New Directions in STD Diagnosis and Treatment Laura

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New Directions in STD Diagnosis and Treatment Laura Bachmann, MD, MPH Ina Park, MD,

New Directions in STD Diagnosis and Treatment Laura Bachmann, MD, MPH Ina Park, MD, MS Alabama/North Carolina STD/HIV Prevention Training Center and Wake Forest University Health Sciences California STD/HIV Prevention Training Center and STD Control Branch, California Department of Public Health

Disclosures • Dr. Bachmann: grant funding from Cepheid and Melinta: • Dr. Park: no

Disclosures • Dr. Bachmann: grant funding from Cepheid and Melinta: • Dr. Park: no disclosures • Non-FDA approved tests that may be mentioned: pharyngeal and rectal testing for GC and CT; TV testing in men.

Outline • Overview of CDC STD Treatment Guidelines Development Process • Top 11 updates

Outline • Overview of CDC STD Treatment Guidelines Development Process • Top 11 updates for women’s health providers – – – 1) Screening recommendations 2) Recommendations for GC/CT diagnostic tests 3) New-ish chlamydia treatment 4) Changes to gonorrhea recommended/alternative therapy 5) Partner management guidelines 6) HPV vaccine and Primary HPV screening 7) New genital warts treatment 8) Genital herpes epidemiology 9) Trichomonas screening, diagnosis, and treatment 10) BV treatment 11) New section: Mycoplasma genitalium

Development of CDC STD Treatment Guidelines Answer the “Key Questions” Enlistment of Subject Matter

Development of CDC STD Treatment Guidelines Answer the “Key Questions” Enlistment of Subject Matter Experts Key Questions Systematic Review of Evidence Background papers Tables of evidence Guidelines Meeting, April 2013 Rate the quality of the evidence Identify critical gaps in knowledge (research agenda) Write the Guidelines document Online: www. cdc. gov/std/treatment

Development of CDC STD Treatment Guidelines • Recommended regimens (“in the box”) preferred over

Development of CDC STD Treatment Guidelines • Recommended regimens (“in the box”) preferred over alternative regimens • Treatments are typically alphabetized unless there is a preferred choice • Recommendations in this talk are based on the 2014 CDC Treatment Guidelines Draft Guidance • Language in yellow highlighted boxes reflects changes proposed, actual language may differ

1) STD Screening for Women Sexually Active adolescents & up to age 25 Routine

1) 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 Chlamydia Gonorrhea (<25 years of age or risk) HIV Syphilis serology Hep. Bs. Ag Hep C (if high risk) CDC 2014 STD Tx Guidelines-Draft at www. cdc. gov/std/treatment

Diagnostics for GC/CT

Diagnostics for GC/CT

Major conclusions NAATs recommended for detection of genital tract infections in men and women

Major conclusions NAATs recommended for detection of genital tract infections in men and women – with and without symptoms - highly sensitive and specific compared to culture - less dependent on specimen collection and handling Optimal specimen types are: First catch urine for men Self collected vaginal swabs from women NAATs recommended for: detection of rectal and oropharyngeal infections

2) NAAT Vaginal Swab is preferred specimen type Vaginal Swabs • Sensitivity is equal

2) NAAT Vaginal Swab is preferred specimen type Vaginal Swabs • Sensitivity is equal or greater to cervical swabs or urine • Self-collection option well accepted by women of all ages • Less specimen processing required at clinical site than with urine Post-hysterectomy • Urine NAATs should be used (could perform urethral swab for NAAT) Hobbs STD 2008, Chernesky STD 2005

Chlamydia • Updated estimates: 2. 8 million cases in US annually Satterwhite, STD 2013

Chlamydia • Updated estimates: 2. 8 million cases in US annually Satterwhite, STD 2013 • Hetero male screening: Still not routinely recommended, certain venues only (corrections, STD clinics, etc) • Addition of a new (ish) treatment regimen Recommended treatment (non-pregnant): v Azithromycin 1 g orally in a single dose v Doxycycline 100 mg orally twice daily for 7 days Recommended treatment (pregnant): v. Azithromycin 1 g orally in a single dose v. Amoxicillin 500 mg po TID x 7 days

3) Chlamydia Treatment Proposed Changes Additional Alternative Regimen (non-pregnant): v. Doxycycline (delayed release) 200

