Cefepime Versus Piperacillin-Tazobactam for the Treatment of Intra-Abdominal Infections Secondary to Potential AmpC Beta-Lactamase-Producing Organisms.

Background: Recent studies have established cefepime as an effective treatment option for AmpC beta-lactamase (AmpC) Enterobacterales; however, the efficacy of beta-lactam/beta-lactamase inhibitors is unclear. Objective: The objective of this study was to determine if piperacillintazobactamis an appropriate alternative to cefepime for the treatment of intra-abdominal infections (IAIs) secondary to AmpC-producing organisms. Methods: This multicenter, retrospective cohort study was conducted in hospitalized adults with an IAI caused by an AmpC-producing organism and received either cefepime or piperacillin-tazobactam for definitive treatment after a source control procedure. The primary outcome was a composite of surgical site infections, recurrent IAIs, or in-hospital mortality. Secondary outcomes included the individual components of the composite outcome, hospital length of stay (LOS), microbiologic failure, study antibiotic duration, time to clinical resolution, and incidence of Clostridioides difficile infection (CDI). Results: This study included 119 patients. There was no difference in the primary outcome between the cefepime and piperacillin-tazobactam groups (35% vs 27%, P = 0.14). Microbiological failure was the only secondary outcome with an observed difference between groups (17% vs 0%, P = 0.01): hospital LOS (15 vs 13 days, P = 0.09), days of therapy (7 vs 7 days, P = 0.87), time to clinical resolution (7 vs 4 days, P = 0.30), and CDI (1% vs 2%, P = 0.58) were all similar.

Supratherapeutic Tacrolimus Concentrations With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients Requiring Hospitalization: A Case Series Using Rifampin for Reversal.

Nirmatrelvir/ritonavir was recently granted emergency use authorization for mild to moderate coronavirus disease 2019. Drug-drug interactions between ritonavir and tacrolimus are underappreciated by nontransplant providers. We describe 2 solid organ transplant recipients prescribed nirmatrelvir/ritonavir for outpatient use who developed tacrolimus toxicity requiring hospitalization and were managed with rifampin for toxicity reversal.

Hidden Fluids in Plain Sight: Identifying Intravenous Medication Classes as Contributors to Intensive Care Unit Fluid Intake.

Introduction: Fluid stewardship targets optimal fluid management to improve patient outcomes. Intravenous (IV) medications, flushes, and blood products, collectively referred to as hidden fluids, contribute to fluid intake in the intensive care unit (ICU). The impact of specific IV medications on fluid intake is unknown. Objective: Characterize IV medication classes based on contribution to ICU fluid intake by frequency of administration and total volume infused to identify targets for fluid stewardship. Methods: This multi-center, retrospective nested cohort study included patients admitted to a medical or surgical ICU between January 2017 and December 2018. The primary outcome was to identify the volume contribution of specific IV medication classes administered over the first 3 ICU days. Secondary outcomes were the administration frequency of these medications and their proportion of total daily volume intake over the first 3 ICU days. Results: The study included 210 patients. The largest mean administration volumes over the course of the first 3 ICU days were attributed to antibacterials (968 ± 846 mL), vitamins/minerals/electrolytes (416 ± 935 mL), pain/agitation/delirium agents (310 ± 512 mL), and vasoactive agents (282 ± 744 mL). The highest frequencies over the course of the first 3 ICU days were attributed to antibacterials (n = 180; 86%), pain/agitation/delirium agents (n = 143; 68%), vitamins/minerals/electrolytes (n = 123; 59%), and vasoactive agents (n = 96; 46%). IV medications contributed 2601 ± 2573 mL of fluid volume per patient over the first 3 ICU days, accounting for 42% ± 29% of overall volume. Conclusion: IV medications contribute over 40% of total fluid intake within the first 3 days of ICU admission, with antibacterials as top contributors by administration volume and frequency. Future research implementing fluid stewardship to ICU fluid sources, such as concentrating IV medications, switching IV medications to oral formulations, de-escalation of antibacterials, and reduction of maintenance fluids, should be performed to minimize hidden fluids from IV medications.

Intravenous to oral antibiotics versus intravenous antibiotics: a step-up or a step-down for extended spectrum ß-lactamase (ESBL)-producing urinary tract infections without concomitant bacteraemia?

The Infectious Diseases Society of America (IDSA) recommends numerous antibiotics for the treatment of urinary tract infections (UTIs) caused by extended-spectrum ß-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.