What is the difference in treatment for urethritis versus urinary tract infections (UTIs)?

Urethritis vs UTI: Key Treatment Differences

Urethritis and UTIs require fundamentally different antimicrobial approaches because they target distinct pathogens: urethritis is primarily a sexually transmitted infection requiring coverage for Chlamydia trachomatis and Neisseria gonorrhoeae, while UTIs are caused by enteric bacteria (primarily Enterobacterales) requiring different antibiotic classes.

Pathogen Differences

Urethritis:

• Primarily caused by sexually transmitted organisms: N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and Trichomonas vaginalis 1
• Transmitted via sexual contact and requires partner treatment 1

UTIs:

• Caused by enteric bacteria, predominantly Escherichia coli, Klebsiella species, Enterobacter species, Proteus species 2
• Not sexually transmitted; related to urinary tract colonization 2

Diagnostic Approach Differences

Urethritis requires:

• Gram stain of urethral discharge or urethral smear for preliminary gonococcal diagnosis 1
• Nucleic acid amplification test (NAAT) on first-void urine or urethral swab for C. trachomatis and N. gonorrhoeae 1
• Urethral swab culture for gonorrhea-positive NAAT to assess antimicrobial resistance 1
• Diagnosis confirmed by mucopurulent discharge, ≥2 WBCs per oil immersion field on Gram stain, or ≥10 WBCs per high-power field in first-void urine 3, 4

UTIs require:

• Urine culture before treatment in complicated cases, pregnant women, diabetics, or recurrent infections 5
• Standard urinalysis for pyuria and bacteriuria 2

Treatment Regimens: The Critical Distinction

Urethritis Treatment

For gonococcal urethritis (empiric or confirmed):

• Ceftriaxone 1g IM or IV single dose PLUS azithromycin 1g PO single dose 1
• Alternative if cephalosporin allergy: Gentamicin 240mg IM single dose plus azithromycin 2g PO single dose 1

For non-gonococcal urethritis (when pathogen unidentified):

• Doxycycline 100mg PO twice daily for 7 days 1
• Alternative: Azithromycin 500mg PO day 1, then 250mg PO for 4 days 1

For confirmed C. trachomatis:

• Azithromycin 1.0-1.5g PO single dose OR doxycycline 100mg PO twice daily for 7 days 1, 6

For M. genitalium:

• Azithromycin 500mg PO day 1, then 250mg daily for 4 days 1
• If macrolide-resistant: Moxifloxacin 400mg daily for 7-14 days 1

For T. vaginalis:

• Metronidazole or tinidazole 2g PO single dose 1

UTI Treatment

For uncomplicated UTI:

• Trimethoprim-sulfamethoxazole (if local resistance <20%) 2
• Nitrofurantoin for cystitis 5
• Fluoroquinolones only if resistance <10% and no recent fluoroquinolone use 1
• Duration: 1-7 days for cystitis 5

For complicated UTI with systemic symptoms:

• Amoxicillin plus aminoglycoside, OR second-generation cephalosporin plus aminoglycoside, OR IV third-generation cephalosporin 1
• Duration: 7-14 days minimum 5

Critical Management Differences

Urethritis-specific requirements:

• Mandatory sexual partner treatment while maintaining confidentiality 1
• Abstain from sexual intercourse for 7 days after treatment initiation and until partners treated 3, 4
• In mild symptoms, delay treatment until NAAT results available to guide pathogen-directed therapy 1
• Test of cure not recommended before 3 weeks (false positives possible) 3
• Repeat screening in 3 months for all sexually transmitted infections 3

UTI-specific requirements:

• No partner treatment needed 2
• Manage underlying urological abnormalities 1
• Remove or replace indwelling catheters before antimicrobial therapy if catheter-associated 1
• Do not treat asymptomatic bacteriuria except in pregnancy, before urologic procedures, or in specific high-risk populations 1

Common Pitfalls

Do not confuse the two conditions:

• Using fluoroquinolones or trimethoprim-sulfamethoxazole for urethritis will miss gonococcal and chlamydial infections 1
• Using ceftriaxone/azithromycin for UTI is inappropriate and promotes resistance 1
• Failing to treat sexual partners in urethritis leads to reinfection 1

For persistent urethritis after initial treatment:

• Confirm urethritis with microscopy before retreating 7
• If doxycycline was first-line: switch to azithromycin 5-day regimen plus metronidazole 400-500mg twice daily for 5-7 days 1, 7
• If azithromycin was first-line: switch to moxifloxacin 400mg daily for 7-14 days OR doxycycline plus metronidazole 1, 7