Leishmania (L.) tropica, Türkiye'de dahil olmak üzere Eski Dünya'da kutanöz leishmaniasisden (KL) sorumlu en önemli türdür. KL tedavisinde intralezyoner ve intramuskuler yoldan beş değerlikli antimon bileşikleri yaygın olarak kullanılmaktadır, fakat bu ajanlara karşı artan direnç alternatif ilaçların geliştirilmesini gerekli kılmaktadır. Bu çalışmada, makrolid grubundan iki antibiyotik olan azitromisin ve klaritromisinin L. topica'nın RPMI 1640 besiyerindeki promastigotlar ve makrofaj serisindeki amastigotlar üzerine olan antileishmanial aktiviteleri değerlendirilmiştir. Azitromisin ve klaritromisinin promastigotlar üzerindeki ED50 değerleri sırasıyla 5 µg/ml ve
Leishmania (L.) tropica is one of the most common species responsible for cutaneous leishmaniasis (CL) in the Old World including Turkey. The pentavalent antimonials are widely used as intralesional and/or intramuscular in the treatment of CL, but increase in resistance to these agents led to investigations on alternative drugs. In vitro antileishmanial activities of two macrolides, azithromycin and clarithromycin were evaluated on promastigotes in RPMI 1640 medium and amastigotes in macrophage series of L. tropica. ED50 values of azithromycin and clarithromycin were found to be 5 µg/ml and <5 µg/ml on promastigotes, and 50-75 µg/ml and <3 µg/ml on amastigotes, respectively, while ED90 values of the same drugs were 75 µg/ml and 25 µg/ml on promastigotes and 100 µg/ml and 10 µg/ml on amastigotes, respectively. Our data suggested that clarithromycin and azithromycin were effective on both L. tropica promastigotes and amastigotes in vitro. Clarithromycin was found to be more effective than azithromycin at lower concentrations on promastigotes and amastigotes. In vivo studies should be planned to detect intracellular concentrations of these drugs for the effective route and dosage
___
Molyneux DH, Killick-Kendrick R: Morphology, ultrastructure and lifecycles. In, Peters W, Killick-Kendrick R (Eds): The Leishmaniases in Biology and Medicine. Vol. 1. Biology and Epidemiology, pp. 1-120, Academic Press, London, 1987.
Seaman J, Mercer J, Sondorp HE, Herwaldt BL: Epidemic visceral leishmaniosis in Southern Sudan: Treatment of severely debilitated patients under wartime conditions and with limited resources. Ann Intern Med, 124, 664-672, 1996.
Hewitt S, Reyburn H, Ashford R, Rowland M: Anthroponotic cutaneous leishmaniasis in Kabul, Afghanistan: Vertical distribution of cases in apartment blocks. Trans R Soc Trop Med Hyg, 92 (3): 273-274, 1998.
Berman JD: Chemotherapy for leishmaniasis: Biochemical mechanisms, clinical efficacy, and future strategies. Rev Infect Dis, 10, 560-586, 1988.
Araujo FG, Shepard RM, Remington JS: In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis, 10, 519-524, 1991.
Brun-Pascaud M, Rajagopalan-Levasseur P, Chau F, Bertrand G, Garry L, Derouin F, Girard PM: Drug evaluation of concurrent Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium complex infections in a rat model. Antimicrob Agents Chemother, 42 (5): 1068-1072, 1998.
Giacometti A, Cirioni O, Scalise G: In vitro activity of macrolides alone and in combination with artemisin, atovaquone, dapsone, minocycline or pyrimethamine against Cryptosporidium parvum. J Antimicrob Chemother, (3): 399-408, 1996.
Hicks P, Zwiener RJ, Squires J, Savell V: Azithromycin therapy for Cryptosporidium parvum infection in four children infected with human immunodeficiency virus. J Pediatr, 129, 297-300, 1996.
Taylor WR, Richie TL, Fryauff DJ, Picarima H, Ohrt C, Tang D, Braitman D, Murphy GS, Widjaja H, Tjitra E, Ganjar A, Jones TR, Basri H, Berman J: Malaria prophylaxis using azithromycin: A double-blind, placebo-controlled trial in Irian Jaya, Indonesia. Clin Infect Dis, 28, 74-81, 1999.
Krolewiecki A, Leon S, Scott P, Abraham D: Activity of azithromycin against Leishmania major in vitro and in vivo. Am J Trop Med Hyg, 67 (3): 277, 2002.
Mallison DJ, Coombs GH: Interaction of Leishmania metacyclics with macrophages. Int J Parasitol, 19 (6): 647-656, 1989.
Berman JD: Treatment of New World cutaneous and mucocutaneous leishmaniasis. Clin Dermatol, 14, 519-522, 1996.
Berman JD: Human leishmaniasis: Clinical, diagnostic and chemo- therapeutic developments in the last 10 years. Clin Infect Dis, 24, 684-703,
Murray HW, Oca MJ, Granger AM, Schreiber RD: Requirement for T cells and effect of lymphokines in successful chemotherapy for anintracellular infection. Experimental Visceral Leishmaniasis. J Clin Invest, (4): 125-127, 1989.
