Prevention and Treatment of Sexually Transmitted Diseases: An Update



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Am Fam Physician. 2007 Dec 15;76(12):1827-1832.

  Patient information: See related handout on sexually transmitted diseases, written by the author of this article.

The Centers for Disease Control and Prevention recently published revised guidelines for the prevention and treatment of sexually transmitted diseases. One new treatment strategy is the use of azithromycin as a primary, rather than alternative, medication for pregnant women with Chlamydia trachomatis infection. Quinolone-resistant Neisseria gonorrhoeae infection continues to increase in the United States; therefore, quinolones are no longer recommended for treatment of this infection. Expedited partner therapy gives physicians another option when addressing the need to treat partners of persons diagnosed with N. gonorrhoeae or C. trachomatis infection. Tinidazole is now available in the United States and can be used to manage trichomoniasis, including trichomoniasis resistant to metronidazole. Shorter courses of antiviral medication can be used for episodic therapy of recurrent genital herpes. Because of increasing resistance, close follow-up is required if azithromycin is used as an alternative treatment in the management of primary or secondary syphilis. Unexpected increases in the rates of lymphogranuloma venereum have occurred in the Netherlands, and physicians should remain vigilant for symptoms of this disease in the United States.

The Centers for Disease Control and Prevention (CDC) recently released updated guidelines for the prevention and treatment of sexually transmitted diseases (STDs).1 These guidelines were developed through a systematic review of evidence that has become available since the 2002 guidelines were issued, as well as through expert consultation.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References Comments

Azithromycin (Zithromax) is recommended as a first-line treatment for Chlamydia trachomatis infection during pregnancy.

A

46

Based on randomized controlled trials

Quinolones should not be used in the treatment of Neisseria gonorrhoeae infection.

C

9

Based on expert opinion

Provision of expedited partner treatment lessens the risk of reinfection for patients treated for N. gonorrhoeae or C. trachomatis infection.

B

1012

Based on limited randomized controlled trial evidence

Tinidazole (Tindamax) is an appropriate treatment option for metronidazole (Flagyl)-resistant trichomoniasis.

B

14, 1618

Based on limited studies


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1760 or http://www.aafp.org/afpsort.xml.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

View Table

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References Comments

Azithromycin (Zithromax) is recommended as a first-line treatment for Chlamydia trachomatis infection during pregnancy.

A

46

Based on randomized controlled trials

Quinolones should not be used in the treatment of Neisseria gonorrhoeae infection.

C

9

Based on expert opinion

Provision of expedited partner treatment lessens the risk of reinfection for patients treated for N. gonorrhoeae or C. trachomatis infection.

B

1012

Based on limited randomized controlled trial evidence

Tinidazole (Tindamax) is an appropriate treatment option for metronidazole (Flagyl)-resistant trichomoniasis.

B

14, 1618

Based on limited studies


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1760 or http://www.aafp.org/afpsort.xml.

Health Education

Education and counseling are the main strategies in the prevention and control of STDs. Evaluation includes addressing key areas of sexual health referred to as the Five P's: Partners, Prevention of pregnancy, Protection from STDs, Practices, and Past history of STDs. Addressing this information with patients creates an opportunity for physicians to provide counseling and education while taking into account each patient's individual risk factors and goals. The use of motivational interviewing focuses on the specific behaviors of the patient and places a greater emphasis on moving toward individually defined, achievable, risk-reduction goals. Table 11 lists symptoms and diagnoses of selected STDs.

Table 1

Symptoms and Diagnoses of Sexually Transmitted Diseases

Disease Symptoms Laboratory diagnosis

Chlamydia

Asymptomatic, or dysuria, discharge (penile or vaginal), pain with sex, abdominal or testicular pain, breakthrough bleeding

Nucleic acid amplification test of urine, endocervical sample, or urethral sample

Gonorrhea

Asymptomatic, or dysuria, discharge (penile or vaginal), pain with sex, abdominal or testicular pain, breakthrough bleeding

Nucleic acid amplification test of urine, endocervical sample, or urethral sample; gonococcal culture for rectal or pharyngeal specimens

