Neisseria gonorrhoeae

Aka: Neisseria gonorrhoeae, Gonococcal Infection, Gonorrhea, Gonococcus, Gonococci, Gonococcemia, Disseminated Gonococcus, Multi-Resistant Neisseria Gonorrhea, Gonococcal Urethritis, Gonococcal Cervicitis, Gonococcal Proctitis

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II. Epidemiology

  1. Much less common than Chlamydia
  2. International Incidence: Nearly 87 Million cases in 2016
  3. Incidence: 500 to 700,000 cases per year in the United States
    1. Decreasing except in inner city, Drug Abuse (crack)
    2. Second most common reportable Sexually Transmitted Disease
  4. Highly contagious: 50% transmission
  5. Chlamydia coexists in 45-50% of patients with Gonorrhea
  6. Most common in young women
    1. Ages 15 to 19 years old
    2. Incarcerated women under age 35 years

III. Risk Factors

  1. Adults
    1. See Sexually Transmitted Disease
    2. Age <25 years old
    3. Black race
    4. Prior Sexually Transmitted Disease
    5. Drug Abuse
    6. Prostitutes
    7. Men who have Sex with Men
    8. Inconsistent Condom use
    9. Multiple sex partners
  2. Children
    1. Mothers with prior Sexually Transmitted Disease
    2. Mothers with Substance Abuse
    3. Mothers without Prenatal Care
    4. Sexual abuse
    5. No ophthalmic chemoprophylaxis at delivery (Ocular Gonorrhea)
  3. References
    1. (2005) Ann Fam Med 3(3): 263-7 [PubMed]

IV. Pathophysiology

  1. Caused by Neisseria gonorrhoeae
  2. Incubation: 2-7 days

V. Findings: Symptoms and Signs - General

  1. Urinary Symptoms
    1. Urinary Frequency
    2. Urinary urgency
    3. Dysuria
  2. Copious Urethral discharge
    1. Green, yellow, or sanguinous discharge
  3. Meatus and anterior Urethra inflammation
  4. Conjunctivitis
    1. Direct inoculation
    2. Copious exudate
    3. Beefy Conjunctiva
    4. Serious complications
      1. Corneal Ulceration or opacification
      2. Visual loss
      3. Globe Perforation
  5. Pharyngitis
    1. Rarely the only site of infection
      1. Accompanies Cervicitis in 10-20% of cases
    2. Usually asymptomatic or only mild in up to 90% of cases
    3. Associated with anterior cervical adenopathy
    4. More common in Men who have Sex with Men, HIV Infection or other STD
  6. Proctitis
    1. Receptive anal intercourse (especially in Men who have Sex with Men)
    2. Mild anal irritation or itching to Rectal Pain
    3. Mucopurulent discharge
    4. Painful Defecation or tenesmus
    5. May cause Acute Diarrhea

VI. Findings: Symptoms and Signs - Women (asymptomatic in 95% of cases)

  1. Delayed diagnosis is common with risk of Pelvic Inflammatory Disease or Disseminated Gonococcus
  2. Mucopurulent Cervicitis (most common presentation)
    1. Onset 5-10 days after exposure
    2. Odorless Vaginal Discharge (observed from os)
    3. Vaginal Bleeding or spotting (may present as Metrorrhagia)
    4. Friable Cervix bleeds easily
  3. Bartholin's gland inflammation
  4. Skene's gland inflammation

VII. Findings: Symptoms and Signs - Men (symptomatic in 90% of cases)

  1. Symptom onset within 2-6 days of exposure (may be delayed up to 30 days after exposure)
  2. Dysuria
  3. Epididymitis (unilateral Testicular Pain)
  4. Purulent discharge from Urethra meatus

VIII. Findings: Disseminated Gonococcus - Rheumatologic (<3% of cases)

  1. Gonococcal Arthritis
    1. Suppurative Monoarticular, Oligoarticular or Polyarticular presentations
    2. Aseptic Joint Aspiration does not exclude Disseminated Gonococcus
    3. Seeding of joint from bacteremia
    4. Requires joint wash-out
  2. Dermatitis-Arthritis Syndrome
    1. See Gonorrhea for Management (this page refers primarily to Gonococcal Arthritis)
    2. Bacteremia Classic Triad (onset 2 weeks after initial infection)
      1. Polyarticular Tenosynovitis
        1. Wrists and hands
        2. Ankles and feet
      2. Polyarthralgia
        1. Joints are typically not purulent (do not require wash-out)
      3. Dermatitis (75% of cases)
        1. Distal extremity lesions on dorsal surfaces
        2. Papules or Pustules (2 to 10) on purpuric base with necrotic areas

