Sexually Transmitted Diseases and Infections Fall 2024 PDF

Sexually Transmitted Diseases and infections Joshua Wollen, Pharm.D. [email protected] PHAR 5338: Integrated Infectious Diseases 2 Module Fall 2024 Objectives š Identify relative prevalence for sexually transmitted diseases in the United States š Recall goals of therapy for each sexually...

Sexually Transmitted Diseases and infections Joshua Wollen, Pharm.D. [email protected] PHAR 5338: Integrated Infectious Diseases 2 Module Fall 2024 Objectives š Identify relative prevalence for sexually transmitted diseases in the United States š Recall goals of therapy for each sexually transmitted disease š Match clinical presentation and/or diagnostic information of a sexually transmitted disease to its treatment regimen of choice š Match drug information to drugs from treatment regimens of choice š Select appropriate follow-up measures for each sexually transmitted disease 2 Principal References š 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. š Guideline: Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70(4): 1-187. 3 Why is this important? Public health Complications Prevalence risks Psychosocial Healthcare Duration consequences costs 4  General Epidemiology US STD Incidence 2013 to 2022 100,000 Cases Chlamydia/Gonorrhea 20 70000 18 60000 Cases of 1º & 2º Syphilis 16 14 50000 12 40000 10 30000 8 6 20000 4 10000 2 0 0 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 Chlamydia Gonorrhea Syphilis 5 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm  2022 Texas STD Epidemiology Texas’s Texas Rank Texas incidence National average share of (cases/100K) (cases/100k) (cases/100k) cases (%) Chlamydia 9.4 16th 518 495 Gonorrhea 9.6 17th 206 194.4 Primary/secondary 7.9 26th 15.5 17.7 syphilis Congenital syphilis 24.6 4th 246.8 102.5 6 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm Clinical Prevention Strategy 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 CDC STD Prevention Measures for patients 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  Expedited Partner Therapy (EPT) š Also called patient-delivered partner therapy (PDPT) š Only one partner is assessed by prescriber š Therapy provided to patient to deliver to partner š No prescriber-patient relationship established for non-patient partner š In Texas, EPT is permissible by law š EPT encouraged for gonorrhea and chlamydia by Texas DSHS 9 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.  STD Lesions Urethritis, Skin & mucous vulvovaginitis, & membrane lesions cervicitis Chlamydia Gonorrhea Syphilis Anogenital warts Trichomoniasis Genital herpes Genital herpes 10 Urethritis š Discharge may be clear, mucopurulent, or very purulent š Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus š Dysuria š Hematuria š Feeling of genital heaviness š Epididymitis or prostatitis if untreated 11 Cervicitis š Mucopurulent secretions from endocervical canal š N. gonorrhoeae and C. trachomatis š Herpes simplex virus š Dysuria š Abnormal uterine bleeding š Lower abdominal pain š Dyspareunia š Postcoital bleeding 12  Vulvovaginitis š Inflammation of internal and external female genitals š Trichomonas vaginalis or Candida albicans š Vulvular itching or irritation š Dysuria š Dyspareunia š Purulent vaginal discharge š May contain blood š Abnormal “musty” odor 13  Chancres Skin and Mucous Condyloma latum Membrane Herpetic vesicles Lesions Condyloma acuminata 14 Chancres šPrimary syphilis šUsually painless šHighly infectious šSite of transmission šSolitary 15 Condyloma Latum šSecondary syphilis šAnogenital šRaised nodules or plaques šHighly infectious 16 Palmar-plantar Rash šSecondary syphilis šPalms and soles of feet šPigmented, macular lesions 17 Herpetic Vesicles šHerpes simplex virus Ulcers šMultiple lesions šUsually in clusters šMay be more Papules painful in women Vesicles 18  š Human papillomavirus š Anogenital Condyloma š Cauliflower-like masses acuminata š May be oncogenic š Internal/external 19 Overview Clinical Etiology Presentation Treatment Epidemiology Diagnosis 20  21 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 Chlamydia Etiology šChlamydia trachomatis šIntracellular šSexual or vertical transmission šEquivalent transmission 22  Chlamydia Epidemiology š Most commonly reported STD in the US š At risk populations šFemale < 25 YO šMSM šLow socioeconomic status 23 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm  2022 Chlamydia cases/100k – age/sex 24 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm  Chlamydia Clinical Presentation š Men often asymptomatic š Urethritis š Cervicitis š