of both groups (27/95 vs. 16/58; P = 0.91). The primary outcome components were similar: re-admission (26% vs. 26%; P = 0.95); hospital mortality (2% vs. 2%; P = 1.0); and change in antibiotics (0% vs. 2%; P = 0.38). Mean hospital LOS and direct antibiotic costs were 8 ± 6 days vs. 5 ± 2 days (P < 0.01) and US$278 ± 244 vs. US$180 ± 104 (P < 0.01), respectively. Adverse events were similar, except diarrhoea (15% vs. 2%; P = 0.01). There was no difference in clinical failure, re-admission rate, re-admission due to a recurrent UTI, mortality rate or antibiotic change between groups. The switch group was associated with reduced hospital LOS and inpatient antibiotic costs., Competing Interests: Competing interests None declared., (Copyright © 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Alterations in cefepime pharmacokinetic (PK) exposure and decreased bacterial susceptibility increase the risk of treatment failure. The impact of susceptible-dose-dependent (SDD) minimum inhibitory concentrations (MICs), i.e. 4-8 µg/mL, on target attainment rates for cefepime in febrile neutropenia (FN) is unclear. We sought to identify optimal cefepime regimens against SDD cefepime MICs in FN using a modelling and simulation approach. Creatinine clearance (CL Cr ) and body surface area (BSA) covariate-adjusted models of clearance were evaluated. Monte Carlo simulations representing 10 000 patients were completed to assess various dosing strategies (i.e. 3-8 g/day infused over 0.5-24 h, replaced every 6-24 h) and predict probabilities of target attainment (PTAs) for unbound cefepime. Nine patients received cefepime 2 g every 8 h (q8h) (0.5-h infusion). A two-compartment PK model with BSA- and CL Cr -adjusted clearance was fit to the data. Mean population values for total clearance (6.3 ± 1.1 L/h), intercompartmental clearance (6.9 ± 2.8 L/h), and central (14.8 ± 3.8 L) and peripheral (10.9 ± 4.6 L) distribution volumes were all estimated with <50% CV. Simulated dosing regimens of 3-4 g/day administered as continuous infusions and doses of 2 g administered q6h (0-5 h infusion) to q8h (4-h infusion) achieved ≥90% PTA at MICs up to 8 µg/mL. Simulated regimens of 1 g q8h (4-h infusion) or 1 g q6h (0.5-h infusion) achieved ≥90% PTA only against MICs up to 4 µg/mL. High-dose prolonged infusion or more frequent cefepime regimens may be necessary to treat FN organisms with SDD MICs., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)