Lecture 21 Women’s Reproductive Infectious Diseases and Genitourinary Infections Elwood

VULVOVAGINITIS: TRICHOMONIASIS: INFECTIOUS Protozoan• Trichomoniasis OVERVIEW: RISK FACTORS: Bacterial • (BV) • Protozoan! • Sexual contact with a confirmed or • Syphilis • Anaerobic parasitic flagellated suspected case • Gonorrhea protozoal infection • Unprotected sex with a resident of • Chlamydia • Most common non-viral STI an area with high burden and/or Viral • HSV • 3.1% reproductive-aged women high risk of antimicrobial resistance • HPV • 180 million infectious annually • History of previous infection Fungal • Yeast • Not reportable • History of other STIs, including HIV NON- Dermatosis• Lichen sclerosis • Sex workers & their sexual partners INFECTIOUS • Eczema

• Contact SYMPTOMS: • Sexually active youth < 25 yrs old • Atopic dermatitis FEMALES: • Street-involved youth and other • Psoriasis • Asymptomatic homeless populations • Bechet’s • Abdominal pain, dysuria • Individuals who have sex with Malignancy• Vulvar intraepithelial neoplasia • Vulvitis, , pruritus, multiple partners • Vaginal intraepithelial neoplasia • Profuse discharge; frothy TESTING: yellow/green CORE PRINCIPLES: • Antigen • Wet mount – • Associated with • Correct diagnosis • Culture must be received • PPROM, PTB, PP w/in 1 hr • Understand the organism you are targeting • NAAT • Correct medication, at the correct dose for the correct duration MALES: • “Treatment failure” • Asymptomatic TREATMENT: • Urethritis, prostatitis, • Metronidazole 2 g PO x 1 dose VAGINAL MICROBIOMES: vagina is seen as a microbiome rather than epididymitis • Metronidazole 500 mg PO BID x 7 d occupied by single organisms

BACTERIAL VAGINOSIS:

OVERVIEW: CLINICAL DIAGNOSIS OF BV: • The most prevalent cause of and odour AMSEL’S CRITERIA – 3 of the following 4 criteria • The most common cause of infectious vaginitis in both Vaginal pH > • Normal 3.8 – 4.5 pregnant and non-pregnant women 4.7 • Low pH • Prevalence rates are 10-30% in pregnant and 10% in non- o Inhibits bacterial growth pregnant women presenting to their GP o Decreases bacterial attachment • Elevated in: POTENTIAL COMPLICATIONS: o o Intercourse • Preterm labor & delivery • Postpartum endometritis o Lack of estrogen (post-menopausal) • PPROM • SSI • Elevated pH associated with BV & trich • SA • Subclinical PID Discharge • • Chorioamnionitis • Increased rates of HIV Homogenous appearance of discharge Amine odour • Produced by products from anaerobic bacterial metabolism • Elevation of pH (KOH, seminal fluid) RISK FACTORS: • Volatilizes amines from protein attachment • Black race • Using vaginal douches or Clue cells on • Represent bacteria attached to vaginal epithelial cell • Smokers intravaginal products microscopy • Most specific when: o 400 x power • Although not currently considered a STI, BV has been o > 20% of epithelial cells are clue cells consistently associated with sexual activity • Gram stain diagnosis: Nugent’s Criteria o It is more common in those sexually active, and the risk seems to increase with both number of sexual partners ALTERNATIVE THERAPIES: and frequency of intercourse PROBIOTICS • Species & strains of Lactobacillus are species tropic • To date, no strains commercially available in Canada which TREATMENT OF BACTERIAL VAGINOSIS: colonize the human vagina

• Metronidazole 500 mg PO BID x 7 days* (* 75-85% effective) • Therefore, little utility in txt of BV or yeast with probiotics • Metronidazole gel 0.75%, one applicator (5g) PV daily x 5 days* VAGINAL • More women in placebo group still had BV at end of F/U • Clindamycin cream 2%, one applicator (5g) PV x 7 days VITAMIN C • Total length of F/U in vitamin C study = 20 days TABLETS • Further studies show mixed results ALTERNATIVES: • Metronidazole 2 g PO x single dose BV IN PREGNANCY: • Clindamycin 300 mg PO BID x 7 days • If bacterial vaginosis is diagnosed in a symptomatic woman, treatment is indicated o Metronidazole 500 mg PO BID x 7 days RECURRENT BV: 1/3 will recur in 3 mo (important to reconfirm dx) o Clindamycin 300 mg PO BID x 7 days (as alternative) 1. Metronidazole 500 mg PO BID x 10-14 days • Topical agents are not recommended 2. If PO metronidazole is ineffective, use metronidazole gel 0.75%, • High rates of recurrence in some women one applicator (5g) daily x 10 days, then 2x/week x 3-6 months • Evidence for screening women with history of pre-term birth at 12-16 weeks and

treat regardless of symptoms • Condoms may ↓ likelihood of recurrence in sexually active ♀ • Avoid douching

