Am Fam Physician. 1999;60(6):1716-1722
This is Part II of a two-part article on drug treatment of sexually transmitted diseases. Part I, “Herpes, Syphilis, Urethritis, Chlamydia and Gonorrhea,” appeared in the October 1 issue (Am Fam Physician 1999; 60:1387–94).
The Centers for Disease Control and Prevention (CDC) released new guidelines for the treatment of sexually transmitted diseases (STDs) in 1998. Several treatment advances have been made since the previous guidelines were published. Part II of this two-part series on STDs describes recommendations for the treatment of diseases characterized by vaginal discharge, pelvic inflammatory disease, epididymitis, human papillomavirus infection, proctitis, proctocolitis, enteritis and ectoparasitic diseases. Single-dose therapies are recommended for the treatment of several of these diseases. A single 1-g dose of oral azithromycin is as effective as a seven-day course of oral doxycycline, 100 mg twice a day, for the treatment of chlamydial infection. Erythromycin and ofloxacin are alternative agents. Four single-dose therapies are now recommended for the management of uncomplicated gonococcal infections, including 400 mg of cefixime, 500 mg of ciprofloxacin, 125 mg of ceftriaxone or 400 mg of ofloxacin. Advances in the treatment of bacterial vaginosis also have been made. A seven-day course of oral metronidazole is still recommended for the treatment of bacterial vaginosis in pregnant women, but intravaginal clindamycin cream and metronidazole gel are now recommended in nonpregnant women. Single-dose therapy with 150 mg of oral fluconazole is a recommended treatment for vulvovaginal candidiasis. Two new topical treatments, podofilox and imiquimod, are available for patient self-administration to treat human papillomavirus infection. Permethrin cream is now the preferred agent for the treatment of pediculosis pubis and scabies.
This article focuses on vaginal infections, pelvic inflammatory disease and genital warts, with brief mention of proctitis, enteritis and ectoparasitic infections. It should be noted that vaginal candidiasis and bacterial vaginosis are included in the following discussion, although these infections are not sexually transmitted. They are frequently diagnosed at the same time as sexually transmitted diseases (STDs), however, and the treatments often overlap.
Vaginitis
The three diseases that are most commonly associated with vaginitis are bacterial vaginosis, trichomoniasis and candidiasis. Diagnosis is based on pH measurement and microscopic examination of the vaginal discharge. Symptoms of vaginitis include vaginal discharge, vulvar itching, or both, with or without vaginal odor. Vulvovaginal candidiasis is not transmitted sexually but is evaluated at the same time as screening for STDs.
BACTERIAL VAGINOSIS
Bacterial vaginosis is the most common cause of vaginal discharge or malodor. It occurs when the normal flora of the vagina that produces Lactobacillus species is replaced with anaerobic bacteria. Bacterial vaginosis occurs more often in women who have multiple sexual partners, but it is not known if it is transmitted sexually. At this time, treatment for male sex partners is not recommended.
All women with symptomatic disease require treatment, including those who are pregnant. Studies have shown that bacterial vaginosis is associated with preterm delivery in pregnant women who are already at high risk for preterm delivery. Bacterial vaginosis is also associated with pelvic inflammatory disease, endometritis and vaginal cuff cellulitis after invasive procedures.
A seven-day course of oral metronidazole (Flagyl) is recommended for the treatment of bacterial vaginosis. In addition, intravaginal clindamycin cream (Cleocin) and metronidazole gel (Metrogel) are recommended treatments in nonpregnant women.1 Table 1 shows treatment regimens that are approved for use in pregnant women.
TRICHOMONIASIS
Trichomoniasis is a disease associated with vaginal discharge that is caused by the protozoan Trichomonas vaginalis. Trichomoniasis is transmitted sexually, yet men usually remain asymptomatic. Trichomoniasis in women is characterized by a diffuse, malodorous, yellow-green discharge and vulvar irritation. As with bacterial vaginosis, vaginal trichomoniasis may be associated with adverse pregnancy outcomes.
