Sexually Transmitted Infections Kelly Ruhstaller MD March 15, 2013 Overview • Review pathophysiology of common sexually transmitted infections including chlamydia, gonorrhea, trichimonas, herpes • Discuss pharmacologic treatment of the above listed infections • Review complications and treatment of pelvic infections including pelvic inflammatory disease and tuboovarian abscess Treatment Guidelines • All pharmacologic regimen recommendations are based on the 2010 CDC STD Treatment Guidelines publication Chlamydia trachomatis: epidemiology • • • • Most common bacterial STD In 2011 1.4 million cases reported to the CDC 1 in 15 teenage females infected Risk factors: • • • • • Age (adolescents and young adults) Black race Being unmarried Multiple sexual partners History of STDs • Infection does not result in immunity Chlamydia: Infection • Gram-negative bacteria, obligate intracellular organism • Two part life-cycle: • Elementary bodies infect cell and replicate • Cell ruptures, elementary bodies infect surrounding cells • Common for infection to be asymptomatic • Approximately 7-14 day incubation period for women and 510 days for men Chlamydia: symptoms • In women, common manifestation is cervicitis and mucopurulent discharge • • • • Cervical friability or edema Dull lower abdominal pain Dysuria Post-coital and intermenstrual bleeding • In men, most common symptom is urethritis and urethral discharge • • • • • Discharge white and thin Epididymitis Prostatisis (?) Proctitis Reactive arthritis Chlamydia: clinical signs Chlaymdia: clinical signs Chlamydia: testing/diagnosis • CDC recommends annual testing for sexually active women younger than 25, all pregnant women and older women with risk factors • Most common type of test is the NAAT • Nucleic acid amplification testing • Sample can be collected from cervix, vaginal discharge, urine • Test of cure • Pregnant women, persistent symptoms or suboptimal treatment • Retesting • Anyone treated should be test 3-12 months later to evaluate for reinfection Chlamydia: treatment • Due to the life cycle of chlamydia (ie only lives intracellularly) the antibiotic regimen must have good cellular penetration and intracellular activity • Life cycle of bacterium is long, requiring either extended treatment regimens or Abx with long half-life • Both macrolides and tetracyclines have excellent activity againist chlamydial infections Chlamydia: treatment Chlamydia: treatment • Azithromycin and Doxycycline have 97 and 98% efficacy • Azithromycin: • • • • • Half-life of 5-7 days, can be given as a single dose Treatment can be witnessed by provider ensuring treatment Safe in pregnancy Minimal side effects: mild GI upset Limitation to therapy is cost • Doxycycline: • Lower cost • Longer treatment course, potential for decreased compliance • Cannot be used in pregnancy due to skeletal and tooth damage in children of mothers treated with drug Chlamydia: treatment • Levofloxacin and ofloxacin: • Excellent efficacy, but requires a full week of treatment • Cannot be used in pregnancy, breastfeeding women or adolescents <18 yo due to concern for skeletal ab • More expensive • Erythromycin: • High degree of GI upset • Cure rates of only 85-89% • For use in pregnant women who cannot tolerate Azithromycin Chlamydia: complications • • • • • • • • Pelvic Inflammatory Disease Fitzhugh-Curtis Perihepatitis Infertility Ectopic pregnancy Increased risk of HIV infection Conjuctivits Lymphogranuloma venereum Preterm delivery Neisseria gonorrhea: epidemiology • Second most common bacterial STI • Most common in adolescents and young adults: • Women aged 15-19 yo • Men aged 20-24 yo • Risk factors: • • • • • • • African american Younger Southeastern US Unmarried, young adults Low educational and socioeconomic status New partner History of STD Gonorrhea: Infection • Four stages of infection: • Attachment, local invasion, proliferation and local inflammatory response/dissemination • In women: • • • • • Cervicitis Urethritis Pharyngitis PID Disseminated • In men: • • • • • Urethritis Epididymitis Proctitis Pharyngitis Disseminated Gonnorhea: clinical signs Gonorrhea: clinical signs Gonorrhea: diagnosis • Gram stain of urethral discharge (men only) • NAATs • Culture Gonorrhea: treatment • Goal of therapy: highly effective at all anatomic sites, be able to be given as a single dose and be well tolerated Gonorrhea: treatment Gonorrhea: treatment Gonorrhea: antimicrobial resistance Gonorrhea: resistance • Gonorrhea’s resistance to several classes of antibiotics was first noted in the 1940s when resistance to sulfonamides was noted • The CDC’s Gonococcal Isolate Sensitivity Project (GISP) was started in 1986 • Has since determined resistance to penicillins, tetracyclines, macrolides and fluroquinolones Gonorrhea: resistance to cephalosporins • MIC: minimum inhibitory concentration • Increasing MICs to both cefixime and ceftriaxone indicating increased resistance • MIC > 0.25mcg/mL is considered “elevated” • 15% of gonococcal isolates found to have elevated MIC • Evidence of cefixime treatment failure in Japan and Europe • Increased resistance to cetriaxone emerging • Worldwide increasing resistance • Several cases of resistance to ceftriaxone documented in Europe and Asia • Recommend dual therapy with azithromycin due to increasing rates of cephalosporin resistance Gonorrhea: Follow-up • Test of cure: • Pregnant women • Any patient who receives