Sexually Transmitted Diseases and Infections PDF Fall 2023

Joshua Wollen, Pharm.D. [email protected] PHAR 5338: ID2 Module Fall 2023 § Identify relative prevalence for sexually transmitted diseases in the United States § Recall goals of therapy for each sexually transmitted disease § Match clinical presentation and/or diagnostic information of a se...

Joshua Wollen, Pharm.D. [email protected] PHAR 5338: ID2 Module Fall 2023 § Identify relative prevalence for sexually transmitted diseases in the United States § Recall goals of therapy for each sexually transmitted disease § Match clinical presentation and/or diagnostic information of a sexually transmitted disease to its treatment regimen of choice § Match drug information to drugs from treatment regimens of choice § Select appropriate follow-up measures for each sexually transmitted disease 2 § Textbook: Yvonne B, Humberto J. Sexually Transmitted Infections. In: DiPiro JT, Yee GC, Michael Posey LL, Haines ST, Nolin TD, Ellingrod VL. eds. DiPiro: Pharmacotherapy A Pathophysiologic Approach, 12e. McGraw Hill; 2021. § Guidelines: Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70(4): 1-187. 3 Public health risks Complications Prevalence Duration Psychosocial consequences Healthcare costs 4 20 60000 18 50000 16 14 40000 12 10 30000 8 20000 6 4 10000 2 0 Cases of 1º & 2º Syphilis 100,000 Cases Chlamydia/Gonorrhea US STD Incidence 2013 to 2021 0 2013 2014 2015 2016 Chlamydia 2017 Gonorrhea Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 2018 2019 2020 2021 Syphilis 5 Texas’s share of cases (%) Texas Rank (cases/100K) Texas incidence (cases/100k) National average (cases/100k) Chlamydia 9.1 20th 507 496 Gonorrhea 9.1 20th 219 214 Primary/secondary syphilis 7.2 25th 13.1 16.2 Congenital syphilis 24 5th 182 77.9 Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 6 Accurate risk assessment and counseling using prevention services and changes in sexual behavior Pre-exposure vaccination Identifying symptomatic and asymptomatic infected persons Effective diagnosis, treatment, counseling, and follow-up of infected persons Evaluation, treatment, and counseling of sex partners of infected persons 7 Accurate sex education Abstinence Vaccination Decrease sex partners Mutual monogamy Condoms Get tested 8 Centers for Disease Control and Prevention. How you can prevent sexually transmitted diseases. CDC Website. Updated February 22, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/prevention/default.htm Previous Standard in Texas Fall 2022 Standard in Texas Middle school Middle school • Abstinence only • Abstinence and contraception • Emphasis on abstinence High school • Abstinence and contraception • Optional High school • Abstinence and contraception • Optional Not all school districts offer sex education Comprehensive sex education gaps: gender identity, sexual orientation, affirmative consent, etc. 9 Waller A. Texas Board Revises Sex Education Standards to Include more Birth Control. New York Times. Nov 20, 2020. Accessed Nov 23, 2020. Available at: https://www.nytimes.com/2020/11/20/us/texas-sex-education.html. § Also called patient-delivered partner therapy (PDPT) § Only one partner is assessed by prescriber § Therapy provided to patient to deliver to partner § No prescriber-patient relationship established for non-patient partner § In Texas, EPT is permissible by law § EPT encouraged for gonorrhea and chlamydia by Texas DSHS Centers of Disease Control. Legal Status of Expedited Partner Therapy (EPT). CDC Website. March 24, 2020. Available at: https://www.cdc.gov/std/ept/legal/default.htm. Accessed May 11, 2020. Texas Department of State Health Services. Expedited Partner Therapy. Texas Health and Human Services website. April 1, 2020. Available at: https://www.dshs.state.tx.us/hivstd/ept/default.shtm. Accessed May 11, 2020. 10 STD Lesions Urethritis, vulvovaginitis, & cervicitis Skin & mucous membrane lesions Chlamydia Gonorrhea Syphilis Trichomoniasis Genital herpes Genital herpes Anogenital warts 11 § Discharge may be clear, mucopurulent, or very purulent § Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus § Dysuria § Hematuria § Feeling of genital heaviness § Epididymitis or prostatitis if untreated 12 § Mucopurulent secretions from endocervical canal § N. gonorrhoeae and C. trachomatis § Herpes simplex virus § Dysuria § Abnormal uterine bleeding § Lower abdominal pain § Dyspareunia § Postcoital bleeding Image source: http://www.merckmanuals.com//media/manual/professional/images/mucopurulent_cervicitis_high.jpg? 13 § Inflammation of internal