Trichomoniasis

Asymptomatic, or vaginal discharge with odor or itching

Saline wet mount; rapid antigen testing; Trichomonas culture

Genital herpes simplex virus

Asymptomatic, or recurrent, painful vesicular or ulcerative lesions in the genital area

Viral culture; type-specific serologic test

Syphilis

Asymptomatic, or painless ulcer (chancre), systemic rash including palms and soles, cardiovascular and neurologic involvement

Serologic tests (nontreponemal and treponemal); darkfield examination

Lymphogranuloma venereum

Inguinal adenopathy, self-limited papule or ulcer, proctocolitis

Procedures not readily available to differentiate lymphogranuloma venereum from nonlymphogranuloma venereum Chlamydia trachomatis


Information from reference 1.

Table 1   Symptoms and Diagnoses of Sexually Transmitted Diseases

View Table

Table 1

Symptoms and Diagnoses of Sexually Transmitted Diseases

Disease Symptoms Laboratory diagnosis

Chlamydia

Asymptomatic, or dysuria, discharge (penile or vaginal), pain with sex, abdominal or testicular pain, breakthrough bleeding

Nucleic acid amplification test of urine, endocervical sample, or urethral sample

Gonorrhea

Asymptomatic, or dysuria, discharge (penile or vaginal), pain with sex, abdominal or testicular pain, breakthrough bleeding

Nucleic acid amplification test of urine, endocervical sample, or urethral sample; gonococcal culture for rectal or pharyngeal specimens

Trichomoniasis

Asymptomatic, or vaginal discharge with odor or itching

Saline wet mount; rapid antigen testing; Trichomonas culture

Genital herpes simplex virus

Asymptomatic, or recurrent, painful vesicular or ulcerative lesions in the genital area

Viral culture; type-specific serologic test

Syphilis

Asymptomatic, or painless ulcer (chancre), systemic rash including palms and soles, cardiovascular and neurologic involvement

Serologic tests (nontreponemal and treponemal); darkfield examination

Lymphogranuloma venereum

Inguinal adenopathy, self-limited papule or ulcer, proctocolitis

Procedures not readily available to differentiate lymphogranuloma venereum from nonlymphogranuloma venereum Chlamydia trachomatis


Information from reference 1.

A visit with a physician for the screening, diagnosis, or treatment of STDs also provides an opportunity for the physician to educate the patient about human immunodeficiency virus (HIV). Patients may not be aware that the presence of an STD may facilitate the transmission of HIV if they are exposed to the virus. Because some patients who are HIV positive are unaware of their diagnosis, the CDC now encourages HIV screening for patients in all health care settings. Although patients may choose not to be tested, written consent for testing is no longer recommended (unless mandated by the state).2

Chlamydia Trachomatis

Chlamydia trachomatis is the most common reportable infectious disease in the United States, with almost 1 million cases reported in 2004.3 Few recommendations have changed for the treatment of persons infected with C. trachomatis; however, azithromycin (Zithromax) is now recommended as a primary, rather than alternative, treatment in pregnant women (Table 2).1 This change occurred because of recent evidence supporting azithromycin as safe and effective during pregnancy.46

Table 2

Treatment of Chlamydia trachomatis Infection

Regimen Agent Dosage

Nonpregnant women

Recommended

Azithromycin (Zithromax)

1 g orally once

Doxycycline (Vibramycin)

100 mg orally twice daily for seven days

Alternative

Erythromycin base

500 mg orally four times daily for seven days

Erythromycin ethylsuccinate

800 mg orally four times daily for seven days

Ofloxacin (Floxin)*

300 mg orally twice daily for seven days

Levofloxacin (Levaquin)

500 mg orally daily for seven days

Pregnant women

Recommended

Azithromycin

1 g orally once

Amoxicillin

500 mg three times daily for seven days

Alternative

Erythromycin base

500 mg four times daily for seven days

or

250 mg four times daily for 14 days†

Erythromycin ethylsuccinate

800 mg four times daily for seven days

or

400 mg four times daily for 14 days†


*— Brand no longer available in the United States.

†— Lower-dose erythromycin regimens may be considered if there is gastrointestinal intolerance to higher dosages.

Information from reference 1.

