Abstract
As yet, only a few drugs are available that are frequently used for the treatment of human toxoplasmosis. Pyrimethamine and sulfadiazine are regularly used in combination and are the first choice for most clinical conditions. However, due to severe side effects that are observed especially with sulfadiazine, other drugs, such as clindamycin, have successfully been used as alternative treatment. Since pyrimethamine might be teratogenic when used in the first weeks of pregnancy, spiramycin has been introduced as first-choice treatment during the first 16–20 weeks of pregnancy. In addition to these four well-established drugs, others such as tetracycline or cotrimoxazole have been studied as therapeutics against toxoplasmosis. Although their effectiveness has been demonstrated to some extent, they have not been accepted as general treatment (Joss 1992). None of these drugs has been shown to completely eliminate the parasite in the human host. Since persistent infection with cysts is the source of reactivated toxoplasmosis, new drugs have been developed that might even be more effective against the cyst stage. The hydroxynaphthoquinone atovaquone and macrolides such as azithromycin, clarithromycin, and roxithromycin are thought to inhibit the tachyzoite and the cyst stage as well, as has been shown in vitro or/and in vivo (Araujo et al. 1991,1992a,1992b; Blais et al. 1993a, Huskinson-Mark et al. 1991).
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References
Araujo FG, Shepard RM, Remington JS (1991) In vivo activity of the macrolide antibiotics azithromycin. roxithromycin and spiramycin against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis 10:519–524
Araujo FG, Huskinson-Mark J, Gutteridge WE, Remington JS (1992a) In vitro and in vivo activities of the hydroxynaphoquinone 566C80 against the cyst form of Toxoplasma gondii. Antimicrob Agents Chemother 36:326–330
Araujo FG, Prokocimer P, Lin T, Remington JS (1992b) Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis. Antimicrob Agents Chemother 36:2454–2457
Beckers CJ, Roos OS, Donald RG, Luft BJ, Schwab JC, Cao Y, Joiner KA (1995) Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics. J Clin Invest 95:367–376
Blais J, Garneau V, Chamberland S (1993a) Inhibition of Toxoplasma gondii protein synthesis by azithromycin. Antimicrob Agents Chemother 37:1701–1703
Blais J, Tardif C, Chamberland S (1993b) Effect of clindamycin on intracellular replication, protein synthesis, and infectivity of Toxoplasma gondii. Antimicrob Agents Chemother 37:2571–2577
Bohne W, Heesemann J, Gross U (1993) Induction of bradyzoite-specific Toxoplasma gondii antigens in gamma interferon-treated mouse macrophages. Infect Immun 61: 1141–1145
Bohne W, Heesemann J, Gross U (1994) Reduced replication of Toxoplasma gondii is necessary for induction of bradyzoite-specific antigens:a possible role for nitric oxide in triggering stage conversion. Infect Immun 62:1761–1767
Cantin L, Chamberland S (1993) In vitro evaluation of the activities of azithromycin alone and combined with pyrimethamine against Toxoplasma gondii. Antimicrob Agents Chemother 37: 1993–1996
Chamberland S, Kirst HA, Current WL (1991) Comparative activity of macrolides against Toxoplasma gondii demonstrating utility of an in vitro microassay. Antimicrob Agents Chemother 35:903–909
Chang HR, Pechere JC (1988) In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin (CP-62, 993), and (A-56268) on Toxoplasma gondii. Antimicrob Agents Chemother 32:524–529
Chang HR, Comte R, Pechere JC (1990) In vitro and in vivo effects of doxycycline on Toxoplasma gondii. Antimicrob Agents Chemother 34:775–780
Derouin F, Chastang C (1989) In vitro effects of folate inhibitors on Toxoplasma gondii. Antimicrob Agents Chemother 33:1753–1759
Derouin F, Chastang C (1990) Activity in vitro against Toxoplasma gondii of azithromycin and clarithromycin alone and with pyrimethamine. J Antimicrob Chemother 25:708–711
Derouin F, Nalpas J, Chastang C (1988) Mesure in vitro de I’effet inhibiteur de macrolides, lincosamides et synergestines sur la croissance de Toxoplasma gondii. Path Bioi 36: 1204–121O.
