Ceftazidime-avibactam plus aztreonam cocktail for the treatment of VIM-producing Pseudomonas aeruginosa infections: good enough to have another?

Abstract

Background: Few active antibiotic options are available to treat MBL-producing Pseudomonas aeruginosa infections, and some of these options are either poorly tolerated or have pharmacokinetic limitations. The use of aztreonam monotherapy for treating MBL-producing P. aeruginosa remains controversial due to the risk of selecting resistant mutants during treatment.

Objectives: To describe the clinical outcomes of patients treated with ceftazidime-avibactam plus aztreonam for VIM-producing P. aeruginosa infections. The assessed outcomes include clinical success, clinical cure, all-cause mortality at day 28, combination therapy-associated adverse events, infection relapse and microbiological recurrence.

Methods: This retrospective observational single-centre study was conducted at Clínica Universidad de Navarra, Pamplona, Spain. Eight patients with VIM-producing P. aeruginosa infections were included. Whole-genome sequencing of isolates was performed at Hospital Universitario Son Espases, Palma, Spain.

Results: All isolates were susceptible to aztreonam and aztreonam-avibactam. No resistance mechanisms against these antibiotics were identified through whole-genome sequencing, except in one isolate that overexpressed the MexAB-OprM efflux pump. Clinical success and clinical cure were achieved in seven of eight patients, while all-cause mortality at day 28 was two of eight. Clinical cure was documented for five different infections and three distinct P. aeruginosa clones. No adverse events related to antibiotic therapy were reported, and no infection relapses occurred after treatment. Microbiological recurrence was observed in two cases.

Conclusions: In our experience, patients with VIM-producing P. aeruginosa infections treated with ceftazidime-avibactam plus aztreonam mostly achieved clinical success. However, given the limited sample size, further research is required to validate these findings.