Arpeet Shah, MD
Ahmer V. Farooq, DO
BASICS
DESCRIPTION
• A sexually transmitted disease (STD) caused by the gram-negative diplococcal bacteria Neisseria gonorrhea
– Clinical manifestations range from asymptomatic disease to disseminated infection
– In men, can cause urethritis, prostatitis, and epididymitis
– In women, can cause cervicitis, salpingitis, endometritis, and pelvic inflammatory disease
– Anorectal and pharyngeal infections may also occur depending on sexual practices
– Pediatrics: Vertical transmission to newborn may result in infection of conjunctiva, rectum, or respiratory tract; rule out sexual abuse in infections of young children
– Disseminated gonococcal infection may occur secondary to distinct strains or host factors and may result in a variety of clinical manifestations including skin lesions, arthritis, pericarditis, endocarditis, and meningitis
EPIDEMIOLOGY
Incidence
• In the United States, gonorrhea remains the 2nd most commonly reported bacterial STD
• The Center for Disease Control and Prevention (CDC) estimates 820,000 new cases per year with over half occurring in young adults ages 15–24
• In 2011, CDC reported the rate of gonorrheal infections to be 104.2/100,000 persons
• Rates in the United States have drastically declined since the 1970s due to the public health measures
• More recently, the rate decreased 11.7% during 2007–2011
RISK FACTORS
• Multiple sexual partners
• Unsafe sexual practices
• Alcohol and substance abuse
• Men have a 20–30% chance and women have a 70–80% chance after having 1 exposure
Genetics
Individuals with inherited or acquired deficiency of complement components C5–C9 are more susceptible to local and systemic gonorrheal infections
PATHOPHYSIOLOGY
• N. gonorrhea is not part of the normal flora of the genitourinary tract (1)
• Bacteria are introduced to the mucosal epithelial surface after direct contact with an infected individual
• Attachment of the bacteria to the mucosal epithelium is mediated by pili (PilC1 and PilC2) and Opa proteins
• Penetration of the organism into submucosal tissue usually takes 24–48 hr
• Invasion of the epithelial triggers a strong response by neutrophils causing sloughing of epithelium, submucosal microabscesses, and purulent drainage
ASSOCIATED CONDITIONS
• Always recommend testing for other STDs
• Commonly associated with concomitant infection with Chlamydia trachomatis
GENERAL PREVENTION
• Delaying onset of sexual activity and reducing the number of new partners
• Consistent condom use
DIAGNOSIS
HISTORY
• Obtain detailed history of sexual activity and partners
• Incubation period of 3–14 days
• Approximately 50% of infections in men are asymptomatic or minimally symptomatic; most common symptoms include dysuria and mucopurulent discharge
• Approximately 50% of women have asymptomatic infection; most common symptoms include vaginal/cervical discharge, dysuria, urinary frequency, abdominal pain, and abnormal menstrual bleeding
• Pregnancy does not change clinical presentation, but does lower incidence of pelvic inflammatory disease (PID)
• Anorectal infection is usually asymptomatic but can produce symptoms of pruritus, tenesmus, rectal bleeding, and discharge
• Pharyngeal infection is usually asymptomatic but can cause sore throat
• Approximately 50–75% of those with disseminated gonococcal infection (DGI) have skin lesions characterized by papules and pustules with surrounding erythema
PHYSICAL EXAM
• In men, mucopurulent urethral discharge may be seen; other signs include testicular/epididymal tenderness
• In women, pelvic exam with speculum may demonstrate mucopurulent cervical discharge; other signs include cervical erythema, edema, and friability as well as cervical motion and adnexal tenderness
• If suspecting anorectal infection, external inspection may reveal few or no signs of infection and anoscopy may be indicated with collection of specimens for culture
• Pharyngeal cases may demonstrate exudative pharyngitis and cervical adenitis
• Conjunctival cases demonstrate severe purulent discharge with crusting and lid edema
DIAGNOSTIC TESTS & INTERPRETATION
Lab (2)
• Gram stain of urethral or endocervical discharge with a swab.
