Abstract & Commentary
STD Management What's New?
By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.
Synopsis: The 2006 Centers for Disease Control and Prevention (CDC) sexually transmitted disease (STD) guidelines have been updated.
Source: Workowski KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010;59(RR-12):1-110.
The latest iteration of the CDC guidelines on the treatment of STDs was finally published at the end of 2010 after finishing a process that began in 2008. The more than 100 pages of text are too voluminous to fully summarize here (and would resist useful summarization at any rate). I will instead focus on some of the changes from the 2006 document. Two areas of change in the guidelines, genital warts and sexual assault, will not be discussed here.
An extensive section of the current document deals in detail with approaches to the prevention of STDs, including: education and counseling; identification of both symptomatically and asymptomatically infected individuals; effective diagnosis, treatment, and counseling of infected individuals and their partners; and vaccination of at-risk individuals. Education and counseling begins with evaluating risk via questions assessing "The Five P's": Partners, Prevention of pregnancy, Protection from STDs, Practices (i.e., sexual practices), and Past history of STDs as well as questions regarding risk for HIV infection and viral hepatitis such as a history of injection drug use. Prevention methods discussed include abstinence and reduction in the number of partners, pre-exposure vaccination (HPV, HBV, HAV), male and female condoms, cervical diaphragms, topical microbicides and spermicides, non-barrier contraception including surgical sterilization and hysterectomy, emergency contraception, male circumcision, post-exposure prophylaxis, pre-exposure prophylaxis, and retesting to detect repeat infections.
Preventive, diagnostic, and therapeutic management of special populations is discussed at length. These groups include pregnant women, adolescents, children, men who have sex with men (MSM), women who have sex with women, and individuals confined to correctional facilities.
Women with cervicitis should be evaluated for evidence of pelvic inflammatory disease and tested for the presence of infection with Chlamydia trachomatis and Neisseria gonorrheae using a nucleic acid amplification test (NAAT), as well as for trichomoniasis and bacterial vaginosis. If microscopy fails to detect Trichomonas vaginalis, further testing, such as culture, should be performed. While infection with Mycoplasma genitalium is possible, commercially available tests for this pathogen are not available.
Symptomatic women with bacterial vaginosis should be treated with one of three regimens: metronidazole 500 mg orally twice daily for 7 days; metronidazole gel 0.75% intravaginally once daily for 5 days; or clindamycin cream 2% intravaginally at bedtime for 7 days. Alternative regimens utilize orally administered tinidazole or clindamycin or intravaginal clindamycin ovules. Options for treatment of women with multiple recurrences include the use of metronidazole gel for 4-6 months or oral metronidazole followed by intravaginal boric acid and long-term suppression with metronidazole gel.
The treatment of chlamydia infections during pregnancy has been challenging since doxycycline and fluoroquinolones are contraindicated. While amoxicillin has previously been recommended for the treatment of C. trachomatis infection in pregnant women, clinical experience suggests that azithromycin may be safe and effective when administered as a single 1 g oral dose. Repeat testing by NAAT should be performed 3 weeks after completion of therapy and, in those infected in the first trimester, again 3 months later. Those with risk of reinfection should be retested during their third trimester.
Doxycyline 100 mg twice daily for 21 days is recommended for the treatment of LGV infection, with erythromycin as an alternative. In addition, "Although clinical data are lacking, azithromycin 1 g orally once weekly for 3 weeks is probably effective based on its chlamydial antimicrobial activity. Fluoroquinolone-based treatments might also be effective, but extended treatment intervals are likely required." In MSM with anogenital chlamydia infection and either proctitis (as determined by proctoscopic examination and the presence of > 10 white blood cells upon high-power field examination of an anorectal smear specimen) or with HIV coinfection, treatment for LGV with 3 weeks of doxycycline can be considered.
M. genitalium accounts for 15%-25% of cases of non-gonococcal urethritis (NGU) in the United States. While both doxycycline and azithromycin are effective for the treatment of chlamydial urethritis, azithromycin (a single 1 g dose) is more effective than the tetracycline derivative for M. genitalium infection. Moxifloxacin (400 mg daily for 7 days) also is effective against this infection and is among the acceptable alternative therapies in individuals with recurrent NGU.
Antibiotic-resistant Neisseria gonorrheae
The emergence of fluoroquinolone resistance in N. gonorrheae is now widespread in the United States and, as a consequence, this class of drugs has not been recommended for the treatment of gonococcal infections since 2007. The only class of acceptable agents at this time are cephalosporins. Resistance to cephalosporins remains rare, as is failure of treatment, especially with ceftriaxone. Approximately 50 cases of failure of oral cephalosporins (cefixime is recommended for oral therapy in the United States) have been reported, with most having occurred in Asia. One possible case of failure of cefixime therapy in Hawaii has been reported. To ensure appropriate antibiotic therapy, clinicians should ask patients with gonorrhea about recent travel to and sexual activity in countries where resistance and treatment failure have been reported.
Indications for Cerebrospinal Fluid (CSF) Examination for Neurosyphilis
Patients with apparent latent syphilis who demonstrate any of the following should have a prompt CSF examination: compatible neurologic or ophthalmologic signs or symptoms, findings suggestive of tertiary syphilis, or serological treatment failure. Quantitative non-treponemal serologic tests should be repeated at 6, 12, and 24 months. "A CSF examination should be performed if 1) titers increase fourfold, 2) an initially high titer (≥ 1:32) fails to decline at least fourfold (i.e., two dilutions) within 12-24 months of therapy, or 3) signs or symptoms attributable to syphilis develop. In such circumstances, even if the CSF examination is negative, retreatment for latent syphilis should be initiated. In rare instances, despite a negative CSF examination and a repeated course of therapy, serologic titers might fail to decline. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear."
HIV infection may be associated with an increased risk of central nervous system involvement by Treponema pallidum. In coinfected patients, clinical and CSF abnormalities consistent with neurosyphilis are associated with a CD4 count ≤ 350 cells/mL and/or an RPR titer ≥ 1:32. Despite this association, in the absence of neurologic symptoms or signs, CSF examination in this setting has not been associated with improved clinical outcomes. However, all HIV-infected persons with evidence of syphilis and who have neurologic symptoms and/or signs should undergo immediate CSF examination. In addition, if there is evidence of failure of treatment of non-CNS or CNS syphilis, repeat CSF examination, as outlined above, is warranted.
Azithromycin-resistant Treponema pallidum
Azithromycin as a single 2 g oral dose has been effective in the treatment of early syphilis, but chromosomal mutations in T. pallidum associated with treatment failure have now been identified in the United States. As a consequence, azithromycin should be used with caution and only when treatment with penicillin or doxycycline is not feasible. It should not be used in MSM or pregnant women.
Sexual Transmission of Hepatitis C Virus
Recent data indicate that sexual transmission of HCV, especially among HIV-infected persons, is more frequent than previously believed. One in 10 individuals with acute HCV infection report contact with a known HCV-infected sex partner as their only risk for infection. Studies of HCV transmission in heterosexual or homosexual couples have yielded somewhat conflicting results, but generally have identified low but increased rates of HCV infection in partners of persons with HCV infection compared with those whose partners are not HCV-infected. The risk appears to rise in parallel with increasing number of sex partners among both heterosexuals and MSM and this risk is further increased if partners are HIV-infected. Transmission clusters have been identified in HIV-infected MSM, often associated with serosorting (i.e., HIV-infected men having sex with one another), group sex, and the use of cocaine and other non-intravenous drugs during sex.