CDC 2015 STD Treatment Guidelines: What s new?

Transcription

1 : What s new? Ellen Opie, RN/FNP, MPH Guest Faculty, CaliforniaPreventionTraining Center Staff, San FranciscoCity Clinic (DPH) Disclosure Information Ellen Opie, RN/FNP MPH I have no financial relationships to disclose Objectives Discuss STD screening recommendations for different populations including youth, gay men, transpersons and HIV-infected individuals. Identify important changes in STD management/treatment strategies in the newest CDC STD Treatment Guidelines Identify key STD prevention recommendations from the 2015 CDC STD Treatment Guidelines 1

2 CDC STD Treatment Guidelines Development Evidence-based on principal outcomes of STD therapy Recommended regimens preferred over alternative regimens Alphabetized unless there is a priority of choice Reviewed April 2013; available June 2015 Pocket guides, teaching slides, charts Populations at Greatest Risk for STDs Youth Nearly 50% of STDs estimated to occur in year olds Racial/ethnic minorities STDs among highest of all racial/ethnic health disparities African-Americans: CT: 5.8 times the rates among whites GC: 12.4 times the rate among whites MSM Account for 75% of syphilis cases in 2013 High rates of HIV co-infection Satterwhite et al, 2013; CDC STD Surveillance Report 2013 Why diagnose and treat STDs? >19 million STDs in U.S. annually Health consequences of untreated STDs Women s reproductive health Untreated Chlamydia (CT) or gonorrhea (GC) may lead to pelvic inflammatory disease (PID) Leading infectious cause of infertility in the U.S. Infant mortality/morbidity Neonatal HIV, herpes simplex virus (HSV) and congenital syphilis HIV acquisition and transmission Health care cost $15.6 billion Satterwhite et al, 2013; Owusu-Edusei et al,

3 Ask 3 essential sexual history questions WHO are your partners? Are you having sex with men, women, or both? What about transgender people? How many new partners in the past 3 months? WHAT are your sexual and drug use practices? Do you have anal sex? (your penis in someone s anus, or someone else s penis in your anus?) top, bottom, or both? Do you use needles to inject drugs? HOW do you prevent STDs/HIV? How do you protect yourself and your partners from STDs or HIV? Tell me about using condoms with your recent partners. What s your approach to talking about HIV status with partners? STD Screening for Women Sexually Active adolescents & up to age 25 Routine chlamydia and gonorrhea screening Other STDs and HIV based on risk Women over 25 years of age STD/HIV testing based on risk Pregnant women HIV+ Women Chlamydia annual Trichomonas Gonorrhea (<25 yrs or risk) HIV Syphilis serology HepBsAg Hep C (if high risk) Trichomonas if HIV+ CDC recommends HIV testing for all patients seeking STD care or with an STD diagnosis CDC 2015 STD Tx Guidelines at Swabs vs. Urine for Women Vaginal Swabs Sensitivity is equal or greater to cervical swabs Self-collection option well accepted women of all ages Less specimen processing required at clinical site than with urine Hobbs STD 2008, Chernesky STD 2005 CDC RECOMMENDS: Nucleic acid amplification tests for detecting GC & CT A self- or clinician-collected vaginal swab A first catch urine specimen is acceptable but might detect 10% fewer infections when compared with vaginal and endocervical swab samples. CDC. MMWR 2014 / 63(RR02);1-19 3

4 Major conclusions NAATs recommended for detection of genital tract infections in men and women with and without symptoms Optimal specimen types are: First catch urine for men Self collected vaginal swabs from women NAATs recommended for: detection of rectal and oropharyngeal infections - not FDA-approved for rectal or pharyngeal specimens but remain the preferred testing method over culture STD Screening for MSM* HIV Syphilis No swabs in urethra Urine GC and CT Rectal GC and CT (receptive anal sex) Pharyngeal GC (receptive oral sex) * At least annually, more frequent (3-6 months) if pt or their sex partners have multiple partners, uses meth, or sexual performance enhancing drugs Other: Hepatitis B SAg (frequency not specified) New! Hep C annually if HIV+ or other risk factors (ulcerative STD, proctitis) (consider Hep A/B pre-vaccination serology) CDC 2015 STD Tx Guidelines Majority of Rectal Infections in MSM are Asymptomatic Rectal Infections 86% 84% Urethral Infections Chlamydia n=316 Gonorrhea n=264 10% Asymptomatic Symptomatic 42% Chlamydia n=315 Gonorrhea n=364 Kent, CK et al, Clin Infect Dis July

