1863. Treatment and Outcomes of Cefoxitin-Non-Susceptible Serratia marcescens, Klebsiella aerogenes, Citrobacter freundii, Enterobacter cloacae , and Morganella morganii Bacteremia with Piperacillin/Tazobactam Versus Cefepime or Carbapenem in Immunocompromised Patients

Abstract

Background. A recent guidance suggested “caution if prescribing piperacillintazobactam for serious infections caused by organisms at high risk of significant AmpC production” and that the preferred antibiotic choice should be either cefepime or a carbapenem, despite an admitted lack of definitive evidence. Examination of this question in immunocompromised patients may provide such evidence Methods. This was a retrospective, single-center study conducted from January 2016 to December 2021. We included immunocompromised patients aged 18 years or older who had a laboratory confirmed blood culture positive for Enterobacterales showing non-susceptibility to cefoxitin and were definitively treated with piperacillintazobactam, cefepime, or a carbapenem. The primary endpoint was a composite of clinical or microbiological failure, which was comprised of in-hospital 30-day mortality, white blood count >12 x 109/L or temperature >38°C on days 5-7, microbiological failure on days 3-5, or microbiological recurrence/relapse on days 5-30. Results. We identified 81 patients who were included for analysis. Baseline characteristics between arms were similar between groups except for more frequent severe neutropenia (p=0.010) and higher Pitt bacteremia scores (p=0.042) in the cefepime/ carbapenem group. Within the piperacillin/tazobactam arm, 17 of 35 (48.6%) had clinical or microbiological failure, compared to 17 of 46 (37.0%) patients in the carbapenem/ cefepime arm (p=0.294). Microbiological failure occurred in 4 of 35 (11.4%) patients treated with piperacillin/tazobactam compared to 0 of 46 (0%) patients treated with a carbapenem/cefepime (p=0.019). In multivariate analysis, patients treated with a carbapenem/cefepime had a 69% lower odds of clinical or microbiological failure compared to those treated with piperacillin/tazobactam (OR = 0.31; 95% confidence interval, 0.10-0.98). Conclusion. In immunocompromised patients with bacteremia due to cefoxitin-non-susceptible Serratia marcescens, Klebsiella aerogenes, Citrobacter freundii, Enterobacter cloacae, or Morganella morganii, definitive treatment with piperacillin/ tazobactam was associated with a higher likelihood of microbiological failure compared with treatment with a carbapenem or cefepime.