Treatment options for trichomoniasis to grow?

A quick check of your next patient’s file shows that she is returning for yet another round of treatment for trichomoniasis. The infection is not responding to standard metronidazole therapy. What is your next move?

Metronidazole has been the drug of choice for Trichomonas vaginalis infections since 1960. It remains effective today, with a cure rate of approximately 95%.1 While metronidazole is an effective treatment for most persons infected with T. vaginalis, the existence of drug-resistant infections is becoming increasingly recognized, says Evan Secor, PhD, a microbiologist with the Atlanta-based Centers for Disease Control and Prevention’s (CDC’s) Division of Parasitic Diseases.

"For example, in 1995, when the Division of Parasitic Diseases began performing the metronidazole susceptibility testing, we received 15 requests," he notes." In 2003, the number of requests for susceptibility testing will exceed 100," he reports.

Metronidazole (Flagyl, GD Searle, Chicago; metronidazole, Watson Pharmaceuticals, Corona, CA) is the only approved drug for use in the United States; however, another drug, tinidazole, is under review by the Food and Drug Admini-stration (FDA). Presutti Laboratories of Arlington Heights, IL, submitted a new drug application in November 2003 for tinidazole for the treatment of trichomoniasis, giardiasis, intestinal amebiasis, and amebic liver abscess.

Tinidazole, which is available in Europe, is available in the United States on a compassionate-use basis from Presutti Laboratories for the treatment of metronidazole-resistant trichomoniasis and metronidazole-resistant giardiasis. It recently was granted orphan drug status by the FDA for the treatment of giardiasis.

If the drug is approved by the FDA, it may be available in 2004, says John Presutti, company president. If the drug does reach U.S. market shelves, it will be competitively priced with other branded antibacterial therapies, he notes.

Take aim at trich

T. vaginalis infections account for nearly one-third of the 15.4 million cases of sexually transmitted diseases (STDs) in the United States.2 The Geneva-based World Health Organization estimates the number of adults with trichomoniasis at 170 million worldwide, which is more than the numbers for gonorrhea, syphilis, and chlamydia combined.3

Signs of trichomoniasis in women can include a yellow, gray, or green frothy vaginal discharge, often accompanied by a foul odor, with burning, itching, soreness, and redness of the vulva or vagina often present. While trichomoniasis is frequently asymptomatic in men, when symptoms are found, they may consist of urethral discharge and irritation.

Trichomoniasis is substantially underdiagnosed in the United States for a number of reasons, says Presutti. Detection of the infection in a clinical setting depends on visual recognition in a fresh vaginal specimen in a wet-mount preparation; however, this technique has limited sensitivity.4 Culture has better sensitivity, but the technique is more cumbersome and labor-intensive, which limits its use for many facilities.5 Recent research indicates that polymerase chain reaction (PCR) testing for the detection of T. vaginalis exceeds that of wet preparation and culture, with a high specificity.4 PCR testing also indicates a higher prevalence of infection in men than found in culture or wet mount.6

The CDC calls for treatment of trichomoniasis with metronidazole, 2 g orally in a single dose.7 If treatment failure occurs, the CDC recommends re-treatment with metronidazole, 500 mg twice a day, for seven days. If treatment failure occurs repeatedly, patients should be treated with a single 2 g dose of metronidazole once a day for three to five days.7

Researchers at CDC began looking at alternative treatment regimens for T. vaginalis following clinicians’ requests for help with metronidazole-resistant cases, says Secor. Scientists focused on tinidazole, which is approved for use in Europe, following reports of its effectiveness against metronidazole-resistant infections.8 Their findings indicate a role for tinidazole in the treatment of trichomoniasis.9

"Tinidazole may be an effective alternative drug to treat patients with metronidazole-resistant infections," says Secor. "Although this study remains to be performed, it may mean that even infections that are sensitive to metronidazole may be able to be treated with lower doses of tinidazole, which could be especially important for those patients with adverse reactions to metronidazole."

Anecdotal data suggest that tinidazole causes fewer side effects than metronidazole, says Secor. If such findings are proven true, use of tinidazole may lead to greater patient compliance with treatment, including compliance of asymptomatic partners to accept treatment, he observes.

References

1. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines. MMWR 1993; 42(RR-14):70-72.

2. Cates W. Estimates of the incidence and prevalence of sexually transmitted diseases in the United States. Sex Transm Dis 1999; 26(Suppl.):S2-S7.

3. World Health Organization. Global Program on AIDS. Geneva: World Health Organization; 1995.

4. Wendel KA, Erbelding EJ, Gaydos CA, et al. Trichomonas vaginalis polymerase chain reaction compared with standard diagnostic and therapeutic protocols for detection and treatment of vaginal trichomoniasis. Clin Infect Dis 2002; 35:576-580.

5. Cohen MS, Hobbs M, Miller W. Expert review on: Trichomonas vaginalis polymerase chain reaction compared with standard diagnostic and therapeutic protocols for detection and treatment of vaginal trichomoniasis. WHO STD Diagnostics Initiative; accessed at www.who.int/std_diagnostics/literature_reviews/issue_2.htm.

6. Wendel KA, Erbelding EJ, Gaydos CA, et al. Use of urine polymerase chain reaction to define the prevalence and clinical presentation of Trichomonas vaginalis in men attending an STD clinic. Sex Transm Infect 2003; 79:151-153.

7. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines — 2002. MMWR 2002; 51(RR06);1-80.

8. Sobel JD, Nyirjesy P, Brown W. Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis. Clin Infect Dis 2001; 33:1,341-1,346.

9. Crowell AL, Sanders-Lewis KA, Secor WE. In vitro metronidazole and tinidazole activities against metronidazole-resistant strains of Trichomonas vaginalis. Antimicrob Agents Chemother 2003; 47:1,407-1,409.