5 HIV and Rectal Infections at SFCC Data from 546 MSM analyzed 24.5% had history of more than 1 prior rectal infection Overall, annual HIV incidence in this group was 3.8% Annual HIV incidence: 10.2% for those with history of rectal infections 1.9% for those with no prior history of rectal infections Number of prior rectal infections: 0 1.9% 1 7.5% % % Kyle Bernstein, PhD, ScM STD Prevention and Control Services April 8, 2008 Proportion of CT/GC MISSED if screening only performed at urethral site (urine), San Francisco, n=3398 patient visits Chlamydia Among asymptomatic MSM CT or GC was found in at least one anatomical site at 16% of these patient visits Gonorrhea Marcus et al, STD Oct 2011; 38: Schachter J, et al. Sex Transm Dis 2008; 35:

6 Extra-genital Chlamydia and Gonorrhea NAAT Testing not FDA-cleared for rectal or pharyngeal specimens but now the preferred testing method over culture Validation procedures can be done by labs to allow use of a non-fda-cleared test or application Two commercial labs (Quest & LabCorp) currently provide GC/CT NAAT for rectal/pharyngeal specimens No resistance testing with NAAT Screening for HIV+ MSM Same recommendations as HIV- MSM plus: Anal Cancer: Annual digital rectal exam may be useful to detect early cancer, some centers perform anal Pap and HRA for abnormal results (ASC-US or worse) HCV : HCV antibody tests should be serially monitored, at least yearly and more frequently depending on local circumstances (HCV prevalence, incidence, resources, and other factors), to detect conversion from HCV-antibody-negative to positive. Screening Transmen and Transwomen Transwomen who have sex with men, use same screening guidelines for MSM. Consider anatomy and behavior to guide screening Transmen diverse group both in anatomy and behavior. Some may be very high risk (MSM behavior). Still need to consider vaginal & cervical disease, cervical cancer. Represents new section in 2015 Guidelines 6

7 Case Scenario Jewell 19 year old transwoman, has protected insertive & receptive anal sex, and unprotected oral sex with men. She has no symptoms, and no history of STDs. Reportedly HIV- 6m ago. She does not use drugs. What screening tests will you order today? Urine, pharyngeal & rectal NAAT for GC/CT, VDLR (or equiv), HIV +Rectal NAAT for GC Gonorrhea Incidence estimates: 820,000 cases in US annually Urethritis, cervicitis, asymptomatic genital, rectal and pharyngeal infections, PID, proctitis, disseminated disease Treatment: Changes to recommended and alternative treatment recommendations and followup test-of-cure Partner treatment: Stronger recommendations for patient delivered partner therapy, and consider concurrent patient-partner therapy Repeat testing 3 months after treatment Case Scenario Jewel Rectal NAAT GC positive (CT-) What is recommended regimen to treat her Gonorrhea? 1. Cefixime 400 mg PO + azithromycin 1 g PO 2. Azithromcyin 2 gm PO 3. Ceftriaxone 250 mg IM + azithromycin 1 g PO 4. Ofloxacin 400 mg PO 7

8 Gonorrhea Dual Therapy Uncomplicated Genital, Rectal, or Pharyngeal Infections Ceftriaxone 250 mg IM in a single dose * Regardless of CT test result PLUS* New in 2015: Move doxycycline from recommended to alternative drug for cotreatment due to high level of tetracycline resistance ( 23.7 % in 2013) among GC isolates Azithromycin 1 g orally X or Doxycycline 100 mg BID x 7 days* What does dual therapy mean? Ceftriaxone and azithromycin administered on the same day Preferably simultaneously and under direct observation Audience Question: If patient was treated presumptively for urethritis with azithromycin and GC test result returns +, 3 days later, what do you do??? Gonorrhea Treatment Alternatives Anogenital Infections ALTERNATIVE CEPHALOSPORINS: Cefixime 400 mg orally once PLUS Dual treatment with azithromycin 1 g (preferred) or doxycycline 100 mg BID x 7 days, regardless of CT IN CASE OF SEVERE ALLERGY: Azithromycin 2 g orally once 2015 Revisions: (Caution: GI intolerance, emerging resistance) Gentamicin 240 mg IM or 5mg/kg IM + azithromycin 2g PO OR Gemifloxacin 320 mg orally + azithromycin 2g PO Doxy removed as cotreatment (unless azithro allergy) 8

