Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections
Jorgensen SCJ, Trinh TD, Zasowski EJ, Lagnf AM, Bhatia S, Melvin SM, Steed ME, Simon SP, Estrada SJ, Morrisette T, Claeys KC, Rosenberg JR, Davis SL, and Rybak MJ. Real-World Experience With Ceftazidime-Avibactam for Multidrug-Resistant Gram-Negative Bacterial Infections. Open Forum Infect Dis 2019; 6(12).
Open Forum Infect Dis
Background: We conducted this study to describe the clinical characteristics, microbiology, and outcomes of patients treated with ceftazidime-avibactam (CZA) for a range of multidrug-resistant Gram-negative (MDR-GN) infections.
Methods: This is a multicenter, retrospective cohort study conducted at 6 medical centers in the United States between 2015 and 2019. Adult patients who received CZA (≥72 hours) were eligible. The primary outcome was clinical failure defined as a composite of 30-day all-cause mortality, 30-day microbiological failure, and/or failure to resolve or improve signs or symptoms of infection on CZA.
Results: In total, data from 203 patients were evaluated. Carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas spp were isolated from 117 (57.6%) and 63 (31.0%) culture specimens, respectively. The most common infection sources were respiratory (37.4%), urinary (19.7%), and intra-abdominal (18.7%). Blood cultures were positive in 22 (10.8%) patients. Clinical failure, 30-day mortality, and 30-day recurrence occurred in 59 (29.1%), 35 (17.2%), and 12 (5.9%) patients, respectively. On therapy, CZA resistance developed in 1 of 62 patients with repeat testing. Primary bacteremia or respiratory tract infection and higher SOFA score were positively associated with clinical failure (adjusted odds ratio [aOR] = 2.270, 95% confidence interval [CI] = 1.115-4.620 and aOR = 1.234, 95% CI = 1.118-1.362, respectively). Receipt of CZA within 48 hours of infection onset was protective (aOR, 0.409; 95% CI, 0.180-0.930). Seventeen (8.4%) patients experienced a potential drug-related adverse effect (10 acute kidney injury, 3 Clostridioides difficile infection, 2 rash, and 1 each gastrointestinal intolerance and neutropenia).
Conclusions: Ceftazidime-avibactam is being used to treat a range of MDR-GN infections including Pseudomonas spp as well as CRE.