Cefepime vs carbapenems for treating third-generation cephalosporin-resistant AmpC ß-lactamase-hyperproducing Enterobacterales bloodstream infections: a multicenter retrospective study.

OBJECTIVES: AmpC ß-lactamase-hyperproducing Enterobacterales (ABLHE) bloodstream infections (BSI) are emerging and leading to therapeutic challenges worldwide. Prescriptions of carbapenems may lead to the emergence of resistance. This study aimed to compare cefepime with carbapenems for the treatment of third-generation cephalosporin-resistant ABLHE BSI. METHODS: This retrospective multicenter study included patients with ABLHE BSI from two tertiary hospitals in France, between July 2017 and July 2022. Non-AmpC-producing Enterobacterales, extended-spectrum ß-lactamase, and carbapenemase-producing Enterobacterales were excluded. Cefepime was prescribed only in case of minimal inhibitory concentration ≤1 mg/l. The primary outcome was 30-day in-hospital mortality from the date of index blood culture. Secondary outcomes were infection recurrence and treatment toxicity. An inverse probability of treatment weighting approach was used to balance the baseline characteristics between the two groups. RESULTS: We analyzed 164 BSI, which included 77 in the cefepime group and 87 in the carbapenem group. In the weighted cohort, the 30-day mortality rates were similar between the cefepime group (23.3%) and the carbapenem group (19.6%) with a relative risk of 1.19 (95% confidence interval, 0.61-2.33 P = 0.614). No significant difference in recurrence or toxicity was found between the two groups. CONCLUSION: This study adds evidence in favor of the use of cefepime for treating third-generation cephalosporin-resistant ABLHE BSI in case of minimal inhibitory concentration ≤ 1 mg/l, which could spare carbapenems.

Evolving epidemiology and antimicrobial resistance in spontaneous bacterial peritonitis: a two-year observational study.

BACKGROUND: Current recommendations for empirical antimicrobial therapy in spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since microbial epidemiology and the management of patients have changed, whether these recommendations are still appropriate must be confirmed. METHODS: An observational study that exhaustively collected the clinical and biological data associated with positive ascitic fluid cultures was conducted in four French university hospitals in 2010-2011. RESULTS: Two hundred and sixty-eight documented positive cultures were observed in 190 cirrhotic patients (median age 61.5 years, 58.5% Child score C). Of these, 57 were classified as confirmed SBP and 140 as confirmed bacterascites. The predominant flora was Gram-positive cocci, whatever the situation (SBP, bacterascites, nosocomial/health-care related or not). Enteroccocci (27.7% E. faecium) were isolated in 24% of the episodes, and in 48% from patients receiving quinolone prophylaxis. E. coli were susceptible to amoxicillin-clavulanate and to third-generation cephalosporins in 62.5% and 89.5% of cases, respectively. No single antibiotic allowed antimicrobial coverage of more than 60%. Only combinations such as amoxicillin + third-generation cephalosporin or cotrimoxazole allowed coverage close to 75-80% in non-nosocomial episodes. Combinations based on broader spectrum antibiotics should be considered for empirical therapy of nosocomial infections. CONCLUSIONS: Our study confirmed the changing spectrum of pathogens in SBP and bacterascites, and the need for more complex antibiotic strategies than those previously recommended. Our findings also underline the need for new clinical trials conducted in the current epidemiological context.