Last update:
20-Sep-2007

OBJECTIVE Based on the immunomodulatory properties of clarithromycin in experimental studies, its effect on sepsis in the clinical setting was investigated.

METHOD A double-blind, randomized, placebo-controlled, multicenter trial was conducted on 200 patients with sepsis from ventilator-associated pneumonia (VAP). Clarithromycin (1 g) was administered intravenously once daily for three consecutive days. The effects on survival and on the resolution of sepsis and VAP were evaluated through follow-up for 28 days.

RESULTS Patients treated with placebo or clarithromycin were matched for age, sex and disease severity; the type of pathogen and susceptibility to the administered antimicrobials did not differ between the two groups. Serious adverse events were observed in 0% and 3%, respectively (Ρ=NS). The sepsis resolved in 58% and 64%, respectively (P=0.65) within a median period of 11.00 and 6.00 days (P=0.021). VAP resolved in 54% and 61%, respectively (Ρ=NS) within a median period of 11.50 and 7.00 days (P=0.006). Sepsis-attributable mortality after 16 days was 21% and 10%, respectively (P=0.049) among all patients enrolled and 54.5% and 25.0%, respectively among patients with multiple organ failure (P=0.036). Risk of death after 28 days with multiple organ failure decreased by a factor of 2.75 with administration of clarithromycin. Kaplan-Meier analysis revealed prolongation of survival for 28 days from the early signs of sepsis (P=0.021) in patients with septic shock treated with clarithromycin.

CONCLUSIONS The earlier resolution of sepsis and the dramatic decrease in the risk of death in multiple organ failure observed in the patients treated with clarithromycin, signal new perspectives for the utilization of clarithromycin in (a) VAP, (b) septic shock, and (c) multiple organ failure.

Key words: Clarithromycin, Multiple organ dysfunction, Sepsis, Survival, Ventilator-associated pneumonia.