Maddalena Giannella1, Enrico Maria Trecarichi2, Daniele Roberto Giacobbe3, Francesco Giuseppe De Rosa4, Matteo Bassetti5, Alessandro Bartoloni6, Michele Bartoletti7, Angela Raffaella Losito2, Valerio Del Bono3, Silvia Corcione4, Sara Tedeschi7, Francesca Raffaelli2, Carolina Saffioti3, Teresa Spanu8, Gian Maria Rossolini9, Anna Marchese10, Simone Ambretti11, Roberto Cauda2, Claudio Viscoli3, Russell Edward Lewis7, Pierluigi Viale7, Mario Tumbarello2. 1. Infectious Diseases Unit, Department of Medical and Clinical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy. Electronic address: maddalena.giannella@libero.it. 2. Institute of Infectious Diseases, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy. 3. Infectious Diseases Division, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy. 4. Department of Infectious Diseases, Amedeo di Savoia Hospital, University of Turin, Turin, Italy. 5. Infectious Disease Division, Santa Maria Misericordia University Hospital, Udine. 6. Infectious and Tropical Diseases Unit, Careggi Hospital, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 7. Infectious Diseases Unit, Department of Medical and Clinical Sciences, S. Orsola-Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy. 8. Institute of Microbiology, Catholic University of the Sacred Heart, A. Gemelli Hospital, Rome, Italy. 9. Clinical Microbiology and Virology Unit, Department of Experimental and Clinical Medicine, Florence Careggi University Hospital, University of Florence, Florence, Italy. 10. Section of Microbiology-DISC, University of Genoa and IRCCS San Martino- IST, Genoa, Italy. 11. Unit of Clinical Microbiology, S. Orsola-Malpighi University Hospital, Bologna, Italy.
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.
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 HDcarbapenem combination on 14-day mortality, a multivariate Cox regression analysis was performed. Due to imbalances between patients, a propensity score for receiving HDcarbapenem 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 HDcarbapenem-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 HDcarbapenem use (HR 0.69, 95%CI 0.47-1.00, P = 0.05) were protective factors. When adjusted for the propensity score, HDcarbapenem 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 HDcarbapenem was also observed for strains with carbapenem MIC ≥16 mg/L. CONCLUSIONS: In patients receiving combination therapy for CR-KP BSI, the use of HDcarbapenem seems to be associated with better outcome, even in the presence of high-level carbapenem resistance.
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Authors: O Lima; A Sousa; R Longueira-Suárez; A Filgueira; C Taboada-Martínez; C Portela-Pino; A Nodar; F Vasallo-Vidal; L Martinez-Lamas; A Pérez-Landeiro; M Rubianes; M T Pérez-Rodríguez Journal: Eur J Clin Microbiol Infect Dis Date: 2022-08-08 Impact factor: 5.103
Authors: O Lima Rodríguez; A Sousa; María Teresa Pérez-Rodríguez; L Martínez-Lamas; R Longueira Suárez; C Taboada Martínez; C Portela Pino; F Vasallo Vidal; A Pérez-Landeiro; M Crespo Casal Journal: Medicine (Baltimore) Date: 2021-04-09 Impact factor: 1.817