Table 2   Treatment of Chlamydia trachomatis Infection

View Table

Table 2

Treatment of Chlamydia trachomatis Infection

Regimen Agent Dosage

Nonpregnant women

Recommended

Azithromycin (Zithromax)

1 g orally once

Doxycycline (Vibramycin)

100 mg orally twice daily for seven days

Alternative

Erythromycin base

500 mg orally four times daily for seven days

Erythromycin ethylsuccinate

800 mg orally four times daily for seven days

Ofloxacin (Floxin)*

300 mg orally twice daily for seven days

Levofloxacin (Levaquin)

500 mg orally daily for seven days

Pregnant women

Recommended

Azithromycin

1 g orally once

Amoxicillin

500 mg three times daily for seven days

Alternative

Erythromycin base

500 mg four times daily for seven days

or

250 mg four times daily for 14 days†

Erythromycin ethylsuccinate

800 mg four times daily for seven days

or

400 mg four times daily for 14 days†


*— Brand no longer available in the United States.

†— Lower-dose erythromycin regimens may be considered if there is gastrointestinal intolerance to higher dosages.

Information from reference 1.

Neisseria Gonorrhoeae

Since the publication of the 2002 STD treatment guidelines, the rate of quinolone-resistant Neisseria gonorrhoeae has continued to increase throughout the United States. As resistance increases, recommendations continue to change. Previous recommendations focused on the high levels of resistance in areas of Asia and the Pacific, California, Hawaii, and in some specific populations in the United States (e.g., men who have sex with men). In 2004, 6.8 percent of isolates collected by the CDC's Gonococcal Isolate Surveillance Project were resistant to ciprofloxacin (Cipro); when samples from California and Hawaii were excluded, 3.6 percent of isolates were resistant.7

Quinolone-resistant N. gonorrhoeae is more common in men who have sex with men than in men who have sex exclusively with women (23.8 versus 2.9 percent, respectively)7; however, the rate of quinolone-resistant N. gonorrhoeae continues to increase among heterosexual persons. In heterosexual men, the prevalence rose from 0.9 percent in 2002 to 3.8 percent in 2005,8 and preliminary data from the first six months of 2006 indicate an increase to 6.7 percent.9  Current guidelines reflect these changes (Table 31) by no longer recommending quinolones as treatment for N. gonorrhoeae infection.9

Table 3

Treatment of Uncomplicated Neisseria gonorrhoeae Infection

Regimen Agent Dosage

Cervical, urethral, or rectal infection

Recommended

Ceftriaxone (Rocephin)

125 mg IM once

Cefixime (Suprax)

400 mg orally once

Alternative

Single-dose cephalosporin regimens*

Pharyngeal infection

Recommended

Ceftriaxone

125 mg IM once


note: Quinolones should not be used to treat Neisseria gonorrhoeae infection. All therapies should also include the treatment of Chlamydia trachomatis infection if it has not been ruled out.

IM = intramuscularly.

*— See original guidelines for specific dosages.

Information from reference 1.

Table 3   Treatment of Uncomplicated Neisseria gonorrhoeae Infection

View Table

Table 3

Treatment of Uncomplicated Neisseria gonorrhoeae Infection

Regimen Agent Dosage

Cervical, urethral, or rectal infection

Recommended

Ceftriaxone (Rocephin)

125 mg IM once

Cefixime (Suprax)

400 mg orally once

Alternative

Single-dose cephalosporin regimens*

Pharyngeal infection

Recommended

Ceftriaxone

125 mg IM once


note: Quinolones should not be used to treat Neisseria gonorrhoeae infection. All therapies should also include the treatment of Chlamydia trachomatis infection if it has not been ruled out.

IM = intramuscularly.

*— See original guidelines for specific dosages.

Information from reference 1.

Expedited Partner Treatment

It is standard practice to recommend that sex partners of patients diagnosed with an STD be treated to decrease the risk of reinfection and to decrease the incidence and prevalence of STDs among social networks. The primary goal is for the patient's sex partners to be seen by a physician for testing, treatment, and education. However, there may be clinical situations in which this cannot be accomplished (e.g., because of patient, partner, or resource limitations). In these circumstances, the CDC recommends that physicians consider using expedited partner treatment.

