Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections: a two-center, matched case–control study

摘要

BackgroundRecent 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. MethodsThis 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). ResultsThe 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 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). ConclusionsImproved 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 registrationClinicalTrials.gov NCT03094494 . Registered 28 March 2017.