3) Chlamydia Treatment Proposed Changes Additional Alternative Regimen (non-pregnant): v. Doxycycline (delayed release) 200 mg QD x 7 d – Equally efficacious to BID doxy, less GI side effects – More $$$$ Proposed Alternative Regimen (PREGNANCY): v. Amoxicillin 500 mg po TID x 7 days - CT persistence documented in vitro after treatment prompted removal from recommended to alternate

Gonorrhea • Incidence estimates: 820, 000 cases in US annually • Treatment: Many changes

Gonorrhea • Incidence estimates: 820, 000 cases in US annually • Treatment: Many changes to recommended and alternative treatment recommendations and follow-up test -of-cure

Gonorrhea Treatment Pre-Antibiotics 5 weeks of rest Avoid sex Avoid alcohol Urethral Dilation Still

Gonorrhea Treatment Pre-Antibiotics 5 weeks of rest Avoid sex Avoid alcohol Urethral Dilation Still recommended today 2 weeks of urethral irrigation

4) Gonorrhea Dual Therapy Uncomplicated Genital, Rectal, or Pharyngeal Infections Ceftriaxone 250 mg IM

4) Gonorrhea Dual Therapy Uncomplicated Genital, Rectal, or Pharyngeal Infections Ceftriaxone 250 mg IM in a single dose PLUS* • Regardless of CT test result Proposed: Move doxycycline from recommended to alternative for dual therapy CDC 2010 STD Treatment Guidelines www. cdc. gov/std/treatment Azithromycin 1 g orally (preferred) or Doxycycline 100 mg BID x 7 days

What does dual therapy mean? • Ceftriaxone and azithromycin administered on the same day

What does dual therapy mean? • Ceftriaxone and azithromycin administered on the same day • Preferrably simultaneously and under direct observation

Gonorrhea Treatment Alternatives Anogenital Infections ALTERNATIVE CEPHALOSPORINS: v Cefixime 400 mg orally once PLUS

Gonorrhea Treatment Alternatives Anogenital Infections ALTERNATIVE CEPHALOSPORINS: v Cefixime 400 mg orally once PLUS v Dual treatment with azithromycin 1 g (preferred) or doxycycline 100 mg BID x 7 days, regardless of CT IN CASE OF SEVERE ALLERGY: v Azithromycin 2 g orally once Gentamicin 240 mg IM or 5 mg/kg IM + azithromycin 2 g PO (Caution: GI intolerance, emerging resistance) OR Gemifloxacin 320 mg orally + azithromycin 2 g PO

Alternative Urogenital GC Regimens v Non-comparative randomized trial in adults with urethral or cervical

Alternative Urogenital GC Regimens v Non-comparative randomized trial in adults with urethral or cervical gonorrhea 1. Gentamicin 240 mg IM + azithromycin 2 g PO, or 2. Gemifloxacin 320 mg PO + azithromycin 2 g PO v Rationale for regimens § Additive effect between gentamicin and azithromycin (in vitro) § Gemifloxacin more active against GC with known ciprofloxacin resistance § Drugs already available in U. S. v Per-protocol efficacy: § Gentamicin + AZ=100% (202/202) § Gemifloxacin + AZ=99. 5% (198/199) v Nausea was common (27% and 37%), (3% and 7%) vomited <1 hr after administration Kirkcaldy, CID 2014

Who needs a test of cure? • Patients with pharyngeal GC treated with an

Who needs a test of cure? • Patients with pharyngeal GC treated with an alternative regimen, 14 days after tx, using either culture or NAAT • Cases of suspected treatment failure (culture and simultaneous NAAT)

Antibiotic-Resistant Gonorrhea

Antibiotic-Resistant Gonorrhea

Bolan et al. New England Journal of Medicine 2012.

Bolan et al. New England Journal of Medicine 2012.

