What to do for a 31-year-old male patient with a history of non-gonococcal urethritis and a known doxycycline (antibiotic) allergy, experiencing itchiness without hives after taking doxycycline?

Management of Doxycycline-Induced Itchiness Without Hives in Non-Gonococcal Urethritis

Stop doxycycline immediately and switch to erythromycin base 500 mg orally four times daily for 7 days or azithromycin 1 g orally as a single dose, as itchiness without hives may represent an early hypersensitivity reaction that could progress to more severe manifestations. 1

Immediate Clinical Decision-Making

Discontinue doxycycline now. While isolated itchiness without hives is less severe than urticaria, it represents a potential hypersensitivity reaction that warrants medication cessation in the context of a documented doxycycline allergy history. 1

• Do not attempt to continue doxycycline or switch to other tetracyclines (minocycline, tetracycline), as cross-reactivity within the tetracycline class makes this unsafe. 2
• Monitor closely for progression to hives, angioedema, respiratory symptoms, or anaphylaxis over the next 24-48 hours, which would require emergency intervention. 2

Alternative Treatment Regimens for NGU

The CDC provides clear alternative regimens when doxycycline cannot be used:

First-Line Alternatives:

• Erythromycin base 500 mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 1
• Azithromycin 1 g orally as a single dose 2, 3

If Erythromycin Not Tolerated:

• Erythromycin base 250 mg orally four times daily for 14 days (lower dose, longer duration) 1
• Erythromycin ethylsuccinate 400 mg orally four times daily for 14 days 1

Symptomatic Management of Itchiness

• Administer antihistamines such as diphenhydramine or hydroxyzine for symptomatic relief of pruritus. 2
• Reassess in 24-48 hours to ensure symptoms are resolving and not progressing to more severe allergic manifestations. 2

Treatment Efficacy Considerations

While azithromycin offers the convenience of single-dose therapy, the evidence shows comparable efficacy between regimens:

• Clinical cure rates for NGU are similar between azithromycin (80-86%) and doxycycline (76-91%) in multiple studies. 4, 5, 6, 7
• Chlamydia trachomatis eradication is excellent with both azithromycin (83-100%) and erythromycin-class antibiotics. 4, 5, 6
• Ureaplasma urealyticum cure rates are modest with all regimens (45-75%), so persistent symptoms may require extended therapy. 5, 7

Critical Partner Management

• All sexual partners with contact within 60 days of diagnosis must be evaluated and treated with an appropriate alternative regimen (not doxycycline). 2, 8
• Both patient and partners must abstain from sexual intercourse for 7 days after completing single-dose azithromycin therapy or until completion of multi-day regimens. 2, 8

Follow-Up Strategy

• Return for evaluation if symptoms persist or recur after completing alternative therapy. 1
• Test-of-cure is not routinely recommended after azithromycin or erythromycin unless symptoms persist or reinfection is suspected. 2
• If symptoms persist after first alternative regimen, consider re-treatment with extended erythromycin (14 days) to cover possible tetracycline-resistant Ureaplasma urealyticum. 1

Common Pitfalls to Avoid

• Never attempt desensitization for tetracycline allergy in NGU treatment, as excellent alternatives exist without this risk. 2
• Do not use fluoroquinolones (ofloxacin, levofloxacin) as first-line alternatives when erythromycin or azithromycin are available, given antimicrobial stewardship concerns. 1
• Do not dismiss isolated itchiness in a patient with documented doxycycline allergy—this represents a contraindication to continued use. 2
• Ensure compliance with multi-day regimens by counseling on the importance of completing the full course, as single-dose azithromycin may improve adherence. 4, 6