Trichomoniasis is treated with oral metronidazole (Flagyl). Topical metronidazole is not recommended. Table 1 shows treatment regimens in pregnant and nonpregnant women.
| Disease | Recommended regimens | Agent | Dosage | Cost* |
|---|---|---|---|---|
| Bacterial vaginosis | Recommended regimens in on pregnant women | Metronidazole (Flagyl) | 500 mg orally twice daily for 7 days | $ 6.50 to 9.00 (generic) |
| Clindamycin cream (Cleocin) | 2%, one full applicator intravaginally at bedtime for 7 days | 40.00 (brand/40 g) | ||
| Metronidazole gel (Metrogel) | 0.75%, one full applicator intravaginally twice daily for 5 days | 35.00 (brand/20 g) | ||
| Alternative regimens in nonpregnant women | Metronidazole | 2 g orally in a single dose | 11.50 (brand) 1.50 to 3.00 (generic) | |
| Clindamycin | 300 mg orally twice daily for 7 days | 46.00 (brand) | ||
| Recommended regimens in pregnant women (second trimester) | Metronidazole | 500 mg orally twice daily for 7 days | 6.50 to 9.00 (generic) | |
| Metronidazole | 2 g orally in a single dose | 11.50 (brand) 1.50 to 3.00 (generic) | ||
| Clindamycin | 300 mg orally twice daily for 7 days | 46.00 (brand) | ||
| Trichomoniasis | Recommended regimen | Metronidazole | 2 g orally in a single dose | 11.50 (brand) 1.50 to 3.00 (generic) |
| Alternative regimen | Metronidazole | 500 mg orally twice daily for 7 days | 6.50 to 9.00 (generic) | |
| Recommended regimen in pregnant women (second trimester) | Metronidazole | 2 g orally in a single dose | 11.50 (brand) 1.50 to 3.00 (generic) | |
| Vulvovaginal candidacies | Recommended intravaginal agents | Butoconazole (Femstat) | 2% cream, 5 g intravaginally for 3 days | 14.00 (brand/15 g) |
| Clotrimazole (Lotrimin) | 1% cream, 5 g intravaginally for 7 to 14 days | 6.00 to 9.00 (brand) | ||
| Clotrimazole | 100-mg vaginal tablet daily for 7 days | 10.50 (generic) | ||
| Clotrimazole | 100-mg vaginal tablet, two tablets daily for 3 days | 4.50 (generic) | ||
| Clotrimazole (Mycelex-G) | 500-mg vaginal tablet, one tablet in a single application | 15.00 (brand) | ||
| Miconazole (Monistat) | 2% cream, 5 g intravaginally for 7 days | 15.00 (brand) | ||
| Miconazole | 200-mg vaginal suppository, one daily for 3 days | 30.00 (brand) | ||
| Miconazole | 100-mg vaginal suppository, one daily for 7 days | 12.00 (brand) | ||
| Nystatin (Mycolog II) | 100,000-unit vaginal tablet, one daily for 14 days | 17.50 to 29.50 (brand) | ||
| Tioconazole (Vagistate-1) | 6.5% ointment, 5 g intravaginally in a single application | 14.50 (brand/4.6 g) | ||
| Terconazole (Terazole) | 0.4% cream, 5 g intravaginally for 7 days | 29.00 (brand/45 g) | ||
| Terconazole | 0.8% cream, 5 g intravaginally for 3 days | 29.00 (brand/20 g) | ||
| Terconazole | 80-mg vaginal suppository, one daily for 3 days | 29.00 (brand) | ||
| Recommended oral agent | Fluconazole (Diflucan) | 150-mg tablet taken orally in a single dose | 11.50 (brand) |
VULVOVAGINAL CANDIDIASIS
Symptoms of vulvovaginal candidiasis include pruritis, vaginal discharge and, sometimes, vaginal soreness, vulvar burning, dyspareunia and external dysuria. Vulvovaginal candidiasis can occur concomitantly with an STD or following antimicrobial therapy.
Several topical agents are still recommended for the treatment of vulvovaginal candidiasis and are first-line therapies in pregnant women. An oral agent, fluconazole (Diflucan), has now been labeled for use in the treatment of vulvovaginal candidiasis.2,3 Systemic effects, side effects and drug interactions must be considered when oral agents are used. Table 1 lists recommended therapies for the treatment of vulvovaginal candidiasis.
Pelvic Inflammatory Disease
Pelvic inflammatory disease is an infection of the upper female genital tract caused by Neisseria gonorrhoeae, Chlamydia trachomatis, or both, although it may also be caused by microorganisms that are part of the normal vaginal flora. Disease can manifest as any combination of endometritis, salpingitis, tubo-ovarian abscess and pelvic peritonitis. The clinical diagnosis of pelvic inflammatory disease is complicated; therefore, the CDC guidelines should be checked for more information about diagnosis.
