title: Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli.
abstract: To assess the efficacy of clarithromycin as an immunomodulator in experimental sepsis with Escherichia coli, acute pyelonephritis was induced after ligation of the right ureter and injection of the test isolate into the renal pelvis in 40 rabbits. Four groups of treatment were applied with administration of therapy on advent of sepsis-associated pulmonary oedema, as follows: A: controls; B: clarithromycin; C: amikacin, D: both agents. Survival was recorded along with estimation of serum levels of endotoxins (LPS), of tumour necrosis factor-alpha (TNFalpha), malondialdehyde (MDA) and of bacterial counts. Mean survival of groups A, B, C and D was 2.51, 7.60, 10.25 and 11.40 days, respectively. Serum levels of TNFalpha and of MDA of group A increased over-time. Pulmonary oedema at 6 h after bacterial challenge was accompanied by increase of TNFalpha and MDA; administration of clarithromycin decreased their values. It is concluded that intravenous clarithromycin might constitute a promising immunomodulatory agent for the management of sepsis since its efficacy was proved after administration on presentation of sepsis-associated pulmonary oedema. The presented findings emphasise the need for further clinical research of the use of clarithromycin for the therapy of Gram-negative sepsis.
authors.affiliation: 4th Department of Internal Medicine, University of Athens, Medical School, Greece. giamarel@internet.gr
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
authors.forename: Fotini
authors.initials: F
authors.lastname: Baziaka
authors.forename: Anastasia
authors.initials: A
authors.lastname: Antonopoulou
authors.forename: Pantelis
authors.initials: P
authors.lastname: Koutoukas
authors.forename: Vassilios
authors.initials: V
authors.lastname: Kousoulas
authors.forename: Lambros
authors.initials: L
authors.lastname: Sabracos
authors.forename: Charalambos
authors.initials: C
authors.lastname: Panagou
authors.forename: Despina
authors.initials: D
authors.lastname: Perrea
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000208:Acute Disease; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017291:Clarithromycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000097:blood; D008315:Malondialdehyde / Q000097:blood; D011704:Pyelonephritis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D011817:Rabbits; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000583:Amikacin; D017291:Clarithromycin