BASICSPaul Lyons, MD
BASICS
DESCRIPTION
A sexually or vertically transmitted bacterial infection caused by Neisseria gonorrhoeae:
• N. gonorrhoeae is a fastidious gram-negative intracellular diplococcus (1)[A].
• Present as conjunctival, pharyngeal, urogenital, or anorectal infections. Urogenital infections are the most common (1)[A].
• Hematogenous dissemination leads to fever, cutaneous lesions, arthralgias, purulent or sterile arthritis, tenosynovitis, endocarditis, or (rarely) meningitis (1)[A].
• Asymptomatic carrier states occur in both sexes.
• In newborns, gonococcal ophthalmia neonatorum, a purulent conjunctivitis, may occur after vaginal delivery by an infected mother, potentially leading to blindness if not treated promptly (1,2)[A].
• System(s) affected: cardiovascular, musculoskeletal, nervous, reproductive, skin/exocrine
• Synonym(s): gonococcal infection (GC); clap
EPIDEMIOLOGY
• Predominant age: 15 to 24 years (1,2)[A]
• Predominant sex: women 105/100,000; men 92/100,000 (2)[A]
Incidence
CDC 2015: 820,000 reported cases annually (3)[A]
Prevalence
Incidence and prevalence are roughly equal. The true prevalence is higher due to asymptomatic cases (2)[A]:
• Rates peaked in mid-1970s and fell 74% over the next 20 years with national control program (2)[A].
• Highest rate: women aged 20 to 24 years (578/100,000) followed by women aged 15 to 19 years (521/100,000) (2)[A]
• Blacks (462/100,000) have higher reported rates of infections than whites (31/100,000) (2)[A].
• The southern regions of the United States have higher reported rates; highest reported rates in Mississippi (231/100,000) (2)[A].
ETIOLOGY AND PATHOPHYSIOLOGY
Infection requires four steps: (i) mucosal attachment. Bacterial proteins bind to receptors on host cells, (ii) local penetration/invasion, (iii) local proliferation, (iv) inflammatory response or dissemination. N. gonorrhoeae spreads most commonly through sexual relations.
Genetics
Congenital deficiency of late components of complement cascade (C7–C9) are prone to develop dissemination of local gonococcal infections.
RISK FACTORS
• History of previous gonorrhea infection or other STIs
• Sexual exposure to an infected individual without barrier protection (condom)
• New/multiple sexual partners
• Inconsistent condom use
• Commercial sex work or drug use
• Infants: infected mother
• Children: sexual abuse by infected individual
• Autoinoculation (finger to eye)
GENERAL PREVENTION
• Condoms offer partial protection and must be used appropriately during oral, anal, and vaginal intercourse.
COMMONLY ASSOCIATED CONDITIONS
DIAGNOSIS
HISTORY
• Sexual history
– Number of partners and age of onset of sexual activity; STI history
– New/recent change in sexual partners
– Contact with commercial sex workers
– Condom use
– Menses and possibility of pregnancy
• 10% of men and 20–40% of women are asymptomatic (2)[A].
• If symptomatic, explore the onset, context, duration, timing, severity, and associated symptoms:
– Symptoms (when present) typically appear within 1 to 14 days after exposure (1)[A].
• Ocular symptoms: discharge, itch, redness (1)[A]
• Pharyngeal symptoms: asymptomatic infection (98%), sore throat (1,3)[A]
• GI symptoms: acute diarrhea (1)[A]
• Urinary symptoms: urinary frequency, urgency, dysuria (1)[A]
– Males: scant to copious purulent urethral discharge (82%), dysuria (53%), testicular pain (1%), asymptomatic infection (10%), proctitis
– Females: asymptomatic cervical infection (20%), endocervical discharge (96%), vaginal discharge, Bartholin gland swelling, dysmenorrhea, menometrorrhagia, abdominal pain/tenderness, dyspareunia, cervical motion tenderness, rebound, infertility, chronic pelvic pain
• Either sex, for receptive anal intercourse: rectal discharge, tenesmus, rectal burning; can be asymptomatic
– Fever, chills, malaise, skin rash, arthralgia
– Endocarditis: high fevers
– Meningitis: meningeal signs, headache, skin lesions, fever, altered mental status
PHYSICAL EXAM
• General: fever, chills (1)[A]
• Ocular: purulent discharge, conjunctivitis, chemosis, eyelid edema, corneal ulceration (1)[A]
• Pharynx: exudative pharyngitis (<1%) (1)[A]
• GI: acute diarrhea, hyperactive bowel sounds (1)[A]
• Genitourinary (GU) (1)[A]
– Males: urethral discharge, testicular tenderness (1%)
– Females: endocervical discharge, Bartholin gland abscess, abdominal pain/tenderness, cervical motion tenderness, rebound tenderness
• Either sex, for receptive anal intercourse: rectal discharge; rectal exam may be normal (1)[A].
