Ceftazidime 2g / Avibactam 500mg powder for solution for infusion vials

Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until 12 February 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80–100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [n = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65–1.41].

Abstract licence: CC BY 4.0

The emergence of antimicrobial resistance in Gram-negative bacteria (GNB) is a major global concern. Ceftazidime–avibactam (CAZ–AVI) has been identified as a potential treatment option for complicated infections. This meta-analysis aimed to evaluate the global resistance proportions of GNB to CAZ–AVI comprehensively. Studies were searched in Scopus, PubMed, and EMBASE (until September 2024), and statistical analyses were conducted using STATA software (version 20.0). CAZ–AVI resistance proportions were determined in 136 studies, with 25.8% (95% CI 22.2–29.7) for non-fermentative gram-negative bacilli and 6.1% (95% CI 4.9–7.4) for Enterobacterales. The CAZ–AVI resistance proportion significantly increased from 5.6% (95% CI 4.1–7.6) of 221,278 GNB isolates in 2015–2020 to 13.2% (95% CI 11.4–15.2) of 285,978 GNB isolates in 2021–2024. Regionally, CAZ–AVI resistance was highest in Asia 19.3% (95% CI 15.7–24.23.4), followed by Africa 13.6% (95% CI 5.6–29.2), Europe 11% (95% CI 7.8–15.2), South America 6.1% (95% CI 3.2–11.5) and North America 5.3% (95% CI 4.2–6.7). Among GNB resistance profiles, colistin-resistant isolates and XDR isolates exhibited the highest resistance proportions (37.1%, 95% CI 14–68 and 32.1%, 95% CI 18.5–49.6), respectively), followed by carbapenem-resistant isolates and MDR isolates [(25.8%, 95% CI 22.6–29.3) and (13%, 95% CI 9.6, 17.3)]. A high proportion of GNB isolates from urinary tract infections remained susceptible to CAZ–AVI, indicating its potential as a suitable treatment option. However, the increasing resistance trends among GNB are concerning and warrant continuous monitoring to maintain CAZ–AVI's effectiveness against GNB infections.

Abstract licence: CC BY-NC-ND