– Considered positive if neutrophils with intracellular gram-negative diplococci are visualized. Sensitivity and specificity of the Gram stain varies depending on the site of infection and the presence of symptoms.
• Culture has long been considered the gold standard for diagnosis.
– Advantages include high specificity and the ability to test for antibiotic sensitivity.
– Disadvantages include strict transport and storage requirements, specific environmental variables needed for growth (Thayer–Martin agar in CO2 incubator), and delays in obtaining results. Culture is the test of choice for extragenital sites of infection.
• Nucleic acid amplification test (NAAT) use molecular techniques to amplify specific DNA and RNA sequences.
– Optimal specimens are urine samples for males and vaginal swabs for females.
– Advantages include higher sensitivities and comparable specificities of culture, minimal delay in results, noninvasive and self-collected samples, and identification of coinfections.
– Disadvantages include inability to screen for antimicrobial sensitivity. CDC now recommends NAAT as the 1st-line diagnostic test for uncomplicated urogenital gonorrheal infection.
Imaging
• Not indicated in uncomplicated cases
• Computed tomography or pelvic ultrasound if pelvic inflammatory disease (PID) or pelvic abscess suspected
• Retrograde urethrogram if urethral stricture suspected
Pathologic Findings
Gram stain demonstrates gram-negative diplococci found inside of polymorphonuclear cells
DIFFERENTIAL DIAGNOSIS (3)
• Other genitourinary infections including C. trachomatis, Trichomonas vaginalis, Mycoplasma genitalium, and Ureaplasma urealyticum, herpes simplex virus, bacterial vaginosis, and candidiasis
• Also consider noninfectious sources such as foreign body, chemical irritation, allergic reaction, trauma, carcinoma, and leukorrhea of pregnancy
• For women who present with suspected PID, must rule out ectopic pregnancy and other intra-abdominal processes such as appendicitis
TREATMENT
GENERAL MEASURES
• Patients with suspected active infection should abstain from sex until diagnostically excluded or adequately treated
• All sexual partners who have contacted the infected patient within 60 days of diagnosis should also be evaluated
• Treatment with penicillins and tetracycline are not effective due to the high level of penicillinase-producing bacteria and plasmid-mediated high-level tetracycline-resistant bacteria
• Over the last decade, increasing mean minimum inhibitory concentrations of selective cephalosporins have indicated decreasing susceptibility and have impacted current treatment recommendations
• Fluoroquinolone resistance has impacted treatment options and is most prevalent in the states of California and Hawaii
• Macrolide resistance has also been reported
MEDICATION
First Line (4)
• For uncomplicated cases of urethral and endocervical gonorrheal infection, patients must also be treated for concomitant chlamydia infection unless diagnostically excluded
• Ceftriaxone 250 mg IM in 1 dose PLUS azithromycin 1 g PO in 1 dose is the current gold standard
• Ceftizoxime 500 mg IM in 1 dose, cefotaxime 500 mg IM in 1 dose, or cefoxitin 2 g IM with probenecid 1 g PO in 1 dose are alternatives for ceftriaxone
• If an injectable cephalosporin is not an option, alternatives include cefixime 400 mg PO in 1 dose or cefpodoxime 400 mg PO in 1 dose. However, patients who receive these options should return in 1 wk for microbiologic test of cure with culture
• Doxycycline 100 mg BID PO for 7 days is an alternative for azithromycin
Second Line
• The management of those with a penicillin allergy depends on clinical suspicion of true allergy and the severity of the allergy. Most patients with documented penicillin allergy are not found to have an allergy after further testing and only 2% of those with a penicillin positive skin test cross react with cephalosporins. Thus, the physician must decide whether to give a cephalosporin vs. an alternative therapy
• Azithromycin 2 g PO in 1 dose monotherapy treats gonorrhea and chlamydia; however, due to GI side effects and growing macrolide resistance, it is not a preferred regimen unless the patient has a severe penicillin allergy