Conjunctivitis š Oropharyngeal and anorectal lesions š Symptoms less noticeable than gonorrhea 25 Chlamydia Diagnosis Endocervical Urethral or vaginal Urine culture swab swab 26  Chlamydia Screening Recommendations 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 27  Chlamydia Treatment strategy 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) 28 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  Drug Therapy for Chlamydia Doxycycline Nausea, diarrhea, and vomiting – take with food Erosive esophagitis – take with full glass of water Photosensitivity DDIs: Calcium salts, carbamazepine, and phenytoin 29 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 Chlamydia Follow up Symptom No condomless No routine test Adherence persistence sex for 7 days of cure Test of cure for Retest women Test all partners pregnant in 3 months in last 60 days women 4 after treatment weeks 30 Active Learning Question 1 šWhat 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 31  32 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 Gonorrhea Etiology š Neisseria gonorrhoeae š Gram negative diplococci š Intracellular š Sexual or vertical transmission š Increased male to female transmission 33  Gonorrhea Epidemiology š More common in the Southern United States š At risk populations š Male š Age < 25 š MSM 34 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm  2022 gonorrhea cases/100k – age/sex 35 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm 36  Sentinel sites and Regional Laboratories, Gonococcal isolate surveillance Project (GISP), 2021 NOTE: Baltimore and Seattle are both sentinel sites and regional laboratories. 37 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 1970s Penicillins 1980s Tetracyclines 1990s Fluoroquinolones 2007 Azithromycin 2009 Cephalosporins Ohnishi M, Saika T, Hoshina S, Iwasaku K, Nakayama S, Watanabe H, Kitawaki J. Ceftriaxone- 38 Resistant Neisseria gonorrhoeae, Japan. Emerg Infect Dis.17:148-149. doi:10.3201/eid1701.100397.  Neisseria gonorrhoeae — Prevalence of Tetracycline, Penicillin, or Fluoroquinolone Resistance or Elevated Cefixime, Ceftriaxone, or Azithromycin Minimum Inhibitory Concentrations (MICs), by Year — Gonococcal Isolate Surveillance Project (GISP), 2000–2022 39 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm  Resistance or Elevated MIC Patterns of Neisseria gonorrhoeae Isolates to Antimicrobials, Gonococcal Isolate Surveillance Project (GISP), 2022 40 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm Gonorrhea Clinical Presentation š Women often asymptomatic š Urethritis š Cervicitis š Conjunctivitis š Oropharyngeal and anorectal lesions š Symptoms more noticeable than Chlamydia 41 Gonorrhea Diagnosis Endocervical Urethral or vaginal Urine sample swab swab 42  Gonorrhea Screening Recommendations 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 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 43  Gonorrhea Treatment Strategies 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 44 *For patients WITHOUT gonococcal conjunctivitis, gonococcal-related arthritis, gonococcal meningitis, and gonococcal endocarditis.  Drug Therapy for Gonorrhea Ceftriaxone Allergy to cephalosporins Injection site reactions Diarrhea 45 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  Novel treatment for Drug-resistant N. gonorrhoeae Bexsero® for Gepotidacin EVO100 (Evoguard) Gonorrhea Triazaacenaphthlene Vaginal gel for Two-dose vaccine class prevention of Phase I trial endpoint Phase III trial (EAGLE- urogenital is t-cell cross 1) finished April 2024 chlamydia infection reactivity against N. Noninferior (92.% L-lactic acid, citric gonorrhoeae – cure rate) to acid, potassium decreased rates by ceftriaxone + bitartrate 50%! azithromycin (91.2% Phase III data due Phase II trial currently cure rate) summer 2022 enrolling Compared to placebo 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. 46 https://www.gsk.com/en-gb/media/press-releases/eagle-1-phase-iii-data-show-potential-for-gepotidacin-as-a-new-oral-treatment-option-for-uncomplicated-gc/ 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.  