TY - JOUR
T1 - Double carbapenem as a rescue strategy for the treatment of severe carbapenemase-producing Klebsiella pneumoniae infections
T2 - A two-center, matched case-control study
AU - De Pascale, Gennaro
AU - Martucci, Gennaro
AU - Montini, Luca
AU - Panarello, Giovanna
AU - Cutuli, Salvatore Lucio
AU - Di Carlo, Daniele
AU - Di Gravio, Valentina
AU - Di Stefano, Roberta
AU - Capitanio, Guido
AU - Vallecoccia, Maria Sole
AU - Polidori, Piera
AU - Spanu, Teresa
AU - Arcadipane, Antonio
AU - Antonelli, Massimo
PY - 2017/7/5
Y1 - 2017/7/5
N2 - 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.
AB - 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.
KW - Critically ill patients
KW - Double carbapenem
KW - Ertapenem
KW - Infections
KW - Klebsiella pneumoniae
KW - Meropenem
KW - Multidrug-resistant bacteria
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UR - http://www.scopus.com/inward/citedby.url?scp=85021714018&partnerID=8YFLogxK
U2 - 10.1186/s13054-017-1769-z
DO - 10.1186/s13054-017-1769-z
M3 - Article
AN - SCOPUS:85021714018
VL - 21
JO - Critical Care
JF - Critical Care
SN - 1466-609X
IS - 1
M1 - 173
ER -