Neisseria gonorrhoeae

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

1. See Also
   1. Sexually Transmitted Disease
   2. Pelvic Inflammatory Disease
   3. Urethritis
   4. Urethritis in Women
   5. Acute Cervicitis
   6. Proctitis
2. Epidemiology
   1. Much less common than Chlamydia
   2. Incidence: 500-700,000 cases per year
      1. Decreasing except in inner city, Drug Abuse (crack)
      2. Second most common reportable Sexually Transmitted Disease
   3. Highly contagious: 50% transmission
   4. Chlamydia coexists in 45-50% of patients with Gonorrhea
   5. Most common in young women
      1. Ages 15 to 19 years old
      2. Incarcerated women under age 35 years
3. 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]
4. Pathophysiology
   1. Caused by Neisseria gonorrhoeae
   2. Incubation: 2-7 days
5. 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
6. 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
7. 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
8. Findings: Symptoms and Signs - Disseminated Gonococcus (rare - occurs in <3% of patients)
   1. High fever may be present (variable)
   2. More common in pregnancy
   3. Dermatitis (75% of cases)
      1. Rash over trunk, extremities, palms and soles
      2. Present as Papules (bullae, Petechiae may be found)
      3. Necrotic Pustule ("gun metal gray") on red base over distal extremity (wrists, palms and soles)
      4. May progress into Hemorrhagic Pustules
      5. Usually less than 20 total lesions (typically 3 or less)
   4. Polyarticular Tenosynovitis
      1. Wrists and hands
      2. Ankles and feet
   5. Gonococcal Arthritis
      1. Aseptic Joint Aspiration does not rule-out Disseminated Gonococcus
   6. Endocarditis (rare)
   7. Meningitis (rare)
9. 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
10. Differential Diagnosis: Gonorrhea
    1. See Cervicitis
    2. See Vaginitis (or Vaginal Discharge)
    3. See Urethritis
    4. See Neonatal Conjunctivitis
    5. See Proctitis
11. 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]
12. 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)
13. 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 STD
       1. Chlamydia (same DNA probe as for Gonorrhea)
       2. HIV
       3. Syphilis
14. Diagnostic Studies
    1. Endoscopy in suspected Gonococcal Diarrhea
       1. Nonspecific findings limited to Rectum
       2. Biopsy and Culture show superficial exudates
15. Management: Multi-Drug Resistance
    1. Antibiotics that are no longer effective against Gonorrhea
       1. Cefixime or Suprax
          1. Not recommended as of 2012
          2. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm
       2. Ciprofloxacin and other Fluoroquinolones
       3. Penicillins
       4. Sulfanilamide
       5. Tetracyclines (including Doxycycline)
    2. Treatment of Gonorrhea in 2014 is limited to a few agents for dual therapy
       1. See management below
       2. Eradication typically requires Ceftriaxone AND either Azithromycin 1 gram or Doxycycline for 7 days
          1. Cefixime resistant strains are often also resistant to Doxycycline
    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
    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]
16. 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. Treat for Chlamydia (30-50% coinfection) if Gonorrhea positive
       1. Doxycycline 100 mg orally twice daily for 7 days OR
       2. Azithromycin 1 gram orally for 1 dose
    5. Uncomplicated Gonorrhea in non-pregnant patient
       1. Use Azithromycin 1 gram orally in all cases to treat the Gonorrhea infection (regardless of Chlamydia status)
          1. Azithromycin 2 g orally once is effective for Gonorrhea as single agent, but poorly tolerated
       2. Second agent (in addition to Azithromycin)
          1. Ceftriaxone 250 mg IM for 1 dose (preferred option)
             1. Cure rate: 99%
             2. Consider Ceftriaxone 500 mg IM with Azithromycin 2 g orally if treatment failure
          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) 400 mg orally for 1 dose
             1. Not recommended due to increasing resistance in 2012 (see resistance above)
          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]
    6. Uncomplicated Gonorrhea in pregnant patient
       1. Ceftriaxone (Rocephin) 250 mg IM 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 400 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 PO
          3. Spectinomycin 2 g IM (if Penicillin allergic)
             1. High resistance (Cures only 52% of cases)
17. Management: Non-Genital Gonorrhea
    1. Pharyngeal Gonorrhea
       1. Ceftriaxone 250 mg IM for 1 dose AND
       2. One of the following
          1. Azithromycin 1 gram orally for 1 dose (preferred due to higher resistance with Tetracyclines)
          2. Doxycycline 100 mg orally twice daily for 7 days
    2. Conjunctivitis due to Gonorrhea
       1. Ceftriaxone 1 gram IM 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
18. 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
19. 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
20. 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
    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
21. 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)
22. 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
23. 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. Mayor (2012) Am Fam Physician 86(10): 931-8 [PubMed]
    7. Miller (2000) Am Fam Physician 61(2):379-86 [PubMed]