Disclosure Statement. STDs. STDs. Case #1. New in the 2010 Guidelines. Sexually Transmitted Diseases Treatment Guidelines

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1 Sexually Transmitted Diseases Treatment Guidelines Best Practice : CDC 2010 STD Guidelines L. Chesney Thompson, MD Associate Professor and Vice Chair, OB/Gyn Ronald S. Gibbs, MD Professor, OB/Gyn Associate Dean, CME & Professional Development Disclosure Statement There is no disclosure relevant to this presentation, however I am a consultant to Novartis Vaccines and Diagnostics. STDs Learning Objectives At the end of this lecture, the learner should be able to: 1. Implement the CDC recommendations for diagnosis of common STDs. 2. Apply CDC recommended treatments herpes, cervicitis, vaginitis, PID, HIV, and genital warts. STDs 3. Recognize candidates for suppressive therapy for recurrent genital herpes. 4. Screen appropriate candidates for Chlamydia trachomatis infection. 5. Implement a cost-effective approach to women with vulvovaginal itching, discharge, and odor in an office setting. New in the 2010 Guidelines Expanded diagnosis for cervicitis and trichomoniasis. New treatment for BV and genital warts Efficacy of azithromycin for chlamydia in pregnancy. Role of M. genitalium in urethritis/ cervicitis. Increasing antimicrobial resistance of N. gonorrhoeae. STD prevention approaches. Case #1 A 22 yo sexually active woman complains of cyclic vulvar burning and itching, with episodes lasting 3 days every 1-3 months. She has never seen ulcers or blisters. She is asymptomatic and her exam is normal. 1

2 Case #1 Continued Of the following, what is the best next step in management? A. Ask her to make an urgent appointment when she has her next episode. B. Send yeast and bacterial cultures now. C. Send an HSV PCR now. D. Send type specific antibodies for HSV1 and 2 now. Case #2 After returning from spring break, a 20 yo female reports that a male partner just found out he has gonorrhea. Case #2 Continued Which of the following is the best treatment? A. Azithromycin 2gm po B. Ofloxacin 400mg po + azithro 1 gm po C. Ceftriaxone 250 mg IM+azithro 1 gm po D. Spectinomycin 2gm IM+azithro 1 gm po How Common is HSV Infection? Genital herpes a recurrent, sometimes life-long infection. HSV-1 and HSV-2 types. An increasing % of genital HSV due to HSV -1. At least 50 million persons in the U.S. have genital herpes, but most people infected with HSV-2 have not been diagnosed with genital herpes., MMWR 2010;59:1-110 How Common is Genital HSV Infection? Overall, 4% of population has been diagnosed with genital herpes. However, 11-23% have type specific HSV-2 antibodies (G-2 protein). Xu et al JAMA 2006; 296:

3 Genital Herpes Syndromes Primary infection Isolation of HSV-1 or HSV-2 in absence of HSV antibodies in serum. Recurrent infection Reactivation of latent virus, isolation of HSV-1 or HSV-2 in presence of homologous antibodies in serum. Non-primary first episode Isolation of HSV-2 in the presence of HSV-1 antibodies in serum. Brown ZA, et al. Obstet Gynecol Diagnosis of HSV Infection Clinical diagnosis is insensitive and nonspecific. Up to 50% of first episodes are caused by HSV-1*, but most recurrences are by HSV-2. Among college-age population, up to 80% are due to HSV-1.* Virologic and type-specific serologic tests should be available.. MMWR 2010 *Brown ZA. O&G 2005 Laboratory Diagnosis of Herpes Virus Culture preferred in persons with ulcers, but sensitivity declines rapidly; isolates should be typed. Polymerase chain reaction (PCR) more sensitive and increasingly used in many settings. How to Use HSV Type Specific Antibodies Recurrent genital symptoms or atypical symptoms with negative culture. A clinical diagnosis of genital herpes without laboratory confirmation. A partner with genital herpes. Screening for HSV-1 and HSV-2 in general population is not indicated. Genital Herpes Infection: Treatment Oral acyclovir, valacyclovir, famciclovir. Topical- minimal benefit, not recommended. First Clinical Episode of Genital Herpes Acyclovir 400 mg PO tid x 7-10 d Acyclovir 200 mg PO 5x/d x 7-10 d Famciclovir 250 mg PO tid x 7-10 d Valacyclovir 1 g PO bid x 7-10 d Note: Treatment may be extended if healing is incomplete after 10 days of therapy. 3

