California STD/HIV Prevention Training Center STD Clinical Series Gonorrhea California STD/HIV Prevention Training Center STD Clinical Series

Neisseria gonorrhoeae Gram-negative diplococcus Infects non-cornified epithelium Second most common bacterial STD Estimated >1 million US cases per year Incidence highest among adolescents and young adults Causes a range of clinical syndromes Many infections are asymptomatic

History of GC Neisseria gonorrhoeae described by Albert Neisser in 1879 Observed in smears of purulent exudates of urethritis, cervicitis, opthalmia neonatorum Thayer Martin medium enhanced isolation of gonococcus in 1960 AKA “The Clap”

Risk Factors for GC Infection Urban and low SES populations Adolescents > age 20-25 years > older Black/Hispanic > White/API Multiple sex partners Inconsistent use of barrier methods High prevalence in sexual network

GC Sexual Transmission Efficiently transmitted by sexual contact Greater efficiency of transmission from male to female Male to female: 50 - 90% Female to male: 20 - 80% Vaginal & anal intercourse more efficient than oral Can be acquired from asymptomatic partner Increases transmission and susceptibility to HIV 2-5 fold

GC Microbiology Gram-negative diploccocus Infects non-cornified epithelium Cervix Urethra Rectum Pharynx Conjunctiva Observed intracellularly in PMNs on Gram stain

GC Pathogenesis GC are ingested, evade host defenses, and spread through subepithelial tissues Attachment mediated by pili Divides every 20-30 minutes Leads to formation of submucosal abscesses and accumulation of exudate in lumen GC toxins damage cells

Gonococcal Infections in Women Cervicitis Urethritis Proctitis Accessory gland infection (Skene, Bartholin) Pelvic inflammatory disease (PID) Peri-hepatitis (Fitz-Hugh-Curtis) Pregnancy morbidity Conjunctivitis Many infections asymptomatic Pharyngitis DGI

Complications of GC Infections in Women Infertility Ectopic Pregnancy Chronic Pelvic Pain Psychosocial Upper Tract Infection Local Invasion Systemic Infection Genital Infection Congenital Infection HIV Infection

Gonococcal Cervicitis Incubation 3-10 days Symptoms: Vaginal discharge Dysuria Vaginal bleeding Cervical signs : Erythema Friability Purulent exudate STD Atlas, 1997

Pelvic Inflammatory Disease Sx: lower abdominal pain Signs: CMT, uterine/ adnexal tenderness, +/- fever Laparoscopy may show hydrosalpinx, inflammation, abscess, adhesions Adhesions Tube PID often silent STD Atlas, 1997

Gonococcal Bartholinitis Tender swollen Bartholin’s gland with purulent discharge Infection at other sites common STD Atlas, 1997

Bartholin’s Abscess Painful swollen Bartholin’s glands Fluctuant, tender May have expressible purulent discharge

Gonococcal Infections in Men Urethritis Epididymitis Proctitis Conjunctivitis Abscess of Cowper’s/Tyson’s glands Seminal vesiculitis Prostatitis Many infections asymptomatic Pharyngitis DGI Urethral stricture Penile edema

Gonococcal Urethritis Incubation 2-7 days Abrupt onset of severe dysuria Purulent urethral discharge Most urethral infections symptomatic STD Atlas, 1997

Epididymitis Epididymitis Swollen painful epididymis Urethritis Epididymal tenderness or mass on exam STD Atlas, 1997

Gonococcal Infections in Women & Men Urethritis Proctitis Pharyngeal infections Conjunctivitis Disseminated Gonococcal Infection

Gonococcal Ophthalmia in the Adult Marked chemosis and tearing Typically purulent discharge, erythema STD Atlas, 1997

Gonococcal Ophthalmia in the Adult Conjunctival erythema and discharge

Disseminated Gonococcal Infection Gonococcal bacteremia Sources of infection include symptomatic and asymptomatic infections of pharynx, urethra, cervix Occurs in < 5% of GC-infected patients More common in females Patients with congenital deficiency of C7, C8, C9 are at high risk

DGI Clinical Manifestations “Dermatitis-arthritis syndrome” Arthritis: 90% Characterized by fever, chills, skin lesions, arthralgias, tenosynovitis Less commonly, hepatitis, myocarditis, endocarditis, meningitis Rash characterized as macular or papular, pustular, hemorrhagic or necrotic, mostly on distal extremities

DGI Skin Lesion Necrotic, grayish central lesion on erythematous base STD Atlas, 1997

DGI Skin Lesion Papular and pustular lesions on the foot STD Atlas, 1997

DGI Skin Lesion Small painful midpalmar lesion on an erythematous base STD Atlas, 1997

