Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case–control study
Gennaro De Pascale,
Gennaro Martucci,
Luca Montini,
Giovanna Panarello,
Salvatore Lucio Cutuli,
Daniele Di Carlo,
Valentina Di Gravio,
Roberta Di Stefano,
Guido Capitanio,
Maria Sole Vallecoccia,
Piera Polidori,
Teresa Spanu,
Antonio Arcadipane,
Massimo Antonelli
Affiliations
Gennaro De Pascale
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Gennaro Martucci
Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Luca Montini
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Giovanna Panarello
Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Salvatore Lucio Cutuli
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Daniele Di Carlo
Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Valentina Di Gravio
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Roberta Di Stefano
Clinical Pharmacy, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Guido Capitanio
Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Maria Sole Vallecoccia
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Piera Polidori
Clinical Pharmacy, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Teresa Spanu
Institute of Microbiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Antonio Arcadipane
Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione)
Massimo Antonelli
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli
Abstract Background Recent reports have suggested the efficacy of a double carbapenem (DC) combination, including ertapenem, for the treatment of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) infections. We aimed to evaluate the clinical impact of such a regimen in critically ill patients. Methods This case–control (1:2), observational, two-center study involved critically ill adults with a microbiologically documented CR-Kp invasive infection treated with the DC regimen matched with those receiving a standard treatment (ST) (i.e., colistin, tigecycline, or gentamicin). Results The primary end point was 28-day mortality. Secondary outcomes were clinical cure, microbiological eradication, duration of mechanical ventilation and of vasopressors, and 90-day mortality. Forty-eight patients treated with DC were matched with 96 controls. Occurrence of septic shock at infection and high procalcitonin levels were significantly more frequent in patients receiving DC treatment (p < 0.01). The 28-day mortality was significantly higher in patients receiving ST compared with the DC group (47.9% vs 29.2%, p = 0.04). Similarly, clinical cure and microbiological eradication were significantly higher when DC was used in patients infected with CR-Kp strains resistant to colistin (13/20 (65%) vs 10/32 (31.3%), p = 0.03 and 11/19 (57.9%) vs 7/27 (25.9%), p = 0.04, respectively). In the logistic regression and multivariate Cox-regression models, the DC regimen was associated with a reduction in 28-day mortality (OR 0.33, 95% CI 0.13–0.87 and OR 0.43, 95% CI 0.23–0.79, respectively). Conclusions Improved 28-day mortality was associated with the DC regimen compared with ST for severe CR-Kp infections. A randomized trial is needed to confirm these observational results. Trial registration ClinicalTrials.gov NCT03094494 . Registered 28 March 2017.
