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

Complications of GC Infections in Women

Upper Tract Infection Infertility Ectopic Pregnancy Chronic Pelvic Pain Psychosocial

Genital Infection

Local Invasion Systemic 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

Adhesions

Tube

Sx: lower abdominal pain Signs: CMT, uterine/ adnexal tenderness, +/- fever Laparoscopy may show hydrosalpinx, inflammation, abscess, adhesions PID often silent

STD Atlas, 1997

Gonococcal Bartholinitis

Tender swollen Bartholins gland with purulent discharge

Infection at other sites common

STD Atlas, 1997

Bartholins Abscess

Painful swollen Bartholins glands

Fluctuant, tender

May have expressible purulent discharge

Gonococcal Infections in Men

Urethritis Pharyngitis Epididymitis DGI Proctitis Urethral stricture Conjunctivitis Penile edema Abscess of Cowpers/Tysons glands Seminal vesiculitis Prostatitis Many infections asymptomatic

Gonococcal Urethritis

STD Atlas, 1997

Incubation 2-7 days Abrupt onset of severe dysuria Purulent urethral discharge Most urethral infections symptomatic

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 Reiters Syndrome Juvenile Rheumatoid Arthritis Lyme disease

Gonococcal Complications in Pregnancy

Postpartum endometritis Septic abortions Post-abortal PID Gestational bleeding Preterm labor and delivery Premature rupture of membranes

Possible role in:

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
Gram stain DNA probe Culture NAATs * 90-95% 85-90% 80-95% 90-95%
(male urethra exudate)

Specificity
95%

95%
99% 98%

* Able to use URINE specimens

GC Gram Stain

In symptomatic male urethritis: sensitivity and specificity: reliable to diagnose and exclude GC In cervicitis: 95% specificity Not useful in pharyngeal infections
50-70%sensitivity, >95%

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
Azithromycin 1 g PO x 1 or Doxycycline 100 mg PO BID x 7 d
CDC 2002 Guidelines

PLUS if chlamydia is not ruled out:

All sex partners within past 60 days need evaluation and treatment

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 CDC 2002 Norfloxacin 800 mg PO x 1 Guidelines Spectinomycin 2 g IM x 1

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

CDC 2002 Guidelines

Conjunctivitis:

Ceftriaxone 1 g IM x 1 dose

Gonorrhea Treatment
Pregnancy
Must avoid quinolones & tetracycline

Recommended regimens:

Cefixime 400 mg PO x 1 Ceftriaxone 125 mg IM x 1 Azithromycin 1 g PO x 1

CDC 2002 Other appropriate chlamydial regimen Guidelines

PLUS if chlamydia is not ruled out:

Test of cure in 3-4 weeks

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 1014 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 CDC 2002 Guidelines Use 50 mg/kg/d for older children Treat for 10-14d if child weighs 45 kg

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 Cefotaxime

1g IV or IM q 24 h

Alternative Regimens:
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