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Open Access Research article

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

Evangelos J Giamarellos-Bourboulis*, Anastasia Antonopoulou, Maria Raftogiannis, Pantelis Koutoukas, Thomas Tsaganos, Vassiliki Tziortzioti, Charalambos Panagou, Theodoros Adamis and Helen Giamarellou

Author Affiliations

4th Department of Internal Medicine, University of Athens, Medical School, Greece

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BMC Infectious Diseases 2006, 6:31  doi:10.1186/1471-2334-6-31

Published: 21 February 2006

Abstract

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 TNFα 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 TNFα 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.