title: Effect of clarithromycin in patients with suspected Gram-negative sepsis: results of a randomized controlled trial.
abstract: 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.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, 12462 Athens, Greece.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Mylona
authors.forename: Anastasia
authors.initials: A
authors.lastname: Antonopoulou
authors.forename: Iraklis
authors.initials: I
authors.lastname: Tsangaris
authors.forename: Ioannis
authors.initials: I
authors.lastname: Koutelidakis
authors.forename: Androniki
authors.initials: A
authors.lastname: Marioli
authors.forename: Maria
authors.initials: M
authors.lastname: Raftogiannis
authors.forename: Petros
authors.initials: P
authors.lastname: Kopterides
authors.forename: Korina
authors.initials: K
authors.lastname: Lymberopoulou
authors.forename: Maria
authors.initials: M
authors.lastname: Mouktaroudi
authors.forename: Christos
authors.initials: C
authors.lastname: Papageorgiou
authors.forename: Basileios
authors.initials: B
authors.lastname: Papaziogas
authors.forename: Antonia-Panagiota
authors.initials: AP
authors.lastname: Georgopoulou
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.forename: Evangelos
authors.initials: E
authors.lastname: Papadomichelakis
authors.forename: Charalambos
authors.initials: C
authors.lastname: Gogos
authors.forename: Malvina
authors.initials: M
authors.lastname: Ladas
authors.forename: Athina
authors.initials: A
authors.lastname: Savva
authors.forename: Aimilia
authors.initials: A
authors.lastname: Pelekanou
authors.forename: Fotini
authors.initials: F
authors.lastname: Baziaka
authors.forename: Pantelis
authors.initials: P
authors.lastname: Koutoukas
authors.forename: Theodora
authors.initials: T
authors.lastname: Kanni
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Spyridaki
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Maniatis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pelekanos
authors.forename: Antigone
authors.initials: A
authors.lastname: Kotsaki
authors.forename: Ilia
authors.initials: I
authors.lastname: Vaki
authors.forename: Emmanuel E
authors.initials: EE
authors.lastname: Douzinas
authors.forename: Georgios
authors.initials: G
authors.lastname: Koratzanis
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000191:economics; D017291:Clarithromycin / Q000008:administration & dosage* / Q000191:economics; D004311:Double-Blind Method; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality; D017048:Health Care Costs / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D010919:Placebos; D017291:Clarithromycin
keywords: bacteraemia; hospitalization costs; intra-abdominal infection; pyelonephritis; respiratory distress syndrome