Effectiveness of third-generation cephalosporins or piperacillin compared with cefepime or carbapenems for severe infections caused by wild-type AmpC β-lactamase-producing Enterobacterales: A multi-centre retrospective propensity-weighted study

Background: The optimal treatment regimen for infections caused by wild-type AmpC beta-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin +/- tazobactam, cefepime or carbapenem.Methods: All cases of BSI and pneumonia caused by wild-type AmpC beta-lactamase-producing Enter-obacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin +/- tazobactam (piperacillin group), or ce-fepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups.Results: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half ( n = 271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin +/- tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI.Conclusion: Treatment of included BSI or pneumonia caused by wild-type AmpC /3-lactamase-producing Enterobacterales with 3GC or piperacillin +/- tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.(c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Automated summary

The optimal treatment regimen for infections caused by wild-type AmpC beta-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to different types of definitive antibiotic therapy, and found that treatment with 3GC or piperacillin +/- tazobactam was not associated with higher mortality but had an increased risk of treatment failure.