Treatment is usually empiric, and antimicrobial therapy should cover N. gonorrhoeae, C. trachomatis, anaerobes, gram-negative facultative bacteria and streptococci. Parenteral therapy is required in several types of patients, including those who are pregnant, those who do not respond to or are unable to tolerate oral antimicrobial therapy, those with severe illness such as nausea, vomiting or high fever, those with tubo-ovarian abscess and patients who are immunodeficient. Sexual partners of patients with pelvic inflammatory disease should be evaluated and treated; empiric treatment is recommended for gonorrhea and Chlamydia. Recommended antimicrobial regimens are listed in Table 2.
| Recommended regimens | Agent | Dosage | Cost* | ||
|---|---|---|---|---|---|
| Parenteral regimens | Cefotetan (Cefotan) | 2 g IV every 12 hours | $ 46.50 (brand) | ||
| or | |||||
| Cefoxitin (Mefoxin) | 2 g IV every 6 hours | 85.50 (brand) | |||
| plus | |||||
| Doxycycline (Vibramycin) | 100 mg IV or orally every 12 hours | 33.50 (generic) | |||
| Alternative parenteral regimen | Clindamycin (Cleocin) | 900 mg IV every 8 hours | 29.00 (brand) | ||
| plus | |||||
| Gentamicin | IV or IM, 2 mg per kg loading dose, followed by 1.5 mg per kg every 8 hours | 3.00 to 15.00 (generic) | |||
| Oral regimens | Ofloxacin (Floxin) | 400 mg orally twice daily for 14 days | 131.00 (brand) | ||
| Plus | |||||
| Metronidazole (Flagyl) | 500 mg orally twice daily for 14 days | 79.00 (brand) 8.50 to 13.00 (generic) | |||
| Alternative regimen† | Ceftriaxone (Rocephin) | 250 mg IM in a single dose | 13.50 (brand) | ||
| or | |||||
| Cefoxitin | 2 g IM | 21.50 (brand) | |||
| plus | |||||
| Probenecid | 1 g orally in a single dose given once concurrently with cefoxitin | 0.50 to 20.00 (generic) | |||
Epididymitis
Recommendations for treatment of epididymitis that is caused by sexually transmitted organisms remain the same as in previous guidelines. Ofloxacin (Floxin) is recom mended for treatment of epididymitis caused by enteric organisms or occurring in patients who are allergic to cephalosporins or tetracyclines (Table 3).
| Cause | Recommended regimen | Dosage | Cost* | ||
|---|---|---|---|---|---|
| Gonococcal or Chlamydial infection | Ceftriaxone (Rocephin) | 250 mg IM in a single dose | $ 13.50 (brand) | ||
| plus | |||||
| Doxycycline (Vibramycin) | 100 mg orally twice daily for 10 days | 79.50 (brand) 3.50 to 27.00 (generic) | |||
| Enteric organisms | Ofloxacin (Floxin) | 300 mg twice daily for 10 days | 89.00 (brand) | ||
Human Papillomavirus Infection
Human papillomavirus infection manifests as genital warts and is associated with cervical dysplasia. There are over 20 types of human papillomavirus, and not all types exhibit visible warts. Papanicolaou smears often identify associated cellular changes.
The goal of treatment is to eliminate visible genital warts. No evidence indicates that treatment affects the natural course of human papillomavirus infection or decreases its rate of sexual transmission. Two new treatments are available for patients' self-administration: podofilox (Condylox) and imiquimod (Aldara).4 Recommendations for provider administered therapies still exist and are outlined in Table 4. Several factors should be considered when choosing a mode of therapy, such as wart size, wart number, anatomic site of wart, patient preference, cost of therapy, convenience, adverse effects and provider experience. Even with the patient-applied therapies, it is recommended that the health care provider apply the initial treatment to demonstrate the proper application technique.
