What Bugs You? A Sexually Transmitted Infection Review

Transcription

1 What Bugs You? A Sexually Transmitted Infection Review KATIE DESIMONE, PHARM.D. Disclosures I have no financial affiliations with any of the products or therapies discussed in this presentation Objectives Review current guidelines for sexually transmitted infections Discuss treatment options for sexually transmitted infections Review the current recommendations for vaccinations to prevent human papillomavirus Discuss the role of human papillomavirus in malignancies 1

2 Sexually Transmitted Infections in the US Chlamydia HPV Gonorrhea Genital Herpes Vaginitis BV Trichomoniasis Syphilis PID CHLAMYDIA Chlamydia Background & Incidence Most frequently reported infectious disease in the US 1,598,354 cases reported in 2016 Actual number of infections is likely higher Impact Significant contributor to healthcare costs Lifetime direct medical cost estimated at $516.7 million Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance Chlamydia. Atlanta: U.S. Department of Health and Human Services; September

3 Chlamydia Prevalence Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance Chlamydia. Atlanta: U.S. Department of Health and Human Services; September Chlamydia - Microbiology Chlamydia trachomatis Intracellular bacteria similar to that of gramnegative bacteria Cell wall lacks peptidoglycan Not seen with standard gram staining Renders beta-lactam antimicrobials ineffective Chlamydia Risk Factors &Transmission RISK FACTORS New or multiple sex partners History or presence of STIs Lack of barrier contraception Cervical ectopy TRANSMISSION Highly transmittable Approximately 55% between sexual partners Per-act transmission of 10% Slightly higher from men-to-women Vertical transmission Mother-to-infant via genital tract during birth 3

4 Chlamydia Clinical Manifestations MEN Urethritis Dysuria Urethral discharge Epididymitis Unilateral scrotal pain Epididymal swelling Tenderness WOMEN Cervicitis Vague discomfort Spotting Urethritis Dysuria-pyuria syndrome Urinary frequency Pelvic Inflammatory Disease Perihepatitis (Fitz- Hugh-Curtis Syndrome) EITHER GENDER Conjunctivitis Oropharyngeal Infection Proctitis and Proctocolitis Lymphogranuloma venereum (LGV) Reactive Arthritis Chlamydia Clinical Manifestations in Special Populations Conjunctivitis Most common clinical condition from perinatal transmission Occurs in 25% of neonates born to mothers with untreated infections Pneumonia Occurs in 10-15% of neonates born to mothers with untreated infections Appears 4-12 weeks after delivery Urogenital infections Chlamydial infections are infrequent among infants and children in the US Should be considered in cases of inadequate prenatal care Chlamydia Lab Testing Critical component of disease management and prevention Shift from culture-based to molecular based techniques Types of tests Nucleic Acid Amplification Tests (NAATs) Preferred Non-amplification molecular Tests Lower sensitivity than NAATs Not recommended Culture Limited Serology Limited 4

5 Chlamydia Treatment Urogenital infections in Adults and Adolescents (children 8 years old) Recommended Azithromycin 1 gram PO for a single dose OR Doxycycline 100 mg PO twice daily for 7 days Alternatives Erythromycin base 500 mg PO four times daily for 7 days Erythromycin ethylsuccinate 800 mg PO four times daily for 7 days Levofloxacin 500 mg PO daily for 7 days Ofloxacin 300 mg PO twice daily for 7 days Chlamydia Treatment for Special Populations Pregnancy Recommended Azithromycin 1 gram PO for a single dose Alternatives Amoxicillin 500 mg PO three times daily for 7 days Erythromycin base 500 mg PO four times daily for 7 days OR 250 mg PO four times daily for 14 days Erythromycin ethylsuccinate 800 mg PO four times daily for 7 days OR 400 mg PO four times daily for 14 days Ophthalmia Neonatorum or Infant Pneumonia Recommended Erythromycin base OR erythromycin ethylsuccinate 50 mg/kg/day PO divided into four daily doses for 14 days Alternative Azithromycin 20 mg/kg/day PO in one daily dose for 3 days Chlamydia Screening Women Pregnant Women Men Men who have sex with Men (MSM) Persons with HIV Sexually active women under 25 years of age Sexually active women aged 25 years and older if at increased risk Retest approximately 3 months after treatment All pregnant women under 25 years of age Pregnant women, aged 25 and older if at increased risk Retest during the 3rd trimester for women under 25 years of age or at risk Pregnant women with chlamydial infection should have a test-of-cure 3-4 weeks after treatment and be retested within 3 months Consider screening young men in high prevalence clinical settings or in populations with high burden of infection (e.g. MSM) At least annually for sexually active MSM at sites of contact (urethra, rectum) regardless of condom use Every 3 to 6 months if at increased risk For sexually active individuals, screen at first HIV evaluation then at least annually 5

