Clarithromycin is an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae.
OBJECTIVE
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.
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece. giamarel@ath.forthnet.gr
Evangelos J
EJ
Giamarellos-Bourboulis
Vassiliki
V
Tziortzioti
Pantelis
P
Koutoukas
Fotini
F
Baziaka
Maria
M
Raftogiannis
Anastasia
A
Antonopoulou
Theodoros
T
Adamis
Labros
L
Sabracos
Helen
H
Giamarellou
D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D053148:Caspase 3; D020169:Caspases / Q000276:immunology / Q000378:metabolism; D017291:Clarithromycin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011704:Pyelonephritis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D020169:Caspases; D017291:Clarithromycin