IX. Findings: Disseminated Gonococcus - Other

  1. High fever may be present (variable)
  2. Disseminated Gonococcus is more common in pregnancy
  3. Endocarditis (rare)
  4. Meningitis (rare)
  5. Dermatitis (75% of cases)
    1. May be combined as Dermatitis-Arthritis Syndrome (see above)
    2. Rash especially on extremities, palms and soles (may also affect trunk)
    3. Present as Papules (bullae, Petechiae may be found)
      1. Usually less than 10-20 total lesions (typically 3 or less)
    4. May progress into Hemorrhagic Pustules on purpuric base with necrotic areas
      1. Necrotic Pustule ("gun metal gray") on red base over distal, dorsal extremity (wrists, palms and soles)

X. Findings: Symptoms and Signs - Children

  1. Age >1 year
    1. Nearly always associated with sexual abuse
  2. Age <1 year (esp. day of life 2-5)
    1. Attributed to Vaginal Delivery
    2. Pharyngitis
    3. Neonatal Sepsis
    4. Scalp abscess (associated with fetal scalp electrode)
    5. Meningitis
    6. Arthritis
    7. Neonatal Conjunctivitis (Ophthalmia Neonatorum)
      1. Onset 6 days after exposure
      2. Conjunctival inflammation
      3. Mucopurulent Eye Discharge
      4. Evaluation
        1. Gram Stain of Conjunctival discharge for Gram Negative intracellular diplococci
        2. Gonococcal culture
      5. Prompt management prevents Globe Rupture or blindness

XI. Differential Diagnosis: Gonorrhea

  1. See Cervicitis
  2. See Vaginitis (or Vaginal Discharge)
  3. See Urethritis
  4. See Neonatal Conjunctivitis
  5. See Proctitis
  6. See Pharyngitis Causes
  7. See Polyarthritis
  8. See Sexually Transmitted Infection
  9. Secondary Syphilis
  10. Monkeypox (Mpox)

XII. Differential Diagnosis: Disseminated Gonococcal Infection

  1. Hypersensitivity Vasculitis
  2. Infective Endocarditis
  3. Korean hemorrhagic fever
  4. Meningococcemia
  5. Reiter's Syndrome
  6. Sweet's Syndrome
  7. (2005) Am Fam Physician 71(3):534-6 [PubMed]

XIII. Complications

  1. Pelvic Inflammatory Disease (PID) in 10-20% of cases
  2. Fitz-Hugh Curtis Syndrome (rare)
    1. Perihepatitis syndrome that may present as right upper quadrant pain
  3. Systemic Gonorrhea
  4. Chronic Arthritis
  5. Neonatal Gonorrhea
    1. Gonorrheal Conjunctivitis
  6. Preterm Labor
  7. Endocarditis (rare)
  8. Meningitis (rare)

XIV. Labs

  1. Nucleic Acid Amplification Test (DNA probe)
    1. Reliable alternative to culture (preferred for screening)
    2. Sample
      1. Men: Urethra or urine
      2. Women: Cervical swab is preferred
    3. Rapid: 30 minutes
    4. Test Sensitivity: 92-96%
    5. Test Specificity: 94-99%
  2. Gram Stain: Urethral or Cervical Smear
    1. Numerous White Blood Cells
    2. Gram Negative biscuit-shaped diplococci
      1. False PositiveGram Stain (saprophytic Neisseria)
  3. Gonorrhea Culture and Sensitivity
    1. Culture medium of Chocolate agar or Martin-Lewis agar
    2. Required for Disseminated Gonococcus testing
      1. Blood Culture
      2. Throat Culture
      3. Synovial Fluid
  4. Screen all patient for concurrent other Sexually Transmitted Infections
    1. Chlamydia (same DNA probe as for Gonorrhea)
    2. HIV
    3. Syphilis

XV. Diagnostic Studies

  1. Endoscopy in suspected Gonococcal Diarrhea
    1. Nonspecific findings limited to Rectum
    2. Biopsy and Culture show superficial exudates