Chambers HF: Antimicrobial Agents: protein synthesis inhibitos and miscellaneous antibacterial agents. Hardman JG, Limbird LE, Gilman AG (Eds): Goodman & Gilman's The Pharmacological Basis of Therapetutics. 10th ed., p,1239-1271, USA, 2000.
Stott GA: New macrolide antibiotics: Clarithromycin and azithromycin. Am Fam Physician, 46 (3): 863-869, 1992.
Arora SK, Sinha R, Sehgal S: Use of in vitro method to assess different brands of anti-leishmanial drugs. Med Microbiol Immunol, 180, 21-27,
Aybay C, Imir T, Ozkan S, Çağlar K, Sultan N: Effect of several antibiotics on the proliferation of Leishmania major promastigote cells. Turkiye Parazitol Derg, 21 (1): 1-6, 1997.
Chan MM, Tzeng J, Emge TJ, Ho CT, Fong D: Structure function analysis antimicrotubule dinitroanilines against promastigotes of parasitic protozoan Leishmania mexicana. Antimicrob Agents Chemother, 37 (9): 1913, 1993.
Hiraoka O, Satake H, Iguchi S, Matsuda A, Ueda T, Watava Y: Carbocylic inosine as potent anti-leishmanial agent: The metabolism and selective cytotoxic of carbocylic inosine in promastigotes of Leishmania tropica and Leishmania donovani. Biochem Biophy Res Commun, 134 (3): 1121, 1986.
Mukhopadhyay R, Madhubala R: Effect bis(benzyl)polyamine analogs on Leishmania donovani promastigotes. Exp Parasitol, 81, 39-46, 1995.
Sett R, Basu N, Ghosh AK, Das PK: Potential of doxorubicin as an antileishmanial agent. J Parasitol, 78 (2): 350-354, 1992.
Shin IS, Tanifuji H, Arata Y, Morizawa Y, Nakayama T, Watava Y: '-Deoxy-3'-fluoroinosine as a potent antileishmanial agent. The meta- bolism and selective cytotoxic effect of 3'-deoxy-3'-fluoroinosine against in vitro and in vivo. Parasitol Res, 81 (7): 622-626, 1995.
TDR News: No:69. 2002, http://apps.who.int/tdr/publications/ tdrnews/pdf/TDRnews-issue-69.pdf , Accessed: 28.12.2011.
Wataya Y, Hiraoka O: 3'-Deoxyinosine as an anti-Leishmanial agent: the metabolism and cytotoxic of 3'-deoxyinosine in promastigotes of Leishmania tropica. Biochem Biophy Res Commun, 123 (2): 677-83, 1984.
Saha AK, Mukherjee T, Bhaduri A: Mechanism of action amphotericin B on Leishmania donovani promastigotes. Mol Biochem Parasitol, 19, 195- , 1986.
Bonay P, Duran-Chica I, Fresno M, Alarcon B, Alcina A: Antiparasitic effect of the intra-Golgi transport inhibitor megalomicin. Antimicrob Agents Chemother, 42 (10): 2668-2673, 1998.
Tanyuksel M, Bas AL, Araz E, Aybay C: Determination of intra- cellular efficacies of azithromycin against Leishmania major infection in human neutrophils in vitro. Cell Biochem Function, 21 (1): 93-96, 2001.
Chang HR, Pechere JF: In vitro effects of four macrolids (Roxithro- mycin, Spiramycin, Azithromycin and A-56268) on T. gondii. Antimicrobial Agents Chemother, 32 (4): 524-529, 1988.
Blais J, Garneau V, Chamberland S: Inhibition of T. gondii protein synthesis by Azithromycin. Antimicrobial Agents Chemother, 37 (8): 1701-1703, 1993.
Oliveira-Silva F, de Morais-Teixeira E, Rabello A: Antileishmanial activity of Azithromycin against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, and Leishmania (Leishmania) chagasi. Am J Trop Med Hyg, 78 (5): 745-749, 2008.
Prata A, Silva-Vergara ML, Costa L, Rocha A, Krolewiecki A, Silva JC, de Paula EV, Pimenta Junior FG, Giraldo LE: Efficacy of azithromycin in the treatment of cutaneous leishmaniasis. Rev Soc Bras Med Trop, 36, 65-69, 2003.
Silva-Vergara ML, Silva LA, Maneira FR, da Silva AG, Prata A: Case report: Azithromycine in the treatment of mucosal leishmaniasis. Rev Inst Med Trop Sao Paulo, 46, 175-177, 2004.
Momeni AZ, Shafiei A, Emamjoeh M, Aminjavaheri M, Momeni A: Azithromycin is not effective in the treatment of old world cutaneous leishmaniasis. Eur J Dermatol, 16 (6): 701-702, 2006.
Daoud S, Boushi L: Azithromycin, ineffective in the treatment of old- world cutaneous leishmaniasis. Int J Dermatol, 45, 1126-1128, 2006.
Minodier P, Zambelli L, Mary C, Faraut F, Garnier JM, Berbis P: Cutaneous leishmaniasis treated with azithromycin in a child. Ped Infect Dis J, 27 (1): 80-81, 2008.