and external female genitals § Trichomonas vaginalis or Candida albicans § Vulvular itching or irritation § Dysuria § Dyspareunia § Purulent vaginal discharge § May contain blood § Abnormal “musty” odor 14 Image source: https://cached.imagescaler.hbpl.co.uk/resize/scaleWidth/620/cached.offlinehbpl.hbpl.co.uk/news/PGH/C0146927Trichomoniasis-SPL-20170329013645384.jpg Chancres Condyloma latum Herpetic vesicles Condyloma acuminata 15 § Primary syphilis § Usually painless § Highly infectious § Site of transmission § Solitary Image source: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcRaR_xo3_XCnbL7tWeKb7oH_t4Lm92P4yqa7m6tbYVvj0GJbwIRw 16 § Secondary syphilis § Anogenital § Raised nodules or plaques § Highly infectious Image source: https://bestpractice.bmj.com/image/228/en-gb/normal/2287_default.jpg 17 § Secondary syphilis § Palms and soles of feet § Pigmented, macular lesions 18 § Herpes simplex virus § Multiple lesions Ulcers § Usually in clusters § May be more painful in women Papules Image sources: https://www.mshc.org.au/portals/0/Images/HealthProfessional/OnlineEducation/CaseStudies/images/STEROID-MODIFIED_GENITAL_HERPES_01.jpg https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcTWaxfl6yZw6onftHomJN4hzJSp7eLCiGk3nafxIVrytD48NFtjUw https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcSM0dj8Zt4Y3jAiaB_sBpZkmw5ir-gC6EvcPIwt7FUnlATQCc0e Vesicles 19 § Human papillomavirus § Anogenital § Cauliflower-like masses § May be oncogenic § Internal/external 20 Image source: http://3.bp.blogspot.com/-fGlyTrrT8h4/VQRAHZvlElI/AAAAAAAAA2A/pEdkOvR6Wxo/s1600/Genital-Warts-2.jpg Image source: http://www.dermis.net/bilder/CD213/550px/img0153.jpg Clinical Presentation Etiology Epidemiology Treatment Diagnosis 21 22 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 § Chlamydia trachomatis § Intracellular § Sexual or vertical transmission § Equivalent transmission Image source: https://upload.medbullets.com/topic/104071/images/chlamydiatrachomatis.jpg 23 §Most commonly reported STD in the US §At risk populations § Female < 25 YO § MSM § Low socioeconomic status 24 Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 25 § Men often asymptomatic § Urethritis § Cervicitis § Conjunctivitis Image source: http://www.merckmanuals.com//media/manual/professional/images/mucopurulent_cervicitis_high.jpg? § Oropharyngeal and anorectal lesions § Symptoms less noticeable than gonorrhea 26 § Urethral swab § Endocervical or vaginal swab § Urine culture 27 Population Recommendation Women • < 25 and sexually active • ≥ 25 and sexually active if increased risk • Rectal testing based on shared clinical decision making Pregnant Women • < 25 • Retest during 3rd trimester if < 25 OR increased risk MSW • High prevalence clinical settings (incarcerated, adolescent clinics, etc.) MSM • Urethral or rectal testing annually if sexually active regardless of condom use • Every 3-6 months if increased risk Trans and gender-diverse • Trans men to follow recommendations for women Persons with HIV • If sexually active, at first HIV evaluation and annually after • More frequent possibly depending on individual risk behaviors and local epidemiology 28 § Goal: cure of C. trachomatis infection § Regimen of choice § Doxycycline 100 mg PO BID x7 days § Alternative drugs § Azithromycin 1 g PO x1 § Levofloxacin 500 mg PO QD x 7 days § Expedited partner therapy (EPT) 29 Geisler WM, Uniyal A, Lee JY, Lensing SY, Johnson S, Perry RCW, Kadrnka CM, Kerndt PR. Azithromycin versus Doxycycline for Urogenital Chlamydia trachomatis Infection. N Engl J Med. 2015;373:2512-2521. doi: 10.1056/NEJMoa1502599 § Doxycycline § Nausea, diarrhea, and vomiting – take with food § Erosive esophagitis – take with full glass of water § Photosensitivity § DDIs: Calcium salts, carbamazepine, and phenytoin Azithromycin (Systemic). In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 24, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/1768824 Doxycycline. