Clarithromycin is an effective immunomodulator when administered late in experimental pyelonephritis by multidrug-resistant Pseudomonas aeruginosa

被引:19
作者
Giamarellos-Bourboulis, EJ [1 ]
Antonopoulou, A [1 ]
Raftogiannis, M [1 ]
Koutoukas, P [1 ]
Tsaganos, T [1 ]
Tziortzioti, V [1 ]
Panagou, C [1 ]
Adamis, T [1 ]
Giamarellou, H [1 ]
机构
[1] Univ Athens, Sch Med, Dept Internal Med 4, GR-10679 Athens, Greece
关键词
D O I
10.1186/1471-2334-6-31
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background: To apply clarithromycin as an immunomodulatory treatment in experimental urosepsis by multidrug-resistant Pseudomonas aeruginosa. Methods: Acute pyelonephritis was induced in 40 rabbits after inoculation of the test isolate in the renal pelvis. Therapy was administered upon signs of sepsis in four groups: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. Survival and vital signs were recorded; blood was sampled for culture and estimation of pro-inflammatory mediators; monocytes were isolated for determination of apoptotic rate and ex vivo TNF alpha secretion. Quantitative cultures and biopsies of organs were performed after death. Results: Increased rectal temperature and oxygen saturation were found in groups B and D compared to A and C. Mean survival of groups A, B, C and D was 2.65, 7.15, 4.25 and 8.70 days respectively. No differences were noted between groups concerning bacterial load in blood and tissues and serum endotoxins. Serum MDA and total caspase-3 activity of monocytes of group D decreased following treatment compared to other groups. Negative correlation was detected between cytoplasmic caspase-3 and ex vivo secretion of TNF alpha of blood monocytes of group A; similar correlation was not found for any other group. Pathology scores of liver and lung of group B were lower than group A. Conclusion: Clarithromycin administered late in experimental urosepsis by multidrug-resistant P. aeruginosa prolonged survival and ameliorated clinical findings. Its effect is probably attributed to immunomodulatory intervention on blood monocytes.
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