Trovafloxacin is active against Toxoplasma gondii

Drugs currently used for treatment of toxoplasmosis in pregnant women, congenital infections, immunocompromised patients, and patients with the ocular disease are not always effective or may be dangerous to use; therefore, there is a need for more-effective and less-toxic drugs. Recently, we examined a group of fluoroquinolones for in vitro and in vivo activities against Toxoplasma gondii. Among those examined in vitro (ciprofloxacin, fleroxacin, ofloxacin, temafloxacin, and trovafloxacin), only trovafloxacin significantly inhibited intracellular replication of T. gondii without significant toxicity for host cells. In a murine model of acute toxoplasmosis, 100 or 200 mg of trovafloxacin per kg of body weight per day for 10 days protected 100% of infected mice against death. A dose of 50 mg/kg/day protected 90% of the mice, and a dose of 25 mg/kg/day effected prolongation of time to death. The other fluoroquinolones did not have such in vivo activities. These results indicate that trovafloxacin may be useful for treatment of toxoplasmosis in humans.

[1]  H. Neu,et al.  Comparative in vitro activity of a new fluorinated 4-quinolone, T-3262 (A-60969) , 1988, Antimicrobial Agents and Chemotherapy.

[2]  T. Gootz,et al.  Biochemical characteristics and physiological significance of major DNA topoisomerases , 1989, Antimicrobial Agents and Chemotherapy.

[3]  D. Eyles,et al.  An evaluation of the curative effects of pyrimethamine and sulfadiazine, alone and in combination, on experimental mouse toxoplasmosis. , 1955, Antibiotics & chemotherapy.

[4]  T. Noumi,et al.  Intracellular activity of tosufloxacin (T-3262) against Salmonella enteritidis and ability to penetrate into tissue culture cells of human origin , 1990, Antimicrobial Agents and Chemotherapy.

[5]  D. Israelski,et al.  Toxoplasmic encephalitis in patients with AIDS. , 1988, Infectious disease clinics of North America.

[6]  Jerome J. Schentag,et al.  Pharmacokinetics and safety of trovafloxacin (CP-99,219), a new quinolone antibiotic, following administration of single oral doses to healthy male volunteers. , 1995, The Journal of antimicrobial chemotherapy.

[7]  C. Zimmer,et al.  Microbial DNA topoisomerases and their inhibition by antibiotics , 1990, Journal of basic microbiology.

[8]  G. Kenny,et al.  Susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to a new quinolone, trovafloxacin (CP-99,219) , 1996, Antimicrobial agents and chemotherapy.

[9]  D. Hooper,et al.  Fluoroquinolone antimicrobial agents. , 1991, Clinical microbiology reviews.

[10]  D. Mortiboy,et al.  Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219) , 1996, Antimicrobial agents and chemotherapy.

[11]  R. Jones,et al.  In vitro antimicrobial activity of CP-99,219, a novel azabicyclo-naphthyridone , 1993, Antimicrobial Agents and Chemotherapy.

[12]  B. Bendixen,et al.  Sulfadiazine-associated obstructive nephropathy occurring in a patient with the acquired immunodeficiency syndrome. , 1988, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[13]  R. Holzman,et al.  Evaluation of the policy of empiric treatment of suspected Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome. , 1989, The American journal of medicine.

[14]  A. Maxwell The molecular basis of quinolone action. , 1992, The Journal of antimicrobial chemotherapy.

[15]  G. Filice,et al.  Pulmonary toxoplasmosis: a review. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  S. Mitsuhashi,et al.  In vitro and in vivo antibacterial activities of T-3262, a new fluoroquinolone , 1988, Antimicrobial Agents and Chemotherapy.

[17]  D. Hooper,et al.  Fluoroquinolone antimicrobial agents , 1989, Clinical Microbiology Reviews.

[18]  J. Remington,et al.  Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii , 1991, Antimicrobial Agents and Chemotherapy.

[19]  F. Derouin,et al.  Prevalence of pulmonary toxoplasmosis in HIV-infected patients. , 1990, AIDS.

[20]  D. Eyles,et al.  Synergistic effect of sulfadiazine and daraprim against experimental toxoplasmosis in the mouse. , 1953, Antibiotics & chemotherapy.

[21]  J. Remington,et al.  In vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against the cyst form of Toxoplasma gondii , 1992, Antimicrobial Agents and Chemotherapy.

[22]  J. Remington,et al.  Effect of Clindamycin on Acute and Chronic Toxoplasmosis in Mice , 1974, Antimicrobial Agents and Chemotherapy.

[23]  M. Takahata,et al.  In vitro antibacterial activities of tosufloxacin against and uptake of tosufloxacin by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium , 1992, Antimicrobial Agents and Chemotherapy.

[24]  T. Heimberger,et al.  Sulfadiazine-induced crystalluria in a patient with the acquired immunodeficiency syndrome: a reminder. , 1988, The American journal of medicine.

[25]  É. Oksenhendler,et al.  Toxoplasma gondii pneumonia in patients with the acquired immunodeficiency syndrome. , 1990, The American journal of medicine.

[26]  Jerome J. Schentag,et al.  Pharmacokinetics and safety of trovafloxacin (CP-99, 219), a new quinolone antibiotic, following adminstration of single oral doses to healthy male volunteers , 1995 .