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.

Giannella, M., Trecarichi, E. M., Giacobbe, D. R., De Rosa, F. G., Bassetti, M., Bartoloni, A., Bartoletti, M., Losito, A. R., Del Bono, V., Corcione, S., Tedeschi, S., Raffaelli, F., Saffioti, C., Spanu, T., Rossolini, G. M., Marchese, A., Ambretti, S., Cauda, R., Viscoli, C., Lewis, R. E., Viale, P., Tumbarello, M., Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection, <<INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS>>, 2017; 51 (2): 244-248. [doi:10.1016/j.ijantimicag.2017.08.019] [http://hdl.handle.net/10807/111665]

Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection

Trecarichi, Enrico Maria
Secondo
;
Losito, Angela Raffaella;Raffaelli, Francesca;Spanu, Teresa;Cauda, Roberto;Tumbarello, Mario
Ultimo
2018

Abstract

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.
Inglese
Giannella, M., Trecarichi, E. M., Giacobbe, D. R., De Rosa, F. G., Bassetti, M., Bartoloni, A., Bartoletti, M., Losito, A. R., Del Bono, V., Corcione, S., Tedeschi, S., Raffaelli, F., Saffioti, C., Spanu, T., Rossolini, G. M., Marchese, A., Ambretti, S., Cauda, R., Viscoli, C., Lewis, R. E., Viale, P., Tumbarello, M., Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection, <<INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS>>, 2017; 51 (2): 244-248. [doi:10.1016/j.ijantimicag.2017.08.019] [http://hdl.handle.net/10807/111665]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/111665
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