Journal Article

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

Evangelos J. Giamarellos-Bourboulis, Jean-Claude Pechère, Christina Routsi, Diamantis Plachouras, Spyridon Kollias, Maria Raftogiannis, Dimitrios Zervakis, Fotini Baziaka, Apostolos Koronaios, Anastasia Antonopoulou, Vassiliki Markaki, Pantelis Koutoukas, Evangelos Papadomichelakis, Thomas Tsaganos, Apostolos Armaganidis, Vassilios Koussoulas, Anastasia Kotanidou, Charis Roussos and Helen Giamarellou

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 46, issue 8, pages 1157-1164
Published in print April 2008 | ISSN: 1058-4838
Published online April 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/529439
Effect of Clarithromycin in Patients with Sepsis and Ventilator-Associated Pneumonia

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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.

Journal Article.  4168 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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