The emergence of cefiderocol resistance in Pseudomonas aeruginosa from a heteroresistant isolate during prolonged therapy.

Cefiderocol is a siderophore cephalosporin designed to target multi-drug-resistant Gram-negative bacteria. Previously, the emergence of cefiderocol non-susceptibility has been associated with mutations in the chromosomal cephalosporinase (PDC) along with mutations in the PirA and PiuA/D TonB-dependent receptor pathways. Here, we report a clinical case of cefiderocol-resistant P. aeruginosa that emerged in a patient during treatment. This resistance was associated with mutations not previously reported, suggesting potential novel pathways to cefiderocol resistance.

Optimizing antimicrobial prophylaxis strategies in acute leukemia patients: Assessing the efficacy of fluconazole.

BACKGROUND: Acute myeloid (AML) and promyelocytic (APL) leukemia patients are at high risk for infection and mortality. While guidance for infection prevention is provided by the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), each institution may vary in antimicrobial prophylaxis prescribing practices. The discrepancy may be explained by medication intolerance, cost, and low incidence of mold infections in leukemia patients. A recent meta-analysis demonstrated mortality benefits with the use of posaconazole, which was adopted by the NCCN. Despite known risks, it is unclear whether universal mold-active coverage is indicated for all AML and APL patients. OBJECTIVE: To assess the incidence of breakthrough infections in AML and APL patients. METHODS: This was a single-center, retrospective chart review of AML and APL patients receiving induction therapy at Baylor St Luke's Medical Center (BSLMC) between January 2019 and October 2021. The primary outcome assessed the incidence of breakthrough infections. Descriptive statistics were used to summarize the data. RESULTS: A total of 55 patients were included and 54 (98%) had prolonged neutropenia with a median duration of 30 days. Five patients (9.3%) experienced breakthrough infections during induction while 21 individuals (38.9%) during the follow-up period. Aspergillus infections occurred in three patients receiving nonmold coverage compared to none on mold-active agents (p = 1.0) with no statistical difference in mortality. CONCLUSION: Despite the majority of patients not receiving mold-active prophylaxis, nonmold-active prophylaxis may be sufficient with consideration of low aspergillosis incidence.