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Crit Care. 2017 Jul 5;21(1):173. doi: 10.1186/s13054-017-1769-z.

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

Author information

1
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli, Rome, Italy. gennaro.depascalemd@gmail.com.
2
Fondazione Policlinico A. Gemelli. Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy. gennaro.depascalemd@gmail.com.
3
Department of Anesthesia and Intensive Care, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy.
4
Department of Anesthesiology and Intensive Care, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli, Rome, Italy.
5
Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy.
6
Clinical Pharmacy, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy.
7
Institute of Microbiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli, Rome, Italy.

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.

KEYWORDS:

Critically ill patients; Double carbapenem; Ertapenem; Infections; Klebsiella pneumoniae; Meropenem; Multidrug-resistant bacteria

PMID:
28679413
PMCID:
PMC5498909
DOI:
10.1186/s13054-017-1769-z
[Indexed for MEDLINE]
Free PMC Article

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