Published on 18/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Jacqueline A. Guidry and Ted Rosen
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Gonorrhea is a common and potentially severe sexually transmitted disease caused by the Gram-negative aerobic diplococcus Neisseria gonorrhoeae. This organism primarily infects the mucous membranes of the urethra, endocervix, rectum, and pharynx. The disease can also become disseminated, causing petechial or acral pustular skin lesions, tenosynovitis, arthralgia, true septic arthritis, perihepatitis, and less commonly endocarditis or meningitis. Dissemination is more common in women. Conversely, the infection may be asymptomatic.
Individuals with gonorrhea should be treated as promptly as possible: (a) to prevent regional infection such as epididymitis or pelvic inflammatory disease leading to infertility or ectopic pregnancy; (b) to prevent disseminated gonococcal infection, which occurs in about 1–3% of cases; and (c) to stop transmission to sexual partners. Prompt management has become especially important due to resurgence in incidence of gonococcal disease in the US and increasing antimicrobial resistance worldwide.
Gonococcal urethritis is typically characterized by mucopurulent to frankly purulent discharge along with a burning sensation during urination. In the absence of discharge, dysuria may be the only symptom.
Gonococcal cervicitis is characterized by a mucopurulent or purulent endocervical exudate. However, a cervical discharge is not specific for a gonococcal infection, and gonococcal infection of the cervix is often asymptomatic.
Pharyngeal infection is asymptomatic in more than 90% of cases.
Rectal infection is prevalent in homosexual men, causing anal discharge and pain. In women, rectal infection results from spread through vaginal secretions and does not necessarily imply anal intercourse.
Patients in whom gonorrhea is suspected should be investigated using the most sensitive and specific tests, though empiric treatment of the symptoms may be recommended for patients at high risk for infection who are deemed unlikely to return for a follow-up evaluation.
Patients infected with N. gonorrhoeae are often co-infected with Chlamydia trachomatis and should be treated with azithromycin or doxycycline to cover this organism, with or without diagnostic evidence of chlamydial disease. Patients with gonorrhea should be tested for both syphilis and HIV.
Patients should be instructed to return for evaluation if symptoms persist or recur after therapy, and to abstain from sexual intercourse until they and their sexual partners are cured. Because re-infection is so common, the CDC recommends that all patients with known gonorrhea return for re-testing 3 months post-treatment. A test-of-cure 3 to 4 weeks post-treatment is no longer recommended.
Antimicrobial resistance is a real threat and treatment options for gonococcal disease are increasingly limited. To abate further spread of resistant strains of N. gonorrhoeae, physicians should strongly encourage patient referral of any sexual partner within the preceding 60 days for evaluation and treatment, and obtain culture(s) to evaluate individual antimicrobial susceptibility in any patient whose symptoms do not resolve with initial treatment.
Men
Microscopic examination of Gram-stained urethral secretions
Culture on Thayer–Martin medium
Non-culture test based upon immunodiagnostics, as available
Women
Janier M, Lassau F, Casin I, Grillot P, Scieux C, Zavaro A, et al. Sex Transm Dis 1995; 22: 244–52.
N. gonorrhoeae was found in 21% of patients with urethral discharge and in no patient without discharge. Treatment for N. gonorrhoeae in patients without discharge in the absence of proven contact with an infected patient is not recommended.
Workowski KA, Berman S. MMWR Recomm Rep 2010; 59(RR12): 49–55.
Because of its high specificity (>99%) and sensitivity (>95%), a Gram stain of a male urethral specimen that demonstrates polymorphonuclear leukocytes with intracellular Gram-negative diplococci can be considered diagnostic for infection with N. gonorrhoeae in symptomatic men. Culture is the most widely available option for diagnosis in asymptomatic men, in women, and in non-genital sites (rectum and pharynx). Non-culture tests cannot provide antimicrobial susceptibility results but can rapidly and accurately confirm a clinical diagnosis.
MMWR 2002; 51(RR-15): 1–48.
Non-culture tests called nucleic acid hybridization tests and nucleic acid amplification tests (NAATs) have been developed. Commercial NAATs differ in their amplification methods and their target nucleic acid sequences. The majority of commercial NAATs have been cleared by the FDA to detect C. trachomatis and N. gonorrhoeae in endocervical swabs and urethral swabs from men. The sensitivity of NAATs might be less when using urine than when using an endocervical swab. Testing of rectal and oropharyngeal specimens with NAATs is not recommended.
