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, Luca Montini, Teresa Spanu, Massimo Antonelli, Maria Sole Vallecoccia, Gennaro Martucci, Giovanna Panarello, Daniele Di Carlo, Roberta Di Stefano, Guido Capitanio, Piera Polidori, Antonio Arcadipane

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35 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)173-N/A
JournalCritical Care
Volume21
DOIs
Publication statusPublished - 2017

Keywords

  • Adult
  • Aged
  • Anti-Bacterial Agents
  • Carbapenems
  • Case-Control Studies
  • Critical Care and Intensive Care Medicine
  • Critically ill patients
  • Double carbapenem
  • Drug Resistance, Multiple
  • Ertapenem
  • Female
  • Humans
  • Infections
  • Italy
  • Klebsiella Infections
  • Klebsiella pneumoniae
  • Length of Stay
  • Logistic Models
  • Male
  • Meropenem
  • Microbial Sensitivity Tests
  • Middle Aged
  • Multidrug-resistant bacteria
  • Retrospective Studies
  • Statistics, Nonparametric
  • beta-Lactams

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