Exploring heterogeneity in antibiotic choices for bloodstream infections caused by AmpC-producing enterobacterales: results from a case-vignette study

Purpose: The treatment of bloodstream infections (BSIs) caused by AmpC-producing Enterobacterales (AmpC-E) remains controversial, due to limited clinical evidence and variable resistance profiles. Inappropriate antibiotic choices can induce ampC-encoding gene overexpression, leading to increased risk of therapeutic failure. This study aims to explore the current prescribing preferences among infectious disease (ID) physicians, in complex clinical scenarios involving BSIs caused by AmpC-E. Methods: A web-based case-vignette survey was conducted among a purposive sample of senior ID physicians from 10 ID units in Emilia-Romagna Region, northern Italy. Participants responded to 31 vignettes simulating BSIs caused by Enterobacter cloacae (wild-type or derepressed phenotype) or Serratia marcescens (wild-type phenotype), across varied clinical settings. For each scenario, participants selected their preferred antibiotic regimen. Results: Forty-two ID physicians were invited to participate. Cefepime (48.4%) and meropenem (29.0%) were the most prescribed agents, followed by piperacillin-tazobactam (16.1%) and third-generation cephalosporins (3GC) (6.5%). Cefepime was preferred in milder cases, while meropenem in severe infections, particularly with high inoculum or incomplete source control. Considerable heterogeneity in treatment choices was observed, especially for S. marcescens and E. cloacae with wild-type phenotypes. Agreement among clinicians was highest for intensive care admitted patients. Combination therapies were infrequently proposed (8.8% overall), primarily in the setting of intra-abdominal infections with incomplete source control or ventilator-associated pneumonia. Conclusion: This study highlights significant variability in the treatment of AmpC-E BSIs among ID physicians, reflecting clinical uncertainty and lack of high-quality evidence. Further research and updated, context-specific guidelines are needed to harmonize practice and promote optimal antibiotic stewardship.