1. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study
- Author
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Manel Almela, Angela Raffaella Losito, Deepali Virmani, Silvia Gómez-Zorrilla, Alicia Hernandez, Maria Souli, George L. Daikos, F. Riemenschneider, V. Rucci, José Molina, Carmen Peña, C. I. Marinescu, Mireia Puig-Asensio, Mónica Gozalo, José Miguel Cisneros, E. Ruiz de Gopegui, A. O. Sahin, Joaquín Bermejo, R. San Juan, Esther Calbo, Mario Fernández-Ruiz, Emmanuel Roilides, Warren Lowman, Evelina Tacconelli, Maddalena Giannella, Julia Origüen, Antonio Oliver, M.D. del Toro, Elena Salamanca, Garyphallia Poulakou, Nieves Larrosa, Jorge Galvez, Özlem Kurt Azap, Po-Ren Hsueh, Pierluigi Viale, Elias Iosifidis, Felipe Francisco Tuon, Ilias Karaiskos, Marina de Cueto, V. González, M.C. Fariñas, Belén Gutiérrez-Gutiérrez, M. Xercavins, E. Jové, Athanassios Tsakris, M. E. Cano, Oriol Gasch, Alessandro Russo, Johann D. D. Pitout, Anna Skiada, Michele Bartoletti, Mario Tumbarello, Vicente Pintado, Mitchell J. Schwaber, C. Navarro-San Francisco, O. Zarkotou, Benito Almirante, Murat Akova, E. García-Vázquez, Yohei Doi, Beatriz Mirelis, Álvaro Pascual, Jesús Rodríguez-Baño, David L. Paterson, Federico Perez, N. Prim, Cristina Badia, Luis Martínez-Martínez, J. Gómez, Elena Pérez-Nadales, Julia Guzmán-Puche, José Ramón Paño-Pardo, Mario Venditti, Yehuda Carmeli, J. Torre-Cisneros, Ö. Helvaci, D. Fontanals, Enrico Maria Trecarichi, Helen Giamarellou, Marco Falcone, Ferran Navarro, Robert A. Bonomo, Rafael Cantón, Anastasia Antoniadou, Germán Bou, Spyros Pournaras, Fe Tubau, Marta Mora-Rillo, Patricia Cordero Ruiz, Gutiérrez-Gutiérrez, Belén, Salamanca, Elena, de Cueto, Marina, Hsueh, Po-Ren, Viale, Pierluigi, Paño-Pardo, José Ramón, Venditti, Mario, Tumbarello, Mario, Daikos, George, Cantón, Rafael, Doi, Yohei, Tuon, Felipe Francisco, Karaiskos, Ilia, Pérez-Nadales, Elena, Schwaber, Mitchell J, Azap, Özlem Kurt, Souli, Maria, Roilides, Emmanuel, Pournaras, Spyro, Akova, Murat, Pérez, Federico, Bermejo, Joaquín, Oliver, Antonio, Almela, Manel, Lowman, Warren, Almirante, Benito, Bonomo, Robert A, Carmeli, Yehuda, Paterson, David L, Pascual, Alvaro, Rodríguez-Baño, Jesú, del Toro, M.D., Gálvez, J., Falcone, M., Russo, A., Giamarellou, H., Trecarichi, E.M., Losito, A.R., García-Vázquez, E., Hernández, A., Gómez, J., Bou, G., Iosifidis, E., Prim, N., Navarro, F., Mirelis, B., Skiada, A., Origüen, J., Juan, R San, Fernández-Ruiz, M., Larrosa, N., Puig-Asensio, M., Cisneros, J.M., Molina, J., González, V., Rucci, V., de Gopegui, E Ruiz, Marinescu, C.I., Martínez-Martínez, L., Fariñas, M.C., Cano, M.E., Gozalo, M., Mora-Rillo, M., Francisco, C Navarro-San, Peña, C., Gómez-Zorrilla, S., Tubau, F., Tsakris, A., Zarkotou, O., Antoniadou, A., Poulakou, G., Pitout, J., Virmani, D., Torre-Cisneros, J., Guzmán-Puche, J., Helvaci, Ã ., Sahin, A.O., Pintado, V., Ruiz, P., Bartoletti, M., Giannella, M., Tacconelli, E., Riemenschneider, F., Calbo, E., Badia, C., Xercavins, M., Gasch, O., Fontanals, D., and Jové, E.
- Subjects
Male ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Combination therapy ,030106 microbiology ,Bacteremia ,Settore MED/17 - MALATTIE INFETTIVE ,beta-Lactamases ,03 medical and health sciences ,Pharmacotherapy ,Drug Therapy ,Bacterial Proteins ,Risk Factors ,medicine ,Humans ,Propensity Score ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Retrospective cohort study ,Odds ratio ,Anti-Bacterial Agents ,Drug Therapy, Combination ,Female ,Klebsiella Infections ,Klebsiella pneumoniae ,medicine.disease ,Infectious Diseases ,Infectious Diseases, bloodstream infection, carbapenemase-prodicing Enterobacteriaceae ,N/A ,Combination ,Propensity score matching ,Cohort ,business - Abstract
Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0â7 [low mortality score] vs 8â15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0â33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33â0·62]; p
- Published
- 2017