Effect of Clarithromycin in Patients with Sepsis and Ventilator‐Associated Pneumonia

Autor: Christina Routsi, Thomas Tsaganos, Anastasia Antonopoulou, Vassilios Koussoulas, Pantelis Koutoukas, Vassiliki Markaki, Diamantis Plachouras, Dimitrios Zervakis, Evangelos Papadomichelakis, Spyridon Kollias, Evangelos J. Giamarellos-Bourboulis, Fotini Baziaka, Anastasia Kotanidou, Jean-Claude Pechère, Helen Giamarellou, Apostolos Koronaios, Apostolos Armaganidis, Charis Roussos, Maria Raftogiannis
Rok vydání: 2008
Předmět:
Zdroj: Clinical Infectious Diseases. 46:1157-1164
ISSN: 1537-6591
1058-4838
DOI: 10.1086/529439
Popis: Background Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP). Methods Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. Results The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P = .011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (p = .049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (p = .047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (p = .004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P = .25). Conclusions Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VAP.
Databáze: OpenAIRE