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 24, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6792 30 § Adherence § Symptom persistence § No condomless sex for 7 days § No routine test of cure § Test all partners in last 60 days § Retest women in 3 months after treatment § Test of cure for pregnant women 4 weeks 31 § What is the treatment goal for a patient with a Chlamydia trachomatis infection? a) Reduce duration and severity of symptoms b) Reduce frequency and severity of symptoms c) Clinical cure d) Removal of lesion 32 33 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 § Neisseria gonorrhoeae § Gram negative diplococci § Intracellular § Sexual or vertical transmission Image source: https://721news.com/wp-content/uploads/2018/03/Habitat-and-Morphology-of-Neisseriagonorrhoeae.jpg § Increased male to female transmission 34 §More common in the Southern United States §At risk populations § Male § Age < 25 § MSM 35 Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www cdc gov/std/statistics/2021/default htm Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 36 Screen capture from: https://www.cdc.gov/drugresistance/biggest_threats.html 37 38 NOTE: Baltimore and Seattle are both sentinel sites and regional laboratories. Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 39 1970s • Penicillins 1980s • Tetracyclines 1990s • Fluoroquinolones 2007 • Azithromycin 2009 • Cephalosporins Ohnishi M, Saika T, Hoshina S, Iwasaku K, Nakayama S, Watanabe H, Kitawaki J. CeftriaxoneResistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis.17:148-149. doi:10.3201/eid1701.100397. 40 Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 41 Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 42 § Women often asymptomatic § Urethritis § Cervicitis § Conjunctivitis § Oropharyngeal and anorectal lesions § Symptoms more noticeable than Chlamydia 43 § Urethral swab § Endocervical or vaginal swab § Urine sample 44 Population Recommendation Women • < 25 and sexually active • ≥ 25 and sexually active if increased risk • Oropharyngeal and Rectal testing based on shared clinical decision making Pregnant Women • < 25 • Retest during 3rd trimester if < 25 OR increased risk MSW • High prevalence clinical settings (incarcerated, adolescent clinics, etc.) MSM • Oropharyngeal, urethral or rectal testing annually if sexually active regardless of condom use • Every 3-6 months if increased risk Trans and genderdiverse • Trans men to follow recommendations for women Persons with HIV • If sexually active, at first HIV evaluation and annually after • More frequent possibly depending on individual risk behaviors and local epidemiology 45 § Goal: cure of N. gonorrhoeae infection § Regimen of choice* § Weight < 150 kg: ceftriaxone 500 mg IM x1 § Weight ≥ 150 kg: ceftriaxone 1 g IM x1 § Chlamydia coinfection § Ceftriaxone + doxycycline § EPT § Cefixime 800 mg x1 *For patients WITHOUT gonococcal conjunctivitis, gonococcal-related arthritis, gonococcal meningitis, and gonococcal endocarditis. 46 §Ceftriaxone § Allergy to CPN § Injection site reactions § Diarrhea 47 Ceftriaxone. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 23, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6563 Gepotidacin • Triazaacenaphthlene class • Phase III currently enrolling estimated completion 10.31.23 • Comparison to single dose ceftriaxone + azithromycin EVO100 (Evoguard) • • • • Vaginal gel for prevention of urogenital chlamydia infection L-lactic acid, citric acid, potassium bitartrate Phase III data due summer 2022 Compared to placebo Bexsero® for Gonorrhea • Meningococcal vaccine being tested in Kenya by a team from Oxford • Comparing t-cell cross reactivity against N. gonorrhoeae • Study ended February 2022 – no results published yet World Health Organization. Antibacterial products in clinical development for priority pathogens. https://www.who.int/research-observatory/monitoring/processes/health_products/en/ Updated November 2020. Accessed November 28, 2020. Taylor SN, Marrazzo J, Batteiger BE, Hook EW, et. Al. Single-dose zoliflodacin (ETX0914) for treatment of urogenital gonorrhea. N Engl J Med. 2018;379:1835-1845. doi:10.1056/NEJMoal706988 Chen MY, McNulty A, Avery A, Whiley D, Tabrizi SN, Hardy D, Das AF, Nenninger A, Fairley CK, Hocking JS, Bradshaw CS, Donovan B, Howden BP, Oldach D; Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial. Lancet Infect Dis. 2019 Aug;19(8):833-842. 48 § Preliminary clinical trial for Zoliflodacin v ceftriaxone + azithromycin § 70:70:40 enrollment for zoliflodacin 3 g, zoliflodacin 2 g and standard of care, respectively n=141 mITT § Checked for cure at one week and safety checkup at one month § Cure rates in figure for anogenital and rectal infections § Oropharyngeal cure rates were 50% for 2 g and 82% for 3 g (100% Standard of care) § No significant increase in adverse events – most were gastrointestinal Zoliflodacin 3g 96% cure Zoliflodacin 2g 96% cure Standard of care 100% cure 49 Taylor SN, Marrazzo J, Batteiger BE et al. Single-Dose Zoliflodacin (ETX0914) for treatment of Urogenital Gonorrhea. N Engl J Med.2018;379:1835-1845. § Spiropyridinetrione class § Inhibits DNA biosynthesis § Phase