Cephalosporin treatment failures • Oral cephalosporin treatment failures reported worldwide – Japan, Hong Kong,

Cephalosporin treatment failures • Oral cephalosporin treatment failures reported worldwide – Japan, Hong Kong, England, Austria, Norway, France, South Africa, and Canada • Ceftriaxone treatment failures in pharyngeal gonorrhea and a few isolates with high-level ceftriaxone resistance reported Unemo Eurosurveillance 2011 | Tapsall J Med Microbiol 2009 | Ohnishi EID 2011 | Allen JAMA 2012

Suspected GC Treatment Failure After Recommended Dual Therapy What do I do? CULTURE: if

Suspected GC Treatment Failure After Recommended Dual Therapy What do I do? CULTURE: if GC culture not available call your local health department STD controller REPEAT TREATMENT: Gemifloxacin 320 mg + AZ 2 g OR gentamicin 240 mg IM + AZ 2 g REPORT: To your local health department STD program within 24 hours, or call CDC 404 -639 -8659 for advice TREAT PARTNERS: Within 60 days with same regimen as patient receives TEST OF CURE (TOC): Patient returns in 7 -14 week for TOC culture and NAAT * If reinfection suspected instead of treatment failure, OK to repeat treatment with CTX 250 + AZ 1 g

CT/GC Partner Treatment

CT/GC Partner Treatment

CT/GC Partner Management Options Ø Patient referral • Ask patient to notify partner and

CT/GC Partner Management Options Ø Patient referral • Ask patient to notify partner and ensure treatment • Have patient bring partner to clinic for concurrent treatment • Internet-based anonymous notification Ø Expedited partner treatment (EPT) • Patient-delivered partner treatment (PDPT) • Health department field-delivered treatment • Pharmacy-based Ø Provider or clinic-based referral Ø Health department referral Ø Concurrent patient and partner treatment

5) Proposed Partner Management • Clinical evaluation first-line option • Concurrent patient-partner therapy may

5) Proposed Partner Management • Clinical evaluation first-line option • Concurrent patient-partner therapy may be effective for patients with one partner • Offer PDPT routinely to heterosexual pts with CT/GC if partner cannot be promptly treated – Dual therapy (cefixime 400 mg + azithromycin 1 g) is crucial if PDPT is offered

Legal Status of Expedited Partner Therapy, 9/2014

Legal Status of Expedited Partner Therapy, 9/2014

Retesting for Repeat Infection

Retesting for Repeat Infection

Retesting Recommendations • Retest all women and men with CT/GC 3 months after treatment

Retesting Recommendations • Retest all women and men with CT/GC 3 months after treatment • Opportunistic retesting should occur anytime within 1 -12 months, regardless of the reason for visit • Test of cure is not routinely recommended – Exceptions: Pregnancy, treatment failure

HPV 101 Over 170 types of HPV classified Updated incidence/prevalence estimates (CDC): • 14

HPV 101 Over 170 types of HPV classified Updated incidence/prevalence estimates (CDC): • 14 million new infections per year • 79 million people infected in the US de. Villiers, 2013, Virology Satterwhite, 2013, STD

6) HPV Vaccines Bivalent: GSK Cervarix® • • Types 16, 18 Prevents cervical cancer

6) HPV Vaccines Bivalent: GSK Cervarix® • • Types 16, 18 Prevents cervical cancer FDA-approved for females 10 -25 3 -dose series; $365 Quadrivalent: Merck Gardasil® • • Types 6, 11, 16, 18 Prevents warts, cervical cancer, anal cance FDA-approved for females and males 9 -26 3 -dose series; $375 Nonavalent: Merck V 503 • Types 6, 11, 16, 18, 31, 33, 45, 52, 58 • FDA biologics license application Dec 2013 Gardasil PI. Cervarix PI.

Reduction in pre-cancer endpoints Nonavalent vs quadrivalent vaccine Endpoint Nonavalent n=7099 Quadrivalent n=7105 %

Reduction in pre-cancer endpoints Nonavalent vs quadrivalent vaccine Endpoint Nonavalent n=7099 Quadrivalent n=7105 % reduction CIN 2/3 or AIS, VIN 2/3, Va. IN 2/3 1 30 96. 7% (80. 9 -99. 8) Non-inferior immunogenicity for types 6/11/16/18 CIN = Cervical Intraepithelial Neoplasia AIS = Adenocarcinoma in situ VIN = Vulvar Intraepithelial Neoplasia Va. IN = Vaginal Intraepithelial Neoplasia Merck, EUROGIN Abstract SS 8 -4, Nov 2013

HPV among women who have sex with women • HPV is common among WSW

HPV among women who have sex with women • HPV is common among WSW (13 -30%) even those who never reported having male partners • Pap abnormalities have been reported in WSW who report no previous sex with men • Routine cervical cancer screening should be performed for WSW, and HPV vaccine should be offered (if age eligible) Marrazzo JM, JID 1998 Marrazzo JM, AJPH 2001

