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.

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 / Oliva, A; Volpicelli, L; Di Bari, S; Curtolo, A; Borrazzo, C; Cogliati Dezza, F; Cona, A; Agrenzano, S; Mularoni, A; Trancassini, M; Mengoni, F; Stefani, S; Raponi, G; Venditti, M. - In: JAC-ANTIMICROBIAL RESISTANCE. - ISSN 2632-1823. - 4:6(2022), pp. 1-11. [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

Oliva, A
;
Volpicelli, L;Di Bari, S;Curtolo, A;Borrazzo, C;Cogliati Dezza, F;Cona, A;Trancassini, M;Mengoni, F;Stefani, S;Raponi, G;Venditti, M
2022

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.
2022
kpc-producing bacteria; klebsiella pneumoniae; ceftazidime/avibactam plus fosfomycin
01 Pubblicazione su rivista::01a Articolo in rivista
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 / Oliva, A; Volpicelli, L; Di Bari, S; Curtolo, A; Borrazzo, C; Cogliati Dezza, F; Cona, A; Agrenzano, S; Mularoni, A; Trancassini, M; Mengoni, F; Stefani, S; Raponi, G; Venditti, M. - In: JAC-ANTIMICROBIAL RESISTANCE. - ISSN 2632-1823. - 4:6(2022), pp. 1-11. [10.1093/jacamr/dlac121]
File allegati a questo prodotto
File Dimensione Formato  
Oliva_Effect_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 367.5 kB
Formato Adobe PDF
367.5 kB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1683513
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 14
social impact