4 Episodic Therapy for Recurrent Genital Herpes Initiate within 1 day of lesion onset or during prodrome. Provide supply of meds or Rx to self-initiate treatment. Episodic Therapy for Recurrent Genital Herpes Acyclovir 400 mg PO tid x 5 d Acyclovir 800 mg PO bid x 5 d Acyclovir 800 mg PO tid x 2 d Famciclovir 125 mg PO bid x 5 d Famciclovir 1000 mg PO bid x 1 d Episodic Therapy for Recurrent Genital Herpes, Cont d Famciclovir 500 mg, followed by 250 mg bid x 2 days Acyclovir 500 mg PO bid x 3 d Valacyclovir 1.0 g PO qd x 5 d Suppressive Therapy for Recurrent Genital Herpes Acyclovir 400 mg PO bid Famciclovir 250 mg PO bid Valacyclovir 500 mg PO qd* Valacyclovir 1.0 gram PO qd *May be less effective in those with 10 episodes/year HSV Suppressive Therapy Reduces frequency of genital herpes by 70-80% in pts with frequent recurrences. Generally recommended for 6 outbreaks/year, also effective when less frequent. Consider re-evaluating or reducing dose after 1 st year. Once Daily Valacyclovir (VAL) to Reduce Risk of Transmission of Genital Herpes 1484 immunocompetent, monogamous couples, discordant for HSV-2. Partner with HSV-2 randomized to either 500 mg VAL qd or placebo for 8 months. All counseled re: safer sex and offered condoms. Corey, L. et al., NEJM 2004; 350:

5 Daily VAL to Reduce HSV- 2 Transmission Daily VAL to Reduce HSV-2 Transmission, Cont d Symptomatic Acquisition Overall Acquisition VAL PLAC P (N=743) (N=741) N% 4 (0.5) 16 (2.2) (1.9) 27 (3.6) 0.04 Acquisition HSV-1/2 HSV DNA detected (dys) VAL PLAC P (N=743) (N=741) N(%) 4 (1.9) 31 (4.2) 0.01 (2.9) (10.8) <0.001 Corey, L. et al., NEJM 2004; 350:11-19 Corey, L. et al., NEJM 2004; 350:11-19 Prevention Against HSV-2 Infection in Susceptible Women 528 monogamous couples discordant for HSV-2 infection. Acquisition in women about 1/1000 acts of intercourse (9.7% of women, 1.9% of men). Prevention Against HSV-2 Infection in Susceptible Women Condom use >25% of acts protective (Adj HR , 95 CI ) for women, but not for men. Changes in behavior (decreased acts when partner has lesion) reduced HSV=2 infection over time. Wald A, et al. JAMA 2001; 285: Wald A, et al. JAMA 2001; 285: Chlamydial Cervicitis Chlamydia trachomatis: Screening Annual screening of all sexually active women 25 years and older women with risk factors (e.g., new sex partner or multiple partners). Evidence insufficient to recommend routine screening in sexually active young men, but should be considered in settings of high prevalence (e.g. adolescent clinics, correctional facilities, STD clinics). 5

6 2010 CDC Regimens for C. trachomatis, Non pregnancy* Recommended: Azithromycin, 1 gm (single dose) Doxycycline, 100 mg bid x 7 d Alternatives: Erythromycin base, 500 mg qid x 7 d Erythromycin ethylsuccinate, 800 mg qid x 7d Ofloxacin, 300 mg bid x 7 d Levofloxacin, 500 mg x 7 d 2010 CDC Regimens for C. trachomatis in Pregnancy* Recommended: Azithromycin 1gm orally Amoxicillin, 500mg tid x 7d Alternatives: Erythromycin base, 500mg qid x 7d Erythromycin base, 250mg qid x 14d Erythromycin ethylsuccinate, 800mg qid x 7d Erythromycin ethylsuccinate, 400mg qid x 14d *All regimens are oral. *All regimens are oral. Repeat testing 3 weeks after completion of therapy recommended for all pregnant women. Chlamydia trachomatis Gonococcal Cervicitis Follow-up Except for pregnancy, no test of cure routinely advised, but retest for re-infection at 3 months. Partners Instruct patients to refer partners for evaluation, testing, and treatment. N. gonorrhoeae: Screening All sexually active women, including those who are pregnant, if they are at increased risk. Women < 25 years are at highest risk. Others are: previous gonorrhea, other STDs, new or multiple partners, inconsistent condom use, commercial sex worker, drug use, high prevalence communities. Not recommended for men and women at low risk. Antibiotic-Resistant N. gonorrhoeae (ARNG) CDC had recommended single dose quinolones beginning Resistance noted by 2000 in Asia and Pacific Islands and by 2002 in California By 2006, resistance or intermediate resistance had increased to 14% (compared with 2% in 2000) for United States ; USPSTF MMWR 2007;56:

7 Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum* Ceftriaxone 250 mg in a single intramuscular (IM) dose, IF NOT AN OPTION Cefixime 400 mg in a single oral dose Single dose injectable cephalosporin (ceftizoxime,cefoxitin, cefotaxime) PLUS Azithromycin 1 gm po doxycycline 100 mg po BID x 7d. Uncomplicated Gonococcal Infections of the Cervix, Urethra and Rectum Alternative Regimens Spectinomycin 2 g in a single IM dose Cephalosporin single-dose regimens Not available in the United States, but 98% effective except for pharyngeal infection. Other single-dose cephalosporin regimens that are considered alternative treatment regimens against uncomplicated urogenital and anorectal gonococcal infections include ceftizoxime 500mg IM; or cefoxitin 2g IM, administered with probenecid 1g orally; or cefotaxime 500mg IM. Some evidence indicates that cefpodoxime 400mg and cefuroxime axetil 1g might be oral alternatives. Uncomplicated Gonococcal Infections of the Pharynx* Ceftriaxone 250 mg in a single IM dose PLUS Azithromycin 250 mg IM single dose Doxycycline 100 mg a day for 7 days *For all adult and adolescent patients, regardless of travel history or sexual behavior. Information regarding management of these infections in patients with documented severe allergic reactions to penicillin s or cephalosporin's is available at Uncomplicated Gonococcal Infections Azithromycin (2gm) is effective against uncomplicated gonococcal infection (99%), but concerns over resistance to macrolides restrict its use to limited circumstances. Azithromycin 1 gm not recommended. N. gonorrhoeae Follow-up If diagnosed with uncomplicated gonorrhea and treated with recommended regimens, no test of cure routinely needed, but retest at 3 months for re-infection. Partners Instruct patients to refer partners for evaluation, testing, and treatment. Disseminated Gonococcal Infection Updated treatment regimens available at Pelvic Inflammatory Disease Updated treatment regimens available at Epididymitis Updated treatment regimens available at 7

8 2010 CDC Regimens for Uncomplicated N.gonorrhoeae, Cervix, Urethra, Rectum in Pregnancy Do not use quinolones or tetracyclines. Use a recommended or alternate cephalosporin. If intolerance, use IM Spectinomycin 2gm, but not available in US. Azithromycin or amoxicillin recommended for C. trachomatis. Cervicitis-Etiology Chlamydia trachomatis N. gonorrhoeae Trichomonas vaginalis Genital herpes Other Mycoplasma genitalium Bacterial vaginosis Diseases Characterized by Vaginal Discharge Trichomoniasis Vulvovaginal candidiasis Bacterial vaginosis Office Evaluation of Patient with Vaginitis ph determination. Amine odor test. Saline prep for true clue cells, T. vaginalis. KOH prep for yeasts. Culture for yeasts, if above are nondiagnostic, using selective media. 8

9 Diagnosis of Trichomoniasis Microscopy only 60-70% sensitive. Culture most sensitive and specific commercially available method (eg. In Pouch System) STD Guidelines Diagnosis of Trichomoniasis OSOM Trichomoniasis Rapid Test (Genzyme), immuno chromographic dipstick, takes 10 minutes. Affirm VP III (Becton Dickson), nucleic acid probe for T. vaginalis (G. vaginalis and C. albicans) takes 45 minutes. APTIMA T. Vaginalis. All of these are more sensitive than wet prep. False positives might occur, especially in low prevalence groups. CDC, 2010 STD Treatment Guidelines Treatment of Trichomoniasis with Metronidazole (MTZ) Dose: 2 gm PO (single dose). Alternative: 500 mg bid x 7 d. Efficacy: 90 95%. Partner: Treat. Follow-up: months in None, if asymptomatic, but consider rescreen in 3 women. Side effects: Nausea, vomiting, headache, blood dyscrasia. Avoid alcohol for 24 hrs. CDC, after 2010 completion. STD Treatment Guidelines Treatment of Trichomoniasis with Metronidazole, Cont d Pregnancy: 2 gm PO, but asymptomatic women should not be treated. Metronidazole gel, approved for treatment of V, is not recommended for trichomoniasis.* Efficacy is 50%. Treatment of Trichomoniasis with Tinidazole Dose: 2 gm orally, single dose. Efficacy: %. Partner: Treat. Follow-up: months in None, if asymptomatic, but consider rescreen in 3 women. Side effects: Avoid alcohol for 72 hours after completion. Pregnancy: Category C, safety in pregnancy not well CDC, evaluated STD Treatment Guidelines 9

