Effect of Antibiotic Selection on Clinical Outcomes in Patients with Bloodstream Infections Caused by AmpC β-lactamase–producing Enterobacterales Phuong Giao Nguyen Tran, Christopher M. Bland, Susan E. Smith, Caroline Turpin, Rachel Musgrove St. Joseph's/Candler Health System
Background: Antibiotic resistance remains a major global health threat. Bacterial production of β-lactamases is a key resistance mechanism, with AmpC β-lactamases commonly identified in some Enterobacterales isolates. Mortality from bacteremia caused by AmpC-producing organisms has been reported to be significant. The 2024 Infectious Diseases Society of America (IDSA) guidance recommends cefepime or carbapenems for the treatment of infections caused by organisms at moderate risk of significant AmpC production and advises against ceftriaxone and piperacillin/tazobactam due to concerns about inducible resistance. However, clinical studies have not yet demonstrated superior outcomes with cefepime or carbapenems compared with ceftriaxone or piperacillin/tazobactam in this setting.
Methods: A multicenter, retrospective chart review was conducted during the period of January 2015 to December 2025. Eligible patients were adults 18 years of age or older and admitted to either St. Joseph’s Hospital or Candler Hospital with at least one blood culture isolating Hafnia alvei, Enterobacter cloacae, Citrobacter freundii, Klebsiella aerogenes, Yersinia enterocolitica, or Serratia marcescens. Patients were excluded if the initial antibiotic regimen was started at an outside hospital, if empiric therapy included a fluoroquinolone, or if blood cultures were polymicrobial. The primary objective was to determine if the use of IDSA-nonpreferred antibiotics (ceftriaxone, piperacillin/tazobactam) as empiric therapy in patients with bloodstream infections caused by AmpC β-lactamase–producing Enterobacterales results in increased incidents of suboptimal patient outcomes, as measured by greater rates of mortality, compared with IDSA-preferred agents (cefepime, meropenem). Secondary outcome measures include requirement of change of antibiotic therapy, total duration of antibiotic therapy, incidence of relapsed bacteremia, and incidence of Clostridium difficile infection while inpatient. All qualitative data points were evaluated using Chi-square analysis. All quantitative data points were evaluated using t-test analysis. A p-value of less than 0.05 was considered statistically significant.
Results: A total of 184 patients were screened and 146 of those patients were included in the analysis. The remaining 38 patients were excluded based on the criteria mentioned above, with the most common being polymicrobial blood cultures. The breakdown of the organisms isolated is as follows – 59 Enterobacter cloacae isolates (40%), 48 Serratia marcescens isolates (33%), 29 Klebsiella aerogenes isolates (20%), 9 Citrobacter freundii isolates (6%), and 1 Hafnia alvei isolate (1%). There was no statistically significant difference with regards to in-hospital mortality between the IDSA-nonpreferred antibiotics (ceftriaxone, piperacillin/tazobactam) and the IDSA-preferred agents (cefepime, meropenem) (p > 0.05). Secondary objectives were comparable between the two groups as well.
Conclusions: Use of IDSA-preferred agents, such as cefepime or meropenem, did not lead to improved clinical outcomes in patients with bacteremia caused by AmpC-producing organisms. However, this study has several important limitations. Notably, the study period spanned the COVID-19 pandemic, which may have introduced confounding factors affecting patient outcomes, including mortality. The true clinical significance must be assessed in larger, prospective, randomized control trials.
