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. 1996 Jun;40(6):1352–1359. doi: 10.1128/aac.40.6.1352

Paradoxical effect of clindamycin in experimental, acute toxoplasmosis in cats.

M G Davidson 1, M R Lappin 1, J R Rottman 1, M B Tompkins 1, R V English 1, A T Bruce 1, J Jayawickrama 1
PMCID: PMC163330  PMID: 8726000

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.

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Selected References

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  1. Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
  2. Araujo F. G., Remington J. S. Effect of clindamycin on acute and chronic toxoplasmosis in mice. Antimicrob Agents Chemother. 1974 Jun;5(6):647–651. doi: 10.1128/aac.5.6.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Black C. M., Israelski D. M., Suzuki Y., Remington J. S. Effect of recombinant tumour necrosis factor on acute infection in mice with Toxoplasma gondii or Trypanosoma cruzi. Immunology. 1989 Dec;68(4):570–574. [PMC free article] [PubMed] [Google Scholar]
  4. Breitschwerdt E. B., Davidson M. G., Aucoin D. P., Levy M. G., Szabados N. S., Hegarty B. C., Kuehne A. L., James R. L. Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs. Antimicrob Agents Chemother. 1991 Nov;35(11):2375–2381. doi: 10.1128/aac.35.11.2375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown S. A., Dieringer T. M., Hunter R. P., Zaya M. J. Oral clindamycin disposition after single and multiple doses in normal cats. J Vet Pharmacol Ther. 1989 Jun;12(2):209–216. doi: 10.1111/j.1365-2885.1989.tb00662.x. [DOI] [PubMed] [Google Scholar]
  6. Brown S. A., Zaya M. J., Dieringer T. M., Hunter R. P., Nappier J. L., Hoffman G. A., Hornish R. E., Yein F. S. Tissue concentrations of clindamycin after multiple oral doses in normal cats. J Vet Pharmacol Ther. 1990 Sep;13(3):270–277. doi: 10.1111/j.1365-2885.1990.tb00776.x. [DOI] [PubMed] [Google Scholar]
  7. Chang H. R., Grau G. E., Pechère J. C. Role of TNF and IL-1 in infections with Toxoplasma gondii. Immunology. 1990 Jan;69(1):33–37. [PMC free article] [PubMed] [Google Scholar]
  8. Dannemann B. R., McCutchan J. A., Israelski D. M., Antoniskis D., Leport C., Luft B. J., Chiu J., Vildé J. L., Nussbaum J. N., Orellana M. Treatment of acute toxoplasmosis with intravenous clindamycin. The California Collaborative Treatment Group. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):193–195. doi: 10.1007/BF01964461. [DOI] [PubMed] [Google Scholar]
  9. Davidson M. G., Lappin M. R., English R. V., Tompkins M. B. A feline model of ocular toxoplasmosis. Invest Ophthalmol Vis Sci. 1993 Dec;34(13):3653–3660. [PubMed] [Google Scholar]
  10. Davidson M. G., Rottman J. B., English R. V., Lappin M. R., Tompkins M. B. Feline immunodeficiency virus predisposes cats to acute generalized toxoplasmosis. Am J Pathol. 1993 Nov;143(5):1486–1497. [PMC free article] [PubMed] [Google Scholar]
  11. Derouin F., Nalpas J., Chastang C. Mesure in vitro de l'effet inhibiteur de macrolides, lincosamides et synergestines sur la croissance de Toxoplasma gondii. Pathol Biol (Paris) 1988 Dec;36(10):1204–1210. [PubMed] [Google Scholar]
  12. Dubey J. P., Frenkel J. K. Feline toxoplasmosis from acutely infected mice and the development of Toxoplasma cysts. J Protozool. 1976 Nov;23(4):537–546. doi: 10.1111/j.1550-7408.1976.tb03836.x. [DOI] [PubMed] [Google Scholar]