ETX0914 (zoliflodacin) Clinical Trial š Preliminary clinical trial for Zoliflodacin v Zoliflodacin ceftriaxone + azithromycin 3g 96% cure š 70:70:40 enrollment for zoliflodacin 3 g, zoliflodacin 2 g and standard of care, Zoliflodacin respectively n=141 mITT 2g 96% cure š Checked for cure at one week and safety checkup at one month Standard of care 100% cure š Cure rates in figure for anogenital and rectal infections š Oropharyngeal cure rates were 50% for 2 g and 82% for 3 g (100% Standard of care) Innoviva® planning to file for FDA approval beginning of š No significant increase in adverse events – most were gastrointestinal next year. 47 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. https://www.infectioncontroltoday.com/view/new-antibiotic-zoliflodacin-offers-hope-against-multidrug-resistant-gonorrhea  Zoliflodicin for gonorrhea šSpiropyridinetrione class šInhibits DNA biosynthesis šPhase III completed July 2023 š Noninferiority of microbiological cure of urogenital infection compared to IM ceftriaxone + azithromycin šRelative cure rate difference 5.31% (95% CI 1.38-8.65) š90.9% cure rate for zoliflodacin 48 https://clinicaltrials.gov/study/NCT04297436 Gonorrhea Follow up Symptom No condomless sex Adherence Test partners persistence for 7 days Test of cure for higher risk patients in No routine test of Test all partners in 7-14 days cure last 60 days Oropharyngeal Repeat infection 49 Active Learning Question 2 š 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 50 51 Syphilis Etiology š Treponema pallidum š Spirochete bacterium š Sexual, blood, and vertical transmission š Increased transmission from male to male 52  Syphilis Epidemiology š Uncommon but increasing š Congenital syphilis incidence increasing rapidly š Texas is 4th nationally š At risk populations š Male š MSM š Low socioeconomic status 53  2022 syphilis cases/100k – age/sex 54 Adapted from CDC surveillance data, 2022. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2021. Atlanta: U.S. Department of Health and Human Services; Updated January 30, 2024. Accessed October 23, 2024. https://www.cdc.gov/std/statistics/2022/figures.htm  Primary Secondary Neurosyphilis Latent Tertiary Stages of Syphilis 55 Primary Syphilis š 3-6 weeks post transmission š Chancres š Painless š Highly infectious š Occur at site of transmission 56 Secondary Syphilis 4-6 weeks post transmission Condyloma latum Palmar-plantar rash lesions Lymphadenopathy Patchy hair loss Fever Malaise 57  Typically asymptomatic Latent Non-transmissible Syphilis May last for years Early latent < 12 months post transmission Late latent > 12 months post transmission 58 Tertiary Syphilis š10-30 years post transmission šRare šOrgan damage šMostly CV and CNS affected šMay result in death 59 Neurosyphilis May occur at Presentation CSF findings any phase Usually > 6 Headache ↑ protein months post Poor motor ↑ leukocytes transmission function ↓ glucose Paralysis Positive for T. Dementia pallidum 60  Syphilis Diagnosis š Darkfield microscopy š 3 negative slides to rule out š Definitive diagnosis if positive š Primary and secondary syphilis 61 Syphilis diagnosis contd. 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) 62 Serological Quantitative test 0.5 0.5 0.5 0.5 0.5 mL mL mL mL mL Serum Serum Serum Serum 0.5 mL Serum NS NS NS NS Serum 0.5 0.5 0.5 0.5 0.5 mL mL mL mL mL NS NS NS NS NS 1:1 1:2 1:4 1:8 1:16 1:32 63 Population Recommendation Women Increased risk MSW Sexually active and < 29 Increased risk Syphilis Screening MSM Sexually active and < 29 Recommendations Annually if sexually active Every 3-6 months if increased risk Trans and Annually based on reported gender-diverse exposure Persons with If sexually active, at first HIV HIV evaluation and annually after More frequent possibly depending on individual risk behaviors and local epidemiology 64  Maternal Syphilis Testing First prenatal visit ONLY CDC High risk patients require additional testing after 28 weeks and delivery ALL pregnant persons must be tested Texas law at first prenatal visit, after 28 weeks, and at delivery 65 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.sh  Syphilis Treatment Strategies š Goal: cure of T. pallidum infection š 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 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 Neurosyphilis Pen G procaine 2.4 million units IM daily AND probenecid 500 mg PO QID x10-14 days 66 *Can also be as continuous infusion Alternative therapies Penicillin allergy Desensitization Primary/secondary (14 days) and latent Verified IgE-mediated allergy (28 days) Exceptions: Steven-Johnson syndrome, Doxycycline 100 mg PO BID toxic epidermal necrolysis, interstitial Tetracycline 500 mg PO QID nephritis, and hemolytic anemia Ceftriaxone 1-2 g IM/IV daily x10-14 Neurosyphilis, pregnancy, and days (primary/secondary only) congenital syphilis Questionable ability to follow up 67  Syphilis Drug Therapy Allergy possible Seizures Injection site Nausea and diarrhea Jarisch-Herxheimer reactions reaction (early syphilis) Pretreat with antipyretics 68 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 