• Disseminated syndromes (1)[A]:
– Fever, chills, malaise, tenosynovitis, maculopapular-pustular rash, polyarthralgia—typically large joints (knee, wrist, ankle), purulent arthritis
– Endocarditis: rapid cardiac valve destruction, heart murmurs, high fevers
– Meningitis: meningeal signs, headache, skin lesions, fever, altered mental status
DIFFERENTIAL DIAGNOSIS
Chlamydia trachomatis, UTIs, other vaginitis, or urethritis (bacterial, viral, or parasitic)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
• Nucleic acid amplification (NAAT) is the most sensitive and specific test for N. gonorrhoeae (2)[A]. Other options:
– Genital culture
– Add pharyngeal culture in adolescents.
– Gram stain (recommended for urethritis)
– Urethral smear, sensitivity in symptomatic male: ≥95%; sensitivity of endocervical smear in infected woman: 40–60%; specificity: 100%
• DNA probes and polymerase chain reaction (PCR) sensitivity: 92–99% dependent on population; specificity: >97%; can replace culture
• Blood culture is 50% sensitive in disseminated disease. Joint fluid culture is 50% sensitive in septic arthritis. Screen for additional STIs, especially chlamydia, syphilis, and HIV.
• Imaging is not generally recommended.
Follow-Up Tests & Special Considerations
• Test of cure not generally recommended (1,2,3)[A].
• Consider follow-up testing in cases of recurrent infection, when oral cephalosporin treatment is used, and/or in areas with significant antibiotic resistance (2,3)[A].
• Pelvic ultrasound or CT scan may demonstrate thick, dilated fallopian tubes or abscess formation.
Diagnostic Procedures/Other
Culdocentesis may demonstrate free purulent exudate and provide material for Gram staining and culture. Gram-staining material from unroofed skin lesions may show typical organisms.
Test Interpretation
• Gram-negative intracellular diplococci
• Nonpathologic gram-negative diplococci may be found in extragenital locations. For this reason, Gram stain of pharyngeal or rectal swabs is not recommended.
TREATMENT
GENERAL MEASURES
• STI counseling and condom use
• In children and adolescents, suspect sexual abuse.
MEDICATION
• N. gonorrhoeae multidrug antimicrobial resistance continues to increase. In 2006, there were five recommended regimens for treating uncomplicated gonorrheal infection; this has been reduced to one primary option in the United States. CDC recommends dual therapy for all uncomplicated GC infections in U.S. adults and adolescents (both to treat for concomitant chlamydia and to increase efficacy against drug-resistant strains) (2,3,4)[A].
• Quinolones are not recommended (2,3,5)[A].
• If treatment fails, check culture and sensitivities and report to CDC through local health authorities (2,3,4)[A].
• Treat with regimen that is also effective against uncomplicated genital chlamydial infection (2,3,5)[A].
First Line
– Ceftriaxone 250 mg IM in a single dose
– PLUS treatment for chlamydia (azithromycin 1 g PO single dose or doxycycline 100 mg PO BID for 7 days)
• Pharyngitis: ceftriaxone 250 mg IM once PLUS treatment for chlamydia (azithromycin 1 g PO single dose or doxycycline 100 mg PO BID for 7 days) (1,2,3)[A]
• Conjunctivitis: ceftriaxone, 1 g IM single dose (1,2,3)[A]
• Pelvic inflammatory disease (PID): Parenteral and oral treatments are equivalent for mild to moderate severity PID. If using IV therapy, switch to PO within 24 to 48 hours of clinical improvement (1,2,3)[A].
– Cefotetan 2 g IV q12h OR cefoxitin 2 g IV q6h + doxycycline 100 mg PO or IV q12h
– Clindamycin 900 mg IV q8h + gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) q8h. Daily dosing (3 to 5 mg/kg) can be substituted.
– Preferred “oral” regimen includes the following:
Ceftriaxone 250 mg IM once + doxycycline 100 mg PO BID for 14 days
With or without metronidazole 500 mg PO BID for 14 days
– Ceftriaxone 1 g IM or IV q24h until 24 to 48 hours after improvement begins, then switch to cefixime 400 mg PO BID to complete at least 1 week of antibiotic treatment. Also treat for chlamydial infection.
– Ceftriaxone 1 to 2 g IV q12h 10 to 14 days for meningitis; 4 weeks for endocarditis
• Contraindications: Doxycycline is contraindicated in pregnancy and young children.
