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

Abstract

Background Recently, KPC-producing Klebsiella pneumoniae (KPC-Kp) with resistance to ceftazidime/avibactam (CZA-R) have been described, including KPC-variants which restore carbapenem susceptibility. Aim of the study was to analyze the clinical characteristics and outcomes of infections caused by CZA-R KPC-Kp. Materials/methods From 2019 to 2021, a retrospective two-center study including patients with infections due to CZA-R KPC-Kp hospitalized at two Academic Hospitals in Rome was conducted. Demographic and clinical characteristics were collected. Principal outcome was 30-d 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 4.5 (±2.7). Thirty-four patients (57.6%) had infections caused by CZA-resistant and meropenem (MEM)-susceptible strains. A previous CZA therapy was observed in 40 patients (67.8%), mostly in patients with MEM-S KPC-variant (79.4% vs 52%, p=0.026). 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=0.006). 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’s severity, understanding the optimal therapy in patients with KPC-Kp CZA-R infections is of crucial importance.

Real-world use of imipenem/cilastatin/relebactam for the treatment of KPC-producing Klebsiella pneumoniae complex and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa infections: a single-center preliminary experience

“…This brings to another interesting feature of IMI/REL, that is its activity toward KPC-producing strains exhibiting resistance to CTV, a profile which first emerged in 2018 and, since then, has been increasingly reported worldwide ( European Centre for Disease Prevention and Control, 2018 ; di Bella et al, 2021 ; Sader et al, 2021 ; Shields et al, 2022 ; Campogiani et al, 2023 ; di Pilato et al, 2023 ; Oliva et al, 2023 ).…”

Clinical effectiveness of cefiderocol for the treatment of bloodstream infections due to carbapenem-resistant Acinetobacter baumannii during the COVID-19 era: a single center, observational study

“…The indicative parameters of early (48–72 h) clinical improvement were at least one of the following: discontinuation of treatment with inotropic drugs if the patient was previously in septic shock, disappearance of fever for at least 48 consecutive hours after the start of treatment, reduction of serum procalcitonin values by at least 80% compared to the initial value or achievement of a serum PCT value < 0. 5 ng/mL, a reduction of at least 75% of the maximum achieved value of c-reactive protein (PCR) [ 28 ].…”