 • Roche HPV testing with 16/18 genotyping recommended 13 -0 by advisory panel

• Roche HPV testing with 16/18 genotyping recommended 13 -0 by advisory panel • Would replace Pap starting at 25 years of age • Larger FDA body agreed with advisory panel • Professional societies (ASCCP, ACS, etc) decide whether to recommend it in national guidelines

Genital warts

Genital warts

7) Genital Wart Treatment New recommended regimens v Imiquimod 3. 75% cream, apply daily

7) Genital Wart Treatment New recommended regimens v Imiquimod 3. 75% cream, apply daily v. Move podophyllin resin from recommended to alternative category v. Case reports of severe systemic toxicity due to misuse

8) Genital Herpes • • Incidence estimates: 776, 000 new infections per year Prevalence

8) Genital Herpes • • Incidence estimates: 776, 000 new infections per year Prevalence estimates: 48. 5 million persons infected Diagnosis: Currently culture and serology Proposed: NAATS are most sensitive and increasingly available • Treatment: No changes proposed

HSV-1 • HSV-1 still increasing as a cause of genital herpes • Depending on

HSV-1 • HSV-1 still increasing as a cause of genital herpes • Depending on population, proportion of genital herpes caused by HSV-1 ranges from 30 -78% Wald, A STI 2006 Roberts et al, STD 2003

HSV Acquisition among Women Aged 18 -30 in the Control Arm of the Herpevac

HSV Acquisition among Women Aged 18 -30 in the Control Arm of the Herpevac trial Included subjects n=3438 No disease suspected N=3196 Not infected n=3075 HSV-1 n=92 Suspected Disease n=242 HSV-2 n=29 Not infected n=180 HSV-1 n=35 HSV-2 n=27 HSV-1 infection rate > 2 x the HSV-2 infection rate (2. 5 vs 1. 1 per 100 person-years) Bernstein, Clin Infect Dis 2013: 56

More Genital Herpes • Prevention: HSV suppression therapy in HIV/HSV-2 co-infected patients does not

More Genital Herpes • Prevention: HSV suppression therapy in HIV/HSV-2 co-infected patients does not reduce risk of HIV transmission • Guidelines on management of neonates born to women with genital HSV lesions published Kimberlin, DW, Pediatrics, Feb 2013

9) Trichomonas vaginalis • Sexually transmitted parasite • Estimated prevalence in US: – 3.

9) Trichomonas vaginalis • Sexually transmitted parasite • Estimated prevalence in US: – 3. 1% in the general female population – Prevalence increases with age • Highest rates in AA (13. 3%; 95%CI 10 -17. 7%) • Symptoms not predictive – 8. 7% women from 21 states undergoing testing for GC/CT (N=7593) – 2. 5 -23. 2% of adolescents – 8. 6 -38% of drug users Sutton et al. Clin Infect Dis 2007; Van der Pol et al JID 2005; Miller et al Sex Transm Dis 2005; Plitt et al Sex Transm Dis 2005; Forhan et al Pediatrics 2009; Miller et al JID 2008; Ginocchio et al Jclin Microbiol 2012

TV Prevalence rates by age Ginocchio et al. J Clin Microbiol 2012, 50(8): 2601

TV Prevalence rates by age Ginocchio et al. J Clin Microbiol 2012, 50(8): 2601 16 p e r c e n t a g e 14 12 10 TV 8 CT 6 GC 4 2 0 >18 and <20 y >20 and <30 y >30 and <40 y >/=40 y

Trichomonas vaginalis and HIV • Most common curable STD in HIV+ women – 6

Trichomonas vaginalis and HIV • Most common curable STD in HIV+ women – 6 -44% prevalence – 18 -36% repeat infection rate (8% in HIV-neg) – Routine annual screening recommended • Multiple studies support the epidemiological association between TV and HIV • HIV+ women with TV had higher prevalence of HIV RNA in vaginal secretions • TV treatment reduces vaginal HIV shedding (over 1 -3 month period) Watts 2006, Mostad 1997, Moodley 2003, Magnus 2003, Cu-Uvin 2002, Miller 2008, Kissinger 2009, Gatski 2010

Trichomoniasis: Diagnosis Nucleic Acid Amplification Tests (Vaginal swab) § BD Probe Tec Qx §