Expedited partner treatment is the practice of treating sex partners of persons diagnosed with an STD without medical evaluation or prevention counseling; this is usually done by providing the patient with appropriate treatment to give to his or her partner. Three randomized controlled trials sponsored by the CDC evaluated the behavioral and clinical outcomes of expedited partner treatment compared with traditional treatment programs through patient or physician referral. In summary, the evidence supports expedited partner treatment as an option in patients with N. gonorrhoeae or C. trachomatis infection1012; however, it is important for physicians to be aware of their state's legal provision for this practice.

Trichomoniasis

Since publication of the 2002 STD treatment guidelines, options for the diagnosis and treatment of trichomoniasis have continued to improve. Tinidazole (Tindamax), a nitroimidazole that is similar to metronidazole (Flagyl), has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of trichomoniasis. A review of randomized controlled trials suggests that tinidazole is equivalent or superior to metronidazole, with the recommended metronidazole regimen resulting in cure rates of 90 to 95 percent and the recommended tinidazole regimen resulting in cure rates of 86 to 100 percent (Table 41).1,13 Additionally, it is estimated that approximately 2.5 to 5 percent of Trichomonas vaginalis isolates now show some level of resistance to metronidazole.1,14 Tinidazole has a higher serum half-life and better penetration into the genitourinary tissues,15,16 which suggests that it is a potential treatment for metronidazoleresistant trichomoniasis.14,17,18

Table 4

Treatment of Trichomoniasis

Regimen Agent Dosage

Recommended

Metronidazole (Flagyl)*

2 g orally once

Tinidazole (Tindamax)*†

2 g orally once

Alternative

Metronidazole*

500 mg orally twice daily for seven days


*— Patients should be advised to avoid consuming alcohol during treatment with metronidazole or tinidazole. Abstinence from alcohol should continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.

†— Tinidazole is U.S. Food and Drug Administration pregnancy category C; its safety during pregnancy has not been well evaluated.

Information from reference 1.

Table 4   Treatment of Trichomoniasis

View Table

Table 4

Treatment of Trichomoniasis

Regimen Agent Dosage

Recommended

Metronidazole (Flagyl)*

2 g orally once

Tinidazole (Tindamax)*†

2 g orally once

Alternative

Metronidazole*

500 mg orally twice daily for seven days


*— Patients should be advised to avoid consuming alcohol during treatment with metronidazole or tinidazole. Abstinence from alcohol should continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.

†— Tinidazole is U.S. Food and Drug Administration pregnancy category C; its safety during pregnancy has not been well evaluated.

Information from reference 1.

Diagnostic options for trichomoniasis have also expanded. Although the most common diagnostic method for trichomoniasis involves microscopy of vaginal secretions, the sensitivity of this method is only 60 to 70 percent. Additional FDA-approved, point-of-care tests include the Osom Trichomonas Rapid Test, which uses immunochromatographic capillary flow dipstick technology, and the BD Affirm VPIII Microbial Identification Test, which is a nucleic acid probe test. Both have a sensitivity of more than 83 percent and specificity of more than 97 percent; however, false-positive results are a concern in areas of low disease prevalence.1

Genital Herpes Simplex Virus

Most persons infected with genital herpes simplex virus (HSV) do not show clinical signs of disease. However, antiviral treatments for persons with clinical symptoms provide some symptomatic relief, as well as a lower viral burden and potential for transmission. Additional alternatives for episodic treatment of recurrent genital HSV require a shorter duration of treatment (one or two days of treatment versus five days of treatment) (Table 51). Suppressive therapy can reduce genital HSV recurrences by 70 to 80 percent in patients with at least six recurrences per year1; however, in the revised guidelines, there is greater emphasis on the use of suppressive therapy to reduce disease transmission. One study of daily treatment with 500 mg of valacyclovir (Valtrex) decreased the rate of viral transmission in heterosexual partners.19 Patients wi

Table 5

Treatment of Genital Herpes Simplex Virus

Type Agent Dosage

First clinical episode

Acyclovir (Zovirax)

400 mg orally three times daily for seven to 10 days

or

200 mg orally five times daily for seven to 10 days

Famciclovir (Famvir)

250 mg orally three times daily for seven to 10 days

Valacyclovir (Valtrex)

