Clinical Characteristics of Patients Who Acquired Gram-Negative Bacteria During Ceftazidime-Avibactam Therapy.

Abstract

Introduction: Ceftazidime-avibactam (CZA) is recommended to treat infections caused by carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa with difficult-to-treat resistance. The selective pressure of CZA results in the isolation of multidrug-resistant Gram-negative bacteria (MDR-GNB), causing superinfection or hospital-wide spread. We aimed to study the clinical characteristics of patients who acquired GNB during CZA treatment.

Methods: Adult patients treated with CZA for ≥ 5 days for proven or suspected MDR-GNB were retrospectively enrolled at Taipei Veterans General Hospital between December 2019 and June 2021. GNB acquisition was defined as new GNB species resulting in infection or colonization isolated during the period from 5 days after the initiation of CZA until the end of treatment. Clinical features were compared between patients who acquired GNB from clinical specimen and those who did not. Multivariable analysis was used to explore risk factors for acquisition of GNB and 28-day mortality in patients who acquired GNB.

Results: Among 321 patients treated with CZA, 68 GNB were identified in 55 patients (17.1%). Elizabethkingia species (n = 15) was the most common GNB, followed by Acinetobacter species (n = 13) and Burkholderia cenocepacia (n = 11). The presence of diabetes mellitus, and mechanical ventilation were independent risk factors for GNB acquisition. There was a statistically nonsignificant trend toward increased 28-day mortality in patients with GNB acquisition compared to those without (38.2% vs. 27.8%, P = 0.105). Cerebrovascular disease and acquired GNB resulting in infection were associated with 28-day mortality in patients who acquired GNB.

Conclusions: Elizabethkingia species, Acinetobacter species, and B. cenocepacia were the major GNB acquired during CZA treatment. A trend toward increased mortality was observed in patients with GNB acquisition during CZA treatment. Further studies on optimal treatments for these patients were warranted.