What is the recommended empiric treatment regimen for male sexually transmitted infections (STIs)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: December 5, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Empiric Treatment for Male STIs

For symptomatic males with suspected sexually transmitted infections, treat empirically with dual therapy covering both gonorrhea and chlamydia: ceftriaxone 500 mg IM single dose PLUS doxycycline 100 mg orally twice daily for 7 days. 1

When to Treat Empirically

Empiric treatment is indicated for males with urethritis when:

  • Mucopurulent or purulent urethral discharge is present 2
  • Gram stain shows ≥5 WBCs per oil immersion field 2
  • First-void urine microscopy demonstrates ≥10 WBCs per high-power field 2
  • Positive leukocyte esterase test on first-void urine 2

If none of these criteria are present, empiric treatment is still recommended for men at high risk who are unlikely to return for follow-up evaluation. 2 This recognizes the reality of clinical practice where loss to follow-up is common and untreated infections lead to ongoing transmission and complications.

Recommended Empiric Regimen

Primary Recommendation

  • Ceftriaxone 500 mg IM single dose 1
  • PLUS Doxycycline 100 mg orally twice daily for 7 days 1

This updated 2020 CDC recommendation increases ceftriaxone from the previous 250 mg dose to 500 mg due to evolving resistance patterns, while maintaining doxycycline for chlamydia coverage when coinfection has not been excluded. 1

Alternative Single-Dose Option (When Compliance is Uncertain)

  • Ceftriaxone 500 mg IM single dose 1
  • PLUS Azithromycin 1 g orally single dose 2

Azithromycin offers the advantage of directly observed single-dose therapy, maximizing compliance, but is more expensive and causes more gastrointestinal side effects (35% of patients, with 10% moderate and 3% severe). 3 The single-dose azithromycin option is particularly valuable when you cannot ensure the patient will complete a 7-day doxycycline course. 2

Rationale for Dual Therapy

Dual therapy is essential because:

  • Chlamydia coinfection occurs in a substantial proportion of gonorrhea cases 4
  • Testing delays mean you cannot wait for results before treating 2
  • Untreated chlamydia leads to complications including epididymitis, urethral stricture, and facilitates HIV transmission 2
  • Reinfection from untreated partners is the primary cause of treatment failure 4

Special Considerations for Mycoplasma genitalium

If persistent or recurrent urethritis occurs after standard treatment, test for M. genitalium using NAAT with macrolide resistance testing when available. 5 For suspected M. genitalium:

  • Azithromycin is preferred over doxycycline (85-95% cure rate vs 30-40%) 5
  • Moxifloxacin 400 mg daily for 7 days is recommended for macrolide-resistant infections 5

Critical Management Steps

Instruct patients to:

  • Abstain from sexual intercourse for 7 days after initiating therapy and until symptoms resolve 2
  • Abstain until all sex partners are treated to prevent reinfection 2
  • Return for evaluation if symptoms persist or recur after completing therapy 2

All sexual partners within the preceding 60 days must be evaluated and treated empirically for both gonorrhea and chlamydia, regardless of symptoms or test results. 4 If the last sexual contact was >60 days before diagnosis, treat the most recent partner. 4

Additional Testing

All patients diagnosed with an STI should receive:

  • Syphilis serology 2
  • HIV testing with counseling 2

This addresses the reality that STIs cluster and patients with one infection are at higher risk for others.

Common Pitfalls to Avoid

Do not:

  • Treat based on symptoms alone without objective evidence of urethritis - this leads to overtreatment and antimicrobial resistance 2
  • Use quinolones (ciprofloxacin, ofloxacin, levofloxacin) for gonorrhea - resistance is now widespread and these are no longer recommended 2, 1
  • Delay treatment waiting for test results - empiric therapy should be initiated immediately when clinical criteria are met 2
  • Forget to treat partners - this is the most common cause of reinfection and treatment failure 4

Medications should be dispensed on-site in the clinic when possible, with the first dose directly observed to maximize compliance. 2

References

Research

Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020.

MMWR. Morbidity and mortality weekly report, 2020

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Empirical Treatment for Gonorrhea-Positive Sexual Partners

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Testing for Mycoplasma genitalium in Males

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.