DGI Skin Lesion Pustular erythematous lesions

DGI Skin Lesion Papular erythematous skin lesion

DGI Differential Diagnosis Meningococcemia Staphylococcal sepsis or endocarditis Other bacterial septicemias Acute HIV infection Thrombocytopenia & arthritis Hepatitis B prodrome Reiter’s Syndrome Juvenile Rheumatoid Arthritis Lyme disease

Gonococcal Complications in Pregnancy Postpartum endometritis Septic abortions Post-abortal PID Possible role in: Gestational bleeding Preterm labor and delivery Premature rupture of membranes

Vertical Transmission and Neonatal Complications on Gonorrhea Overall vertical transmission rate ~30% Neonatal complications include: Ophthalmia neonatorum Disseminated gonococcal infection (sepsis, arthritis, meningitis) Scalp abscess (if fetal scalp monitor used) Vaginal and rectal infections Pharyngeal infections

Gonococcal Ophthalmia Neonatorum Lid edema, erythema and marked purulent discharge Preventable with ophthalmic ointment STD Atlas, 1997

GC Infections in Children Vulvovaginits Urethritis Proctitis All cases should be considered possible evidence of sexual abuse Culture should be obtained

GC Diagnostic Methods Gram stain smear Culture Antigen Detection Tests: EIA & DFA Nucleic Acid Detection Tests Probe Hybridization Nucleic Acid Amplification Tests (NAATs) Hybrid Capture

Gonorrhea Diagnostic Tests Sensitivity 90-95% 85-90% 80-95% Specificity  95%  99%  98% Gram stain (male urethra exudate) DNA probe Culture NAATs * * Able to use URINE specimens

GC Gram Stain In symptomatic male urethritis: >95% sensitivity and specificity: reliable to diagnose and exclude GC In cervicitis: 50-70%sensitivity, 95% specificity Not useful in pharyngeal infections Accessory gland infection: similar to male urethritis Proctitis: similar to cervicitis

Gram Stain for GC: Urethral Smear Numerous PMNs Gram negative intracellular diplococci STD Atlas, 1997

Gram Stain for GC: Cervical Smear PMN with Gram negative intracellular diplococci STD Atlas, 1997

GC Culture Requires selective media with antibiotics to inhibit competing bacteria (Modified Thayer Martin Media, NYC Medium) Sensitive to oxygen and cold temperature Requires prompt placement in high-CO2 environment (candle jar, bag and pill, CO2 incubator) In cases of suspected sexual abuse, culture is the only test accepted for legal purposes

GC Culture Candle Jar STD Atlas, 1997

GC Culture Specimen Streaking Cervical and Urethral STD Atlas, 1997

GC Culture After 24 Hours STD Atlas, 1997

Gonorrhea Treatment Genital & Rectal Infections in Adults Recommended regimens: Cefixime 400 mg PO x 1 or Ceftriaxone 125 mg IM x 1 or Ciprofloxicin 500 mg PO x 1 or Ofloxacin 400 mg PO x 1 or Levofloxacin 500 mg PO x 1 PLUS if chlamydia is not ruled out: Azithromycin 1 g PO x 1 or Doxycycline 100 mg PO BID x 7 d All sex partners within past 60 days need evaluation and treatment CDC 2002 Guidelines

Gonorrhea Treatment Genital & Rectal Infections in Adults Alternative regimens: Ceftizoxime 500 mg IM x 1 Cefotaxime 500 mg IM x 1 Cefoxitin 2 g IM x 1 plus probenecid 1 g PO x 1 Gatifloxacin 400 mg PO x 1 Lomefloxacin 400 mg PO x 1 Norfloxacin 800 mg PO x 1 Spectinomycin 2 g IM x 1 CDC 2002 Guidelines

Empiric Co-Treatment of CT Infections Empiric co-treatment for chlamydia is cost effective if co-infection rate 20-40% and doxycycline used Prevalence monitoring in California demonstrates that ~50% of GC cases are co-infected with CT Consider testing rather than treating if local co-infection is low

Gonorrhea Treatment Extra-Genital Sites in Adults Pharyngeal infection: Ceftriaxone 125 mg IM x 1 or Ciprofloxicin 500 mg PO x 1 or PLUS if chlamydia is not ruled out: Azithromycin 1 g PO x 1 or Doxycycline 100 mg PO BID x 7 d Conjunctivitis: Ceftriaxone 1 g IM x 1 dose CDC 2002 Guidelines