Trichomoniasis: Diagnosis Nucleic Acid Amplification Tests (Vaginal swab) § BD Probe Tec Qx § Hologic APTIMA Both FDA approved Sens/Spec : 96 -98%, 98 -100% Saline Wet Mount § Motile trichomonads § p. H > 4. 5 § Whiff test may be positive Sens/Spec: 35 -82%, 99 -100% Point-of-care tests § OSOM trichomonas rapid test (Genzyme) § Affirm VP III (BD) Culture (In. Pouch TV, Bio. Med Diagnostics) Sensitivity: 75 -87% Specificity: 100% OSOM Sens/Spec: 82 -95%, 99 -100% Affirm VP Sens/Spec: 83 -90 %, ~100% Miller and Nyirjesy, Curr Infect Dis Rep 2011 13: 595 -603; Schwebke JCM Dec 2011; p 4106 -4111

2014 CDC STD Treatment Guidelines: Trichomoniasis (proposed) New Episode Tinidazole 2 g PO single

2014 CDC STD Treatment Guidelines: Trichomoniasis (proposed) New Episode Tinidazole 2 g PO single dose OR Metronidazole 2 g PO single dose Metronidazole 500 mg po BID for 7 days (alternative, rec if HIV+) Treatment Failure of 2 g metronidazole single dose* Metronidazole 500 mg BID x 7 d Treatment Failure – Additional Options* Tinidazole or Metronidazole 2 g PO daily x 5 d 7 d Tinidazole 2 -3 g PO daily x 14 d plus intravaginal tinidazole -

Trichomonas Proposed: • Retesting recommended for women 3 months after treatment • NAAT can

Trichomonas Proposed: • Retesting recommended for women 3 months after treatment • NAAT can be done as soon as 2 weeks after treatment • Not enough data to support retesting men

Stop me if you’ve heard this before… • JG is a 35 yo African-American

Stop me if you’ve heard this before… • JG is a 35 yo African-American female who presents to clinic with 3 d history of abnormal vaginal discharge and odor • No other symptoms • PMH – BV diagnosed 6 times in the last year (at least 3 of 4 Amsel Criteria fulfilled at each diagnosis) • No douching • 2 male partners/6 mo; Condoms “sometimes”

Physical Exam and Lab Clue cells p. H = 7; Whiff test +

Physical Exam and Lab Clue cells p. H = 7; Whiff test +

It’s always this straightforward, right?

It’s always this straightforward, right?

Bacterial Vaginosis Curriculum Diagnosis BV Diagnosis: Amsel Criteria Ø Vaginal p. H >4. 5

Bacterial Vaginosis Curriculum Diagnosis BV Diagnosis: Amsel Criteria Ø Vaginal p. H >4. 5 Amsel Criteria: Must have at least three of the following findings: Ø Presence of >20% per HPF of "clue cells" on wet mount examination Ø Positive amine or "whiff" test Ø Homogeneous, nonviscous, milky-white discharge adherent to the vaginal walls 51

10) BV Treatment (no new rx ) Recommended: • Metronidazole 500 mg orally twice

10) BV Treatment (no new rx ) Recommended: • Metronidazole 500 mg orally twice a day for 7 days • Metronidazole gel 0. 75%, one full applicator (5 grams) intravaginally, once a day for 5 days • Clindamycin cream 2%, one full applicator (5 grams) intravaginally at bedtime for 7 days Alternative regimens: • Tinidazole 2 gm po qd x 2 days • Tinidazole 1 gm po qd x 5 days • Clindamycin 300 mg orally twice a day for 7 days • Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days

Treatment in Pregnancy • Pregnant women with symptomatic disease should be treated with –

Treatment in Pregnancy • Pregnant women with symptomatic disease should be treated with – Metronidazole 500 mg twice a day for 7 days – Metronidazole 250 mg three times a day for 7 days – Clindamycin 300 mg orally twice a day for 7 days • Treatment of asymptomatic high-risk pregnant women (those who have previously delivered a premature infant) – NOT RECOMMENDED

Recurrent BV: Management • Suppression with metronidazole gel twice weekly for 4 -6 months

Recurrent BV: Management • Suppression with metronidazole gel twice weekly for 4 -6 months • Oral metronidazole, then intravaginal boric acid, then suppressive metronidazole gel twice weekly for 4 -6 months • Oral metronidazole administered monthly with fluconazole

