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JAC Advance Access published online on March 20, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl084
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received November 5, 2005
Revised January 22, 2006
Accepted February 22, 2006

Original article

Clarithromycin is an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae

Evangelos J. Giamarellos-Bourboulis 1 *, Vassiliki Tziortzioti 1, Pantelis Koutoukas 1, Fotini Baziaka 1, Maria Raftogiannis 1, Anastasia Antonopoulou 1, Theodoros Adamis 1, Labros Sabracos 1, and Helen Giamarellou 1

1 4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece

* To whom correspondence should be addressed.
Evangelos J. Giamarellos-Bourboulis, E-mail: giamarel{at}ath.forthnet.gr


  Abstract

Objectives: To apply clarithromycin as an immunomodulatory treatment in experimental infection caused by pan-resistant Klebsiella pneumoniae.

Methods: Acute pyelonephritis was induced in 80 rabbits after inoculation of the test isolate in the renal pelvis. Rabbits were divided into eight groups, with 10 animals in each group. In groups A-D, therapy was administered simultaneously with bacterial challenge as follows: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. In groups E-H, therapy was administered 24 h after bacterial challenge as follows: E, controls; F, intravenous clarithromycin; G, amikacin; and H, both agents. Blood was sampled for estimation of tumour necrosis factor-{alpha} (TNF-{alpha}) and malondialdehyde (MDA); monocytes were isolated for determination of intracellular activity of caspase-3 and ex vivo TNF-{alpha} secretion. Four days after bacterial challenge, animals were sacrificed for quantitative cultures and biopsies of organs.

Results: Serum TNF-{alpha} at 48 h was lower in groups B, C and D compared with group A. Activity of caspase-3 of monocytes was lower at 48 h in group D compared with group A. Bacterial loads of liver and spleen were decreased in group D compared with those of group A. The numbers of inflammatory cells of spleen of group B were lower compared with those of group A; those of kidney and mesenteric lymph nodes of group D were lower than those of group A. Serum MDA of group H was lower than that of group E and serum TNF-{alpha} of group F was lower compared with that of group E. TNF-{alpha} of monocyte supernatants and activity of caspase-3 of monocytes of group F were lower than those of group E. Bacterial tissue loads did not differ among groups E, F, G and H. The numbers of inflammatory cells of liver of groups F and H were lower compared with those of group E; those of kidney of groups F, G and H were lower compared with those of group E.

Conclusions: Clarithromycin administered intravenously in experimental infection caused by pan-resistant K. pneumoniae attenuated systemic inflammatory response and local tissue damage. This effect is probably attributed to immunomodulatory intervention on blood monocytes.

Keywords: K. pneumoniae; immunomodulation; apoptosis; resistance.
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