1 g orally twice daily for seven to 10 days

Episodic therapy for recurrent genital herpes

Acyclovir

400 mg orally three times daily for five days

or

800 mg orally twice daily for five days

or

800 mg orally three times daily for two days

Famciclovir

125 mg orally twice daily for five days

or

1 g orally twice daily for one day

Valacyclovir

500 mg orally twice daily for three days

or

1 g orally once daily for five days

Suppressive therapy for recurrent genital herpes

Acyclovir

400 mg orally twice daily

Famciclovir

250 mg orally twice daily

Valacyclovir

500 mg orally once daily*

or

1 g orally once daily


*— This dosage may be less effective than other valacyclovir or acyclovir dosing regimens in patients with frequent recurrences (more than 10 per year).

Information from reference 1.

Table 5   Treatment of Genital Herpes Simplex Virus

View Table

Table 5

Treatment of Genital Herpes Simplex Virus

Type Agent Dosage

First clinical episode

Acyclovir (Zovirax)

400 mg orally three times daily for seven to 10 days

or

200 mg orally five times daily for seven to 10 days

Famciclovir (Famvir)

250 mg orally three times daily for seven to 10 days

Valacyclovir (Valtrex)

1 g orally twice daily for seven to 10 days

Episodic therapy for recurrent genital herpes

Acyclovir

400 mg orally three times daily for five days

or

800 mg orally twice daily for five days

or

800 mg orally three times daily for two days

Famciclovir

125 mg orally twice daily for five days

or

1 g orally twice daily for one day

Valacyclovir

500 mg orally twice daily for three days

or

1 g orally once daily for five days

Suppressive therapy for recurrent genital herpes

Acyclovir

400 mg orally twice daily

Famciclovir

250 mg orally twice daily

Valacyclovir

500 mg orally once daily*

or

1 g orally once daily


*— This dosage may be less effective than other valacyclovir or acyclovir dosing regimens in patients with frequent recurrences (more than 10 per year).

Information from reference 1.

th HSV are encouraged to consider suppressive treatment as part of the overall strategy in reducing transmission, regardless of the number of recurrences per year.

Syphilis

Rates of primary and secondary syphilis increased for the fifth consecutive year in 2005 (8,176 cases reported) to their highest levels since 1997.1  Penicillin G benzathine continues to be the primary antibiotic treatment recommended (Table 61). The CDC guidelines also include a discussion of treatment with doxycycline (Vibramycin), tetracycline, and ceftriaxone (Rocephin) in patients who are allergic to penicillin. The use of azithromycin is also discussed. Although earlier studies suggested that azithromycin given as a single 2-g dose might be effective,20,21 several cases of treatment failure, as well as reported cases of isolate resistance have been noted, suggesting that close follow-up is needed if azithromycin is used.22

Table 6

Treatment of Syphilis

Type Agent Dosage

Primary, secondary, and early latent

Penicillin G benzathine

2.4 million units IM once

Late latent, latent of unknown duration, and tertiary

Penicillin G benzathine

2.4 million units IM weekly for three weeks


IM = intramuscularly.

Information from reference 1.

Table 6   Treatment of Syphilis

View Table

Table 6

Treatment of Syphilis

Type Agent Dosage

Primary, secondary, and early latent

Penicillin G benzathine

2.4 million units IM once

Late latent, latent of unknown duration, and tertiary

Penicillin G benzathine

2.4 million units IM weekly for three weeks


IM = intramuscularly.

Information from reference 1.

Lymphogranuloma Venereum

Lymphogranuloma venereum (LGV) is caused by C. trachomatis serovars L1, L2, or L3. Although still relatively uncommon in the United States and in western European countries, a significant increase in cases was noted in the Netherlands in 2004 among men who have sex with men.23 The CDC addresses this concern by adding information to the guidelines about the clinical presentation of LGV. Presentation can include a nontender papule that may ulcerate after three to 30 days at the site of inoculation, and signs of proctocolitis (e.g., mucoid or hemorrhagic discharge, anal pain, constipation, fever or tenesmus) in persons with a history of rectal exposure to the bacteria. These symptoms in at-risk patients should prompt further diagnostic and treatment consideration. Diagnosis is primarily clinical because culture and nucleic acid amplification testing are not specific for LGV caused by C. trachomatis. If a patient has symptoms and specific typing is desired, contact with state or local health departments is often required. The CDC continues to recommend a three-week course of doxycycline when symptoms or testing suggest LGV, although erythromycin is an alternative (Table 71).