6 Case A 26-year-old woman presents to the health department after having unprotected sex 6 weeks prior and requests a pregnancy test, which is positive. Based on her last menstrual period, she is 18 weeks into her pregnancy. She consents to STD screening at the same time. Two days later, the health department notifies her that she has tested positive for chlamydia. Which one of the following is recommended for treatment of cervical Chlamydia trachomatis infection in this pregnant patient? A) Amoxicillin-clavulanate875 mg/125 mg twice daily for 10 days B) Dicloxacillin 250 mg for times daily for 10 days C) Doxycycline 100 mg twice daily for 7 days D) Azithromycin 1 g orally in a single dose GONORRHEA Gonorrhea Background & Incidence Significant public health problem 468,514 reported cases in 2016 Increase from 2015 Rate decreased from Likely underestimated reporting Total lifetime direct medical cost in 2008 ~$162.1 million 6

7 Gonorrhea Prevalence Gonorrhea - Microbiology Neisseria gonorrhoeae Oxidase-positive, gram-negative diplococcus Rapid replication by binary fission Infects mucous-secreting epithelial cells Pathology Attached to epithelial cells via surface structures Ability to alter these structures leads to evasion Gonorrhea Risk Factors & Transmission RISK FACTORS Multiple or new sex partners Inconsistent condom use Areas with high disease prevalence Adolescent, females particularly Lower socio-economic status Use of drugs Exchange of sex for drugs or money African American TRANSMISSION VIA Male to female via semen Vagina to male urethra Rectal intercourse Fellatio (pharyngeal infection) Perinatal transmission (mother to infant) Gonorrhea associated with increased transmission of and susceptibility to HIV infection 7

8 Gonorrhea Clinical Manifestations MEN Urethritis Dysuria Urethral discharge Anorectal Infections Anal irritation Painful defecation Constipation Scant rectal bleeding Anal pruritus WOMEN Cervicitis Vague discomfort Spotting Anorectal Infections Accessory gland infection Bartholin s glands Skene s glands Pelvic Inflammatory Disease (PID) May be asymptomatic May present with lower abdominal pain, discharge, dyspareunia, irregular menstrual bleeding and fever Fitz-Hugh-Curtis Syndrome Perihepatitis EITHER GENDER Ocular Infection Pharyngeal Infection Disseminated Gonococcal Infection Gonorrhea Lab Testing Critical component of disease management and prevention Shift from culture-based to molecular based techniques Types of tests Nucleic Acid Amplification Tests (NAATs) Most sensitive Non-amplification molecular Tests Lower sensitivity than NAATs Gram Stain Reliable in men Culture Used in antimicrobial resistance Gonorrhea Treatment Adults and Adolescents Recommended Ceftriaxone 250 mg IM + azithromycin1 gram PO Replace ceftriaxone with gemifloxacin or gentamicin if PCN/cephalosporin allergy Alternatives Cefixime + azithromycin Cefixime + doxycycline Pregnancy Recommended Cephalosporin + azithromycin Alternatives Do not give flouroquinolones or tetracyclines to pregnant women 8

9 Gonorrhea Antibiotic Resistance Expedited Partner Therapy CDC recommends EPT for chlamydia and gonorrhea infections Similar recommendations as primary treatment Chlamydia azithromycin 1 gram x 1 dose Gonorrhea cefixime 400 mg x 1 dose + azithromycin Not recommended for MSM Case A 26-year-old male patient presents to clinic with dysuria and urethral discharge. He recently attended a bachelor party where he had unprotected intercourse with a female sex worker. Two days later, he had sex with his girlfriend without using a condom. He is diagnosed with urethral gonorrhea and treated with recommended therapy. The health department is contacting the commercial sex worker for treatment. The patient asks what his girlfriend should do since she is about to leave on an extended trip and will not be able to come to the clinic. Given the situation, which of the following is TRUE regarding expedited partner management of sex partners of patients diagnosed with gonococcal infection? A) Cefixime 400 mg orally in a single dose and azithromycin 1 g orally in a single dose is the recommended regimen when expedited therapy is used for gonorrhea contacts B) Levofloxacin 750 mg orally in a single dose and doxycycline 100 mg twice daily for 7 days is the recommended regimen when expedited therapy is used for gonorrhea contacts C) Expedited partner therapy is not recommended when the partner is not an established patient at the clinic D) Expedited partner therapy is not recommended for heterosexual patients as it has only been studied in men who have sex with men 9

