Effect of ceftazidime/avibactam plus fosfomycin combination on 30 day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study

A Oliva; L Volpicelli; S Di Bari; A Curtolo; C Borrazzo; F Cogliati Dezza; A Cona; S Agrenzano; A Mularoni; M Trancassini; F Mengoni; S Stefani; G Raponi; M Venditti

doi:10.1093/jacamr/dlac121

Effect of ceftazidime/avibactam plus fosfomycin combination on 30 day mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae: results from a multicentre retrospective study

JAC Antimicrob Resist. 2022 Dec 7;4(6):dlac121. doi: 10.1093/jacamr/dlac121. eCollection 2022 Dec.

Authors

A Oliva¹, L Volpicelli¹, S Di Bari¹, A Curtolo¹, C Borrazzo², F Cogliati Dezza¹, A Cona³, S Agrenzano³, A Mularoni³, M Trancassini¹, F Mengoni¹, S Stefani⁴, G Raponi¹, M Venditti¹

Affiliations

¹ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy.
² Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome 00185, Italy.
³ Unit of Infectious Diseases, ISMETT-IRCCS Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Via E. Tricomi, 5, Palermo 90127, Italy.
⁴ Department of Biomedical and Biotechnological Sciences. Policlinico Hospital, University of Catania, Via Androne 81, Catania 95124, Italy.

Abstract

Introduction: The primary outcome of the study was to evaluate the effect on 30 day mortality of the combination ceftazidime/avibactam + fosfomycin in the treatment of bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp).

Materials and methods: From October 2018 to March 2021, a retrospective, two-centre study was performed on patients with KPC-Kp BSI hospitalized at Sapienza University (Rome) and ISMETT-IRCCS (Palermo) and treated with ceftazidime/avibactam-containing regimens. A matched cohort (1:1) analysis was performed. Cases were patients receiving ceftazidime/avibactam + fosfomycin and controls were patients receiving ceftazidime/avibactam alone or in combination with in vitro non-active drugs different from fosfomycin (ceftazidime/avibactam ± other). Patients were matched for age, Charlson comorbidity index, ward of isolation (ICU or non-ICU), source of infection and severity of BSI, expressed as INCREMENT carbapenemase-producing Enterobacteriaceae (CPE) score.

Results: Overall, 221 patients were included in the study. Following the 1:1 match, 122 subjects were retrieved: 61 cases (ceftazidime/avibactam + fosfomycin) and 61 controls (ceftazidime/avibactam ± other). No difference in overall mortality emerged between cases and controls, whereas controls had more non-BSI KPC-Kp infections and a higher number of deaths attributable to secondary infections. Almost half of ceftazidime/avibactam + fosfomycin patients were prescribed fosfomycin without MIC fosfomycin availability. No difference in the outcome emerged after stratification for fosfomycin susceptibility availability and dosage. SARS-CoV-2 infection and ICS ≥ 8 independently predicted 30 day mortality, whereas an appropriate definitive therapy was protective.

Conclusions: Our data show that fosfomycin was used in the treatment of KPC-Kp BSI independently from having its susceptibility testing available. Although no difference was found in 30 day overall mortality, ceftazidime/avibactam + fosfomycin was associated with a lower rate of subsequent KPC-Kp infections and secondary infections than other ceftazidime/avibactam-based regimens.