Paradoxical effect of clindamycin in experimental, acute toxoplasmosis in cats

Abstract

Cats were experimentally inoculated parenterally with the ME49 strain of Toxoplasma gondii to characterize the efficacies of two different dosages of orally administered clindamycin hydrochloride in the treatment of ocular toxoplasmosis. Concentrations of clindamycin hydrochloride at levels previously suggested to be inhibitory to T. gondii replication in vitro were achieved in the serum and aqueous humor but not in the cerebrospinal fluid. Antibiotic therapy, initiated 7 days after inoculation, resulted in no significant difference in the morphometric severity of ocular posterior segment lesions compared with that in the control groups. Treatment appeared to blunt T. gondii-specific immunoglobulin M production but had no significant effect on immunoglobulin G titers. Paradoxically, clindamycin administration was associated with increased morbidity and mortality from hepatitis and interstitial pneumonia, which are characteristic of generalized toxoplasmosis. Serum tumor necrosis factor alpha activity was detected at moderate levels in all groups of cats and correlated with the severity of clinical disease. The results of the study suggest that clindamycin, when administered at this specific time interval following inoculation, does not ameliorate ocular lesions and has a detrimental effect on the clinical course of acute, experimental toxoplasmosis in cats. The factors responsible for and the relevance of this detrimental effect to naturally occurring toxoplasmosis in humans and pet cats were not clear from the study but may relate to an antibiotic-associated decrease in the antitoxoplasmic activity of phagocytic cells responsible for the control of T. gondii.

Immunopathogenesis of toxoplasmosis

“…This effect was responsible for the severe intraocular presentation of the disease compared with the control group [369].…”

“…Recurrence was prominent after transplant surgery [400,401]. Recurrence was most probably due to rupture of the cysts and dissemination of infection [369]. Other studies showed that their combined use was not associated with any adverse effect, nor was it associated with delay in onset of inacitivity [402][403][404][405], except in very selective severely inflamed eyes, in which corticosteroid use resulted in a poor outcome [404][405][406][407].…”

Elevated Interleukin-10-to-Interleukin-12 Ratio in Feline Immunodeficiency Virus-Infected Cats Predicts Loss of Type 1 Immunity to Toxoplasma gondii

“…Twelve cats were inoculated intrapressed at a constant rate in cells, to control for sample-to-sample venously with 5 1 10 6 TCID 50 of cell-free virus culture supernatant variation in efficiency of mRNA isolation. as described by Davidson et al [27]. The remaining 10 cats were…”

“…The NCSU 1 strain of FIV was originally is different than the length of the cDNA products [33]. The competisolated from a naturally infected cat at the North Carolina State itive fragment also contains primer sites for glyceraldehyde-3-University College of Veterinary Medicine and has been described phosphate dehydrogenase (G3PDH), a housekeeping gene exin detail elsewhere [18,27,30]. Twelve cats were inoculated intrapressed at a constant rate in cells, to control for sample-to-sample venously with 5 1 10 6 TCID 50 of cell-free virus culture supernatant variation in efficiency of mRNA isolation.…”

“…Defective APC function, such as decreased IL-12 production, could lead to a defective or absent type 1 response and the inability to control infections JID 1998; lymphadenopathy, followed by a long asymptomatic period in Lymphocyte subset analysis. Blood was collected for a comwhich the CD4:CD8 ratio declines due to a progressive deplete blood cell count and lymphocyte subset analysis using twocolor flow cytometry as previously described [27,28]. T cell subcrease in CD4 cells and a CD8 lymphocytosis [17 -20].…”