Man with a “Drip” • A 23 yo male presents for evaluation of a

Man with a “Drip” • A 23 yo male presents for evaluation of a urethral discharge. • He has been seen in STD clinic 15 times between 5/22/12 and 9/2/14 – Sometimes visible discharge on exam, sometimes not – On 9 occasions a urethral Gram stain performed • 5 times <5 PMN/hpf • 4 times >5 PMN/hpf – GC documented 5/23/13, otherwise, tested for GC and CT at each of the 15 visits and always negative • Most recently treated with 1 gm Azithromycin orally once; partner received treatment; GC and CT neg

Today he presents with thick, white discharge…now what? Source: Diepgen TL, Yihune G et

Today he presents with thick, white discharge…now what? Source: Diepgen TL, Yihune G et al. Dermatology Online Atlas

NGU Clinical syndrome characterized by: • Urethral inflammation • Symptoms: urethral discharge, dysuria, meatal

NGU Clinical syndrome characterized by: • Urethral inflammation • Symptoms: urethral discharge, dysuria, meatal pruritis Lab criteria include (any): • Mucopurulent or purulent discharge. • Gram stain of urethral secretions demonstrating >/=5 WBCs per oil immersion field** • Positive leukocyte esterase test on first-void urine or microscopic examination of first-void urine sediment demonstrating >10 WBCs per high power field. **Anticipate cutoff will be lowered to >/=2 WBC/hpf with 2014

Should we change the Gram stain PMN cutoff for clinical diagnosis of urethritis in

Should we change the Gram stain PMN cutoff for clinical diagnosis of urethritis in men with urethral signs and/or symptoms? Gram stain stratum Number CT+ % 95% CI 0 2612 126 4. 8 4. 0 -5. 7 1 1083 71 6. 6 5. 2 -8. 1 2 284 46 16. 2 12. 2 -20. 8 3 627 93 14. 8 12. 2 -20. 8 4 753 136 18. 0 15. 4 -20. 9 5 609 156 25. 6 22. 2 -29. 2 6 297 103 34. 7 29. 4 -40. 2 7 249 61 24. 4 19. 4 -30. 0 8 358 122 34. 0 29. 3 -39. 0 9 139 54 38. 8 31. 0 -47. 1 10 533 220 41. 2 37. 1 -45. 4 >10 3878 1699 43. 8 42. 3 -45. 5 Reitmeijer Sex Trans Dis 2012; 39(1): 18 -20

Urethritis: Etiologies • Infectious – N. gonorrhoeae – NGU • • Non-infectious – Chemical

Urethritis: Etiologies • Infectious – N. gonorrhoeae – NGU • • Non-infectious – Chemical – Allergic – Autoimmune C. trachomatis • ? Frequency U. urealyticum M. genitalium T. vaginalis HSV Other bacteria (i. e. GNR, <5%) UNKNOWN! (20 -30%)

Does MG cause male urethritis? Odds Ratio (95% CI) 5. 1 (1. 4 -27.

Does MG cause male urethritis? Odds Ratio (95% CI) 5. 1 (1. 4 -27. 4) 3. 6 (1. 0 -16. 2) 3. 5 (1. 4 -8. 7) 9. 1 (1. 4 -281. 8) 20. 3 (2. 8 -416 5. 0 (0. 6 -234. 8) 3. 2 (1. 0 -12. 5) 6. 8 (2. 0 -36. 1) 4. 1 (2. 1 -7. 8) 5. 4 (1. 7 -19. 2) 6. 4 (2. 2 -19. 9) 1. 2 (07 -1. 9) 2. 0 (0. 9 -4. 6) 5. 4 (2. 3 -13. 0) 6. 1 (1. 4 -54. 2) 0. 93 (0. 19 -3. 90) 13. 6 (1. 8 -281. 9) 8. 8 (2. 5 -37. 0) 7. 2 (1. 6 -36. 5) 5. 2 (0. 6 -120. 0) 12. 5 (2. 9 -113. 0) 14. 9 (4. 2 -80. 0) 15. 3 (4. 7 -78. 7) 5. 3 (1. 6 -20. 0) 2. 3 (1. 1 -4. 7) 4. 7 (3. 2 -6. 7) 3. 8 (1. 7 -8. 2) 3. 4 (0. 4 -158. 4) 4. 3 (2. 5 -7. 6) 5. 5 (1. 2 -24. 9) 6. 8 (0. 8 -309. 4) 5. 5 (1. 8 -22. 2) 3. 23 (1. 28 -8. 02) 0. 52 (0. 13 -1. 55) 2. 94 (1. 12 -9. 76) 16. 5 (2. 56 -694. 9) ∞ (1. 2 -∞) ∞ (1. 3 -∞) ∞ (0. 8 -∞) 3/8/2021 • Acute urethritis – 38 studies – 15% MG+ (median) in urethritis cases – 22% MG+ (median) in NCNGU cases • Persistent urethritis – 6 studies – 12 -14% MG+ men with persistent/recurrent urethritis Compliments: Dr. 60 Lisa