III completed July 2023 § Just announced two weeks ago (11/1/23) that met its primary endpoint § Noninferiority of microbiological cure of urogenital infection compared to IM ceftriaxone + azithromycin https://clinicaltrials.gov/study/NCT04297436 50 § Encapsulated N. gonorrhoeae vaccine § Targets native outer membrane vesicles § Intravacc/Therapyx § Preclinical stages 51 § Adherence § Symptom persistence § Test partners § No condomless sex for 7 days § No routine test of cure § Test all partners in last 60 days § Test of cure for higher risk patients in 7-14 days § Oropharyngeal § Repeat infection 52 § A patient is picking up their medication to treat gonorrhea at your community pharmacy. Which adverse effect would you communicate to this patient? a) This product is flammable b) This drug may worsen existing kidney damage c) This drug may cause a metallic taste in the mouth after use d) This drug can cause irritation at the injection site 53 54 http://m.cdn.blog.hu/ju/juharizsuzsanna/image/2014-12/kol3.jpg § Treponema pallidum § Spirochete bacterium § Sexual, blood, and vertical transmission § Increased transmission from male to male Image source: https://step1.medbullets.com/microbiology/104060/treponemapallidum--syphilis 55 § Uncommon but increasing § Congenital syphilis incidence increasing rapidly § Texas is 3rd nationally § At risk populations § Male § MSM § Low socioeconomic status 56 Adapted from CDC surveillance data, 2021. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated April 11, 2023. Accessed November 7, 2023. https://www.cdc.gov/std/statistics/2021/default.htm 57 Primary Secondary Neurosyphilis Latent Tertiary 58 §3-6 weeks post transmission §Chancres § Painless § Highly infectious § Occur at site of transmission Image source: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcRaR_xo3_XCnbL7tWeKb7oH_t4Lm92P4yqa7m6tbYVvj0GJbwIRw 59 § 4-6 weeks post transmission § Condyloma latum § Palmar-plantar rash lesions § Lymphadenopathy § Patchy hair loss § Fever § Malaise Image source: https://bestpractice.bmj.com/image/228/en-gb/normal/2287_default.jpg, http://arup.utah.edu/media/bdt/Syphilis-Maggie-Hopkins.pdf 60 § Typically asymptomatic § Non-transmissible § May last for years § Early latent < 12 months post transmission § Late latent > 12 months post transmission 61 § 10-30 years post transmission § Rare § Organ damage § Mostly CV and CNS affected § May result in death 62 May occur at any phase • Usually > 6 months post transmission Presentation • Headache • Poor motor function • Paralysis • Dementia CSF findings • ↑ protein • ↑ leukocytes • ↓ glucose • Positive for T. pallidum 63 § Darkfield microscopy § 3 negative slides to rule out § Definitive diagnosis if positive § Primary and secondary syphilis Image source: http://www.mast-diagnostica.com/MASTD_dt/IFD-Bild-FTAABS-IgG.jpg 64 Non-treponemal tests • Rapid plasma reagin (RPR) • Venereal disease research laboratory (VDRL) Treponemal tests • • • • Fluorescent treponemal antibody absorbed (FTA-ABS) Treponema passive particle agglutination (TP-PA) Enzyme immunoassays (EIA) Chemiluminescence immunoassays (CIA) 65 0.5 mL 0.5 mL 0.5 mL Serum 0.5 mL 0.5 mL 0.5 mL Serum Serum Serum NS NS NS NS 0.5 mL NS 0.5 mL NS 1:16 1:32 Serum Serum 0.5 mL NS 0.5 mL NS 0.5 mL NS 1:1 1:2 1:4 1:8 Image source: https://image.slidesharecdn.com/serology-110707203122phpapp02/95/serology-in-infectious-diseases-77-728.jpg?cb=1310070868 66 Population Recommendation Women • Increased risk MSW • Sexually active and < 29 • Increased risk MSM • Sexually active and < 29 • Annually if sexually active • Every 3-6 months if increased risk Trans and gender-diverse • Annually based on reported exposure Persons with HIV • If sexually active, at first HIV evaluation and annually after • More frequent possibly depending on individual risk behaviors and local epidemiology 67 § CDC § First prenatal visit ONLY § High risk patients require additional testing after 28 weeks and delivery § Texas law § ALL pregnant persons must be tested at first prenatal visit, after 28 weeks, and at delivery 68 Texas Department of Health and Human Services. Syphilis, HIV, and Hepatitis B Testing and Pregnancy. Texas DHHS website. Updated May 20, 2021. Accessed November 12, 2021. Available at: https://www.dshs.texas.gov/hivstd/info/pregnancy.shtm § Goal: cure of T. pallidum infection § Drug regimens of choice for adults Stage Regimen of choice Primary Secondary Benzathine penicillin G 2.4 million units IM x1 Early latent Late latent Neurosyphilis Benzathine penicillin G 2.4 million units IM weekly x3 