Clarithromycin: Immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli

• Published in: Scandinavian journal of infectious diseases 2005-01, Vol.37 (1), p.48-54
• Main Authors: Giamarellos-Bourboulis, Evangelos J., Adamis, Theodoros, Sabracos, Lambros, Raftogiannis, Maria, Baziaka, Fotini, Tsaganos, Thomas, Koutoukas, Pantelis, Plachouras, Diamantis, Karayannacos, Panayotis E., Giamarellou, Helen
• Format: Article
• Language: English
• Subjects: Acute Disease; Amikacin - therapeutic use; Animals; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Bacterial diseases; Bacterial diseases of the urinary system; Bacterial sepsis; Biological and medical sciences; Caspase 3; Caspases - metabolism; Clarithromycin - blood; Clarithromycin - pharmacokinetics; Clarithromycin - therapeutic use; Colony Count, Microbial; Escherichia coli; Escherichia coli - isolation & purification; Escherichia coli - pathogenicity; Escherichia coli Infections - drug therapy; Escherichia coli Infections - metabolism; Human bacterial diseases; Immunologic Factors - blood; Immunologic Factors - therapeutic use; Infectious diseases; Interstitial nephritis; Male; Malondialdehyde - blood; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pulmonary Edema - drug therapy; Pyelonephritis - drug therapy; Pyelonephritis - metabolism; Rabbits; Sepsis - drug therapy; Sepsis - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0036-5548; 1651-1980
• DOI: 10.1080/00365540510026832

The potency of clarithromycin as immunomodulator was assessed in an experimental model of sepsis based on acute pyelonephritis by susceptible Escherichia coli. 55 rabbits were utilized; 5 for preliminary pharmacokinetic study and 50 for treatment. The latter were divided into 5 groups of treatment, A: controls; B: clarithromycin pretreatment; C: amikacin pretreatment; D: clarithromycin treatment on presentation of pulmonary oedema; and E; amikacin treatment on presentation of pulmonary oedema. Survival was recorded; tumour necrosis factor-alpha (TNFα), and malondialdehyde (MDA) were estimated in serum; activities of caspase-3 in monocyte cytosolic extracts were studied; and bacterial counts made in various organs. Median survival of animals of groups A, B, C, D and E was 1.0, 21.0, 12.5, 2.0 and 5.0 d, respectively. TNFα and MDA and monocyte caspase-3 activity of group A increased over time; no increases were detected in groups B and C. Concentrations of MDA and activities of monocytic caspase-3 were decreased after administration of clarithromycin in group D, an effect not occurring in group E. Bacterial load was decreased in renal tissue of group D compared to group A. It is concluded that intravenous clarithromycin might constitute a promising immunomodulator in sepsis even in the advent of pulmonary oedema.