9 Pharyngeal gonorrhea should not be treated with oral cephalosporins Cefixime 400mg PO provides lower bactericidal levels compared to ceftriaxone 250mg IM Time above the MIC is not as prolonged Efficacy is reduced Test of Cure ( TOC) for patients with pharyngeal GC treated with an alternative regimen 14 days after tx (prev 7), culture or NAAT Who needs a test of cure for GC? Patients with pharyngeal GC treated with an alternative regimen Obtain test of cure 14 days after treatment, using either culture or NAAT Cases of suspected treatment failure (culture and simultaneous NAAT) 9

10 Cephalosporin treatment failures Oral cephalosporin treatment failures reported worldwide Japan, Hong Kong, England, Austria, Norway, France, South Africa, and Canada Ceftriaxone treatment failures RARE, all outside US Unemo Eurosurveillance 2011 Tapsall J Med Microbiol 2009 Ohnishi EID 2011 Allen JAMA 2012 Suspected GC Treatment Failure After 1st line Dual Therapy: Most due to reinfection* TEST: with culture and NAAT. If GC culture not available on-site, call local health department STD controller (in CA, call STD Control branch TREAT: Gemifloxacin 320 mg + AZ 2g OR gentamicin 240 mg IM + AZ 2g. Consult ID specialist, STD/HIV PTC, health department, or CDC for guidance on antibiotic regimen* REPORT: To your local health department within 24 hours; report to state health department or call CDC for advice TEST and TREAT PARTNERS: All partners in last 60 days should be tested and treated with same antibiotic regimen as was used for patient TEST OF CURE (TOC): TOC 7-14 days with culture and NAAT * If reinfection suspected and prior RX with Ceftriaxone 250 IM/Azithro 1gm retreat with same regimen *If reinfection suspected and prior RX with Cefixime/Azithro retreat with Ceftriaxone 250 IM plus Azithromcyin 2 gm po PCN and Cephalosporin Allergy ~5%-10% cross-reactivity risk with 1st generation cephalosporin in PCN allergic. Newer studies <2.5% cross reactivity Cross reactivity low among 2 nd and 3 rd generation cephalosporin (used for GC treatment) in PCN allergic No evidence of increased anaphylaxis risk Cephalosporin Allergy Allergy 1%-3% exposed, usually rashes Anaphylaxis is rare event Pichichero. Pediatrics 2005;115: Yates. Am Jour Medicine 2008;121:

11 Chlamydia not much new. Updated estimates: 2.8 million cases in US annually Hetero male screening: Still not routinely recommended, certain venues only (corrections, STD clinics, etc) Addition of a new (ish) treatment regimen Partner treatment: Stronger recommendations for patient delivered partner treatment and concurrent patientpartner therapy Repeat testing 3 months after treatment: Chlamydia Treatment Adolescents and Adults Recommended regimens (non-pregnant): Azithromycin 1 g orally in a single dose Doxycycline 100 mg orally twice daily for 7 days Doxycycline delayed-release 200 mg tablet QD x 7 d added as new alternative regimen Recommended regimens (pregnant*): Azithromycin 1 g orally in a single dose Amoxicillin 500 mg orally TID x 7 days Amoxicillin 500 TID moved to alternative for pregnant women * Test of cure at 3-4 weeks only in pregnancy 11

12 Chlamydia Treatment: Azithromycin vs Doxycycline Azithromycin < Doxycycline Data from one nongonococcal urethritis trial and several rectal infection studies Meta analysis Pooled cure rates: doxy 97.5%, azithro94.4% Doxycycline marginally more effective than azithromycin for rectal infection More research needed ( RCT) No change in CDC 2015 RX recommendations Hathorn et al STI 2012, Kong et al. CID 2014 GC/CT PARTNER MANAGEMENT Clinical evaluation first-line option Concurrent patient-partner therapy can be effective for those with one primary partner Expedited partner treatment (EPT) preferred: Use of prepackaged medication is recommended Dual therapy (cefixime 400 mg + azithromycin 1 g) is crucial if EPT is used for GC Re-Testing after an STD infection Women who test positive for CT/GC, or trichomonas should be rescreened three months following treatment. Men who test positive for chlamydia or gonorrhea should be rescreened at three months after adequate therapy. All patients with a bacterial STDs or trichomonas should be tested for other STDs including CT/GC, syphilis, and HIV 12