  13. Dubey J. P., Swan G. V., Frenkel J. K. A simplified method for isolation of Toxoplasma gondii from the feces of cats. J Parasitol. 1972 Oct;58(5):1005–1006. [PubMed] [Google Scholar]
  14. Dubey J. P., Yeary R. A. Anticoccidial activity of 2-sulfamoyl-4,4-diaminodiphenylsulfone, sulfadiazine, pyrimethamine and clindamycin in cats infected with Toxoplasma gondii. Can Vet J. 1977 Mar;18(3):51–57. [PMC free article] [PubMed] [Google Scholar]
  15. Engstrom R. E., Jr, Holland G. N., Nussenblatt R. B., Jabs D. A. Current practices in the management of ocular toxoplasmosis. Am J Ophthalmol. 1991 May 15;111(5):601–610. doi: 10.1016/s0002-9394(14)73706-7. [DOI] [PubMed] [Google Scholar]
  16. Ferguson J. G., Jr Clindamycin therapy for toxoplasmosis. Ann Ophthalmol. 1981 Jan;13(1):95–100. [PubMed] [Google Scholar]
  17. Filice G. A., Pomeroy C. Effect of clindamycin on pneumonia from reactivation of Toxoplasma gondii infection in mice. Antimicrob Agents Chemother. 1991 Apr;35(4):780–782. doi: 10.1128/aac.35.4.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Guldsten H. Clindamycin and sulphonamides in the treatment of ocular toxoplasmosis. Acta Ophthalmol (Copenh) 1983 Feb;61(1):51–57. doi: 10.1111/j.1755-3768.1983.tb01394.x. [DOI] [PubMed] [Google Scholar]
  19. Hand W. L., Hand D. L., King-Thompson N. L. Antibiotic inhibition of the respiratory burst response in human polymorphonuclear leukocytes. Antimicrob Agents Chemother. 1990 May;34(5):863–870. doi: 10.1128/aac.34.5.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hand W. L., King-Thompson N. L. Contrasts between phagocyte antibiotic uptake and subsequent intracellular bactericidal activity. Antimicrob Agents Chemother. 1986 Jan;29(1):135–140. doi: 10.1128/aac.29.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hand W. L., King-Thompson N. L. Membrane transport of clindamycin in alveolar macrophages. Antimicrob Agents Chemother. 1982 Feb;21(2):241–247. doi: 10.1128/aac.21.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Harper J. S., 3rd, London W. T., Sever J. L. Five drug regimens for treatment of acute toxoplasmosis in squirrel monkeys. Am J Trop Med Hyg. 1985 Jan;34(1):50–57. doi: 10.4269/ajtmh.1985.34.50. [DOI] [PubMed] [Google Scholar]
  23. Harris C., Salgo M. P., Tanowitz H. B., Wittner M. In vitro assessment of antimicrobial agents against Toxoplasma gondii. J Infect Dis. 1988 Jan;157(1):14–22. doi: 10.1093/infdis/157.1.14. [DOI] [PubMed] [Google Scholar]
  24. Hirth R. S., Nielsen S. W. Pathology of feline toxoplasmosis. J Small Anim Pract. 1969 Apr;10(4):213–221. doi: 10.1111/j.1748-5827.1969.tb04041.x. [DOI] [PubMed] [Google Scholar]
  25. Hofflin J. M., Remington J. S. Clindamycin in a murine model of toxoplasmic encephalitis. Antimicrob Agents Chemother. 1987 Apr;31(4):492–496. doi: 10.1128/aac.31.4.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Israelski D., Remington J. Activity of gamma interferon in combination with pyrimethamine or clindamycin in treatment of murine toxoplasmosis. Eur J Clin Microbiol Infect Dis. 1990 May;9(5):358–360. doi: 10.1007/BF01973746. [DOI] [PubMed] [Google Scholar]
  27. Jacobs G., Lappin M., Marks A., Greene C. E. Effect of clindamycin on factor-VII activity in healthy cats. Am J Vet Res. 1989 Mar;50(3):393–395. [PubMed] [Google Scholar]
  28. Jacobson M. A., Besch C. L., Child C., Hafner R., Matts J. P., Muth K., Wentworth D. N., Deyton L. Toxicity of clindamycin as prophylaxis for AIDS-associated toxoplasmic encephalitis. Community Programs for Clinical Research on AIDS. Lancet. 1992 Feb 8;339(8789):333–334. doi: 10.1016/0140-6736(92)91649-s. [DOI] [PubMed] [Google Scholar]