Lecture 21 Women’s Reproductive Infectious Diseases and Genitourinary Infections Elwood

VULVOVAGINAL : Candida albicans (mostly) OVERVIEW: TREATMENT OPTIONS FOR UNCOMPLICATED VVC: • Common – 75% women will be affected in their lifetime (OTC) Cream/ointment 1% once daily x 7 days • Common member of vaginal microbiome (20% of women) 2% once daily x 3 days 10% once only RISK FACTORS: Insert/ovule/suppository 200 mg once daily x 3 days 500 mg once only • Sexual activity • Immunosuppression Miconazole (OTC) Cream/ointment 2% once daily x 7 days • Antibiotic use (ex// poorly controlled HIV 4% once daily x 3 days • Pregnancy infection or diabetes) Insert/ovule/suppository 100 mg once daily x 7 days

400 mg once daily x 3 days SIGNS AND SYMPTOMS: 1200 mg once only • A thick cottage-cheese-like discharge associated with Fluconazole (OTC) Oral 150 mg once only vaginal and vulvar: Terconazole (Rx) Cream 0.4% once daily x 7 days o Pruritus o Edema o Pain o External dysuria TREATMENT IN PREGNANCY: o Burning o Dyspareunia • o Erythema Yeast infections are more common in pregnancy • Require longer courses of therapy o Topical azole treatments = safe and first line INDICATIONS FOR CULTURES: o Nystatin = alternative • Treatment failure • AVOID oral fluconazole and boric acid • Unclear diagnosis

COMPLICATED VCC:

DEFINITION: RECURRENT VCC: • Recurrent (≥ 4 episodes in 12 months) Induction Imidazole cream 10-14 days (dose as uncomplicated) • Associated with severe symptoms Fluconazole (oral) 150 mg x 3 doses (72 hours apart) • Result of a non-albicans species Boric acid insert 300-600 mg daily x 14 days • Present in a compromised host Maintenance Clotrimazole insert 500 mg once monthly x 6 months Fluconazole (oral) 150 mg once weekly PELVIC EXAMINATION (DIAGNOSIS): Boric acid insert 300 mg daily x 5 days at beginning of each menstrual cycle • Thick discharge and pruritis non-specific Ketoconazole (oral) 100 mg once daily • Erythema/edema

• Thick, white clumped vaginal discharge NON-VAGINAL VCC: • pH < 4.5 Boric acid insert 300-600 mg nightly x 14 nights • Gram stain: budding yeast and pseudohyphae and PMNs Flucytosine cream 5 g once daily x 14 days • Whiff test is negative Amphotericin B suppository 50 mg once daily x 14 days Nystatin suppository 100,000 U once daily x 3-6 months

COMPARING BV vs. VVC vs. TRICH: BV VVC TRICH Predisposing factors • Sexually active • Sexually active • Multiple partners • New partner • Current/recent antibiotics • IUD • Pregnancy • Corticosteroids • Diabetes • Immunocompromised Symptoms • Vaginal discharge • Vaginal discharge • Vaginal discharge • Fishy odor • Itch • Itch • Asymptomatic • Dyspareunia • Dysuria • Asymptomatic • Asymptomatic Signs • White/grey thin discharge • White, clumpy & curdy discharge • Frothy discharge (yellow/green) • +ve whiff test • Erythema and edema of the vagina and • “Strawberry ”

HERPES SIMPLEX: HSV PATHOGENESIS: CLINICAL CLASSIFICATION OF HSV INFECTION: • Enters body thru mucocutaneous sites due to direct contact First Primary • First outbreak • DNA virus – latent in cells, causing long-term evasion of episode infection • New infection immune system and capability of reactivation • No previous exposure to HSV • Seronegative for HSV-1 & HSV-2 DIAGNOSIS: Non-primary • First outbreak • Culture or viral PCR of lesion infection • New infection • If unable to detect virus, do NOT assume it is not herpes • Previous infection with HSV • Seropositive for HSV-1 or HSV-2 • Type specific serology helpful in select circumstances Recurrent • Recurrent HSV outbreak that follows a first outbreak of HSV infection

Lecture 21 Women’s Reproductive Infectious Diseases and Genitourinary Infections Elwood HERPES SIMPLEX (CONTINUED):

