Carolina Saffioti, Maddalena Giannella, Pierluigi Viale, Silvia Corcione, Claudio Viscoli, Simone Ambretti, Gian Maria Rossolini, Mario Tumbarello, Michele Bartoletti, Teresa Spanu, Angela Raffaella Losito, Alessandro Bartoloni, Russell E. Lewis, Anna Marchese, Sara K. Tedeschi, Matteo Bassetti, Enrico Maria Trecarichi, Valerio Del Bono, Daniele Roberto Giacobbe, Francesca Raffaelli, Roberto Cauda, Francesco Giuseppe De Rosa, Giannella, Maddalena, Trecarichi, Enrico Maria, Giacobbe, Daniele Roberto, De Rosa, Francesco Giuseppe, Bassetti, Matteo, Bartoloni, Alessandro, Bartoletti, Michele, Losito, Angela Raffaella, del Bono, Valerio, Corcione, Silvia, Tedeschi, Sara, Raffaelli, Francesca, Saffioti, Carolina, Spanu, Teresa, Rossolini, Gian Maria, Marchese, Anna, Ambretti, Simone, Cauda, Roberto, Viscoli, Claudio, Russel Edward Lewi, Viale, Pierluigi, and Tumbarello, Mario
Objectives: To evaluate the impact of high-dose (HD) carbapenem-based combination therapy on clinical outcome in patients with monomicrobial carbapenem-resistant Klebsiella pneumoniae (CR-KP) bloodstream-infection (BSI). Methods: Post hoc analysis of all adult patients with CR-KP BSI who were treated with a combination antibiotic regimen, collected over a six-year period in six large Italian teaching hospitals. To control for confounding effects of HD carbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HD carbapenem was added to the model. Results: 595 patients with CR-KP BSI were analysed, 77% of isolates showed a carbapenem MIC ≥16 mg/L, 428 (71.9%) received HD carbapenem-based combination therapy. Overall, 127 patients (21.3%) died within 14 days after BSI onset. Multivariate analysis showed the Charlson comorbidity index (HR 1.31, 95%CI 1.20–1.43, P < 0.001), septic shock at BSI onset (HR 3.14, 95%CI 2.19–4.50, P < 0.001), and colistin-resistant strain (HR 1.52, 95%CI 1.02–2.24, P = 0.03) were independently associated with 14-day mortality, whereas admission to surgical ward (HR 0.44, 95%CI 0.25–0.78, P = 0.005) and HD carbapenem use (HR 0.69, 95%CI 0.47–1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HD carbapenem use showed a greater protective effect (HR 0.64, 95%CI 0.43–0.95, P = 0.03). Stratifying the model for carbapenem MIC, the benefit of HD carbapenem was also observed for strains with carbapenem MIC ≥16 mg/L. Conclusions: In patients receiving combination therapy for CR-KP BSI, the use of HD carbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.