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


CONCLUSIONS
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.
Giamarellos-Bourboulis
Evangelos J
EJ
4th Department of Internal Medicine, University of Athens, Medical School, Greece. giamarel@ath.forthnet.gr
Antonopoulou
Anastasia
A
Raftogiannis
Maria
M
Koutoukas
Pantelis
P
Tsaganos
Thomas
T
Tziortzioti
Vassiliki
V
Panagou
Charalambos
C
Adamis
Theodoros
T
Giamarellou
Helen
H
D000583:Amikacin / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017291:Clarithromycin / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D008070:Lipopolysaccharides / Q000097:blood; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009000:Monocytes / Q000187:drug effects; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011704:Pyelonephritis / Q000188:drug therapy*; D011817:Rabbits; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000583:Amikacin; D017291:Clarithromycin