Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial.
Giamarellos-Bourboulis, Evangelos J. 1,*; Mylona, Vassiliki 2; Antonopoulou, Anastasia 1,3; Tsangaris, Iraklis 3; Koutelidakis, Ioannis 4; Marioli, Androniki 2; Raftogiannis, Maria 1; Kopterides, Petros 3; Lymberopoulou, Korina 2; Mouktaroudi, Maria 1; Papageorgiou, Christos 3; Papaziogas, Basileios 4; Georgopoulou, Antonia-Panagiota 2; Tsaganos, Thomas 1; Papadomichelakis, Evangelos 3; Gogos, Charalambos 5; Ladas, Malvina 2; Savva, Athina 1; Pelekanou, Aimilia 1; Baziaka, Fotini 1; Koutoukas, Pantelis 1; Kanni, Theodora 1; Spyridaki, Aikaterini 1; Maniatis, Nikolaos 3; Pelekanos, Nikolaos 1; Kotsaki, Antigone 1; Vaki, Ilia 1; Douzinas, Emmanuel E. 6; Koratzanis, Georgios 2; Armaganidis, Apostolos 3
[Article]
Journal of Antimicrobial Chemotherapy.
69(4):1111-1118, April 2014.
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Background: A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis.
Methods: Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes.
Results: The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502).
Conclusions: Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.
(C) British Society for Antimicrobial Chemotherapy 2014. Published by Oxford University Press. All rights reserved.