Samarawickrama A, Alexander S, Ison C. J Med Microbiol 2011; 60: 1779–81.
This detects a specific epitope on the L7/L12 ribosomal protein of N. gonorrhoeae with sensitivity and specificity of 99.4% and 88.7%, respectively.
Portilla I, Lutz B, Montalvo M, Mogabgab J. Sex Transm Dis 1992; 19: 94–8.
The only current CDC-recommended options for treating N. gonorrhoeae infections are cephalosporins. The 400 mg dose of cefixime cured 97% of uncomplicated urogenital and anorectal gonococcal infections. The advantage of cefixime is that it can be administered orally.
Workowski KA, Berman S. MMWR Recomm Rep 2010; 59(RR12): 50–1.
Ceftriaxone in a single injection of 250 mg is a safe, effective dose for uncomplicated gonococcal infection at all anatomic sites. Compared to ceftriaxone, cefixime does not provide the same magnitude of bactericidal effect nor is it as efficacious in treating pharyngeal gonococcal infections.
All patients with gonorrhea should also be treated with azithromycin or doxycycline to (a) treat possible co-infection with Chlamydia trachomatis, and (b) gain additive microcidal effects for N. gonorrhoeae.
Unemo M, Golparian D, Stary A, Eigentler A. Euro Surveill 2011; 16: 1–3.
Globally the susceptibility of N. gonorrhoeae to antimicrobial therapy, including first-line treatment options ceftriaxone and cefixime, is decreasing.
Bignell C, Fitzgerald M, Guideline Development Group, British Association for Sexual Health and HIV UK. Int J STD AIDS 2011; 22: 541–7.
Three cases of cefixime failure were reported in the UK in 2011. First-line treatment for gonococcal infection in the UK is now ceftriaxone 500 mg intramuscularly plus azithromycin 1 g orally with test of cure recommended in all cases. Cefixime is only advised when intramuscular injection is contraindicated or refused by the patient.
Newman LM, Moran JS, Workowski KA. Clin Infect Dis 2007; 44(Suppl 3): S84–101.
Both cefopodoxime and cefuroxime were determined to meet the minimum efficacy for alternate treatment regimens for urogenital infections of N. gonorrhoeae. Cefuroxime was also efficacious in rectal infections. The efficacy of cefpodoxime was significantly lower (78.9%) for pharyngeal infections.
Ison CA, Mouton JW, Jones K, Fenton KA, Livermore DM, North Thames Audit Group. Sex Transm Infect 2004; 80: 386–8.
Historical small trials demonstrated efficacy of cefuroxime for the treatment of N. gonorrhoeae. It is used as first-line gonorrhea treatment in up to 10% of patients in the UK. Pharmacodynamic studies involving samples from 179 patients found the duration of MIC90 to be significantly shorter with cefuroxime as opposed to ceftriaxone and cefixime: 6.8–11.2 hours and 22–50 hours, respectively.
Katz AR, Komeya AY, Soge OO, Kiaha MI, Lee MV, Wasserman GM, et al. CID 2012; 54: 841–3.
Eight isolates with reduced susceptibility to azithromycin were identified in Hawaii followed by laboratory documentation of the first isolate with high level azithromycin resistance in California. Previously, strains with high level resistance had been documented in Argentina, Scotland, England, Wales, and Ireland.
Galimand M, Gerbaud G, Courvalin P. Antimicrob Agents Chemother 2000; 44: 1365–6.
It is rare for a patient to be infected with a spectinomycin-resistant strain, but spectinomycin is expensive and must be injected. Spectinomycin is useful for patients who cannot tolerate cephalosporins and quinolones.
Pfizer discontinued US-based distribution of spectinomycin in November 2005.
MMWR Morb Mortal Wkly Rep 2007; 56: 332–6.
Owing to the increasing resistance, CDC no longer recommends the use of fluoroquinolones for patients who acquired their infection in the US, Asia, or the Pacific Islands. Recent data suggest that resistant strains comprise about 13% of all American-acquired isolates.
