Bacteremia caused by carbapenemase-producing and carbapenems-susceptible Klebsiella pneumoniae: clinical outcome, impact of COVID-19 and efficacy of ceftazidime/avibactam

Abstract

Bacteremia caused by carbapenemase-producing Klebsiella pneumoniae (CP-KPN-B) are a serious complication in hospitalized patients due to high morbidity and mortality rates and multi-resistance to antibiotics. There are very few studies comparing CP-KPN-B and those caused by carbapenems-susceptible K. pneumoniae (CS-KPN-B) in Argentina. The aim of this work was to compare the clinical and microbiological features of CP-KPN-B and CS-KPN-B.

An observational, retrospective, descriptive study was carried out to evaluate patients suffering K. pneumoniae bacteremia from 11/2019 to 03/2022 at the Hospital Privado Universitario de Cordoba. Demographic data, comorbidities and mortality were analyzed, among other variables. Bacterial typing was assessed by MALDI-TOF. Antimicrobial susceptibility testing was determined using VITEK-2. Carbapenemase types were identified by PCR (KPC, NDM, VIM, IMP, OXA-48/163). For statistical analysis of categorical data, comparison of proportions using Chi square was performed using MedCalc 14.8.1.

A total of 66 CP-KPN-B and 49 CS-KPN-B cases were studied. Carbapenemase types detected were KPC-70% (p<0.05), NDM-24%, KPC+NDM-5% and OXA-48/163-1%. A larger proportion of male patients (64%, p<0.05) was found in CP-KPN-B. Median age (CP-KPN-B/CS-KPN-B) was 58/64 years (p>0.05). Prior use of carbapenems was 41%/6%, appropriate empirical antibiotic treatment was 35%/75%, stay at critical care unit at the time of bacteremia was 50%/16% and median total length of hospitalization was 30/15 days (p<0.05). 30-day mortality in CP-KPN-B/CS-KPN-B was 39%/18% (OR 2.9; p=0,02). In CP-KPN-B patients treated with ceftazidime/avibactam (Caz/Avi, n=25) vs. other antibiotics (n=41), 30-day mortality was 20% and 51%, respectively (OR 4.2; p=0.02). No statistically significant differences in mortality of CP-KPN-B treated with Caz/Avi were observed in comparison with CS-KPN-B. In patients with CP-KPN-B and COVID-19 (n=13) vs. those with CP-KPN-B and other comorbidities, 30-day mortality was 77% and 30%, respectively (OR 4.2; p=0.01).

Clearly, patients suffering CP-KPN-B showed increased morbidity and worse prognosis. Association of CP-KPN-B and COVID-19 resulted in a marked increase in mortality. Caz/Avi was the best therapeutic option in CP-KPN-B, equaling mortality with CS-KPN-B.