Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales.

Antonio Vena ,Chiara Sepulcri ,Francesca Raumer ,Alessandra Oliva ,Silvia Corcione ,Filippo Del Puente ,Sergio Carbonara ,Roberto Luzzati ,Silvia Boni ,Claudio Maria Mastroianni ,Daniele Roberto Giacobbe ,Anna María Cattelan ,Nadia Castaldo ,Marianna Meschiari ,Alessandro Capone ,Antonio Cascio ,Cristina Mussini ,Francesco Giuseppe De Rosa ,Matteo Bassetti

doi:10.3390/antibiotics9020071

Abstract

Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.

Highlights

This study is the largest evaluation of a cohort of patients treated with ceftazidime-avibactam for different types of infections due to gram−negative bacteria (GNB) other than carbapenems-resistant Enterobacterales
In line with the pooled clinical cure rate observed in prior trials (85%) [19], about 90% of all assessed patients in our study were deemed an overall treatment success at the end of ceftazidime-avibactam treatment
This high clinical cure rate was observed despite our study population having a higher prevalence of infections caused by MDR, XDR, or pandrug resistant (PDR) pathogens, underlying comorbidities and use of ceftazidime-avibactam as secondary therapy

Summary

Introduction

In real-life experiences, high rates of favorable response to ceftazidime-avibactam treatment are reported in patients with infections due to carbapenem−resistant Enterobacterales (CRE), with an overall success rate of about 70% [9,10,11,12,13,14,15], whereas post-marketing experience regarding the use of ceftazidime-avibactam for infections due to MDR-GNB other than CRE remains scarce [16,17,18] information regarding features associated with clinical failures and the emergence of resistance in this group of patients are even scarcer For this reason, in this multicenter study we describe our experience about the use of ceftazidime-avibactam for the treatment of infections due to MDR-GNB other than CRE in 13 Italian hospitals.

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Conclusion