doses Aqueous crystalline penicillin G 3-4 million units IV Q4H x 10-14 days* OR Pen G procaine 2.4 million units IM daily AND probenecid 500 mg PO QID x10-14 days *Can also be as continuous infusion 69 § Penicillin allergy § Primary/secondary (14 days) and latent (28 days) § Doxycycline 100 mg PO BID § Tetracycline 500 mg PO QID § Ceftriaxone 1-2 g IM/IV daily x10-14 days (primary/secondary only) § Desensitization § Verified IgE-mediated allergy § Exceptions: Steven-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, and hemolytic anemia § Neurosyphilis, pregnancy, and congenital syphilis § Questionable ability to follow up 70 § Allergy possible § Seizures § Injection site reactions § Nausea and diarrhea § Jarisch-Herxheimer reaction (early syphilis) § Pretreat with antipyretics Penicillin G Benzathine and Penicillin G Procaine. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 21, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7459 71 § Adherence § Symptom persistence § Partner treatment regardless of serology § Primary, secondary, and early latent - all partners in last 90 days § Partner treatment if serologically positive § § § § Primary – 3 months + duration of symptoms Secondary – 6 months + duration of symptoms Early latent – 1 year Late latent – long term partners § Abstinence until asymptomatic (> 7 days) § Routine test of cure in 6 and 12 months (and 24 if latent) 72 § Randomized open-label study of MSM in France having condomless sex and using HIV PrEP. (n=232) § 1:1 doxycycline 200 mg within 24 hours after condomless sex or no prophylaxis § Primary endpoint: incidence of first bacterial STD (chlamydia, gonorrhea, or syphilis) after enrollment § § Occurrence of first STD in PEP lower than no-PEP (HR 0.53, p=0.008) Difference in 9-month probability of STD at followup was 20% less in PEP group (p=0.007) § Secondary endpoints § § Median of 680 mg used monthly in PEP group (3.4 doses/month) No significant difference in adverse effects of doxycycline group vs no PEP 73 Molina JM, Charreau I, Chidiac C. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomized substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018;18(3):308-317 § Randomized open-label study of MSM and transwomen (n=502) taking HIV PrEP or living with HIV § 2:1 doxycycline 200 mg within 72 hours after condomless sex or standard care § Primary endpoint: incidence of ≥1 bacterial STD (chlamydia, gonorrhea, or syphilis) every quarter at 270 days § Doxycycline showed relative risk reduction of about 20% (slightly higher in HIV prep group) § Secondary endpoints § § § Rates of tetracycline resistant N. gonorrheae occurred in 38% of doxycycline group and 13% of standard of care group (baseline 27%) Rates of tetracycline resistant S. aureus occurred in 16% of doxycycline group and 8% of standard of care group No serious adverse events reported in doxycycline group 74 Luetemeyer AF, Donnell D, Dombrowski JC, et al. Posexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023;388:1296-1306. § May see bigger trials around doxycycline for PEP in the future § Need to further assess impact on drug resistance specifically with gonorrhea § Not currently addressed in the CDC guideline § Need to assess outside of MSM population Steen R, Chersich M, Gerbase A et al. Periodic presumptive treatment of curable sexually transmitted infections among sex workers: a systematic review. AIDS. 2012;26:437-445. Harrison WO, Hooper RR, Wiesner PJ. A trial of minocycline given after exposure to prevent gonorrhea. N Engl J Med. 1979;300:1074-1078. Bolan RK, Beymer MR, Weiss RE et al. Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: A randomized, controlled pilot study. 2015;42(2):98-103. Chow EPF, Fairley CK. Use of doxycycline prophylaxis among gay and bisexual men in Melbourne. Lancet HIV. 2019;6(9):e568-e569. Chow EPF, Fairley CK. Doxycycline post-exposure prophylaxis: let the debate begin. Lancet Infec Dis. 2018;18(3):233-234. 