Clinical Characteristics and Outcome of Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae Carbapenemase-Producing Klebsiella pneumoniae Infections: A Retrospective, Observational, 2-Center Clinical Study

Alessandra Oliva; Laura Campogiani; Giulia Savelloni; Pietro Vitale; Alessandra Lodi; Frederica Sacco; Alessandra Imeneo; Lorenzo Volpicelli; Riccardo Polani; Giammarco Raponi; Loredana Sarmati; Mario Venditti

doi:10.1093/ofid/ofad327

Clinical Characteristics and Outcome of Ceftazidime/Avibactam-Resistant Klebsiella pneumoniae Carbapenemase-Producing Klebsiella pneumoniae Infections: A Retrospective, Observational, 2-Center Clinical Study

Open Forum Infect Dis. 2023 Jun 30;10(7):ofad327. doi: 10.1093/ofid/ofad327. eCollection 2023 Jul.

Authors

Affiliations

¹ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
² Infectious Disease Clinic, Policlinico Tor Vergata, Rome, Italy.
³ Department of System Medicine, Tor Vergata University, Rome, Italy.
⁴ Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.

Abstract

Background: Recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) with resistance to ceftazidime/avibactam (CZA-R) has been described, including KPC variants that restore carbapenem susceptibility. The aim of the study was to analyze the clinical characteristics and outcomes of infections caused by CZA-R KPC-Kp.

Methods: From 2019 to 2021, a retrospective 2-center study including patients with infections due to CZA-R KPC-Kp hospitalized at 2 academic hospitals in Rome was conducted. Demographic and clinical characteristics were collected. Principal outcome was 30-day all-cause mortality. Statistical analyses were performed with Stata-IC17 software.

Results: Overall, 59 patients were included (mean age, 64.4 ± 14.6 years; mean Charlson comorbidity index score, 4.5 ± 2.7). Thirty-four patients (57.6%) had infections caused by CZA-R and meropenem (MEM)-susceptible strains. A previous CZA therapy was observed in 40 patients (67.8%), mostly in patients with MEM-susceptible KPC variant (79.4% vs 52%, P = .026). Primary bacteremia was observed in 28.8%, followed by urinary tract infections and pneumonia. At infection onset, septic shock was present in 15 subjects (25.4%). After adjustment for confounders, only the presence of septic shock was independently associated with mortality (P = .006).

Conclusions: Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to MEM. Nevertheless, one-third of patients had never received CZA before KPC-Kp CZA-R. Since the major driver for mortality was infection severity, understanding the optimal therapy in patients with KPC-Kp CZA-R infections is of crucial importance.

Keywords: KPC variant; carbapenems; ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae; ceftazidime/avibactam-resistant meropenem-susceptible KPC-producing Klebsiella pneumoniae; meropenem/vaborbactam.