10 Refractory Trichomoniasis 1. Retreat with MTZ 500 mg bid x 7 d. 2. Next, 2 gm MTZ or tinidazole single dose daily x 5 d. 3. Get expert consultation. 4. Culture; e.g., Diamond s medium: susceptibility. 5. Check CBC, LFTs, neurology exam. Refractory Trichomoniasis, Cont d 6. Tinidazole 1 gm bid (or 500 mg qid) x d* PLUS Furazolidine in 3% Nonoxynyl 9 cream (100 gm/5 ml), 1 applicator full (5 gm) bid x 14 d.* 7. Other regimens such as topical Paromomycin (very irritating). 8. Contact CDC , *Personal Communication, CDC December, 2003 CDC, Vulvovaginal Candidiasis 75% of women will have >/= 1 episode % will have >/= 2 episodes % harbor yeasts vaginally, no symptoms. Species Causing Yeast Vulvovaginitis Candida albicans Candida glabrata Candida tropicalis Candida pseudotropicalis Other Candida species* Saccharomyces cerevisiae (Baker s yeast) *C. parapsilosis, C. krusei, C. lusitaniae 10

11 Diagnosis of Candidiasis Self diagnosis inadequate. Microscopy 75%. Culture more sensitive. PCR 2X more sensitive than culture. Identification of Candida in asymptomatic women is not an indication for treatment. Clinical Conditions When A Yeast Culture is Helpful* Suspected yeast infection with negative KOH prep**. Recurrent infection**. KOH prep shows budding yeast only. Failure of therapy. *After Sobel, Management of VVC, Wayne State 1997 **McCormack AJOG, 1988; Njirjesy AJOG, 1995; Eckert, Ob/Gyn,1998. Getting a Proper Yeast Culture Collection with usual swab and transport medium. Communicate to lab the need for yeast identification (e.g., Saboraud s media). Selection of Therapy for Candidiasis Uncomplicated Complicated Frequency: Infrequent/Sporadic Recurrent Microscopy: Pseudohyphae/ Budding yeast only, Hyphae, likely likely nonalbicans C. albicans Host: Normal Immunosuppressed, pregnant uncontrolled DM, debilitated, Selection of Therapy for Candidiasis, Cont d. Uncomplicated Complicated Regimen: Any, including More intensive single dose CDC, 2010, STD Guidelines (> 7 days) Treatment of Uncomplicated Vulvovaginal Candidiasis Butoconazole 2% cream, 5 g intravaginally for 3 d***, Butoconazole 2% cream, 5 g (Butaconazole 1- sustained release), single intravaginal application, 11

12 Treatment of Uncomplicated Vulvovaginal Candidiasis, Cont d Clotrimazole 1% cream, 5 g intravaginally for 7-14 d,*** Clotrimazole 2% cream, 5gm vaginally x3 d *** Over-the-counter (OTC) preparations Treatment of Uncomplicated Vulvovaginal Candidiasis, Cont d Miconazole 2% cream, 5 g intravaginally for 7 d*, Miconazole 100 mg vaginal suppository, one suppository for 7 d***, Miconazole 200 mg vaginal suppository, one suppository for 3 d***, Miconazole 4% cream, 5g vaginally x 3d *** Over-the-counter (OTC) preparations Treatment of Uncomplicated Vulvovaginal Candidiasis, Cont d Miconazole 1200 mg suppository, one suppository for 1 d, Nystatin 100,000-unit vaginal tablet, one tablet for 14 d, Tioconazole 6.5% ointment, 5 g intravaginally in a single application***, Treatment of Uncomplicated Vulvovaginal Candidiasis, Cont d Terconazole 0.4% cream, 5 g intravaginally for 7 d, Terconazole 0.8% cream, 5 g intravaginally for 3 d, Terconazole 80 mg vaginal suppository, one suppository for 3 d. Oral Agent: Fluconazole 150 mg oral tablet, one tablet in single dose. Treatment of Complicated Vulvovaginal Candidiasis Culture for species. Longer duration of therapy (e.g. 2-3 doses of fluconazole, d.1, d.4, d.7). Vaginal boric acid. Maintenance regimens. Partner treatment no data support [routine] treatment of sex partners. Men with balanitis benefit from topical antifungals. Treatment of Candida Vulvovaginitis Topical agents may lead to local burning and irritation. Oral agents occasionally cause nausea, abdominal pain and headache and are rarely associated with increased LFTs. Clinically important interactions with oral agents and other drugs, including astemizole, calcium channel blockers, tacrolimus, and others. CDC 2010, STD Guidelines 12