XVI. Management: Multi-Drug Resistance

  1. Antibiotics that are no longer effective against Gonorrhea
    1. Cefixime or Suprax
      1. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm
      2. Not recommended as of 2012
    2. Ciprofloxacin and other Fluoroquinolones
    3. Penicillins
    4. Sulfanilamide
    5. Tetracyclines (including Doxycycline)
  2. Treatment of Gonorrhea in 2020 no longer requires dual therapy (due to rising resistance rates for other conditions)
    1. See management below
    2. Eradication typically requires Ceftriaxone 500 mg IM (1 gram IM/IV if weight > 150 kg, dose increased in 2020)
    3. Other agents may be considered (see below)
      1. Cefixime resistant strains are often also resistant to Doxycycline
      2. Zoliflodacin may be effective
  3. Risk of untreatable Gonorrhea is a real possibility
    1. Men who have Sex with Men have increased Azithromycin and Ceftriaxone MICs
      1. Kirkcaldy (2013) Ann Intern Med 158(5 Pt 1): 321-8 [PubMed]
    2. Gonorrhea treatment failures have exceeded 6% in Toronto, Canada
      1. Allen (2013) 309(2): 163-70 [PubMed]
    3. Rising MICs to all antibiotics against Gonorrhea may be a harbinger of untreatable Gonorrhea
      1. Bolan (2012) N Engl J Med 366(6): 485-7 [PubMed]
  4. Obtain standard cultures in patients returning with possible treatment failures
    1. Gonococcal Culture is required to evaluate for drug resistance and susceptibility
    2. DNA probes can not be used to determine Antibiotic Resistance
    3. Consider reinfection from insufficiently treated sexual partners (most common cause of "treatment failure")
    4. Consult infectious disease and public health department if multidrug resistance is suspected
  5. References
    1. Glauser (2014) Crit Dec Emerg Med 28(11): 2-10
    2. MMWR Morb Mortal Wkly Rep (1995) 44:761-5 [PubMed]
    3. Fox (1997) J Infect Dis 175: 1396-403 [PubMed]

XVII. Management: Uncomplicated Gonorrhea

  1. Refer all sexual exposures for treatment
  2. See Pelvic Inflammatory Disease for that protoco
  3. Re-test for Gonorrhea (as well as Chlamydia and Trichomonas) again in 3 months after treatment (high risk of recurrence)
  4. Gonorrhea management
    1. Ceftriaxone 500 mg IV or IM for one dose (1 gram IM/IV if weight > 150 kg or 330 lb) OR
    2. Gentamicin 240 mg IM and Azithromycin 2 g orally for one dose OR
    3. Cefixime 800 mg orally once
      1. Alternative agent but NOT recommended due to Antibiotic Resistance
  5. Chlamydia management if not excluded (not indicated for Gonorrhea treatment without Chlamydia as of 2020)
    1. Chlamydia coninfection rates are 30-50%
    2. Doxycycline 100 mg twice daily for 7 days (preferred as of 2020 in non-pregnant patients) OR
    3. Azithromycin 1 g orally for 1 dose (in pregnant patients)
  6. Uncomplicated Gonorrhea in non-pregnant patient
    1. Azithromycin is no longer recommended for Gonorrhea managament if Chlamydia has been excluded
    2. Second agent (in addition to Azithromycin)
      1. Ceftriaxone 500 mg IM/IV for 1 dose (1 gram IM/IV if weight > 150 kg, dose increased in 2020)
      2. Cefotaxime 500 mg IM for 1 dose (not typically used, as Ceftriaxone is the standard treatment)
      3. Spectinomycin 2 g IM for 1 dose (not available in the United States, and resistance risk)
    3. Severe Cephalosporin allergy (e.g. Anaphylaxis or Toxic Epidermal Necrolysis)
      1. Gentamicin 5 mg/kg (<45 kg) up to 240 mg IM and Azithromycin 2 grams orally for 1 dose OR
      2. Gemifloxacin 320 mg orally and Azithromycin 2 grams orally for 1 dose
      3. Recheck for cure in 1-2 week
      4. Consult infectious disease
    4. Agents to avoid
      1. Cefixime (Suprax) 800 mg orally for 1 dose
        1. Not recommended due to increasing resistance in 2012 (see resistance above)
        2. If Cefixime is used due to lack of alternatives, then 800 mg dose is recommended
      2. Quinolones should no longer be used for Gonorrhea in U.S. due to high resistance
        1. Exception: Gemifloxacin with Azithromycin
        2. (2007) MMWR Morb Mortal Wkly Rep 56(14):332-6 [PubMed]
  7. Uncomplicated Gonorrhea in pregnant patient
    1. Ceftriaxone (Rocephin) 500 mg IM (1 gram IM/IV if weight > 150 kg or 330 lb) AND
    2. Azithromycin 2 grams PO for 1 dose
      1. Indicated for Cephalosporin resistance
      2. High-dose related GI intolerance is common
      3. One gram dose may not be effective for Gonorrhea
      4. Retest one week later to confirm clearance
    3. Older regimens that are no longer recommended
      1. Combined regimen 1 (not recommended due to Cefixime resistance; see above)
        1. Cefixime 800 mg PO for one dose and
        2. Erythromycin Base 500 mg PO tid for 7 days
        3. Retest one week later to confirm clearance
      2. Amoxicillin 3 g PO AND Probenecid 1 gram orally
      3. Spectinomycin 2 g IM (if Penicillin allergic)
        1. High resistance (Cures only 52% of cases)
        2. No longer available in the United States

