Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli.
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 (TNFalpha), 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. TNFalpha 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.
Giamarellos-Bourboulis
Evangelos
E
4th Department of Internal Medicine, University of Athens Medical School, Athens, Greece. giamarel@internet.gr
Adamis
Theodoros
T
Sabracos
Lambros
L
Raftogiannis
Maria
M
Baziaka
Fotini
F
Tsaganos
Thomas
T
Koutoukas
Pantelis
P
Plachouras
Diamantis
D
Karayannacos
Panayotis
P
Giamarellou
Helen
H
D000208:Acute Disease; D000583:Amikacin / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D017291:Clarithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004926:Escherichia coli / Q000302:isolation & purification / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism; D007155:Immunologic Factors / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D011654:Pulmonary Edema / Q000188:drug therapy*; D011704:Pyelonephritis / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000583:Amikacin; D053148:Caspase 3; D020169:Caspases; D017291:Clarithromycin