10 VAGINITIS Background Dynamic ecosystem that contains approximately 10 9 bacterial colony-forming units. Normal vaginal discharge is clear to white, odorless, and of high viscosity Normal bacterial flora is dominated by lactobacilli Lactic acid helps to maintain a normal vaginal ph of 3.8 to 4.2 Some lactobacilli also produce H 2 O 2 Acidic environment and other host immune factors inhibits the overgrowth of bacteria Vaginitis Classification & Presentation Classifications Clinical Presentation Bacterial vaginosis (BV) (40%-45%) Trichomoniasis (15%-20%) Vulvovaginal candidiasis (20%-25%) Vaginal discharge Vulvar itching Irritation Odor 10

11 Bacterial Vaginosis Most common cause of vaginitis in reproductive age women Overall prevalence is 29% Displacement of lactobacilli by anaerobic bacteria Not considered a true STI Linked to sexual behavior RISK FACTORS African American Two or more sex partners in previous six months/new sex partner Douching Lack of barrier protection Absence of or decrease in lactobacilli Lack of H 2 O 2 -producing lactobacilli Bacterial Vaginosis Treatment Recommended Metronidazole 500 mg PO twice daily for 7 days Gel 0.75% (1 applicator 5 g) intravaginally at bedtime for 5 days Clindamycin Cream 2% (1 applicator 5 g) intravaginally at bedtime for 7 days Alternatives Tinidazole 2 grams PO daily for 2 days 1 gram PO daily for 5 days Clindamycin 300 mg PO twice daily for 7 days Ovules 100 mg intravaginally at bedtime for 3 days Bacterial Vaginosis Treatment in Special Populations Pregnancy/Breastfeeding Treat to prevent adverse obstetrical outcomes Avoid tinidazole HIV infection Clindamycin ovules might weaken latex Recurrent BV Recurrence is common Metronidazole intravaginal gel twice weekly for 4 to 6 months OR Metronidazole 500 mg twice daily (or tinidazole 500 mg twice daily) for 7 days followed by intravaginal boric acid 600 mg daily for 21 days followed by intravaginal metronidazole gel (0.75%) twice weekly for 4 to 6 months. 11

12 Trichomoniasis Trichomonas vaginalis Single-celled flagellated anaerobic protozoan parasite Almost always sexually transmitted 1.1 million new cases annually RISK FACTORS Older age Multiple sex partners Drug use (marijuana, crack cocaine, alcohol, cigarettes) Unprotected sex with non-primary partner Presence of STIs at baseline Low socioeconomic status Douching Black race Trichomoniasis Treatment Adults and Adolescents Recommended Metronidazole 2 grams PO for a single dose Tinidazole 2 grams PO for a single dose Alternatives Metronidazole 500 mg PO twice daily for 7 days Special Populations Pregnancy Metronidazole 2 grams PO for a single dose HIV infection Metronidazole 500 mg PO twice daily for 7 days PELVIC INFLAMMATORY DISEASE (PID) 12

13 PID Background and Incidence Clinical syndrome comprising a spectrum of infectious and inflammatory diseases of the upper female genital tract Ascending spread of organisms from the vagina or cervix Incidence is decreasing, but cost is high $1.88 billion in cost in 1998 PID Microbiology & Risk Factors Most cases are polymicrobial RISK FACTORS Age Age of sexual debut Number of sexual partners History of PID Vaginal douching IUD Oral contraceptive use PID Clinical Manifestations Wide array of presentations Many patients are asymptomatic Symptoms are often non-specific Acute Inflammatory complications Local tissue damage Chronic Ectopic pregnancy Infertility Chronic pelvic pain 13

14 PID Treatment Parenteral Recommended Cefotetan 2 g IV + doxycycline IV/PO both every 12 hours Cefoxitin 2 g IV + doxycycline IV/PO both every 12 hours Clindamycin 900 mg IV every 8 hours + gentamicin Alternatives Ampicillin-sulbactam 3 g IV every hours + doxycycline IV/PO every 12 hours Intramuscular/Oral Recommended Ceftriaxone 250 mg IV + doxycycline PO every 12 hours +/- metronidazole 500 mg twice daily for 14 days Cefoxitin 2 g IM for one dose + doxycycline PO every 12 hours + probenecid 1 gram PO for one dose +/- metronidazole 500 mg twice daily for 14 days SYPHILIS Syphilis Background & Incidence Represented in terms of primary and secondary disease Peak of cases in 1930s-1940s Near eradication in 1990s Increase in cases in cases 27,814 cases 16.5% increase from million dollars per year cost 14