  29. Johnson J. D., Hand W. L., Francis J. B., King-Thompson N., Corwin R. W. Antibiotic uptake by alveolar macrophages. J Lab Clin Med. 1980 Mar;95(3):429–439. [PubMed] [Google Scholar]
  30. La Follette G., Gambertoglio J., White J. A., Knuth D. W., Lin E. T. Determination of clindamycin in plasma or serum by high-performance liquid chromatography with ultraviolet detection. J Chromatogr. 1988 Oct 14;431(2):379–388. doi: 10.1016/s0378-4347(00)83106-0. [DOI] [PubMed] [Google Scholar]
  31. Lakhanpal V., Schocket S. S., Nirankari V. S. Clindamycin in the treatment of toxoplasmic retinochoroiditis. Am J Ophthalmol. 1983 May;95(5):605–613. doi: 10.1016/0002-9394(83)90378-1. [DOI] [PubMed] [Google Scholar]
  32. Lappin M. R., Cayatte S., Powell C. C., Gigliotti A., Cooper C., Roberts S. M. Detection of Toxoplasma gondii antigen-containing immune complexes in the serum of cats. Am J Vet Res. 1993 Mar;54(3):415–419. [PubMed] [Google Scholar]
  33. Lappin M. R., Greene C. E., Winston S., Toll S. L., Epstein M. E. Clinical feline toxoplasmosis. Serologic diagnosis and therapeutic management of 15 cases. J Vet Intern Med. 1989 Jul-Sep;3(3):139–143. doi: 10.1111/j.1939-1676.1989.tb03089.x. [DOI] [PubMed] [Google Scholar]
  34. Lappin M. R., Roberts S. M., Davidson M. G., Powell C. C., Reif J. S. Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii-specific antibodies and antigens in the aqueous humor of cats. J Am Vet Med Assoc. 1992 Oct 1;201(7):1010–1016. [PubMed] [Google Scholar]
  35. Leport C., Bastuji-Garin S., Perronne C., Salmon D., Marche C., Briçaire F., Vilde J. L. An open study of the pyrimethamine-clindamycin combination in AIDS patients with brain toxoplasmosis. J Infect Dis. 1989 Sep;160(3):557–558. doi: 10.1093/infdis/160.3.557. [DOI] [PubMed] [Google Scholar]
  36. Levy R. M., Bredesen D. E., Rosenblum M. L. Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature. J Neurosurg. 1985 Apr;62(4):475–495. doi: 10.3171/jns.1985.62.4.0475. [DOI] [PubMed] [Google Scholar]
  37. Mack D. G., McLeod R. New micromethod to study the effect of antimicrobial agents on Toxoplasma gondii: comparison of sulfadoxine and sulfadiazine individually and in combination with pyrimethamine and study of clindamycin, metronidazole, and cyclosporin A. Antimicrob Agents Chemother. 1984 Jul;26(1):26–30. doi: 10.1128/aac.26.1.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. McMaster P. R., Powers K. G., Finerty J. F., Lunde M. N. The effect of two chlorinated lincomycin analogues against acute toxoplasmosis in mice. Am J Trop Med Hyg. 1973 Jan;22(1):14–17. doi: 10.4269/ajtmh.1973.22.14. [DOI] [PubMed] [Google Scholar]
  39. Noess A., Hauge B., Solberg C. O. Effects of clindamycin and cefuroxime on leukocyte membrane receptors and function. Chemotherapy. 1989;35(3):193–199. doi: 10.1159/000238670. [DOI] [PubMed] [Google Scholar]
  40. Parker G. A., Langloss J. M., Dubey J. P., Hoover E. A. Pathogenesis of acute toxoplasmosis in specific-pathogen-free cats. Vet Pathol. 1981 Nov;18(6):786–803. doi: 10.1177/030098588101800609. [DOI] [PubMed] [Google Scholar]
  41. Pedrol E., González-Clemente J. M., Gatell J. M., Mallolas J., Miró J. M., Graus F., Alvarez R., Mercader J. M., Berenguer J., Jiménez de Anta M. T. Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy. AIDS. 1990 Jun;4(6):511–517. doi: 10.1097/00002030-199006000-00003. [DOI] [PubMed] [Google Scholar]
