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Gonorrhea. California STD/HIV Prevention Training Center STD Clinical Series. Neisseria gonorrhoeae. Gram-negative diplococcus Infects non-cornified epithelium. Second m ost common bacterial STD Estimated >1 million US cases per year Incidence highest among adolescents and young adults

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Gonorrhea l.jpg

Gonorrhea

California STD/HIV Prevention Training CenterSTD Clinical Series


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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


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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”


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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


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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


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GC Microbiology

  • Gram-negative diploccocus

  • Infects non-cornified epithelium

    • Cervix

    • Urethra

    • Rectum

    • Pharynx

    • Conjunctiva

  • Observed intracellularly in PMNs on Gram stain


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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


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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


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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


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Gonococcal Cervicitis

  • Incubation 3-10 days

  • Symptoms:

    • Vaginal discharge

    • Dysuria

    • Vaginal bleeding

  • Cervical signs :

    • Erythema

    • Friability

    • Purulent exudate

STD Atlas, 1997


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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


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Gonococcal Bartholinitis

  • Tender swollen Bartholin’s gland with purulent discharge

  • Infection at other sites common

STD Atlas, 1997


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Bartholin’s Abscess

  • Painful swollen Bartholin’s glands

  • Fluctuant, tender

  • May have expressible purulent discharge


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Gonococcal Infections in Men

  • Pharyngitis

  • DGI

  • Urethral stricture

  • Penile edema

  • Urethritis

  • Epididymitis

  • Proctitis

  • Conjunctivitis

  • Abscess of Cowper’s/Tyson’s glands

  • Seminal vesiculitis

  • Prostatitis

    Many infections asymptomatic


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Gonococcal Urethritis

  • Incubation 2-7 days

  • Abrupt onset of severe dysuria

  • Purulent urethral discharge

  • Most urethral infections symptomatic

STD Atlas, 1997


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STD Atlas, 1997

Epididymitis

Epididymitis

  • Swollen painful epididymis

  • Urethritis

  • Epididymal tenderness or mass on exam


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Gonococcal Infections in Women & Men

  • Urethritis

  • Proctitis

  • Pharyngeal infections

  • Conjunctivitis

  • Disseminated Gonococcal Infection


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Gonococcal Ophthalmiain the Adult

  • Marked chemosis and tearing

  • Typically purulent discharge, erythema

STD Atlas, 1997


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Gonococcal Ophthalmia in the Adult

  • Conjunctival erythema and discharge


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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


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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


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DGI Skin Lesion

  • Necrotic, grayish central lesion on erythematous base

STD Atlas, 1997


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DGI Skin Lesion

  • Papular and pustular lesions on the foot

STD Atlas, 1997


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DGI Skin Lesion

  • Small painful midpalmar lesion on an erythematous base

STD Atlas, 1997


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DGI Skin Lesion

  • Pustular erythematous lesions


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DGI Skin Lesion

  • Papular erythematous skin lesion


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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


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Gonococcal Complications in Pregnancy

  • Postpartum endometritis

  • Septic abortions

  • Post-abortal PID

    Possible role in:

    • Gestational bleeding

    • Preterm labor and delivery

    • Premature rupture of membranes


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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


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Gonococcal Ophthalmia Neonatorum Gonorrhea

  • Lid edema, erythema and marked purulent discharge

  • Preventable with ophthalmic ointment

STD Atlas, 1997


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GC Infections in Children Gonorrhea

  • Vulvovaginits

  • Urethritis

  • Proctitis

  • All cases should be considered possible evidence of sexual abuse

  • Culture should be obtained


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GC Diagnostic Methods Gonorrhea

  • Gram stain smear

  • Culture

  • Antigen Detection Tests: EIA & DFA

  • Nucleic Acid Detection Tests

    • Probe Hybridization

    • Nucleic Acid Amplification Tests (NAATs)

    • Hybrid Capture


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Gram stain Gonorrhea

(male urethra exudate)

DNA probe

Culture

NAATs *

Sensitivity

90-95%

85-90%

80-95%

90-95%

Gonorrhea Diagnostic Tests

Specificity

 95%

 95%

 99%

 98%

* Able to use URINE specimens


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GC Gram Stain Gonorrhea

  • 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


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Gram Stain for GC: Urethral Smear Gonorrhea

  • Numerous PMNs

  • Gram negative intracellular diplococci

STD Atlas, 1997


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Gram Stain for GC: Cervical Smear Gonorrhea

  • PMN with Gram negative intracellular diplococci

STD Atlas, 1997


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GC Culture Gonorrhea

  • 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


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GC Culture Candle Jar Gonorrhea

STD Atlas, 1997


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GC Culture Specimen Streaking GonorrheaCervical and Urethral

STD Atlas, 1997


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GC Culture After 24 Hours Gonorrhea

STD Atlas, 1997


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Gonorrhea Treatment GonorrheaGenital & 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


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Gonorrhea Treatment GonorrheaGenital & 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


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Empiric Co-Treatment of GonorrheaCT 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


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Gonorrhea Treatment GonorrheaExtra-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


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Gonorrhea Treatment GonorrheaPregnancy

Must avoid quinolones & tetracycline

Recommended regimens:

  • Cefixime 400 mg PO x 1

  • Ceftriaxone 125 mg IM x 1

    PLUSif 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


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Gonorrhea Treatment GonorrheaNeonates

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


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Gonorrhea Treatment GonorrheaNeonates

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


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Gonorrhea Treatment GonorrheaChildren

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


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DGI Treatment GonorrheaInitial 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


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DGI Treatment GonorrheaSubsequent 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


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GC Antimicrobial Resistance Gonorrhea

  • 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


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Use of Fluoroquinolones to GonorrheaTreat 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)


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CipR GC in California Gonorrhea

  • 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.


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GC Patient Counseling Gonorrhea

  • 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


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GC Partner Management Gonorrhea

  • 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


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GC Prevention Strategies Gonorrhea

  • 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


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Gonorrhea Screening GonorrheaCalifornia 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


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Gonorrhea Screening in Pregnancy Gonorrhea

  • 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


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