CEFTAZIDIME-AVIBACTAM FOR THE TREATMENT OF INFECTIONS DUE TO AEROBIC GRAM-NEGATIVE ORGANISMS IN PATIENTS WITH LIMITED TREATMENT OPTIONS- A SYSTEMATIC REVIEW AND META-ANALYSIS
Author(s)
Guerreiro R1, Alarcao J2, Pinheiro B2, Borges M2, Silva Miguel L2, Inês M3, Costa J4
1Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 11, Portugal, 2Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal, 3Laboratórios Pfizer, Lisbon, Portugal, 4Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
Presentation Documents
OBJECTIVES : To evaluate the effectiveness of ceftazidime-avibactam (CAZ-AVI) compared to colistin for the treatment of infections due to aerobic Gram-negative organisms in adult patients with limited treatment options, in particular multi-drug resistant (MDR) Enterobacteriaceae and Pseudomonas infections. METHODS : An electronic search was conducted in Medline, EMBASE and ClinicalTrials.gov databases up to June 2018. Data were screened, extracted and appraised independently. Both random-controlled and non-controlled studies were eligible for inclusion providing that data were available on clinical cure, mortality and/or adverse events in patients with MDR Enterobacteriaceae or Pseudomonas infections treated with CAZ-AVI or colistin. A meta-regression was performed to estimate treatment effect of CAZ-AVI compared to colistin, adjusted for study design, using R software. Direct and indirect comparisons were pooled through a random-effect meta-analysis weighted by inverse variance method. Heterogeneity between studies was assessed with χ2 and I2 tests. RESULTS : Overall, 804 references were retrieved from electronic search. After screening, a total of 37 studies (evaluating 361 patients treated with CAZ-AVI and 1,363 treated with colistin) meet inclusion criteria (24 studies in Enterobacteriaceae, 16 in Pseudomonas and 3 studies reported results for both infections). In patients with carbapenem-resistant Enterobacteriaceae infections, CAZ-AVI was associated with higher clinical cure (Odds Ratio [OR]: 1.99; 95%CI: 0.99-4.04) and lower 30-day mortality (OR: 0.79; 95%CI: 0.42-1.48) in comparison to colistin. In patients with MDR Pseudomonas infections, the OR also favored CAZ-AVI over colistin for both clinical cure (OR: 1.27; 95%CI: 0.19-10.81) and 30-day mortality (OR:0.69; 95%CI: 0.16-3.07). The mean proportion of colistin-treated patients with nephrotoxicity and neurotoxicity was 26% and 3%, respectively. CONCLUSIONS : Despite the scarcity of data and methodological limitations of the analysis, the available evidence suggests that CAZ-AVI is associated with a better efficacy and safety profile compared to colistin in patients with limited therapeutic options for infections caused by Gram-negative aerobic organisms.
Conference/Value in Health Info
2019-11, ISPOR Europe 2019, Copenhagen, Denmark
Code
PIN9
Disease
Drugs, Infectious Disease (non-vaccine)