Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli.
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.
Giamarellos-Bourboulis
Evangelos J
EJ
4th Department of Internal Medicine, University of Athens, Medical School, Greece. giamarel@internet.gr
Baziaka
Fotini
F
Antonopoulou
Anastasia
A
Koutoukas
Pantelis
P
Kousoulas
Vassilios
V
Sabracos
Lambros
L
Panagou
Charalambos
C
Perrea
Despina
D
Giamarellou
Helen
H
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
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000583:Amikacin; D017291:Clarithromycin