  42. Pfefferkorn E. R., Nothnagel R. F., Borotz S. E. Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. Antimicrob Agents Chemother. 1992 May;36(5):1091–1096. doi: 10.1128/aac.36.5.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Piketty C., Derouin F., Rouveix B., Pocidalo J. J. In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice. Antimicrob Agents Chemother. 1990 Aug;34(8):1467–1472. doi: 10.1128/aac.34.8.1467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Remington J. S., Vildé J. L. Clindamycin for toxoplasma encephalitis in AIDS. Lancet. 1991 Nov 2;338(8775):1142–1143. doi: 10.1016/0140-6736(91)91997-9. [DOI] [PubMed] [Google Scholar]
  45. Rolston K. V. Treatment of acute toxoplasmosis with oral clindamycin. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):181–183. doi: 10.1007/BF01964456. [DOI] [PubMed] [Google Scholar]
  46. Rothova A., Meenken C., Buitenhuis H. J., Brinkman C. J., Baarsma G. S., Boen-Tan T. N., de Jong P. T., Klaassen-Broekema N., Schweitzer C. M., Timmerman Z. Therapy for ocular toxoplasmosis. Am J Ophthalmol. 1993 Apr 15;115(4):517–523. doi: 10.1016/s0002-9394(14)74456-3. [DOI] [PubMed] [Google Scholar]
  47. Ruf B., Pohle H. D. Role of clindamycin in the treatment of acute toxoplasmosis of the central nervous system. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):183–186. doi: 10.1007/BF01964457. [DOI] [PubMed] [Google Scholar]
  48. Sharma S. D., Catterall J. R., Remington J. S. Parasiticidal activity of macrophages against Toxoplasma. Methods Enzymol. 1986;132:626–637. doi: 10.1016/s0076-6879(86)32046-9. [DOI] [PubMed] [Google Scholar]
  49. Sibley L. D., Adams L. B., Krahenbuhl J. L. Macrophage interactions in toxoplasmosis. Res Immunol. 1993 Jan;144(1):38–40. doi: 10.1016/s0923-2494(05)80095-1. [DOI] [PubMed] [Google Scholar]
  50. Smith R. E. Toxoplasmic retinochoroiditis as an emerging problem in AIDS patients. Am J Ophthalmol. 1988 Dec 15;106(6):738–739. doi: 10.1016/0002-9394(88)90711-8. [DOI] [PubMed] [Google Scholar]
  51. Suzuki Y., Orellana M. A., Schreiber R. D., Remington J. S. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988 Apr 22;240(4851):516–518. doi: 10.1126/science.3128869. [DOI] [PubMed] [Google Scholar]
  52. Tabbara K. F., Dy-Liacco J., Nozik R. A., O'Connor G. R., Blackman H. J. Clindamycin in chronic toxoplasmosis. Effect of periocular injections on recoverability of organisms from healed lesions in the rabbit eye. Arch Ophthalmol. 1979 Mar;97(3):542–544. doi: 10.1001/archopht.1979.01020010286021. [DOI] [PubMed] [Google Scholar]
  53. Tabbara K. F., Nozik R. A., O'Connor G. R. Clindamycin effects on experimental ocular toxoplasmosis in the rabbit. Arch Ophthalmol. 1974 Sep;92(3):244–247. doi: 10.1001/archopht.1974.01010010252017. [DOI] [PubMed] [Google Scholar]
  54. Tabbara K. F., O'Connor G. R. Treatment of ocular toxoplasmosis with clindamycin and sulfadiazine. Ophthalmology. 1980 Feb;87(2):129–134. doi: 10.1016/s0161-6420(80)35268-8. [DOI] [PubMed] [Google Scholar]
  55. Thiermann E., Apt W., Atias A., Lorca M., Olguín J. A comparative study of some combined treatment regimens in acute toxoplasmosis in mice. Am J Trop Med Hyg. 1978 Jul;27(4):747–750. doi: 10.4269/ajtmh.1978.27.747. [DOI] [PubMed] [Google Scholar]

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