Pediatric Considerations
• Children >45 kg: same dosing as adults (1,2,3)[A]
• Children <45 kg: uncomplicated urethral, cervical, rectal, or pharyngeal gonococcal infections (1,2,3)[A]
– Ceftriaxone 125 mg IM in single dose
– Disseminated infections: ceftriaxone 50 mg/kg IV or IM daily (max dose 1 g) in single dose; bacteremia: 7 days; meningitis: 10 to 14 days; endocarditis: 4 weeks
• Ophthalmic neonatorum prophylaxis: single application of erythromycin 0.5% ophthalmic ointment to each eye immediately after delivery (1,2,3)[A]
• Neonatal conjunctivitis: ceftriaxone 25 to 50 mg/kg IV or IM in a single dose (not to exceed 125 mg) (1,2,3)[A]
• Conjunctival exudates should be cultured for definitive diagnosis (1,2,3)[A].
– Ceftriaxone 25 to 50 mg/kg/day IV or IM in a single daily dose for 7 days, with duration of 10 to 14 days if meningitis is documented
– Ceftriaxone 25 to 50 mg/kg IV or IM, not to exceed 125 mg in a single dose
Pregnancy Considerations
• Azithromycin 2 g orally in single dose for women intolerant to cephalosporin
• Treat concurrently with azithromycin or amoxicillin for presumed C. trachomatis coinfection.
• Women with 1st-trimester gonococcal infection should be retested within 3 to 6 months.
• High-risk uninfected pregnant women should be retested during the 3rd trimester.
Second Line
• Due to antimicrobial resistance, combination therapy using two agents with different mechanisms of action improves treatment efficacy and decreases resistance to cephalosporins (1,2,3)[A].
– Use of a second antimicrobial (azithromycin as a single 1-g oral dose or doxycycline 100 mg orally twice daily for 7 days) is recommended for use with ceftriaxone (1,2,3)[A].
– Azithromycin as the second antimicrobial is preferred to doxycycline because of convenience and compliance of single-dose therapy as well as higher resistance with tetracyclines (1,2,3)[A].
• For additional treatment options, see CDC STD treatment guidelines: http://www.cdc.gov/std/tg2015/
ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS
• Hematogenously disseminated infection
• Pneumonia or eye infection in infants
• PID: if unable to take oral medications, significant tubo-ovarian abscess, or patient is pregnant
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
U.S. Preventive Services Task Force (USPSTF) (4)[A]
• Screen all sexually active women, including those who are pregnant if they are at increased risk of infection (young or have other individual/population risk factor): Grade B recommendation
• Insufficient evidence to recommend for or against screening men at increased risk of infection: Grade I recommendation
• No routine screening in men and women who are low risk for infection: Grade D recommendation
• Insufficient evidence to recommend for or against screening in pregnant women who are not at increased risk for infection: Grade I recommendation
• Prophylactic ocular topical medication for all newborns: Grade A recommendation
PATIENT EDUCATION
• Counseling concerning risk reduction, condom use, future fertility, and full STI testing
• Encourage patient to notify partners (from past 60 days); consider EPT.
PROGNOSIS
Complete cure with return to normal function with adequate and timely treatment.
COMPLICATIONS
• Infertility
• Urethral stricture
• Corneal scarring
• Destruction of joint articular surfaces
• Cardiac valvular damage
Pediatric Considerations
Vertical transmission to newborn infants is a significant risk among patients with gonococcal infection at the time of delivery (1,2)[A].
REFERENCES
1. Mayor MT, Roett MA, Uduhiri KA. Diagnosis and management of gonococcal infections. Am Fam Physician. 2012;86(10):931–938.
2. Centers for Disease Control and Prevention. 2010 sexually transmitted diseases treatment guidelines: gonococcal infections. http://www.cdc.gov/std/treatment/2010/gonococcal-infections.htm. Accessed December 22, 2016.
3. Centers for Disease Control and Prevention. 2015 sexually transmitted diseases treatment guidelines: gonococcal infections. https://www.cdc.gov/std/tg2015/gonorrhea.htm. Accessed December 22, 2016.
4. Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012;61(31):590–594.
5. U.S. Preventive Services Task Force. Chlamydia and gonorrhea: screening. http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/chlamydia-and-gonorrhea-screening?ds=1&s=Gonorrhea. Accessed December 22, 2016.
SEE ALSO
Chlamydia Infection (Sexually Transmitted); HIV/AIDS; Pelvic Inflammatory Disease; Syphilis
CODES
ICD10
• A54.9 Gonococcal infection, unspecified
• A54.03 Gonococcal cervicitis, unspecified
• A54.31 Gonococcal conjunctivitis
CLINICAL PEARLS
• Antibiotic resistance is a significant problem. 30% of new gonorrheal infections are resistant to at least one drug. National recommendations have been released to combat antibiotic-resistant bacteria (https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf).
• Due to frequent coinfection and rising drug resistance, treatment for uncomplicated gonorrhea should include two drugs, one of which is effective against chlamydia.
• Screen patients with gonorrhea for chlamydia, syphilis, HIV, and hepatitis.