15 Syphilis - Microbiology Treponema pallidum Corkscrew-shaped, motile microaerophilic bacterium from the spirochete class Syphilis Risk Factors & Transmission RISK FACTORS Men who have sex with men HIV infection History of incarceration History of commercial sex work Methamphetamine use TRANSMISSION Sexual transmission Entry through skin and mucous membranes via abrasions during sexual contact Contagious when lesions or rash is present Predominantly transmitted via genital sites Vertical transmission Transfusion transmission Syphilis Clinical Manifestations Primary Chancre forms at site of inoculation Highly infectious Usually accompanied by lymphadenopathy Secondary Mucocutaneous lesion most common Serologic tests are highest in this stage Latent No clinical evidence of disease Neurosyphilis May occur at any stage 15

16 Syphilis - Treatment PRIMARY SECONDARY EARLY LATENT LATE LATENT NEURO Penicillin G 2.4 million units IM X 1 Penicillin G 2.4 million units IM X 1 Penicillin G 2.4 million units IM X 1 Penicillin G 2.4 million units IM weekly X 3 Penicillin G 2.4 million units/day (divided q4-6h) X 14 days Alternative: Doxycycline 100 mg X 14 days Alternative: Doxycycline 100 mg X 14 days Alternative: Doxycycline 100 mg X 28 days Alternative: Doxycycline 100 mg X 28 days Alternative: Ceftriaxone 2 g daily X days Syphilis - Screening Pregnant Women Men who have sex with Men (MSM) All pregnant women at the first prenatal visit Retest early in the third trimester and at delivery if at high risk At least annually for sexually active MSM Every 3 to 6 months if at increased risk Persons with HIV For sexually active individuals, screen at first HIV evaluation then at least annually More frequent screening might be appropriate depending on individual risk behaviors and the local epidemiology Case SC is a 19-year-old male who presents to the STD clinic because he s had a sore on his penis for one week. Last sexual exposure was three weeks prior, without a condom. Predominantly female partners (three in the last six months), and occasional male partners (two in the past year). Last HIV antibody test (two months prior) was negative. What is the best choice for treatment for this patient? A) Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals B) Benzathine penicillin G 2.4 million units IM in a single dose C) Doxycycline 100 mg PO twice daily for 28 days D) Ceftriaxone 2 grams IV daily for 14 days 16

17 HERPES SIMPLEX VIRUS Herpes Simplex Virus Epidemiology Leading cause of genital ulcer disease worldwide HSV-1 and HSV-2 50 million infected people in the United States Lifetime direct medical costs estimated at $540 million Herpes Simplex Virus - Microbiology Alphaherpesviruses Life cycle Definitions First Clinical Episode Recurrent Severe 17

18 Herpes Simplex Virus Risk Factors HSV-1 Young women College students Men who have sex with men HSV-2 Women African-Americans Old age Increasing number of lifetime sexual partners Herpes Simplex Virus Transmission Greater likelihood from men to women Most are unaware they are infected Asymptomatic when transmission occurs Sexually Perinatally Herpes Simplex Virus Clinical Manifestations Incubation period between HSV acquisition and onset of symptoms is ~4 days Bilateral genital ulcers Pain Itching Dysuria Vaginal/urethral discharge Systemic symptoms 18

19 Herpes Simplex Virus Lab Testing Virologic Tests Polymerase Chain Reaction (PCR) High sensitivity Differentiation between HSV-1 and HSV- 2 Viral Culture High specificity, variable sensitivity Depends on stage of lesion and collection technique Antigen Detection Not recommended Type-Specific Serologic Tests Type Specific IgG- based assay Older assays are unable to differentiate Herpes Simplex Virus - Treatment Oral Antiviral Therapy Oral therapy offers clinical benefit to most patients with symptomatic disease Control or suppression of symptoms Will not eradicate disease First Clinical Episode Therapy Acyclovir 400 mg orally three times a day for 7 10 days Acyclovir 200 mg orally five times a day for 7 10 days Valacyclovir 1 g orally twice a day for 7 10 days Famciclovir 250 mg orally three times a day for 7 10 days Episodic Recurrence and Suppressive Therapy Same agents as others with varying schedule Herpes Simplex Virus- Pregnancy Safety of antivirals not established PO acyclovir may be given for first episode or severe recurrent IV acyclovir should be used for severe infection Recommend using suppressive acyclovir 19