WHO Western Pacific and South East Asian Gonococcal Antimicrobial Surveillance Programmes. Commun Dis Intell 2011; 35: 2–7.
Recent data from China, Hong Kong, Japan and elsewhere in Asia also demonstrate a very high rate of fluoroquinolone resistance. Australia and New Zealand are experiencing 35–45% of isolates quinolone resistant.
Australian Gonococcal Surveillance Programme. Commun Dis Intell 2011; 35: 229–36.
Penicillin has been removed from the standard treatment regimen in Australia because of nation wide isolate resistance (up to 44% in some regions). However, in remote areas of Australia with extremely high disease rates, treatment with penicillin often remains effective. The same is also true in other industrialized countries.
Ross JD, Lewis DA. Sex Transm Infect 2012; 88: 6–8.
Studies of efficacy of gentamicin from the 1970s and 1980s demonstrated cure rates of 65-100% with no report of adverse reactions.
Moran JS. Sex Transm Dis 1995; 22: 39–47.
Pharyngeal infection is more difficult to cure. A cephalosporin regimen is the best choice, as they are likely to cure at least 80% of pharyngeal infections. Spectinomycin is unreliable (i.e., only 52% effective).
Azithromycin may increase efficacy for pharyngeal infection when using oral cephalosporins.
Hospitalization is recommended for initial therapy. The experts recommend ceftriaxone 1.0 g intramuscularly or intravenously every 24 hours as the initial regimen. Treatment can be switched 24–48 hours after improvement begins to cefixime 400 mg twice daily orally to complete at least 7 days of antimicrobial therapy. Acceptable alternate therapies include: cefotaxime or ceftizoxime, both drugs given in a dosage of 1.0 g intravenously every 8 hours.
Cavenee MR, Farris JR, Spalding TR, Barnes DL, Castaneda YS, Wendel GD Jr. Obstet Gynecol 1993; 81: 33–8.
A randomized study on 250 cases comparing ceftriaxone 250 mg intramuscularly, spectinomycin 2 g intramuscularly, and amoxicillin 3 g orally with probenecid 1 g showed efficacy was 95%, 95%, and 89%, respectively. There was no increase in congenital malformations. Ceftriaxone and spectinomycin are the best choices. Pregnant women should not be treated with quinolones or tetracyclines. (Comment: Since spectinomycin is no longer available in the US, ceftriaxone is the default drug of choice.)
Pregnant women who cannot tolerate a cephalosporin should receive azithromycin 2 g in a single dose. They should also be treated for coexisting chlamydial infection with azithromycin or amoxicillin.
Gonococcal ophthalmia is strongly suggested when typical Gram-negative diplococci are identified in conjunctival exudate, justifying presumptive treatment after appropriate cultures have been obtained. The recommended regimen is ceftriaxone 25–50 mg/kg IV or IM in a single dose, not to exceed 125 mg. Local treatment, with or without systemic antibiotics, is inappropriate. Cefotaxime is a recommended alternative.
Gunn RA, O’Brien CJ, Lee MA, Gilchick RA. Sex Transm Dis 2008; 35: 845–48.
This population should be screened annually for gonorrhea infection at the urethral, pharyngeal, and rectal sites.
Patients with suspected treatment failure or persons infected with a strain found to demonstrate in vitro resistance should consult an infectious disease specialist. Patients should be retreated with at least 250 mg of ceftriaxone IM or IV, and ensure partner treatment. The situation should be promptly reported to public health agencies.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Ceftriaxone 250 mg intramuscularly in a single dose + azithromycin 1 g orally
Ceftriaxone 250 mg intramuscularly in a single dose + doxycycline 100 mg twice daily for seven days
Cefixime 400 mg orally in a single dose + azithromycin 1 g orally
Cefixime 400 mg orally in a single dose + doxycycline twice daily for seven days
Cefopodoxime 400 mg orally in a single dose
Cefuroxime 1 g orally in a single dose
Azithromycin 2 g orally in a single dose
Spectinomycin 2 g intramuscularly in a single dose
Ciprofloxacin 500 mg orally in a single dose
Ofloxacin 400 mg orally in a single dose
Penicillin 8 x 106 units intramuscularly plus 1 g of probenecid
Gentamicin 240 mg intramuscularly as a single dose
