What is the appropriate diagnosis and treatment for a 36-year-old male with a 2-week history of itching and penile discharge, positive for Mycoplasma hominis and Ureaplasma parvum, and having a urine culture positive for leukocyte esterase and WBC?

Diagnosis: Nongonococcal Urethritis (NGU)

This patient has documented nongonococcal urethritis caused by Ureaplasma parvum and/or Mycoplasma hominis, and should be treated immediately with doxycycline 100 mg orally twice daily for 7 days. 1, 2, 3

Diagnostic Confirmation

This patient meets CDC criteria for confirmed urethritis based on:

• Positive leukocyte esterase test on first-void urine 4, 2
• Presence of WBCs in urine (>10 WBCs per high-power field) 4, 2
• Clinical symptoms of penile discharge and itching consistent with urethritis 2

The diagnosis is nongonococcal urethritis (NGU) because gonorrhea and chlamydia testing should be performed first, and if negative (as implied by the focus on Mycoplasma/Ureaplasma), these organisms become the likely pathogens. 4

Critical Context About These Organisms

Do not be misled by the positive Ureaplasma parvum and Mycoplasma hominis results alone—these organisms frequently colonize healthy individuals without causing disease. 1, 5

However, this patient has documented urethritis symptoms and objective signs of inflammation, which changes the clinical picture entirely:

• The CDC recommends treating Ureaplasma only when patients have documented urethritis symptoms (mucopurulent discharge, dysuria, urethral pruritis) or objective signs (>5 WBCs per oil immersion field on Gram stain, positive leukocyte esterase, or >10 WBCs per high-power field on first-void urine). 1
• The European STI Guidelines Editorial Board confirms that routine testing for M. hominis and Ureaplasma species is not recommended in asymptomatic individuals, but this patient is symptomatic. 5

Treatment Protocol

First-line treatment: Doxycycline 100 mg orally twice daily for 7 days 4, 1, 2, 3

This regimen is supported by:

• FDA-approved dosing for nongonococcal urethritis caused by C. trachomatis or U. urealyticum 3
• CDC guidelines for NGU management 4, 2
• Research showing 94.6% sensitivity of U. urealyticum to doxycycline and 83.3% sensitivity of M. hominis to doxycycline 6

Alternative regimen (if doxycycline contraindicated):

• Azithromycin 1 g orally as single dose 4, 1, 7
• Erythromycin base 500 mg orally four times daily for 7 days 4, 1, 2

Partner Management

All sexual partners within the preceding 60 days require evaluation and empiric treatment with the same regimen. 1, 2

• Partners with last sexual contact within 30 days of symptom onset should be prioritized for treatment 1, 2
• Both patient and partners must abstain from sexual intercourse for 7 days after completing the 7-day regimen 1

Critical Pitfalls to Avoid

Do not treat based on positive Ureaplasma/Mycoplasma testing alone without documented urethritis—this is the most common error. 1, 5

• Asymptomatic carriage of these organisms occurs in 40-80% of sexually active individuals 5
• The European STI Guidelines Editorial Board warns that routine testing and treatment may result in antimicrobial resistance selection and substantial economic cost 5

Do not assume this is a urinary tract infection (UTI) requiring different antibiotics:

• The CDC advises against treating for UTI based on pyuria alone in patients with confirmed or suspected STI 8
• Leukocyte esterase has 93% sensitivity but only 72% specificity for UTI, and in this context of penile discharge and itching, urethritis is the correct diagnosis 8

Do not confuse U. parvum with U. urealyticum regarding fertility implications:

• Only U. urealyticum (not U. parvum) is associated with male infertility based on meta-analysis evidence 1
• However, this distinction does not change acute treatment, as both respond to doxycycline 1, 6

Follow-Up Strategy

Patients should return for evaluation only if symptoms persist or recur after completing therapy. 4, 2

• If no improvement is seen within 3 days of starting treatment, re-evaluate the diagnosis 2
• Consider testing for Mycoplasma genitalium if symptoms persist, as this organism causes 15-25% of NGU cases and has rising resistance to first-line agents 4
• If symptoms continue beyond 3 months despite appropriate treatment, consider chronic prostatitis/chronic pelvic pain syndrome and refer to urology 2