A Retrospective Review of Treatment Appropriateness and Outcomes of Enterobacteriaceae (with Inducible ampC β-lactamase) Bacteremias at a Large Academic Medical Centre: Opportunities and Implications for Antimicrobial Stewardship.

Background: Infections caused by ampC carrying Enterobacteriaceae can be problematic. β-lactamase production in these organisms can be inducible upon exposure to β-lactams and lead to treatment failure. Choice of antimicrobial therapy is important, as delay in appropriate empiric therapy is associated with mortality, while avoiding unneeded broad-spectrum antimicrobials is an important component of antimicrobial stewardship. There is little data to support the current practice of carbapenems as first-line agents to treat ampC Enterobacteriaceae infections, and a recent study showed cefepime to be as effective as carbapenems. We aimed to study treatment appropriateness and outcomes for ampC Enterobacteriaceae, and explore outcomes for carbapenem-sparing agents. Methods: Microbiology reports identified 49 patients with bacteremia caused by ampC carrying Enterobacteriaceae over 2 years at a large academic medical centre. Appropriateness of empiric and definitive therapy was assessed by 2 independent reviewers. Demographics, comorbidities, microbiology, and antibiogram data was also collected. Clinical outcomes included all-cause mortality, length of stay, and microbiological cure. Results: Only 12% of Enterobacteriaceae bacteremias presented with derepression of the ampC gene upon first culture. Empiric therapy was appropriate (active based on sensitivity) in 78% of patients. For empiric therapy, most received piperacillin-tazobactam [P/T] (61%), while few (8%) received a carbapenem. Definitive therapy was often a fluoroquinolone [FQN] (63%); the rest received a carbapenem (10%), sulfamethoxazole-trimethoprim [SMX-TMP] (8%), or P/T (8%). Five patients (10%) had bacteremia persisting >1 day. In patients with appropriate definitive therapy, clinical outcomes were not different (carbapenem vs non-carbapenem). Conclusion: The majority of patients studied received an appropriate non-carbapenem as definitive therapy with good microbiological and clinical outcomes. The majority of patients also received appropriate empiric therapy. We suggest that non-β-lactams, especially SMX-TMP, should be explored as carbapenem-sparing options for ampC carrying Enterobacteriaceae which represent a large proportion of gram negative infections. Future work should focus on confirming clinical outcomes in a broader sample.