75 § A 21-year-old male with no significant past medical history and no allergies. He presents to the family medicine clinic today with the chief complaint of a ”spot” on his penis. He admits to unprotected intercourse with a non-monogamous female partner 4 weeks ago. A physical exam reveals a chancre on the distal surface of the shaft of the penis. What is the drug regimen of choice you should recommend for RE? a) Benzathine penicillin G 2.4 million units IM x1 b) Benzathine penicillin G 2.4 million units IM weekly x3 doses c) Aqueous crystalline penicillin G 3-4 million units IV Q4H x 10- 14 days d) Pen G procaine 2.4 million units IM daily AND probenecid 500 mg PO QID x10-14 days 76 77 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 § Trichomonas vaginalis § Flagellated protozoa § Sexual, vertical, or surface transmission § Increased female to male transmission Image source: https://cdn.std.uw.edu/doc/386-2/emtrichomonasvaginalisem.jpg 78 § Most common curable STD in the US § Most common non-viral STD in the US/globally § Estimated prevalence of 3.7 million in 2018 § At risk populations § Female < 25 YO § WSW § Douching § Incarcerated persons 79 Centers for Disease Control. Sexually Transmitted Disease Surveillance 2018. https://www.cdc.gov/std/stats18/other.htm#trich. Updated October 7, 2019. Accessed October 28, 2019. § Most patients asymptomatic § Most men have spontaneous resolution § Vulvovaginitis § Urethritis (rare) Image source: https://cached.imagescaler.hbpl.co.uk/resize/scaleWidth/620/cached.offlinehbpl.hbpl.co.uk/news/PGH/C0146927Trichomoniasis-SPL-20170329013645384.jpg 80 § No routine screening for HIV negative women § Suboptimal diagnosis § Vaginal/urethral culture § Wet-mount slide § Urine culture § POC testing § OSOM rapid trichomonas test § Vaginal swab antigen test Image source: http://i54.photobucket.com/albums/g107/xbattery_dollx/Science/Trichomonas.jpg Image source: https://www.sekisuidiagnostics.com/writable/products/images/320x/trichomonasrapid_181_copy1.jpg 81 Population Recommendation Women • High prevalence clinical settings (incarcerated, adolescent clinics, etc.) • If increased risk Persons with HIV • Sexually active women at entry to care and annually thereafter 82 § Goal: cure of T. vaginalis infection § Regimen of choice § Women: metronidazole 500 mg PO BID x7 days § Men: metronidazole 2 g PO x1 § Alternative regimen § Tinidazole 2 g PO x1 83 § 623 women randomized to either single dose or 7- day regimen § Primary outcome: positive T. vaginalis at test-of-cure § Single dose: 19% § 7-day regimen: 11% § RR 0.55, 95% CI (0.34 – 0.70); p<0.0001 § Summary § 7-day course appears to be more effective than single dose § Single dose still provides benefit if compliance is suspect Kissinger P, Muzny CA, Mena LA, Lillis RA, Schwebke JR, Beauchamps, Taylor SN, Schmidt N, Myers L, Augostini, Secor WE, Bradic M, Carlton JM, Martin DH. Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label randomized controlled trial. Lancet Infect Dis. 2018;18:1251-12259. 84 Metronidazole Tinidazole • Nausea and vomiting • Metallic taste • Disulfiram-like reaction • Avoid alcohol for 72 hours while taking and after last dose • Similar to metronidazole • GI effects less common • More expensive • ~5x Tinidazole serum concentration reduced and delayed with food but actual absorption not affected Metronidazole (Systemic). In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 23, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/1798773 Tinidazole. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated July 17, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7772 85 Different mechanism than disulfiram Symptoms • • • • • • • • Flushing Tachycardia Palpitations Vomiting Nausea Dyspnea Acidosis Death 86 § Treat current partner(s) § Abstinence until asymptomatic and partner(s) completed therapy § Usually about 7 days § Routine test of cure in 3 months § Women § Test patient for HIV, syphilis, gonorrhea, and chlamydia 87 § A 22-year-old female is diagnosed and treated for trichomoniasis. Which of the following follow up measures is most appropriate for this patient? a) Test of cure in 3 months b) Test of cure in 6 months c) Abstinence until partner treated d) Abstinence for 3 days 88 89 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 § Herpes simplex virus 2 (HSV-2) § Sexually and vertically transmitted § Occurs in stages Reactivation Recurrent infection Latency Infection of ganglia Primary infection 90 § ~50 million (about 12%) of Americans affected § Herpetic vesicles are most common genital ulcer § In US and globally § At risk populations § Women < 25 YO § MSM 91 § Primary infection § Mostly asymptomatic or minimally symptomatic § Urethritis § Vulvovaginitis § Herpetic vesicles § Flu-like symptoms § Recurrent infection § Prodrome § Herpetic vesicles Image source: https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcSM0dj8Zt4Y3jAiaB_sBpZkmw5irgC6EvcPIwt7FUnlATQCc0e 92 § Tissue culture § Serologic testing § Virologic testing 93 Population Recommendation Women • Type-specific HSV serology could be considered in those presenting for an evaluation, especially if multiple partners Pregnant