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.

Details

Title
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
Author
Oliva, A 1   VIAFID ORCID Logo  ; Volpicelli, L 1 ; S Di Bari 1 ; Curtolo, A 1 ; Borrazzo, C 2 ; F Cogliati Dezza 1 ; Cona, A 3 ; Agrenzano, S 3 ; Mularoni, A 3   VIAFID ORCID Logo  ; Trancassini, M 1 ; Mengoni, F 1 ; Stefani, S 4 ; Raponi, G 1   VIAFID ORCID Logo  ; Venditti, M 1 

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 
Publication year
2022
Publication date
Dec 2022
Publisher
Oxford University Press
e-ISSN
26321823
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1093/jacamr/dlac121
ProQuest document ID
3170597744
Copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. This work is published under https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.