13 Case Scenario Jewel All of her other tests were negative. What will we do for her partners? Send home pre-packaged EPT backs with Dual GC therapy (Cefixime & Azithro) Does she need to come back for a test of cure? No, because she was treated with 1 st line meds Does she need to come back to re-test? When? Yes Needs to return for testing in 3 months Re-Testing Poster available Click on For Providers Urethritis Common Infectious Causes Bacterial STDs: GC 5-20% CT 15-40% Mycoplasma genitalium 15-25% Other etiologies: T. vaginalis 5-20% (regional differences) HSV (marked disparity b/w symptoms and findings) Ureaplasma 0-20%; data inconsistent Adenovirus, enterics, Candida, anaerobes, EBV Sexually Transmitted Diseases, 4 th Edition, Holmes et al 13

14 Emerging Issues: Mycoplasma genitalium recognized cause of urethritis (Etiology in ~ 30% persistent urethritis) Emerging role in Cervicitis and PID (data suggestive) Suspect in persistent or recurrent urethritis and consider in persistent cervicitis and PID No FDA approved diagnostic test -Some centers have done CLIAvalidation Azithromycin superior to doxycycline for M. genitalium urethritis (*AZ efficacy may be declining for M.genitalium) Moxifloxacin effective for M.genitalium *Manhart et al, CID 2013 Case Scenario: Persistent Urethral Discharge 20 Year old Male with female partners, complains of persistent dysuria & urethral discharge. Seen 1 w ago and treated for urethritis (4 WBCs/hpf on gram stain, no GNDs) Seattle PTC Tx: Ceftriaxone 250 IM plus Azithromycin 1 gm PO Dx: discharge on exam, >/= 2 WBCs on gram stain (was 5), +leukocyte esterase 1 st void urine, >/= 10 WBCs spun urine Pt states the discharge never really went away. No sexual exposures in past week (female partners) Case: persisten t urethral discharge GC/CT NAAT both negative from prior visit Urethral discharge confirmed on exam today What does he have, and how would you treat it now? Persistent urethritis 1. Ceftriaxone 250 mg plus azithromycin 1gm orally 2. Doxycycline 100 mg orally BID for 7 days 3. Metronidazole 2 gm orally 4. Moxifloxacin 400 mg orally QD for 7 days plus metronidazole 2 gm orally once See New treatment guidelines 14

15 Persistent NGU Treatment If azithromycin NOT given for 1 st episode: Azithromycin 1 g orally in a single dose PLUS Metronidazole 2 g orally in a single dose OR* Tinidazole 2 g orally in a single dose If azithromycin given for 1 st episode: Moxifloxacin 400 mg orally qd x 7d PLUS Metronidazole 2 g orally in a single dose OR* Tinidazole 2 g orally in a single dose Urology referral if symptoms persist * MSM low probability of T. Vaginalis Syphilis not much new Incidence estimates: 55,000 new cases per year (in % of cases were in MSM) Case Scenario Jewel At her 3 month follow-up for testing, you notice a shallow ulcer on her penis. The patient reports that it is painless and she had not noticed it. You are concerned about primary Syphilis but do not have a Dark Field microscope in your clinic. What are your options? 15

16 Management Issues Primary Syphilis Diagnostic challenges: Access to direct and stat tests limited Serology negative ~25% in early primary Trep tests (e.g., TP-PA, EIA) may have higher sensitivity than non-trep tests in early primary Point of Care tests (Trep/non-trep) Treatment: If serology negative and suspicion is low and F/U likely, repeat serology 2-4 weeks If serology negative and suspicion is high, treat empirically and repeat serology 1 week Always consider presumptive treatment in an at-risk patient Primary Syphilis Images courtesy of Joe Engelman City Clinic Secondary Syphilis Images courtesy of Joe Engelman City Clinic 16