Women • Routine screening among asymptomatic pregnant women NOT recommended MSW • Type-specific HSV serology could be considered in those presenting for an evaluation, especially if multiple partners MSM • Could consider if infections status is unknown with previously undiagnosed genital infection Persons with HIV • Type-specific HSV serology could be considered in those presenting for an evaluation, especially if multiple partners 94 § Initial therapy § Reduce duration and severity of outbreak § Suppressive therapy § Reduce frequency and severity of outbreaks § Episodic therapy § Reduce duration and severity of outbreaks 95 Acyclovir Initial (7-10D)* Suppressive Episodic 400 mg TID 400 mg BID 800 mg BID x5D 800 mg TID x2D Valacyclovir Famciclovir 1 g BID 250 mg TID 500 mg daily** 500 mg BID x3D 1 g daily 1 g daily x5D 250 mg BID 125 mg BID x5D 500 mg x1, then 250 mg BID x2D 1 g BID x1D *Extend treatment duration if healing incomplete after 10 days of therapy ** Valacyclovir 500 mg QD less effective for patients with 10 or more annual episodes Corey et. al. Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes - NEJM. 2004;350:11-20 96 Acyclovir Valacyclovir Famciclovir Renal dose reduction Yes Yes Yes Nephrotoxicity Yes* Yes* No GI upset Nausea, vomiting, diarrhea Stomach upset Nausea Headache Yes Yes Yes *Crystal nephropathy – stay hydrated to reduce Acyclovir (Systemic). In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 24, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/1763800 Valacyclovir. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 24, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7849 Famciclovir. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated October 29, 2021; Accessed November 3, 2021. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6893 97 § Adherence § Psychotherapy § No test of cure 98 99 http://m.cdn.blog.hu/ju/juharizsuzsanna/image/2014-12/kol3.jpg § Human papillomavirus (HPV) § Non-enveloped capsid § Sexual transmission Image source: http://www.cmdrc.com/wp-content/uploads/2015/07/images-Human-Papilloma-Virus363x265.png 100 Palefsky JM (2018). Human Papillomavirus Infections: Epidemiology and disease associations. In Hirsch MS, Bloom A. (Eds.) Up To Date. Available from: https://www-uptodate-com.ezproxy.lib.uh.edu/contents/humanpapillomavirus-infections-epidemiology-and-disease-associations § HPV most common sexually transmitted infection in the US and globally § Estimated prevalence of 79 million in US § Yearly incidence of 14 million § 2013 HPV US prevalence 45.2% men 39.9% women § Decreasing in women due to vaccine § Risk factors § < 25 YO § MSM § HIV McQuillan G, Kruszon-Moran D, Markowitz LE, et al. Prevalence of HPV in adults aged 18-69: United States, 2011-2014. NCHS Data Brief 2017;280:1-8. Centers for Disease Control. Genital HPV Infection – Fact Sheet. https://www.cdc.gov/std/hpv/stdfact-hpv.htm. Updated August 20, 2019. Accessed October 30, 2019. Condyloma acuminatum. In DynaMed [database online]. EBSCO Information Services. http://search.ebscohost.com.ezproxy.lib.uh.edu/login.aspx?direct=true&db=dme&AN=115113&site=dynamed-live&scope=site. Updated February 19, 2018. Accessed August 30, 2018. 101 Flagg EW, Torrone EA. Declines in anogenital warts among age groups most likely to be impacted by human papillomavirus vaccination, United States, 2006–2014. Am J Public Health. 2018;108(1):112–119. Adapted from CDC surveillance data, 2019. Available at: https://www.cdc.gov/std/stats18/STDSurveillance2018-full-report.pdf Flagg EW, Torrone EA. Declines in anogenital warts among age groups most likely to be impacted by human papillomavirus vaccination, United States, 2006–2014. Am J Public Health. 2018;108(1):112–119. Adapted from CDC surveillance data, 2019. Available at: https://www.cdc.gov/std/stats18/STDSurveillance2018-full-report.pdf § Usually asymptomatic § Condyloma acuminatum § Postcoital bleeding § Itching § Burning sensation § Pain 104 Image source: http://3.bp.blogspot.com/-fGlyTrrT8h4/VQRAHZvlElI/AAAAAAAAA2A/pEdkOvR6Wxo/s1600/Genital-Warts-2.jpg Image source: http://www.dermis.net/bilder/CD213/550px/img0153.jpg § Physical exam § Lesion biopsy § Acetic acid test Image source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1194819/bin/genitmed00032-0022-c.jpg 105 § Goal: Removal or remission of warts § Drug regimens of choice (external) § Imiquimod 3.75% cream daily HS § Imiquimod 5% cream three times daily HS § Podofilox 0.5% sol BID x 3days, off x4 days. Repeat < 4x § Sinecatechins 15% thin layer three times daily max 16 weeks § Cryotherapy or Surgical removal § Urethral meatus, vaginal, cervical, or intra-anal warts 106 § Imiquimod § Leave on 8 hours then rinse § Wash hands § Photosensitivity § Inflammation § Xeroderma § Sinecatechins § Minor skin reactions § Vascular eruption § Podofilox § Minor skin reactions § Flammable Podofilox. