{Reference Type}: Multicenter Study
{Title}: 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.
{Author}: Maillard A;Delory T;Bernier J;Villa A;Chaibi K;Escaut L;Contejean A;Bercot B;Robert J;El Alaoui F;Tankovic J;Poupet H;Cuzon G;Lafaurie M;Surgers L;Joseph A;Paccoud O;Molina JM;Bleibtreu A; ;
{Journal}: Int J Antimicrob Agents
{Volume}: 62
{Issue}: 1
{Year}: Jul 2023 6
{Factor}: 15.441
{DOI}: 10.1016/j.ijantimicag.2023.106809
{Abstract}: BACKGROUND: The optimal treatment regimen for infections caused by wild-type AmpC β-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 β-lactamase-producing Enterobacterales 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 cefepime 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.
CONCLUSIONS: Treatment of included BSI or pneumonia caused by wild-type AmpC β-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.