13 Maintenance Regimens for Recurrent Vulvovaginal Candidiasis First line: Oral fluconazole 100, 150, or 200 mg weekly for 6 months. Other: Topical clotrimazole 200 mg twice a week or 500 mg vaginal suppository once weekly. Maintenance Fluconazole for Recurrent Vulvovaginal Candidiasis (VVC) % in remission Sobel JD, et al. NEJM 2004; 351: Time after Therapy (months) Boric Acid Treatment of Candidiasis Regimen: 600 mg in size 0 capsule qd or bid x 14 d. Mechanism: Boron toxicity to yeast. Side effect: Watery discharge. Warnings: Do not use in pregnancy. Toxic orally. Keep away from toddlers. No cunnilingis Boric Acid Treatment of Candidiasis, Cont d Uses: C. glabrata vaginitis. active role treatment. Bacterial Vaginosis (BV) Most prevalent cause of discharge or odor. Most women with BV are asymptomatic. Women with BV are at increased risk for STDs such as HIV, Chlamydia, gonorrhea, and HSV-2. 13

14 Diagnosis of Bacterial Vaginosis (Amsel s criteria) Three of four criteria: Thin, milky, homogeneous discharge. ph > 4.5. Amine, fishy odor. Clue cells (greater than 20%). Diagnosis of Bacterial Vaginosis, Cont d Gram stain acceptable in lab. G. vaginalis culture not recommended. Pap no clinical utility. QuickVue (ph, amines) not recommended. Pip Activity Card (proline-aminopeptidase)*. Affirm VPIII (DNA probe for G. vaginalis)*. OSOM BV Blue*. * Acceptable compared with gram stain Treatment of Bacterial Vaginosis In Non-pregnant Women CDC RECOMMENDATIONS* Metronidazole, 500mg, PO bid x 7 d.* Metronidazole, 0.75%, vaginal gel 5g qd x 5 d. 5g qhs x 7 d.** * Avoid alcohol during and for 24 hours. **May weaken latex condoms/diaphragms. Treatment of Bacterial Vaginosis in Non- Pregnant Women, Cont d CDC Alternate Regimens Clindamycin 300 mg, PO bid x 7 d, Clindamycin ovules 100 g, vaginally qhs x 3 d, Tinidazole 2g PO qd x 3 d, Tinidazole 1g PO qd x 5 d. Metrogel for Persistent BV Regimen: 0.75% gel twice weekly x 4 months. Efficacy: Significantly reduced recurrences compared with placebo during suppression (25% vs 59%, P=0.001) and at 7 month follow up (51% vs 75%, p=0.02 ). Candidiasis is more common with Metrogel (43% vs 20% in placebo, p=0.02). Sobel JD, Ferris D, Schwebke J. et al AJOG 2006; 194:

15 Other Treatment for Persistent BV Oral nitroimidazole followed by intravaginal boric acid, followed by suppressive metronidazole gel. Monthly oral metronidazole administered with fluconazole. STD References 1. Centers for Disease Control & Prevention. STD Treatment Guidelines MMWR 2010; 59 (No. RR-12): Update to CDC s STD Guidelines 2006: Fluroquinolones no longer recommended for Treatment of Gonococcal Infections. MMWR 2007; 56: Sweet RL, Gibbs RG. Infectious Diseases of the Female Genital Tract (5 th ed.) Lippincott, Williams & Wilkins Branson BM, Handsfield HH et al. Revised Recommendation for HIV Testing of Adults, Adolescents, and Pregnant Women in Health-Care Settings. MMWR 2006; 55: