Effect of clarithromycin in patients with suspected Gram-negative sepsis: results
of a randomized controlled trial.
Author(s): Giamarellos-Bourboulis EJ(1), Mylona V, Antonopoulou A, Tsangaris I, Koutelidakis
I, Marioli A, Raftogiannis M, Kopterides P, Lymberopoulou K, Mouktaroudi M,
Papageorgiou C, Papaziogas B, Georgopoulou AP, Tsaganos T, Papadomichelakis E,
Gogos C, Ladas M, Savva A, Pelekanou A, Baziaka F, Koutoukas P, Kanni T,
Spyridaki A, Maniatis N, Pelekanos N, Kotsaki A, Vaki I, Douzinas EE, Koratzanis
G, Armaganidis A.
Affiliation(s): Author information:
(1)4th Department of Internal Medicine, University of Athens, Medical School, 12462
Athens, Greece.
Publication date & source: 2014, J Antimicrob Chemother. , 69(4):1111-8
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.
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