Mortality in KPC-producing<i>Klebsiella pneumoniae</i>bloodstream infections: a changing landscape
Daniele Roberto Giacobbe, Cristina Marelli, Greta Cattardico, Chiara Fanelli, Alessio Signori, Gabriele Di Meco, Vincenzo Di Pilato, Małgorzata Mikulska, Maria Mazzitelli, Anna Maria Cattelan, Carlo Pallotto, Daniela Francisci, Alessandra Calabresi, Andrea Lombardi, Andrea Gori, Valerio Del Bono, Chiara Aldieri, Angela Raffaella Losito, Francesca Raffaelli, Andrea Cortegiani, Marta Milazzo, Filippo Del Puente, Emanuele Pontali, Francesco Giuseppe De Rosa, Silvia Corcione, Alessandra Mularoni, Giovanna Russelli, Mauro Giacomini, Flavia Badalucco Ciotta, Chiara Oltolini, Francesco Saverio Serino, Elena Momesso, Michele Spinicci, Lucia Graziani, Carlo Torti, Enrico Maria Trecarichi, Marco Merli, Federico D’Amico, Anna Marchese, Antonio Vena, Matteo Bassetti
Abstract
OBJECTIVES: To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel β-lactam/β-lactamase inhibitor combinations. MATERIAL AND METHODS: Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project). RESULTS: Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10-1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15-1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74-2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50-2.29, P = 0.866). CONCLUSIONS: Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.