Table 7

Treatment of Lymphogranuloma Venereum

Regimen Agent Dosage

Recommended

Doxycycline (Vibramycin)

100 mg orally twice daily for 21 days

Alternative*

Erythromycin base

500 mg orally four times daily for 21 days


*— Some specialists believe that azithromycin (Zithromax) 1 g orally weekly for three weeks is an effective treatment option, but data are lacking.

Information from reference 1.

Table 7   Treatment of Lymphogranuloma Venereum

View Table

Table 7

Treatment of Lymphogranuloma Venereum

Regimen Agent Dosage

Recommended

Doxycycline (Vibramycin)

100 mg orally twice daily for 21 days

Alternative*

Erythromycin base

500 mg orally four times daily for 21 days


*— Some specialists believe that azithromycin (Zithromax) 1 g orally weekly for three weeks is an effective treatment option, but data are lacking.

Information from reference 1.

The Author

MICHELE VAN VRANKEN, MD, is a family physician at Teen Age Medical Service, Children's Hospital and Clinics of Minnesota in Minneapolis. She also is the medical director of the Annex Teen Clinic in Robbinsdale, Minn., and the West Suburban Teen Clinic in Excelsior, Minn. Dr. Van Vranken received her medical degree from Rush Medical College in Chicago, Ill., and completed a family medicine residency and community and adolescent fellowship at the Ramsey Family and Community Medicine Residency Program, Minneapolis. She also has a certificate of added qualification in adolescent medicine.

Address correspondence to Michele Van Vranken, MD, Teen Age Medical Service, Children's Hospitals and Clinics of Minnesota, 2425 Chicago Ave. S., Minneapolis, MN 55404 (e-mail: michele.vanvranken@childrensmn.org). Reprints are not available from the author.

Author disclosure: Nothing to disclose.

REFERENCES

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8. U.S. Dept. of Health and Human Services. Sexually transmitted disease surveillance 2005 supplement. Gonococcal Isolate Surveillance Project (GISP) annual report 2005. Atlanta, Ga.: Centers for Disease Control and Prevention, National Center for HIV, STD, and TB Prevention, Division of STD Prevention, 2007. http://www.cdc.gov/std/GISP2005/GISPSurvSupp2005short.pdf. Accessed July 17, 2007.

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14. Sobel JD, Nyirjesy P, Brown W. Tinidazole therapy for metronidazole-resistant vaginal trichomoniasis. Clin Infect Dis. 2001;33(8):1341–1346.

15. Schmid G, Narcisi E, Mosure D, Secor WE, Higgins J, Moreno H. Prevalence of metronidazole-resistant Trichomonas vaginalis in a gynecology clinic. J Reprod Med. 2001;46(5):545–549.

16. Sawyer PR, Brogden RN, Pinder RM, Speight TM, Avery GS. Tinidazole: a review of its antiprotozoal activity and therapeutic efficacy. Drugs. 1976;11(6):423–440.

17. Hager WD. Treatment of metronidazole-resistant Trichomonas vaginalis with tinidazole: case reports of three patients. Sex Transm Dis. 2004;31(6):343–345.

18. Hamed KA, Studemeister AE. Successful response of metronidazole-resistant trichomonal vaginitis to tinidazole. A case report. Sex Transm Dis. 1992;19(16):339–340.

19. Corey L, Wald A, Patel R, et al. Valacyclovir HSV Transmission Study Group. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med. 2004;350(1):11–20.

20. Hook EW, Martin DH, Stephens J, Smith BS, Smith K. A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis. 2002;29(8):486–490.

21. Riedner G, Rusizoka M, Todd J, et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med. 2005;353(12):1236–1244.

22. Lukehart SA, Godornes C, Molini BJ, et al. Macrolide resistance in Treponema palladium in the United States and Ireland. N Engl J Med. 2004;351(2):154–158.

23. Centers for Disease Control and Prevention. Lymphogranuloma venereum among men who have sex with men–Netherlands, 2003–2004. MMWR Morb Mortal Wkly Rep. 2004;53(42):985–988.



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