Background: Challenges exist when managing AmpC beta-lactamase producing organisms. Their ability to deactivate common antibiotics (e.g. penicillins, cephalosporins), avoid inhibition by beta-lactamase inhibitors, and upregulate beta-lactamase production results in minimizing the number of treatment options. Cefepime (CEF), an AmpC stable cephalosporin, has generated interest as a primary agent for managing severe infections secondary to these organisms. Therefore, the objective of this study was to assess the clinical utility of CEF for managing bacteremia secondary to AmpC producing organisms.
Methods: This was an IRB approved single-center, retrospective chart review. Adult patients with an AmpC producing organism (i.e. Citrobacter, Enterobacter, or Serratia spp. along with cefoxitin resistance) isolated from blood cultures who received empiric and definitive CEF therapy were included. The primary endpoint was clinical outcome based on the improvement of systemic signs of infection and microbiological clearance at 72 hours and end of therapy (EOT). Secondary endpoints included 7-day and 30-day mortality evaluating site of infection, organism, and MIC.
Results: One hundred thirty-one patients were included in the primary analysis. Clinical improvement within 72 hours was achieved by 71% of patients with 84.7% achieving response at EOT. The mortality at 7- and 30-days was 8.4% and 15.3%, respectively. The majority of patients had a line-related infection (41.2%) but overall wide distributions of infection sites were noted. Source control was achieved in 54.2% of patients improving the likelihood of patient response. Assessment of CEF dosing strategy did not reveal an impact on EOT response (p=0.190) or 7-day mortality (p=0.478). Lack of resistance limited any assessment of dosing strategy and outcome in regards to MIC value. Therapy in 12 (9%) patients was modified from CEF to carbapenems or piperacillin/tazobactam.
Conclusion: The use of CEF definitive therapy was associated with positive clinical outcomes with roughly 85% achieving response at the EOT. Site of infection, in conjunction with low MICs, may play a role in rapid response and low mortality observed in this analysis.
S. Borgert, None
N. Iovine, None
K. Cherabuddi, None
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