alternative therapy • Patient with persistent symptoms • Partner treatment: • Not recommended due to IM treatment being first-line therapy and high rate of resistance • Recommend patient abstain from intercourse for 7 days after treatment Gonorrhea: complications • • • • • • • Pelvic Inflammatory Disease Infertility Fitzhugh-Curtis Perihepatitis Disseminated gonorrhea Preterm Labor/Delivery Opthalmia Neonatorum Disseminated disease in the newborn Disseminated gonorrhea • Two separate manifestations: • Triad of tenosynovitis, dermatitis, polyarthralgia • Purulent arthritis • Treatment: • Ceftriaxone 1g IV/IM daily until symptoms are gone, then 250mg IM x 7 days • Co-treatment with 1g po Azithromycin or 100mg Doxycycline BID x 7 days – treatment for chlamydial co-infection • Do not recommend treatment with agent other than cephalosporin • No oral step-down regimen • Documented PCN allergy: admission, desensitization and treatment with ceftriaxone Trichomonas: epidemiology and infection • • • • • Estimated 3-5 million cases in the US Accounts for 4-35% of vaginitis cases Transmitted by Trichomonas vaginalis Sexually transmitted Incubation period is unknown and infection is often asymptomatic • Only 30-40% of male partners of infected women test positive for the organism due to transient and self-limited infection in men Trichomonas: Infection • Asymptomatic in 75% of men and usually resolves in <10 days • Men may present with urethritis and/or clear to mucopurulent discharge • Women often present with purulent, malodorous discharge • Acute inflammation of vagina and vulva • Classic symptoms of green frothy discharge occurs in <10% of patients and “strawberry cervix” with pinpoint hemorrhages on the cervix occurs in <2% of cases Trichomonas: clinical signs Trichomonas: diagnosis • Wet mount: pH >4.5 and motile trichomonads • Culture: 95% sensitivity, but 7 days to obtain results • NAAT: • • • • Affirm, Aptima and OSOM Results rapidly available Sensitivity: 88-100% Can be collected from urine, vaginal secretions or endocervical samples • Men: only reliable test is PCR, not widely available Trichomonas: treatment • Treat: • All symptomatic women • Non-pregnant, symptomatic women with incidental finding • Male partners Trichomonas: treatment Trichomonas: treatment • Treatment with metronidazole/tinidazole very effective • Do not recommend treatment with topical nitromidazoles • Pregnant women: • Increased rate of premature rupture of membranes and delivery • Treat symptomatic women with metronidazole during any trimester of pregnancy • Breastfeeding women should wait 12-24 hours after last dose to resume feeding • HIV-positive patients: • Recommend treatment with 7 day course • Patient with allergy to nitromidazoles: • Desensitization and treatment with nitromidazole Herpes simplex virus: epidemiology • 50 million individual infected with genital herpes in the US • Mostly caused by HSV-2 but HSV-1 genital infections are increasing • Risk factors: • • • • Increasing age Increasing number of sexual partners African-American Female HSV: transmission • Virus sheds from active lesions and 10% of days with no lesions • The virus invades through the skin and replicates within the nucleus • Virus travels down through sensory and autonomic nerve endings and then persists in latent form by residing in the sacral ganglia HSV: Types of Infection • Primary • Infection in a patient without prior antibodies to HSV1 or 2 • Nonprimary • Infection in a patient who was previously infected with the other HSV type (ie HSV 1 infection in a patient with a previous antibody to HSV 2) • Recurrent • Infection with the same strain of HSV as the patient has previously made antibodies against HSV: symptoms • Primary: • • • • • Incubation period: 4 days Length of symptoms: 19 days Spectrum of mild to severe symptoms Bilateral, painful pustular, ulcerating lesions Additional symptoms: systemic symptoms, local pain and itching, dysuria, painful lymphadenopathy • Nonprimary: • Less severe than primary infection • Recurrent: • Least severe symptoms • Shorter period of symptoms HSV: clinical signs HSV: diagnosis • Culture • Most accurate with vesicles present, unroof lesion and culture base • PCR • Specimen collected from mucocutaneous sites, lesions does not have to be present • Most accurate and can yield results during asymptomatic shedding • Serology • Type specific serology present within weeks of infection and persist lifelong • Cannot distinguish primary vs recurrent infection HSV: treatment • Anti-virals: • Acyclovir: uptake by infected cells, converted to acyclovir triphosphate and inhibits viral DNA polymerase • Famciclovir: converted to penciclovir in the liver and inhibits viral DNA polymerase • Valcyclovir: converted to acyclovir in vivo, acts as acyclovir does and inhibits viral DNA polymerase HSV: treatment • Primary infection (uncomplicated): • • • • • Oral therapy appropriate Treatment should begin within 72 hours of symptoms Treatment results is shorter and less severe course Analgesics and sitz baths improve symptoms Urinary retention can occur because of pain and/or due to sacral root ganglion involvement • Medications: • Acyclovir: 400mg po TID or 200mg po q 5 days • Valcyclovir: 1000mg po BID • Famciclovir: 250mg po TID HSV: treatment • Recurrent infection: • 1. No treatment • 2. Episodic treatment • 3. Suppressive therapy HSV: episodic vs suppressive Questions?