17 Syphilis Treatment (no changes!) Primary, Secondary & Early Latent: Benzathine penicillin G 2.4 million units IM in a single dose Late Latent and Unknown Duration: Benzathine Penicillin G 7.2 million units total, given as 3 doses of 2.4 million units each at 1 week intervals Neurosyphilis: Aqueous Crystalline Penicillin G million units IV daily administered as 3-4 million IV q 4 hr for d In pregnancy, benzathine penicillin is the only recommended therapy. No alternatives Only one dose of PCN Is recommended for early syphilis in HIV-infected persons, extra doses not needed Late Latent Syphilis treatment guidance What is the maximum time allowed between Penicillin doses when treating late latent syphilis? Clinical experience suggests days ok for nonpregnant adults <9 days is best based on limited pharmacologic data In pregnancy, must adhere to strict 7 days between doses 40% of pregnant women are below treponemicidal levels after 9 days If a dose is missed, the entire series must be restarted 17

18 Trichomonas Incidence/prevalence estimates: 1 million new infections annually, 3.7 million women currently infected Screening Recommended annually for HIV+ women Consider NEW: Use screening of nucleic acid other amplification high prevalence tests (NAATs) settings and other highly sensitive/specific tests is recommended for detecting Trich NAATs can be performed on vaginal swabs or urine (wet mount very low sensitivity) Retesting recommended 3 months after treatment for women (insufficient data to recommend for men) Key Prevention Strategies 2015 Already reviewed Screening Re-testing Partner management Pre-exposure Vaccination PrEP Case Scenario Jewell At her next follow-up, Jewell reports less partners and more condom use than at prior visits, but you are concerned about about her two recent STDs. She is HIV negative on a rapid test today. What other prevention actions can you offer today? 18

19 HPV and HPV Vaccines Over 170 types of HPV classified Updated incidence/prevalence estimates (CDC): 14 million new infections per year 79 million people infected in the US devilliers, 2013, Virology Satterwhite, 2013, STD HPV Vaccines Bivalent: GSK Cervarix Types 16, 18 Prevents cervical cancer FDA-approved for females yrs 3-dose series; $365 Quadrivalent: Merck Gardasil Types 6, 11, 16, 18 Prevents warts, cervical cancer, anal cancer FDA-approved for females and males 9-26 yrs 3-dose series; $375 Nonavalent: Merck Gardasil9 Types 6, 11, 16, 18, 31, 33, 45, 52, 58 FDA approved for males & females 9-26 yrs Gardasil PI. Cervarix PI. HPV Vaccine Recommendations Population Gender Age Recommendation All Females 9-26 Routine vaccination with either HPV2, HPV2 or HPV9 All Males 9-21 Routine vaccination with HPV4 or HPV9 MSM and HIV+ Males Permissive recommendation HPV4 or HPV Routine vaccination with HPV4 or HPV9 * Irrespective of history of abnormal Pap, HPV, genital warts MMWR, 2015; Mar 27 19

20 What is PrEP? PrEP = Pre-Exposure Prophylaxis HIV prevention strategy in which an HIVnegative person takes HIV medication to reduce risk of getting HIV Truvada = Tenofovir/Emtricitibine (TDF/FTC) Approved by FDA in 2012 One pill taken daily regardless of plans for sex Greater than 95% effective in preventing HIV infection if taken as prescribed PrEP HIV Pre-Exposure Prophylaxis should be available to sexually active MSM and to adults at high risk of HIV infection per the current CDC recommendations. All clients requesting PrEP should be counseled that high levels of adherence are needed for the best efficacy. 20

21 How do I prescribe PrEP in primary care? Identify patients who may benefit from PrEP CDC guidelines: Sexually-active MSM, heterosexual men and women & IDU at substantial risk MSM or transgender women - condomless anal intercourse with multiple partners MSM or transgender women - syphilis or rectal STI Commercial sex workers Men or women in serodiscordant relationships with positive partners with detectable viral load Peri-conception Additional Resources for Clinicians National Network of STD/HIV Prevention Training Centers California Prevention Training Center CA PTC Clinical Trainings and Resources Clinical Consult Line STD-AtoZ Via website: stdccn.org Lots of different trainings!! Clinical Precepting Technical assistance 21

22 STD Clinical Consultation Network (STDCCN) Provides STD clinical consultation services within 1-3 business days, depending on urgency, to healthcare providers nationally Your consultation request is linked to your regional PTC s expert faculty We are just a click away! Want to know more about STDs? There s an app for that. CDC Treatment Guidelines App for Apple and Android Available now (Search for STD TX ) Call our clinician consultation line at City Clinic