Gonorrhea Treatment Pregnancy Must avoid quinolones & tetracycline Recommended regimens: Cefixime 400 mg PO x 1 Ceftriaxone 125 mg IM x 1 PLUS if chlamydia is not ruled out: Azithromycin 1 g PO x 1  Other appropriate chlamydial regimen Test of cure in 3-4 weeks CDC 2002 Guidelines CalSTDCB 2001

Gonorrhea Treatment Neonates Ophthalmia neonatorum prophylaxis: Silver nitrate 1% aqueous solution topical x 1 Erythromycin 0.5% ointment topical x 1 Tetracycline 1% ointment topical x 1 Ophthalmia neonatorum treatment: Ceftriaxone 25-50 mg/kg IV or IM x 1 NTE 125 mg NTE = not to exceed CDC 2002 Guidelines

Gonorrhea Treatment Neonates Prophylaxis for maternal GC infection: Ceftriaxone 25-50 mg/kg IV or IM x 1 NTE 125 mg Disseminated Gonococcal Infection: Ceftriaxone 25-50 mg/kg/d IV or IM QD x 7 d (use 50 mg/kg/d for older children, treat for 10-14 d if child weighs  45 kg) Cefotaxime 25 mg/kg IV or IM q12h x 7 d NTE = not to exceed CDC 2002 Guidelines

Gonorrhea Treatment Children Uncomplicated genital infection:  45 kg: same as adults  45 kg: ceftriaxone 125 mg IM x 1 (alternative spectinomycin 40 mg/kg IM x 1) Disseminated Gonococcal Infection: Ceftriaxone 25-50 mg/kg/d x 7 d Use 50 mg/kg/d for older children Treat for 10-14d if child weighs  45 kg CDC 2002 Guidelines

DGI Treatment Initial IV Therapy Begin IV therapy for 24-48 hrs, switch to oral therapy for a total of 1 week Recommended regimen: Ceftriaxone 1g IV or IM q 24 h Alternative Regimens: Cefotaxime 1 g IV q 8 h Ceftizoxime 1 g IV q 8 h Ciprofloxacin 400 mg IV q 12 h Ofloxacin 400 mg IV q 12 h Levofloxacin 250 mg IV q 24 h Spectinomycin 2 g IM q 12 h CDC 2002 Guidelines

DGI Treatment Subsequent Oral Therapy Oral therapy for total treatment of 1 week: Recommended Regimes: Cefixime 400 mg PO BID Ciprofloxacin 500 mg PO BID Ofloxacin 400 mg PO BID Levofloxacin 500 mg PO QD CDC 2002 Guidelines

GC Antimicrobial Resistance Resistance in 20%-30% of gonococcal isolates tested in U.S. Plasmid mediated B - Lactamase production High-level tetracycline resistance Chromosomal mediated Confers resistance to PCN, tetracycline, spectinomycin, erythromycin, fluoroquinolones, and/or cephalosphorins

Use of Fluoroquinolones to Treat GC Infection CipR GC up to 40% in Japan, Philippines, parts of SE Asia and the Pacific Islands CipR in Hawaii over 10% Antimicrobial resistance to fluoroquinolones increasing in the continental U.S., but still < 1% Providers should get a travel history and if infection may have been acquired in Hawaii, Asia or the Pacific Islands, patient should be treated with a cephalosporin Treatment failures should be cultured and tested for resistance (and re-treated)

CipR GC in California Prevalence of CipR GC in CA >10% in 2002 CA GC Tx Recommendations: Avoid the use of fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin) to treat GC in California. Use ceftriaxone 125mg IM x 1 to treat uncomplicated gonococcal infections of the cervix, urethra, and rectum Note: cefixime is no longer being manufactured.

GC Patient Counseling Nature of transmission Potential long term and neonatal complications Abstain from sex for at least 3-4 days during treatment (7 days if co-treated for CT) Warning signs and need for follow up Notification and need for treatment of partners

GC Partner Management All sex partners with contact during 60 days preceding the onset of symptoms or test date should be evaluated, tested & treated If no sex partners in previous 60 days, treat the most recent partner

GC Prevention Strategies Health promotion, education & counseling Increased access to condoms Early detection through screening in selected high risk populations Effective diagnosis & treatment Partner management Risk reduction counseling

Gonorrhea Screening California Provisional Guidelines Adolescent females from high prevalence areas All patients with other STDs MSMs with high risk behaviors Pregnant women < 25 years old Adolescents in juvenile halls

Gonorrhea Screening in Pregnancy Screen in 1st trimester and again in 3rd trimester (~32 weeks) for high-risk or high prevalence patients High risk includes new partners, multiple partners, non-mutually monogamous relationship, concurrent STDs Higher prevalence among adolescents, urban, low SES, certain geographic areas