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Gonorrhea: Testing and Treatment of Gonococcal Urethritis

• Gonorrhea: Etiology, Signs and Symptoms
• Gonorrhea: Diagnosis and Treatment

Diagnosis of Gonorrhea

Indications for microbiological testing in men:

Urethral discharge, diagnosis of any other STI, sexual partners with STI, and acute epididymitis in a male under 40 years.

Indications for microbiological testing in women:

Vaginal discharge with risk factors for STI (history, age), diagnosis of any other STI, sexual partners of patients with STI, and acute pelvic inflammatory disease.

Swab tests:

The urethral swab is ideally done after a longer pause in micturition. Further pathogen collection from the anus, pharynx, and cervix depends on history and symptoms. The microbiological diagnosis is possible with different techniques:

NAAT:

With the help of a NAAT (Nucleic Acid Amplification Test), gonococci, chlamydia and mycoplasma are detected with high sensitivity and specificity.

Microscopic diagnosis:

Microscopic detection of pathogens can distinguish between gonorrheal and non-gonorrheal urethritis more reliably than clinical symptoms, enabling correct empirical antibiotic therapy. It is rarely performed due to the effort involved and the availability of simpler alternatives (NAAT). Two microscope slides for Gram stain (gonococcus) and Giemsa stain (Chlamydia) are prepared if a microscopic pathogen detection is sought. Over four leukocytes with intracellular gram-negative diplococci can be seen in a high-power field [fig. microscopy of gonorrhea].

Culture and antimicrobial susceptibility testing:

Culture and antimicrobial susceptibility testing of Neisseria gonorrhoeae is possible with Martin-Lewis plates or Thayer-Martin agar. A pathogen culture is critical in patients who have contraindications for standard therapy with ceftriaxone or who suffer a recurrence. Fast transport routes and special transport media are necessary for a successful culture.

Test of the sexual partner:

To avoid a ping-pong infection, a detailed history and examination of any sexual partner is necessary.

Urin analysis:

After the urethral swab, urine for culture is collected if a urinary tract infection seems possible.

Serological tests:

Other STDs like syphilis, hepatitis, and HIV should be tested.

Notifiable disease:

Gonorrhea is a notifiable disease in many countries, including USA, Canada, UK and Europe.

Treatment of Gonorrhea

When choosing empirical antibiotic therapy, a clinical classification should be made between gonorrheal (characterized by purulent, yellowish discharge) and non-gonorrheal (characterized by watery or whitish discharge) urethritis. In patients without objective symptoms, with minor subjective complaints, who have recently undergone antibiotic therapy for the same complaints, or who have chronic urethritis, the results of the diagnosis should be awaited.

Empirical standard treatment:

First choice for suspected or prooven gonorrhea is a single dose of ceftriaxone 1--2~g i.m. or i.v.

Empirical treatment of co-infection:

Additional doxycycline 100 mg 1-0-1 p.o. for 7 days. Azithromycin is an alternative for patients with contraindications to doxycycline: 500 mg p.o. on the first day und 250 mg p.o. on days 2–5. The German guideline for urethritis recommends a higher off-label dosage of azithromycin over four days: 1000 mg orally on the first day, followed by 500 mg orally for the next three days. The more prolonged therapy is more reliable than the previous standard single-dose therapy with azithromycin against M. genitalium.

Alternative Treatment Options:

If empirical antibiotic therapy with ceftriaxone is not possible, the results of the gonococcal culture with resistance testing should be awaited. Due to the increasing resistance of gonococci to fluoroquinolones and azithromycin, these antibiotics are only a treatment option if sensitivity has been proven (S3 Guideline Urethritis):

• If sensitivity to azithromycin is confirmed by culture: Standard single therapy with azithromycin 1--2 g p.o. or azithromycin over four days: 1000 mg p.o. on the first day, 500 mg p.o. for the next three days. The longer therapy is more reliable against possible co-infection with M. genitalium. 
• In cases of culture-confirmed sensitivity to ciprofloxacin: 500 mg as a single dose.
• Cefixime 400 mg 1-0-0 p.o. for 1(--3) days as an alternative to ceftriaxone; however, pharyngeal manifestations are inadequately treated with this, and increasing resistance to cefixime is to be feared. 
• Spectinomycin 2 g i.m. as a single dose.

Follow-up and Test of Cure:

Patients with persistent symptoms after antibiotic treatment should undergo both a pathogen culture with resistance testing and a NAAT two weeks after completing antibiotic treatment. All patients without symptoms should undergo a test of cure (NAAT) 6–12 weeks after treatment. If this test is positive for gonococci, pathogen culture and resistance testing should be performed before further antibiotic therapy is administered.

Prevention:

Treatment of newborn eyes with an antibiotic ointment containing silver nitrate, erythromycin, or tetracycline (Credé prophylaxis). Use of condoms.

Doxycycline post-exposure prophylaxis (Doxy-PEP) against STIs: A single dose of 200 mg doxycycline within three days of unprotected sexual intercourse reduces the risk of chlamydia infection (by 70–80%), syphilis (by 70–80%), and gonorrhea (by 50%) in high-risk patients (Luetkemeyer et al., 2023).

References

CDC Guidelines: gonococcal infections in adolescents and adults. https://www.cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm

IUSTI, Unemo et ao.: European Guideline on the Diagnosis and Treatment of Gonorrhoea in Adults (2020). https://iusti.org/wp-content/uploads/2020/10/IUSTI-Gonorrhoea-2020.pdf

Luetkemeyer AF, Donnell D, Dombrowski JC, Cohen S, Grabow C, Brown CE, Malinski C, Perkins R, Nasser M, Lopez C, Vittinghoff E, Buchbinder SP, Scott H, Charlebois ED, Havlir DV, Soge OO, Celum C; DoxyPEP Study Team. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023 Apr 6;388(14):1296-1306. doi: 10.1056/NEJMoa2211934.

Robert-Koch-Institut, “Gonorrhoe (Tripper): RKI Ratgeber,” 2023. [Online]. Available: https://www.rki.de/DE/Content/Infekt/EpidBull/Merkblaetter/Ratgeber_Gonorrhoe.html.

DDG, DSTIG, DGU, and RKI, “S3-Leitlinie: Management der Urethritis bei männlichen Jugendlichen und Erwachsenen.” [Online]. Available: https://register.awmf.org/assets/guidelines/013-099l_S3_Management-Urethritis-maennliche-Jugendliche-Erwachsene_2025-02.pdf

  Deutsche Version: Gonorrhoe: Diagnose und Therapie der gonorrhoischen Urethritis.

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