What are the recommended antibiotic regimens for common bacterial sexually transmitted infections (STIs)?

Recommended Antibiotic Regimens for Common Bacterial STIs

For chlamydial infections and nongonococcal urethritis, use either azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days—both are equally effective, but azithromycin ensures compliance through directly observed single-dose therapy. 1

Chlamydia trachomatis Infection

First-Line Treatment Options

Recommended regimens (equally efficacious):

• Azithromycin 1 g orally in a single dose 1
• Doxycycline 100 mg orally twice daily for 7 days 1

Clinical trials demonstrate equal efficacy between these two regimens 1. Azithromycin should be prioritized for patients with questionable compliance, erratic healthcare-seeking behavior, or when directly observed therapy is needed 1. The single-dose regimen provides virtually 100% compliance and eliminates concerns about treatment completion 2.

Alternative Regimens (when first-line options unavailable)

• Erythromycin base 500 mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1
• Ofloxacin 300 mg orally twice daily for 7 days 1
• Levofloxacin 500 mg orally once daily for 7 days 1

Important caveat: Erythromycin is less efficacious than azithromycin or doxycycline, and gastrointestinal side effects frequently discourage compliance 1. Ofloxacin offers no dosing advantage over doxycycline and is more expensive 1.

Nongonococcal Urethritis (NGU)

Treatment Approach

Use the same regimens as for chlamydial infection 1:

• Azithromycin 1 g orally single dose OR
• Doxycycline 100 mg orally twice daily for 7 days

Azithromycin may have superior efficacy for Mycoplasma genitalium-associated urethritis 1. All patients with urethritis should be tested for both N. gonorrhoeae and C. trachomatis before or during treatment 1.

When to Treat Empirically

Empiric treatment without documented urethritis is justified only for:

• High-risk patients unlikely to return for follow-up (e.g., adolescents with multiple partners) 1
• These patients should receive dual therapy covering both gonorrhea and chlamydia 1

Gonococcal Infection

Dual Therapy Requirement

Because coinfection with C. trachomatis occurs frequently in patients with gonococcal infection, presumptive treatment for chlamydia is appropriate when treating gonorrhea 1. The evidence provided focuses on chlamydial treatment, but dual therapy with a cephalosporin (for gonorrhea) plus azithromycin or doxycycline (for chlamydia) is standard practice 3.

Critical Management Principles

Medication Dispensing and Observation

• Medications should be dispensed on-site in the clinic 1
• The first dose should be directly observed to maximize compliance 1
• This approach is particularly important for single-dose azithromycin regimens 1

Sexual Abstinence Requirements

Patients must abstain from sexual intercourse:

• For 7 days after single-dose therapy (azithromycin) 1
• Until completion of 7-day regimens (doxycycline) 1
• Until ALL sex partners are treated to prevent reinfection 1

Partner Management

• All sex partners within the preceding 60 days must be evaluated and treated 1
• Partners should receive the same treatment regimen as the index patient 1
• Failure to treat partners is a major cause of apparent treatment failure, which is actually reinfection 3

Follow-Up and Test of Cure

When Retesting is NOT Needed

Patients treated with azithromycin or doxycycline do NOT require test of cure if:

• Symptoms resolve completely 1
• No reinfection is suspected 1
• These regimens are highly efficacious (>94% cure rates) 1, 4

When Retesting IS Indicated

• If symptoms persist or recur after treatment completion 1
• Consider retesting 3 weeks after erythromycin treatment 1
• Rescreening several months after treatment may detect reinfection in high-risk populations 1

Critical timing consideration: Testing performed less than 3 weeks after treatment may yield false-positive results due to continued excretion of dead organisms 1

Recurrent/Persistent Urethritis Management

Initial Assessment

Before retreating, determine if the patient:

1. Complied with the initial treatment regimen 1
2. Was reexposed to an untreated sex partner 1
3. Has objective signs of urethritis (not just symptoms alone) 1

Treatment Strategy

If non-compliance or reexposure occurred: Retreat with the initial regimen 1

If compliant and no reexposure: Consider alternative pathogens 1:

• Test for Trichomonas vaginalis (intraurethral swab or first-void urine culture) 1
• Some cases after doxycycline may be tetracycline-resistant Ureaplasma urealyticum 1

Recommended regimen for persistent urethritis:

• Metronidazole 2 g orally single dose PLUS
• Erythromycin base 500 mg orally four times daily for 7 days 1

Special Populations

HIV-Infected Patients

HIV-infected patients should receive the same treatment regimens as HIV-negative patients 1. Treatment is vital because cervicitis/urethritis increases HIV shedding and may facilitate HIV transmission 1.

Pediatric Considerations

• Doxycycline is contraindicated in children <8 years due to permanent tooth discoloration and bone growth effects 5
• For children ≥8 years and ≤45 kg: doxycycline 2.2 mg/kg orally every 12 hours (maximum 100 mg per dose) 5, 6
• For children >45 kg (100 lbs): use adult dosing 6
• Azithromycin safety and efficacy for persons ≤15 years has not been established 1

Pregnancy

• Doxycycline is contraindicated in pregnancy (Category D) 5
• Azithromycin is Category B in pregnancy and is preferred 7
• Erythromycin base is an alternative for pregnant patients 1

Common Pitfalls to Avoid

1. Do NOT retreat based on symptoms alone without documenting urethritis by microscopy or laboratory evidence 1
2. Do NOT assume treatment failure without first ruling out reinfection from untreated partners 3
3. Do NOT use quinolones (other than ofloxacin/levofloxacin) for chlamydial infection—they lack proven efficacy 1
4. Do NOT test for cure earlier than 3 weeks after treatment—false positives may occur 1
5. Do NOT use erythromycin as first-line therapy due to inferior efficacy and poor tolerability 1

Pharmacologic Considerations

Azithromycin Advantages

• High tissue distribution with tissue-to-plasma ratios of 70:1 in cervix 7
• Single-dose ensures compliance 1, 2
• Can be taken with food if gastrointestinal upset occurs 8
• Common side effects: nausea, vomiting, abdominal pain, diarrhea 7

Doxycycline Advantages

• Lower cost than azithromycin 1
• Longer history of extensive use and proven safety 1
• High bioavailability and long half-life allowing twice-daily dosing 9
• Should be taken with adequate fluids to reduce esophageal irritation risk 6
• Can be taken with food (absorption not significantly affected), but avoid dairy products within 2 hours 5, 6