Comparative Effectiveness of Non-Carbapenem versus Carbapenem Therapy for Serious Infections Caused by AmpC β-Lactamase-Producing Enterobacteriaceae: A Retrospective Cohort Study

Abstract Introduction: AmpC β-lactamase-producing Enterobacteriaceae pose significant therapeutic challenges, with carbapenems traditionally considered first-line therapy. However, antimicrobial stewardship concerns necessitate evaluation of alternative treatment strategies. Aim To compare clinical outcomes between non-carbapenem and carbapenem therapy for serious AmpC-producing infections. Method We conducted a retrospective cohort study at King Faisal Specialist Hospital & Research Centre, Jeddah, from January 2019 to May 2024. Adult patients with serious infections caused by AmpC β-lactamase-producing Enterobacteriaceae were included. Patients were categorized into carbapenem (meropenem, imipenem, ertapenem) or non-carbapenem (cefepime, piperacillin-tazobactam, fluoroquinolones, trimethoprim-sulfamethoxazole) groups based on primary therapy received. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included 90-day mortality, clinical cure, ICU mortality among ICU patients, microbiological eradication, length of hospital stay, infection recurrence, treatment escalation, and adverse drug reactions. Results Of 1064 patients screened, 125 comprised the analysis cohort (68 carbapenem, 57 non-carbapenem). Enterobacter cloacae complex was the predominant pathogen (48.8%), followed by Klebsiella aerogenes (22.4%). Baseline characteristics were similar between groups. The 30-day mortality was lower in the non-carbapenem group compared to the carbapenem group (12.3% vs 14.7%; absolute risk difference − 2.4%, 95% CI: -12.8% to 8.0%; p = 0.708). Similarly, 90-day mortality favored non-carbapenem therapy (14.0% vs 19.1%; p = 0.429). Clinical cure rates were higher with non-carbapenem therapy (71.9% vs 64.7%; p = 0.350). Among ICU patients, mortality was lower with non-carbapenem therapy (45.5% vs 52.4%; p = 0.710). Treatment escalation was less frequent in the non-carbapenem group (24.6% vs 29.4%; p = 0.550). After multivariable adjustment, non-carbapenem therapy remained associated with lower mortality odds (adjusted OR: 0.73, 95% CI: 0.24–2.21; p = 0.578). Conclusion Non-carbapenem therapy demonstrated comparable clinical effectiveness to carbapenems for serious AmpC β-lactamase-producing Enterobacteriaceae infections, with numerically favorable outcomes. These findings support non-carbapenem agents as viable alternatives, potentially enhancing antimicrobial stewardship efforts while preserving carbapenems for resistant infections.