HSV TRANSMISSION: WHICH TREATMENT OPTIONS TO USE? • Need to counsel about risks of transmission EPISODIC CONTINUOUS o 70% of transmission during asymptomatic shedding • Minimum impact on QOL • Severe impact on QOL o 30% of transmission during symptomatic outbreak • No psycho- sexual, social problems • Not coping • Use of condoms to lessen transmission • Infrequent recurrence • Sexual, social disturbances • Can reduce risks with suppressive antivirals • Mild recurrences • Frequent recurrences • Role of serology to determine partner discordance • Well-defined prodrome • Severe recurrences

• Issues for pregnancy (vertical transmission risk) • Episodes not well defined o Primary infection lesion = 50% risk • Acyclovir 200 mg PO 5x/d x 5 days • Acyclovir 200 mg 5x/day o Or 400 mg PO TID o Or 400 mg PO BID o Recurrent lesion = 2.5% risk • Valacyclovir 500 mg PO BID x 5 d • Famciclovir 250 mg BID o Risk of shedding = 1% • Famciclovir 125 mg PO BID x 5 days • Valacyclovir 500 – 1000 mg daily o Overall risk in HSV-infected woman = 0.025% on any

given delivery day (calculated)

HSV IN PREGNANCY: • Common – 30-40% of seroprevalence in most obstetrical populations HSV PREGNANCY MANAGEMENT: • Transplacental infection – case reports only, multiorgan destruction • Examine: caesarian section if lesion or symptoms • Neonatal infection – rare (1 in 5,000 births) • If primary in third trimester: elective C-section o 50% of these due to primary maternal infection • Consider acyclovir suppression o Skin, CNS, pneumonitis (9-14 days) o Acyclovir 400 mg TID from 36 weeks to delivery

HUMAN PAPILLOMA VIRUS: EPIDEMIOLOGY: THERAPEUTIC OPTIONS: • HPV is a highly prevalent virus PODOPHYLLIN • Unstandardized extract from May apple plant • 1-2% of the US population have visible genital warts • Disrupt mitosis by binding to microtubules • Study of women < 25 yrs old: 10-40% infected • Embryotoxin and neurotoxin • HPV types 6 & 11 most common (150 subtypes) • Excessive absorption can result in coma • Contraindicated in pregnancy • Not preferred NATURAL HISTORY OF HPV: TRICHLOROACETIC • Low cost, simple, relatively effective • Up to 75% of sexually active adults in US have clinical or serologic ACID (85%) • Volume of warts/session depends on pt tolerance evidence of HPV • Repeat weekly • After acquisition, HPV remains for 8-16 months • Large areas unsatisfactory

• Most not detectable at 2 years by PCR • Safe in pregnancy CRYOTHERAPY • Requires fresh supply of liquid nitrogen / cryoprobe DIAGNOSIS: • Depth of thermal injury difficult to judge • Assess for typical appearance • Treatment of large areas generally unsatisfactory • Utilize 3-5% acetic acid to enhance acetowhite appearance (3-5 min) • Repeat every 1-2 weeks o Or can use enhanced magnification alone • Safe in pregnancy • Biopsy if: pigmented, atypical, ulcerated or bleeding; unresponsive to EXCISION • Sx resection – requires training but relatively simple drug therapy, age > 55, cervical warts • Raise epidermis off dermis by injection of aq lidocaine, lift wart and resect with fine scissors TREATMENT: • Cauterize base with silver nitrate • Cannot be predictably eradicated • Rare complication of infection • Goal: • Advantage – single session removal o Decrease tumor burden without cosmetic disfigurement LASER • Requires specific training and expensive equipment o Increase cellular immune response • May require general anesthesia for large wart areas • No improvement with treatment of sex partners • Scarring in up to 26% of patients PODO- • 0.5% solution applied by hand BID 3x/week x 4 wks PHYLLOTOXN • Burning, erythema, and erosions can occur (30-50%) (pt applied) • Contraindicated in pregnancy IMIQUIMOD • 5% cream rubbed on lesions TID x 16 weeks (pt-applied) o Examined q monthly • Potent pro-inflammatory cytokine inducer • Erythema, erosions, excoriating in 30-60%

Lecture 21 Women’s Reproductive Infectious Diseases and Genitourinary Infections Elwood

URINARY TRACT INFECTIONS:

OVERVIEW: SYMPTOMS: POSITIVE PREDICTIVE FACTORS: • One of the most commonly treated infections • Dysuria • Symptoms after intercourse • 50-60% women will experience in a lifetime • Frequency • History of pyelonephritis • Suprapubic pain • Absence of nocturia CLASSIFICATION: • May be hematuria • Prompt resolution of symptoms (48h) after initiation of treatment CYSTITIS • Acute uncomplicated • Complicated DDX: • Beware nocturia & persistence of sx between episodes of treated! • Recurrent UTI • Vaginitis • Women with history of recurrent UTI can self-diagnose accurately PYELONEPHRITIS • Complicated • Acute urethritis (up to 84%) • Uncomplicated • Interstitial cystitis • PID HOST DEFENSES AGAINST UTIs: • Innate response WHAT TO LOOK FOR ON URINAYSIS TO DIAGNOSE A UTI: • Adaptive immune response SIGNIFICANCE OF URINALYSIS FINDING Leukocyte • Released by lysed neutrophils & macrophages = surrogate marker for WBC PATHOGENS IN UTIs: esterase • False positives  dilute • Urinary pathogenic E. coli • False negatives  concentrated urine, proteinuria, glucosuria • Specific toxins and adhesins WBC • > 6-10 + neutrophils/hpf = pyuria • FimH • Sterile pyuria  interstitial nephritis and nephrolithiasis • papA Nitrite • Enterobacteriaceae (Gram-negative bacilli) have nitrate reductase (reduces nitrate to nitrite) COMPLICATED CYSITIS: abnormalities of GU tract • False negatives  bacteria with low levels of nitrate reductase • Obstruction • Indwelling catheters RBC • > 2 RBC/hpf = hematuria • Urolithiasis • Diabetes mellitus • DDx: renal calculi, glomerulonephritis, malignancy … • Pregnancy • Renal failure Casts • WBC casts  kidney inflammation (infectious or non-infectious) • Tumors • Immunosuppression TREATMENT OF UNCOMPLICATED CYSTITIS: DDx: pyelonephritis; consider if it is complicated UTI ALTERNATIVE THERAPIES FOR UTI: • Regionally specific based on antimicrobial resistance patterns! • Multiple studies show evidence for short course treatment in uncomplicated UTI PROBIOTICS: • Locally: nitrofurantoin 100 mg PO BID x 5 days OR Septra DS 1 tab PO BID x 3 days • Some evidence may be beneficial • Pregnant: nitrofurantoin 100 mg PO BID x 7 days OR Cefixime 400 mg PO daily x 7 dats • No strains sold in Canada which colonize the human vagina RECURRENT UTI: CRANBERRY EXTRACT: RECURRENT UTI • 2 uncomplicated UTIs in 6 months OR • PAC = inhibits adhesions • 3 positive cultures within the preceding 12 months

• Unclear evidence and limitations due to ► Txt strategies: continuous prophylaxis, post-coital prophylaxis, unregulated nutraceutical products acute self-treatment, (vaginal) estrogen in post-menopausal women • No consistently supporting evidence RELAPSE • Recurrent infection with the same organism despite adequate txt showing benefit of cranberry extract REINFECTION • Recurrent UTI caused by a different bacterial isolate, or by the same • Do not use grocery store cranberry juice isolated bacteria after a negative intervening culture or an adequate time period (2 weeks) between infections

PYELONEPHRITIS: CLINICAL AND LAB FINDINGS: CONSIDERATIONS FOR HOSPITALIZATION: History • Lower urinary tract sx (frequency, urgency, dysuria) • Comorbidities (renal failure, urologic disorders, DM, liver/cardiac) • Upper urinary tract sx (flank pain) • Hemodynamic instability, toxic instability, very high fever (>39.4o) • Constitutional sx (fever, chills, malaise) • Metabolic derangement (renal dysfunction, acidosis) • GI sx (nausea, vomiting, anorexia, abdominal pain) • Severe flank or abdominal pain Physical • Fever, tachycardia, hypotension • Male sex, pregnancy exam • Costovertebral angle, abdominal, suprapubic tenderness Labs • Urinalysis showing +ve leukocyte esterase test, RISK FACTORS WOMEN: microscopic pyuria or hematuria, or WBC casts • Sexual intercourse ≥ 3 times per week in previous 30 days • Peripheral blood smear showing leukocytosis +/- left shift • UTIs in previous 12 months • Positive blood culture (15-30%) • Diabetes, stress incontinence • Urine culture growing ≥ 105 CFU/mL • New sex partner in previous year GU tract • Complicated acute pyelonephritis occurs in patients with • Recent spermicide use a structural of functionally abnormal GU tract Complicated • Catheter-associated bacteremia TREATMENT: • Emphysematous pyelonephritis

• Extensively drug-resistant organism • Oral ciprofloxacin (500 mg BID) x 7 days +/- initial IV dose • Perinephric or intrarenal abscess • Septra DS 14 days • Urinary obstruction • Consider ciprofloxacin 1000 mg PO daily or levofloxacin 750 mg Pathogens • E. coli (82% in women, 73% in men) daily if resistance rate < 10% (local resistance to E. coli = 28%) • Klebsiella , etc • Consider ceftriaxone 1 g IV x 1 dose if resistance > 10% or susceptibilities not known