title: Clarithromycin Leads to Long-Term Survival and Cost Benefit in Ventilator-Associated Pneumonia and Sepsis.
abstract: Increasing numbers of admissions for sepsis impose a heavy burden on health care systems worldwide, while novel therapies have proven both expensive and ineffective. We explored the long-term mortality and hospitalization costs after adjunctive therapy with intravenous clarithromycin in ventilator-associated pneumonia (VAP). Two hundred patients with sepsis and VAP were enrolled in a published randomized clinical trial; 100 were allocated to blind treatment with a placebo and another 100 to clarithromycin at 1 g daily for three consecutive days. Long-term mortality was recorded. The hospitalization cost was calculated by direct quantitation of imaging tests, medical interventions, laboratory tests, nonantibiotic drugs and antibiotics, intravenous fluids, and parenteral and enteral nutrition. Quantities were priced by the respective prices defined by the Greek government in 2002. The primary endpoint was 90-day mortality; cumulative hospitalization cost was the secondary endpoint. All-cause mortality rates on day 90 were 60% in the placebo arm and 43% in the clarithromycin arm (P = 0.023); 141 patients were alive on day 28, and mortality rates between days 29 and 90 were 44.4% and 17.4%, respectively (P = 0.001). The mean cumulative costs on day 25 in the placebo group and in the clarithromycin group were €14,701.10 and €13,100.50 per patient staying alive, respectively (P = 0.048). Respective values on day 45 were €26,249.50 and €19,303.10 per patient staying alive (P = 0.011); this was associated with the savings from drugs other than antimicrobials. It is concluded that intravenous clarithromycin for three consecutive days as an adjunctive treatment in VAP and sepsis offers long-term survival benefit along with a considerable reduction in the hospitalization cost. (This study has been registered at ClinicalTrials.gov under registration no. NCT00297674.).
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tsaganos
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Raftogiannis
authors.affiliation: 1st Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Pratikaki
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Sofia
authors.initials: S
authors.lastname: Christodoulou
authors.affiliation: 1st Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.affiliation: 2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Papadomichelakis
authors.affiliation: 2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.affiliation: 1st Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Routsi
authors.affiliation: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece egiamarel@med.uoa.gr.
authors.forename: Evangelos J
authors.identifier: 0000-0003-4713-3911
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000890:Anti-Infective Agents / Q000191:economics* / Q000627:therapeutic use; D017291:Clarithromycin / Q000191:economics* / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006115:Greece; D006760:Hospitalization / Q000191:economics*; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy / Q000191:economics* / Q000401:mortality / Q000473:pathology; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy / Q000191:economics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D017741:Survivors / Q000706:statistics & numerical data
chemical_list: D000890:Anti-Infective Agents; D017291:Clarithromycin