Derouin F, Caroff B, Chau F, Prokocimer p, Pocidalo JJ (1992) Synergistic activity of clarithromycin and minocycline in an animal model of acute experimental toxoplasmosis. Antimicrob Agents Chemother 36:2852–2855
Ferguson DJP, Huskinson-Mark J, Araujo FG, Remington JS (1994) An ultrastructural study of the effect of treatment with atovaquone in brains of mice chronically infected with the ME49 strain of Toxoplasma gondii. Int J Exp Path 75:111–116
Fichera ME, Bhopale MK, Roos DS (1995) In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii. Antimicrob Agents Chemother 39: 1530–1537
Gross U, Bohne W (1994) Toxoplasma gondii: strain-and host cell dependent induction of stage conversion. J Euk Microbiol 41: 105–115
Gross U, Bohne W, Soete M, Dubremetz JF (1996) Developmental differentiation between tachy-zoites and bradyzoites of Toxoplasma gondii. Parasitol Today 12:30–33
Haverkos HW (1987) Assessment of therapy for toxoplasma encephalitis. Am J Med 82:907–914
Holfels E, McAuley J, Mack D, Milhous WK, McLeod R (1994) In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine). quinine sulfate, meflo-quine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii. Antimicrob Agents Chemother 38: 1392–1396
Hudson AT (1993) Atovaquone — a novel broad-spectrum anti-infective drug. Parasitol Today 9:66–69
Huskinson-Mark J, Araujo FG, Remington JS (1991) Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii. J Infect Dis 164:170–177
Joss AWL (1992) Treatment. In: Ho-Yen DO, Joss AWL (eds) Human toxoplasmosis. Oxford University Press, Oxford, pp 119–143
Lindsay DS, Blagburn BL, Hall JE, Tidwell RR (1991) Activity of pentamidine and pentamidine analogs against Toxoplasma gondii in cell cultures. Antimicrob Agents Chemother 35: 1914–1916
Mack DG, McLeod R (1984) 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 26:26–30
Parmley SF, Gross U, Sucharczuk A, Windeck T, Sgarlato GD, Remington JS (1994) Two alleles of the gene encoding surface antigen P22 in 25 strains of Toxoplasma gondii. J Parasitol 80:293–301
Pfefferkorn ER (1978) Toxoplasma gondii: the enzymatic defect of a mutant resistant to 5-fluorodeoxyuridine. Exp Parasitol 44:26–35
Pfefferkorn ER, Borotz SE (1994) Comparison of mutants of Toxoplasma gondii selected for resistance to azithromycin, spiramycin, or clindamycin. Antimicrob Agents Chemother 38:31–37
Pfefferkorn ER, Nothnagel RF, Borotz SE (1992) Parasiticidal effect of clindamycin on Toxoplasma gondii grown in cultured cells and selection of a drug-resistant mutant. Antimicrob Agents Chemother 36:1091–1096
Pfefferkorn ER, Borotz SE, Nothnagel RF (1993) Mutants of Toxoplasma gondii resistant to atova-quone (566C80) or decoquinate. J Parasitol 79:559–564
Piketty C, Derouin F, Rouveix B, Pocidalo JJ (1990) 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 34:1467–1472
Romand S, Pudney M, Derouin F, (1993) In vitro and in vivo activities of the hydroxynaphthoquinone atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, or minocycline against Toxoplasma gondii. Antimicrob Agents Chemother 37:2371–2378
Sartorius C, Franklin RM (1991) The use of antisense oligonucleotides as chemotherapeutic agents for parasites. Parasitol Today 7:90–94
Schoondermark-van de Ven E, Melchers W, Camps W, Eskes T, Meuwissen J, Galama J (1994) Effectiveness of spiramycin for treatment of congenital Toxoplasma gondii infection in rhesus monkeys. Antimicrob Agents Chemother 38:1930–1936
Schoondermark-van de Ven E, Galama J, Vree T, Camps W, Baars I, Eskes T, Meuwissen J, Melchers W (1995) Study of treatment of congenital Toxoplasma gondii infection in rhesus monkeys with pyrimethamine and sulfadiazine. Antimicrob Agents Chemother 39: 137–144
Soete M, Camus D, Dubremetz JF (1994) Experimental induction of bradyzoite-specific antigen expression and cyst formation by the RH strain of Toxoplasma gondii in vitro. Exp Parasitol 78:361–370
Tabbara KF, O’Connor GR (1980) Treatment of ocular toxoplasmosis with clindamycin and sulfadiazine. Ophthalmology 87: 129–134
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© 1996 Springer-Verlag Berlin Heidelberg
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Gross, U., Pohl, F. (1996). Influence of Antimicrobial Agents on Replication and Stage Conversion of Toxoplasma gondii . In: Gross, U. (eds) Toxoplasma gondii. Current Topics in Microbiology and Immunology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-51014-4_21
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DOI: https://doi.org/10.1007/978-3-642-51014-4_21
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