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated July 11, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7509 Imiquimod. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 24, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7459 107 §3rd most common cancer diagnosis §9th largest cause of cancer mortality §Directly linked to HPV § HPV detected in 99.7% of cervical cancer § Oncogenic HPV types ≠ anogenital types § Incidence reduced due to HPV vaccine 108 § Gardasil 9 (6, 11, 16, 18, 31, 34, 45, 52, and 58) § 66% of cervical cancers (16, 18), § 90% of anogenital warts (6, 11) § 3 doses – 0,1-2, and 6 months § FDA Approved 9-45 YO in 2018 § CDC/ACIP recommendations § Routine for all at age 11 or 12 § Catch up through age 26 § Now, recommended up to 45 (shared clinical decision making) 109 § Identify the most common genital ulcer in the United States. a) Condyloma acuminata Anogenital warts c) Chancres d) Herpetic lesions b) 110 111 Image source: http://helloflo.com/wp-content/uploads/2016/02/shutterstock_336068534.jpg §Vaginal/cervical infection untreated § Gonorrhea and/or chlamydia (~50%) § Trichomoniasis § Vaginal candidiasis § Bacterial vaginosis 112 Gonorrheal or chlamydial infection Low socioeconomic status Sexually active Previous PID At risk Recent IUD placement 113 § Possibly asymptomatic § Lower abdominal pain § Abnormal bleeding § Dyspareunia/postcoital bleeding § Cervical/uterine tenderness § Fever § ↑ WBCs in vaginal fluid § ↑ ESR and CRP 114 § Goal: cure infection to prevent further damage § Cover for polymicrobial infections § Empiric therapy 115 Bacterial vaginosis • Gardnerella vaginalis, Lactobacillus spp., Bacteriodes fragilis, Mycoplasma hominis, etc. Endocervical infection • Mycoplasma genitalium, N. gonorrhoeae, C. trachomatis, and T. vaginalis Upper reproductive tract flora • Hemophilus ducreyi Many PID infections are polymicrobial • Must cover for anaerobes, gram negative rods, group A and B streptococcus, N. gonorroheae, and C. trachomatis 116 § Regimen 1 § Ceftriaxone 1 g IV every 24 hours § Doxycycline 100 mg PO/IV every 12 hours § Metronidazole 500 mg PO/IV every 12 hours § Regimen 2 § Cefotetan 2 g IV every 12 hours § Doxycycline 100 mg PO/IV every 12 hours § Alternative regimens § Ampicillin- sulbactam + doxycycline § Clindamycin + gentamicin § Regimen 3 § Cefoxitin 2 g IV every 6 hours § Doxycycline 100 mg PO/IV every 12 hours All regimens should be to complete 14 days. Transition to IM/PO after 24-48 hours of clinical improvement. 117 § Regimen 1 § Ceftriaxone 500 mg IM x1 (1 g for > 150 kg) § Doxycycline 100 mg PO BID x 14days § Metronidazole 500 mg PO BID x 14 days § Regimen 2 § Cefoxitin 2 g IM x1 § Doxycycline 100 mg PO BID x 14days § Metronidazole 500 mg PO BID x 14 days § Regimen 3 § Other 3rd gen cephalosporin (ceftizoxime, cefotaxime, § Alternative regimens § Levofloxacin + metronidazole § Moxifloxacin + metronidazole § Azithromycin + metronidazole etc.) § Doxycycline 100 mg PO BID x 14days § Metronidazole 500 mg PO BID x 14 days 118 Anaerobes • Cefotetan • Cefoxitin • Metronidazole Gram negative rods • Ceftriaxone • Cefotetan • Cefoxitin Group A/B Streptococcus • Cefotetan • Cefoxitin • Ceftriaxone N. gonorrhoeae • Cefoxitin • Ceftriaxone • Cefotetan C. trachomatis • Doxycycline 119 § Cefotetan and cefoxitin § GI effects § Cefotetan has disulfiram-like reaction Cefotetan. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 23, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6556 Cefoxitin. In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 23, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6557 Clindamycin (Systemic). In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 28, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/1770161 Gentamicin (Systemic). In: Lexi-Drugs Online [Electronic Database]. Hudson, OH: Lexicomp, Inc. Updated Aug 3, 2018; Accessed Aug 31, 2018. Available from: https://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/1797819 120 § Symptom persistence § Abstain from vaginal intercourse until treatment complete & partner treated § Routine test of cure in 3 months if gonorrheal or chlamydial § Treat all partners < 60 days 121 Joshua Wollen, Pharm.D. [email protected] PHAR 5338: ID2 Module Fall 2023