• Spectinomycin 2 g IM in 1 dose is a safe and effective alternative therapy for those with severe penicillin allergies, but is only available outside the United States
• Quinolones were once a 2nd-line therapy, but due to drug resistance in 10–100% of strains depending on location, they are no longer recommended for the treatment of gonorrhea
SURGERY/OTHER PROCEDURES
• Chronic gonorrheal infection may lead to bulbar urethral strictures requiring urologic intervention
• Gonorrheal abscesses may require incision and debridement procedures
ADDITIONAL TREATMENT
• Patient counseling regarding safe sex practices and abstinence for 7 days following treatment initiation
• Patients should also be offered additional STD testing and pregnancy testing
• Pregnancy considerations
– 1st line still remains ceftriaxone 250 mg IM in 1 dose PLUS azithromycin 1 g PO in 1 dose
– Doxycycline should be avoided during pregnancy
– If the patient has a penicillin allergy, desensitization procedures or 2nd-line treatments such as azithromycin monotherapy are alternatives
– Microbiologic test of cure with culture is recommended
• Ophthalmia neonatorum
– Prevented by routine screening for endocervical infection during pregnancy and prophylactic use of erythromycin ophthalmic solution
ONGOING CARE
PROGNOSIS
>95% of uncomplicated genitourinary gonorrheal infections are cured by 1 course of treatment
COMPLICATIONS
• In males, may lead to bulbar urethral stricture and sterility
• In females, can cause PID leading to chronic pelvic pain, ectopic pregnancy, and sterility
• Genital abscesses may occur in either sex requiring surgical intervention
• Fitz–Hugh–Curtis Syndrome – perihepatitis characterized by acute right or bilateral upper quadrant tenderness – may occur in either sex
• Ocular infection with gonorrhea in adults may lead to corneal scarring and vision loss
• The most common complication of DGI is septic arthritis and arthritis–dermatitis syndrome; extreme cases may lead to destruction of articular surfaces
• Hematogenous spread may lead to endocarditis and meningitis
FOLLOW-UP
• All patients diagnosed with gonorrhea should be tested to rule out repeat infection 3–4 mo after treatment
• All patients who undergo PO cephalosporin therapy and all pregnant patients should undergo microbiologic test for cure using a Gram stain and culture 7 days after treatment
REFERENCES
1. Klausner J, Hook III E. Current Diagnosis and Treatment of Sexually Transmitted Diseases, 1st ed. New York, NY: McGraw-Hill Medical, 2007.
2. Leone PA. Epidemiology, pathogenesis, and clinical manifestations of neisseria gonorrhoeae infection. In: UpToDate, Basow DS, ed. UpToDate. Waltham, MA; 2013.
3. Mandel G, et al. Bennett’s Principles and Practice of Infectious Diseases. 7th ed. New York, NY: Churchill Livingstone; 2010.
4. Swygard H, et al., Diagnosis of Gonococcal Infections. In: UpToDate, Basow DS, ed. UpToDate, Waltham, MA; 2013.
ADDITIONAL READING
www.cdc.gov/std/Gonorrhea/STDFact-gonorrea.htm
See Also (Topic, Algorithm, Media)
• Epididymitis
• Gonorrhea Image 
• Pelvic pain, Female
• Sexually Transmitted Infections (STIs) STDs, General
• Urethra, Discharge
• Urethritis
CODES
ICD9
• 098.0 Gonococcal infection (acute) of lower genitourinary tract
• 098.11 Gonococcal cystitis (acute)
• 098.12 Gonococcal prostatitis (acute)
ICD10
• A54.00 Gonococcal infection of lower genitourinary tract, unsp
• A54.01 Gonococcal cystitis and urethritis, unspecified
• A54.22 Gonococcal prostatitis
CLINICAL/SURGICAL PEARLS
• Maintain a high degree of suspicion for gonorrhea, especially in patients who are in their 20s.
• Most common symptoms include mucopurulent discharge and dysuria.
• Culture has been the gold standard for diagnosis, however, NAAT is now being widely used as a 1st-line diagnostic modality.
• 1st-line treatment includes ceftriaxone 250 mg IM in 1 dose PLUS azithromycin 1 g PO in 1 dose.
• Antibiotic susceptibilities continue to change and vary by geographical location.
• Always council patients regarding safe sex practices.