20 Case A 19-year-old man presents to clinic with a 2-day history of fevers, malaise, and a painful lump in his right groin. About 6 hours prior to the clinic visit, he noticed multiple painful vesicles in the urethral opening and glans of his penis. He had insertive vaginal intercourse without a condom with a woman he met at a college party about 7 days ago. On examination, he has multiple small vesicles, with an erythematous border, on the penile glans and in the urinary meatus. A sample from one of the lesions is sent for herpes simplex virus (HSV) PCR testing. He has no prior history of any genital or oral lesions. A diagnosis of first-episode genital herpes simplex virus (HSV) infection is strongly suspected with a plan to initiate empiric treatment for HSV. Which one of the following is a recommended treatment for first clinical episode of genital herpes? A) Acyclovir 400 mg orally three times a day for 7 to 10 days B) Acyclovir 400 mg orally twice a day for 3 to 5 days C) Valacyclovir 500 mg orally twice a day for 5 to 7 days D) Topical acyclovir applied five times a day for 7 to 10 days HUMAN PAPILLOMAVIRUS (HPV) HPV Epidemiology Most sexually active people will acquire genital HPV at some point More than 90% will resolve spontaneously More than 170 types of HPV have been classified Approximately 40 can infect the human genital tract Genital HPV divided into two groups Low-risk (non-oncogenic) High-risk (oncogenic) Most notably types 16 and 18 Infection with HPV is not required to be reported in any state 20

21 HPV Prevalence HPV - Virology Small, non-enveloped, double-stranded DNA virus High affinity for genital skin and mucosa Infects the basal cell layer of stratified squamous epithelium and stimulates cellular proliferation Affected cells display a broad spectrum of changes HPV Risk Factors & Transmission RISK FACTORS Higher number of sexual partners Lower education level TRANSMISSION Male to female=50-70% Female to male=20% Perinatal transmission can occur during delivery when mother is untreated 21

22 HPV Clinical Manifestations Genital warts Condylomata acuminata Smooth papules Flat papules Keratotic warts Cervical dysplasia Anogenital squamous cell cancers Oropharyngeal cancers Recurrent respiratory papillomatosis HPV Cancer HPV Treatment/Genital Warts Patient-Applied Podofilox 0.5% solution or gel Twice daily for 3 days, followed by 4 day break Imiquimod 3.75% cream Nightly for 16 weeks Imiquimod 5% cream Nightly three times weekly for 16 weeks Sinecatechins 15% ointment Apply three times daily until warts are cleared Provider-Administered Cryotherapy Surgical removal Trichloroacetic acid (TCA) or or bichloroacetic acid (BCA) 22

23 HPV Screening for Cervical Cancer HPV Vaccine History 1990s : HPV 6, 11, 16, Discovery of 18 are linked Cervarix HPV to cancers approved 2013: Study shows HPV decreased 56% among teen girls 2015: ACOG states high efficacy with any of the three vaccines 1970s 2006: 2011: 2014: HPV can lead to cervical cancer Gardasil approved CDC recommends Gardasil for males Gardasil 9 approved HPV Vaccine Gardasil 9 Only HPV vaccine currently available in the US Protects against 9 strains of HPV Vaccine schedule 9-14 years old 2 dose schedule one dose followed by another dose 6-12 months later Safety 3 dose schedule one dose at 0, 2, and 6 months years old 3 dose schedule one dose at 0, 2, and 6 months Worldwide estimated 4 HPV types 5 HPV types 9 HPV types type cause: cause cause a total of: contribution for certain (6, 11, 16, an additional: (6, 11, 16, 18, 31, HPV-related and 18) (31, 33, 45, 52, 33, 45, 52, and cancer and disease and 58) 58) cases Cervical cancer 70% 20% 90% Vulvar cancer 75% 15% 90% Vaginal cancer 65% 20% 85% Anal cancer 85% 5% 10% 90% 95% High-grade cervical 50% 30% 80% precancers Low-grade cervical 25% 25% 50% lesions Genital warts 90% No contribution 90% 23

24 Case A pregnant women has multiple vulvar warts that she wants to have treated. Which one of the following choices is considered an acceptable option for this woman? A) Imiquimod 3.75% cream B) Podofilox 0.5% solution or gel C) Sinecatechins 15% ointment D) Trichloroacetic acid Questions? What Bugs You? A Sexually Transmitted Infection Review KATIE DESIMONE, PHARM.D. 24