Syphilis Follow up š Adherence š Symptom persistence š Partner treatment regardless of serology š Primary, secondary, and early latent - all partners in last 90 days š Partner treatment if serologically positive š Primary – 3 months + duration of symptoms š Secondary – 6 months + duration of symptoms š Early latent – 1 year š Late latent – long term partners š Abstinence until asymptomatic (> 7 days) š Routine test of cure in 6 and 12 months (and 24 if latent) 69  Molina et al. 2018 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 70 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  Luetkemeyer et al. 2023 (DOXYPEP) š Randomized open-label study of MSM and transwomen (n=502) taking HIV PrEP or living with HIV š 2:1 doxycycline 200 mg within 72 hours after condomless sex or standard care š Primary endpoint: incidence of ≥1 bacterial STD (chlamydia, gonorrhea, or syphilis) every quarter at 270 days š Doxycycline showed relative risk reduction of about 20% (slightly higher in HIV prep group) š Secondary endpoints š Rates of tetracycline resistant N. gonorrheae occurred in 38% of doxycycline group and 13% of standard of care group (baseline 27%) š Rates of tetracycline resistant S. aureus occurred in 16% of doxycycline group and 8% of standard of care group š No serious adverse events reported in doxycycline group 71 Luetemeyer AF, Donnell D, Dombrowski JC, et al. Posexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023;388:1296-1306.  Doxycycline as PEP going forward Need to further May see bigger assess impact on Not currently Need to assess trials around drug resistance addressed in the outside of MSM doxycycline for PEP specifically with CDC guideline population in the future gonorrhea 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. 72 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. Active Learning Question 3 š 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 73  74 http://i.livescience.com/images/i/000/025/271/i02/chlamydia-bacteria.jpg?1331497002 Trichomoniasis Etiology š Trichomonas vaginalis š Flagellated protozoa š Sexual, vertical, or surface transmission š Increased female to male transmission 75  Trichomoniasis Epidemiology š Most common curable STD in the US š Most common non-viral STD in the US/globally š Estimated prevalence of 3.7 million in 2018 š At risk populations š Female < 25 YO š WSW š Douching š Incarcerated persons 76 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 Trichomoniasis Clinical Presentation š Most patients asymptomatic š Most men have spontaneous resolution š Vulvovaginitis š Urethritis (rare) 77 Diagnosis š No routine screening for HIV negative women š Suboptimal diagnosis š Vaginal/urethral culture š Wet-mount slide š Urine culture š POC testing š OSOM rapid trichomonas test š Vaginal swab antigen test 78 Trichomoniasis Screening Recommendations 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 79 Trichomoniasis Treatment Strategies šGoal: cure of T. vaginalis infection šRegimen of choice šFemales: metronidazole 500 mg PO BID x7 days šMales: metronidazole 2 g PO x1 šAlternative regimen šTinidazole 2 g PO x1 80  Metronidazole single dose vs 7-day regimen š 623 women randomized to either single dose or 7-day regimen š Primary outcome: positive T. vaginalis at test-of-cure š Single dose: 19% š 7-day regimen: 11% šRR 0.55, 95% CI (0.34 – 0.70); p 150 kg) š Doxycycline 100 mg PO BID x 14days regimens š Metronidazole 500 mg PO BID x 14 days § Levofloxacin + š Regimen 2 metronidazole š Cefoxitin 2 g IM x1 § Moxifloxacin + š Doxycycline 100 mg PO BID x 14days metronidazole š Metronidazole 500 mg PO BID x 14 days § Azithromycin + š Regimen 3 metronidazole š Other 3rd gen cephalosporin (ceftizoxime, cefotaxime, etc.) š Doxycycline 100 mg PO BID x 14days š Metronidazole 500 mg PO BID x 14 days 115 PID bugs and drugs Anaerobes Group A/B Streptococcus Cefotetan Cefotetan Cefoxitin Cefoxitin Ceftriaxone Metronidazole N. gonorrhoeae Cefoxitin Gram negative rods Ceftriaxone Cefotetan Ceftriaxone Cefotetan C. trachomatis Cefoxitin Doxycycline 116  PID Drug Therapy šCefotetan and cefoxitin šGI effects šCefotetan 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 117 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 PID Follow up Abstain from Routine test of cure Symptom vaginal intercourse Treat all partners < in 3 months if until treatment persistence gonorrheal or 60 days complete & partner chlamydial treated 118  Sexually Transmitted Diseases and infections Joshua Wollen, Pharm.D. [email protected] PHAR 5338: Integrated Infectious Diseases 2 Module Fall 2024