XVIII. Management: Non-Genital Gonorrhea

  1. Pharyngeal Gonorrhea
    1. Ceftriaxone 500 mg IM or IV for 1 dose (1 gram IM/IV if weight > 150 kg or 330 lb)
    2. Treat Chlamydia coinfection if not excluded (see above)
    3. Test for cure at 14 days (not recommended for urogenital or rectal Gonorrhea)
  2. Conjunctivitis due to Gonorrhea
    1. Ceftriaxone 1 gram IM or IV for 1 dose
  3. Meningitis due to Gonorrhea
    1. Ceftriaxone 1 to 2 grams IV every 12 hours for 10-14 days
  4. Endocarditis due to Gonorrhea
    1. Ceftriaxone 1 to 2 grams IV every 12 hours for 4 weeks or more

XIX. Management: Disseminated Gonorrhea

  1. Do not use Quinolones for Gonorrhea in U.S. due to high resistance (see above)
  2. Parenteral Treatment Course
    1. Typical Course: 7 days
    2. Meningitis: 10-14 days
  3. Initial Inpatient dosing until symptoms improve for 24-48 hours
    1. CeftriaxoneSodium 1.0 g (50mg/kg) IV/IM every 24 hours or
    2. CefotaximeSodium 1.0 g (25 mg/kg) IV/IM every 8 hours or
    3. CeftizoximeSodium 1.0 g every 8 hours or
    4. Spectinomycin 2 grams IM every 12 hours
  4. Then followed by outpatient 7 day antibiotic course
    1. Cefuroxime Axetil 500 mg twice daily or
    2. Cefixime 400 mg orally twice daily (not recommended due to resistance) or
    3. Amoxicillin 500 mg twice daily plus Probenecid 1 g/day

XX. Management: Children

  1. Urethral, cervical or pharyngeal
    1. Weight <45 kg
      1. Ceftriaxone 125 mg IM for a single dose
    2. Weight >45 kg
      1. Dose as for adults
  2. Bacteremia or Arthritis
    1. Ceftriaxone 50 mg/kg (up to 1 gram) IV or IM every 24 hours for 7 days

XXI. Management: Newborns

  1. Asymptomatic infants born to mothers with untreated Gonorrhea
    1. Ceftriaxone 25-50 mg/kg (up to 250 mg) IV or IM for one dose OR
    2. Cefotaxime 100 mg/kg IV or IM for one dose
  2. Disseminated Gonorrhea or scalp abscess
    1. Ceftriaxone 25-50 mg/kg IV or IM every 24 hours for 7 days OR
    2. Cefotaxime 25-50 mg/kg IV or IM every 12 hours for 7 days
  3. Neonatal Meningitis
    1. Ceftriaxone 25-50 mg/kg IV or IM every 24 hours for 10 to 14 days OR
    2. Cefotaxime 25-50 mg/kg IV or IM every 12 hours for 10 to 14 days
  4. Ophthalmia Neonatorum
    1. Ceftriaxone 25-50 mg/kg (up to 250 mg) IV or IM for one dose
    2. Erythromycin 0.5% ophthalmic ointment is applied to each eye at birth in all newborns in U.S.
      1. Gonococcal Conjunctivitis risk is 30-40% without prophylaxis for infants born to positive mothers
      2. Gonococcal Conjunctivitis in Newborns is a high risk for blindness (even in first 24 hours)

XXII. Management: Follow-up

  1. Test for reinfection at 3-6 months after treatment (Gonorrhea and Chlamydia)
  2. Regularly screen for other Sexually Transmitted Disease (e.g. HIV, Syphilis)

XXIII. Prevention

  1. Treat sexual partners of positive patients (within prior 60 days)
    1. Consider patient-delivered partner therapy
    2. See Expedited partner therapy (CDC recommendation if legal in practicing state)
      1. http://www.cdc.gov/std/ept
  2. Screen sexually active patients under age 26 years
  3. Consistent Condom use

XXIV. References

  1. Apgar (2003) AAFP Board Review, Seattle
  2. Mandell (2000) Infectious Disease, Churchill, p.2249-55
  3. (2000) AAP Redbook p. 254-60
  4. (1998) MMWR Morb Mortal Wkly Rep 47:1-115 [PubMed]
  5. (2015) MMWR Morb Mortal Wkly Rep 64(RR3):1-37 [PubMed]
  6. Cyr (2020) MMWR Morb Mortal Wkly Rep 69(50): 1911-6 [PubMed]
    1. https://www.cdc.gov/mmwr/volumes/69/wr/mm6950a6.htm
  7. Mayor (2012) Am Fam Physician 86(10): 931-8 [PubMed]
  8. Miller (2000) Am Fam Physician 61(2):379-86 [PubMed]
  9. Yonke (2022) Am Fam Physician 105(4): 388-96 [PubMed]

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