MG cure rates with doxycycline and azithromycin Randomized Trials Doxycycline (100 mg bid x

MG cure rates with doxycycline and azithromycin Randomized Trials Doxycycline (100 mg bid x 7 d) vs. Azithromycin (1 g) 87% 67% Microbiologic Cure Doxycycline 45% 31% Mena 2009 40% Azithromycin 30% Schwebke 2011 Manhart 2013 CONCLUSION: AZM (1 g) is superior to DOX (100 mg bid x 7 d). However, efficacy of AZM is not consistently high and may be declining L. Manhart, with permission

NGU Treatment Recommended Alternative • Azithromycin 1 gm PO x 1 • Erythromycin base

NGU Treatment Recommended Alternative • Azithromycin 1 gm PO x 1 • Erythromycin base 500 mg PO QID x 7 days dose • Erythromycin OR ethylsuccinate 800 mg • Doxycycline 100 mg PO QID x 7 days BID x 7 days • Levofloxacin 500 mg QD x 7 days • Ofloxacin 300 mg PO BID x 7 days Discussed: Efficacy of AZ for M. genitalium may be declining Manhart et al, CID 2013

M. genitalium – An Emerging Issue? • National retrospective survey of all M. genitalium

M. genitalium – An Emerging Issue? • National retrospective survey of all M. genitalium testing performed in Denmark (Jan 2006 -Dec 2010) – Macrolide resistance screening 2007 onward • A total of 31 600 specimens from 28 958 patients were tested for M. genitalium, with an increasing trend from 3858 per year in 2006 to 7361 in 2010. • The majority (54%) of the patients were tested in general practice. • For both sexes, the positive rate increased significantly, from 2. 4% to 3. 8% for women and from 7. 9% to 10. 3% for men (P <. 0005). • Macrolide resistance was detected in 38% (385/1008) of the M. genitalium–positive patients, and the highest rate was found in patients tested at sexually transmitted disease clinics (43%) Salado-Rasmussen and Jensen. CID 2014; 59 (1): 24 -30

Microbiologic and Clinical Failure Rates (%) by Visit 60 50 40 CT 30 MG

Microbiologic and Clinical Failure Rates (%) by Visit 60 50 40 CT 30 MG TV 20 No pathogen 10 0 Micro failure Clinical failure V 2 V 3 Sena JID 2012: 206: 357 -65

Persistent/recurrent NGU • Role of CT – debatable • Role of TV – likely

Persistent/recurrent NGU • Role of CT – debatable • Role of TV – likely regional/group {race/ethnicity, hetero} variation • Strong evidence that MG is associated with NGU and failure to eradicate MG is associated with persistent urethritis

Persistent NGU Treatment (proposed) If azithromycin NOT given for 1 st episode: v. Azithromycin

Persistent NGU Treatment (proposed) If azithromycin NOT given for 1 st episode: v. Azithromycin 1 g orally in a single dose PLUS v. Metronidazole 2 g orally in a single dose OR v. Tinidazole 2 g orally in a single dose If azithromycin given for 1 st episode: v Moxifloxacin 400 mg orally qd x 7 d PLUS v. Metronidazole 2 g orally in a single dose OR v. Tinidazole 2 g orally in a single dose

Want to know more about STDs? There’s an app for that. CDC Treatment Guidelines

Want to know more about STDs? There’s an app for that. CDC Treatment Guidelines App for Apple and Android Available now, FREE!

Thank you!! Contact information ina. park@cdph. ca. gov lbachman@wakehealth. edu

Thank you!! Contact information ina. park@cdph. ca. gov lbachman@wakehealth. edu