| Wart location | Recommended regimen | ||
|---|---|---|---|
| Agent | Dosage | Appropriate therapy | |
| External genital area | Podofilox (Condylox) | 0.5% solution or gel (patient-applied) | Twice daily for three days, wait four days, then repeat as necessary for four cycles |
| Imiquimod (Aldara) | 5% cream (patient-applied) | Daily at bedtime three times weekly for up to 16 weeks | |
| Cryotherapy | Physician-applied | Repeat every 1 to 2 weeks | |
| Podophyllum resin | 10 to 25% (physician-applied) | Weekly | |
| Trichloroacetic acid or bichloroacetic acid | 80 to 90% (physician-applied) | Weekly | |
| Surgical removal | |||
| Alternative treatments | |||
| Intralesional interferon | |||
| Laser surgery | |||
| Vaginal | Cryotherapy | With liquid nitrogen | Repeat every 1 to 2 weeks |
| Trichloroacetic acid or bichloroacetic acid | 80 to 90% | Weekly | |
| Podophyllum | 10 to 25% | Weekly | |
| Urethral meatus | Cryotherapy | With liquid nitrogen | Repeat every 1 to 2 weeks |
| Podophyllum | 10 to 25% | Weekly | |
| Anal area | Cryotherapy | With liquid nitrogen | Repeat every 1 to 2 weeks |
| Trichloroacetic acid or bichloroacetic acid | 80 to 90% | Weekly | |
| Surgical removal | |||
| Oral | Cryotherapy | With liquid nitrogen | Repeat every 1 to 2 weeks |
| Surgical removal | |||
Proctitis, Proctocolitis, Enteritis and Ectoparasitic Infections
Mucopurulent proctitis and proctocolitis may be empirically treated as STDs (Table 5) while definitive diagnostic studies are performed. Permethrin cream (Nix) is the preferred agent for treatment of pediculosis pubis and scabies. Lindane (Kwell) and sulfur topical therapies are recommended as alternative regimens. See Table 5 for detailed treatment recommendations.
| Condition | Recommended regimens | ||||
|---|---|---|---|---|---|
| Agent | Dosage | Cost* | |||
| Proctitis, proctocolitis and enteritis | Ceftriaxone (Rocephin) | 125 mg IM in a single dose | $ 14.00 (brand) | ||
| plus | |||||
| Doxycycline (Vibramycin) | 100 mg orally twice daily for 7 days | 55.00 (brand) 2.50 to 19.00 (generic) | |||
| Pediculosis pubis | Permethrin cream (Nix) | 1% cream: apply to affected area and wash off after 10 minutes | 9.00 (brand/2 oz) | ||
| Lindane (Kwell) | 1% shampoo: apply for 4 minutes, then wash (not recommended for use in pregnant or lactating women, or in children under 2 years of age) | 3.00 to 7.00 (generic/2 oz) | |||
| Pyrethrins with piperonyl butoxide | Apply for 10 minutes and wash† | ||||
| Scabies . | Permethrin cream | 1% cream: apply to body from the neck down and wash off after 8 to 14 hours; re-evaluate in one week | 9.00 (brand/2 oz) | ||
| Alternative regimens | |||||
| Lindane | 1% lotion or cream: apply to body from the neck down and wash off after 8 hours; re-evaluate in one week (not recommended for use in pregnant or lactating women, or in children under 2 years of age) | 6.00 to 14.00 (generic/2 oz) | |||
| Sulfur | 6% precipitated in ointment: apply to all areas nightly for 3 nights† | ||||
Additional information about evaluation, diagnosis and treatment of sexually transmitted diseases may be found in “Guidelines for the Treatment of Sexually Transmitted Diseases” published in 1998 by the CDC, along with specific information regarding special patient populations. Table 6 lists side effects of drug classes commonly used to treat STDs.
| Drug | Side effects |
|---|---|
| Cephalosporins | Pain at injection site, diarrhea, allergic reactions, Clostridium difficile colitis, hypoprothrombinemia, platelet dysfunction, eosinophilia, positive Coombs' test, serum sickness, cholelithiasis (associated with use of ceftriaxone [Rocephin]) and, rarely, hemolytic anemia, interstitial nephritis, hepatic dysfunction, convulsions (associated with renal failure), neutropenia, thrombocytopenia and confusion |
| Fluoroquinolones | Gastrointestinal intolerance, headache, insomnia, dizziness, allergic reactions, photosensitivity, elevated liver enzymes and, rarely, papilledema, nystagmus, C. difficile colitis, marrow suppression, anaphylaxis and central nervous system stimulation |
| Penicillins | Rash, serum sickness, positive Coombs' test and, rarely, neutropenia, thrombocytopenia, elevated liver function tests, increased blood urea nitrogen and creatinine levels, headache, confusion and seizures |
| Macrolide antibiotics | Diarrhea, nausea, abdominal pain, rash, cholestatic hepatitis and, rarely, C. difficile colitis and hemolytic anemia |
| Tetracyclines | Gastrointestinal intolerance, stained teeth (in children), hepatotoxicity, photosensitivity, pain with injection and, rarely, allergic reactions, visual disturbances, hemolytic anemia and C. difficile colitis |