Clinical and molecular characteristics of KPC-producing Klebsiella pneumoniae bloodstream infections: Results of a multicentre study

Objective: Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) is a great cause of concern and often associated with bloodstream infections (BSIs) and a high mortality rate. Here we identified the risk factors of KPC-Kp BSIs observed in three Italian hospitals and studied the epidemiology of KPC-Kp strains. Methods: A retrospective analysis of KPC-Kp BSIs was performed from 2014 to 2019 at three hospitals in central Italy (Ancona, Pesaro-Fano, and Perugia). Uni- and multi-variable analyses were performed to evaluate the clinical variables associated with mortality. Pulsed-field gel electrophoresis assay and whole-genome sequencing analysis of KPC-Kp isolates was carried out to identify antibiotic resistance genes and epidemiological relationships among the strains. Results: A total of 219 patients were considered. Mortality on day 30 was 32%, with older age, APACHE II score ≥11, Charlson Comorbidity Index ≥4, and solid tumours more frequent in patients with a negative outcome. Positive outcomes were related to combination therapy with at least two active drugs that also emerged in multivariate analysis. Most KPC-Kp strains belonged to three major sequence types (ST512, ST307, and ST101), while the most common carbapenem resistance gene variant was blaKPC-3. Conclusions: KPC-Kp BSIs remain a challenging infection with a high crude mortality rate. Patient conditions and comorbidities correlate with negative outcomes, while active drugs are correlated with better outcomes. Although collected from different hospitals, the KPC-Kp strains were epidemiologically related, suggesting inter-hospital diffusion. Timely and effective therapy, together with epidemiological surveillance, are crucial to reduce mortality and prevent the spread of nosocomial clones.