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

• Published in: Open forum infectious diseases Vol. 10; no. 7; p. ofad327
• Main Authors: Oliva, Alessandra, Campogiani, Laura, Savelloni, Giulia, Vitale, Pietro, Lodi, Alessandra, Sacco, Frederica, Imeneo, Alessandra, Volpicelli, Lorenzo, Polani, Riccardo, Raponi, Giammarco, Sarmati, Loredana, Venditti, Mario
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.07.2023
• Subjects: Infections; Major; Mortality; Sepsis; meropenem/vaborbactam; carbapenems; KPC variant; ceftazidime/avibactam-resistant KPC-producing; ceftazidime/avibactam-resistant meropenem-susceptible KPC-producing; ceftazidime/avibactam-resistant KPC-producing Klebsiella pneumoniae; ceftazidime/avibactam-resistant meropenem-susceptible KPC-producing Klebsiella pneumoniae
• ISSN: 2328-8957; 2328-8957
• DOI: 10.1093/ofid/ofad327

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. Clinical characteristics and outcomes of infections caused by ceftazidime/avibactam-resistant (CZA-R) Klebsiella pneumoniae carbapenemase (KPC)–producing Klebsiella pneumoniae were analyzed. Ceftazidime/avibactam-resistant and meropenem-susceptible KPC variants accounted for more than half of patients. Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to meropenem. Nevertheless, one-third of patients had never received CZA before isolation of CZA strains. Infection severity was the only independent predictor of 30-day mortality.