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Recurrent Urethritis in a 25-Year-Old Male

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Definition

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Step 1: Clarify the Scenario First

Per CDC STI Guidelines (p. 65): "The initial step in recurrent urethritis is assessing compliance with treatment or potential reexposure to an untreated sex partner."

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Step 2: Etiology of Recurrent Urethritis

Infectious Causes

Per CDC STI Guidelines (p. 82): M. genitalium causes ~15–20% of NGU overall and ~40% of persistent or recurrent urethritis.

Non-Infectious Causes (consider if STI workup negative)

• Reactive arthritis (formerly Reiter's) — urethritis + arthritis + conjunctivitis/uveitis triad
• Traumatic — urethral instrumentation, masturbation trauma
• Chemical — urethral irritants, spermicides
• Stricture — recurrent stasis/secondary infection
• Meatal stenosis

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Step 3: Diagnostic Workup

All cases of recurrent urethritis

1. Confirm urethritis (objective evidence before retreating):
   • Urethral discharge on exam
   • Gram stain of urethral secretions: ≥2 WBC/oil-immersion field
   • First-void urine: positive leukocyte esterase or ≥10 WBC/hpf
2. NAAT panel (urine or urethral swab):
   • N. gonorrhoeae
   • C. trachomatis
   • M. genitalium (with resistance testing for macrolide — 23S rRNA mutation if available)
   • T. vaginalis
3. Additional testing as indicated:
   • HSV PCR (if ulceration or herpetic lesions)
   • Urine culture (if urinary symptoms predominate)
   • HIV and syphilis serology (STI screen)
4. Urethroscopy / urology referral — for recurrent episodes not explained by STI, to rule out stricture, foreign body, or other structural cause

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Step 4: Treatment Algorithm

Scenario A: Compliance failure or reexposure to untreated partner

• Retreat with the original regimen

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Scenario B: Properly treated, no reexposure — manage by prior regimen

If initially treated with azithromycin (for NGU):

• Add metronidazole 2g PO single dose (covers T. vaginalis)
• Plus moxifloxacin 400mg PO OD × 7 days (covers M. genitalium, especially azithromycin-resistant strains)

If initially treated with doxycycline:

• Add azithromycin 1g PO single dose (if M. genitalium suspected and no prior macrolide use)
• If M. genitalium confirmed with macrolide resistance: moxifloxacin 400mg OD × 7–14 days
• Add metronidazole to cover trichomoniasis

If gonorrhea was treated:

• Retest for gonorrhea with culture + sensitivity (resistance concern)
• Ensure chlamydia co-treatment was given

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M. genitalium — Special Consideration

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Step 5: Partner Management

• Trace and treat all sexual partners from the past 60 days
• Ensure partners are tested (not just empirically treated)
• Abstain from sexual intercourse until both patient and partner(s) complete treatment and are symptom-free

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Step 6: When to Refer / Escalate

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Key Takeaways

• M. genitalium is the most important organism to consider in recurrent/persistent urethritis — test with NAAT and resistance profiling.
• Always confirm objective urethritis before retreating to avoid overtreatment.
• Partner treatment failure is the most common preventable cause of recurrence.
• Trichomoniasis is frequently overlooked — always include in the NAAT panel.
• Structural causes (urethral stricture) must be excluded in truly recurrent STI-negative cases.

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UTI in Pregnancy — Clinical Approach

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Why UTI in Pregnancy Deserves Special Attention

• Progesterone → ureteral smooth muscle relaxation → hydroureter and hydronephrosis
• Uterine compression of ureters (especially right-sided)
• Increased urinary glucose and amino acids → bacterial growth medium
• Bladder displacement and incomplete emptying
• Immunological tolerance of pregnancy

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Classification of UTI in Pregnancy

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Step 1: Screen All Pregnant Women for ASB

• Screen with urine culture (not dipstick alone) at the first prenatal visit (typically 12–16 weeks)
• Culture is the gold standard — dipstick leukocyte esterase/nitrites have insufficient sensitivity for screening in pregnancy
• USPSTF 2019: Grade B recommendation for ASB screening in pregnancy

Per Urinary Tract Infections in Pregnant Individuals (p. 2): Screening and treatment of ASB has reduced pyelonephritis incidence by 20–35%.

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Step 2: Diagnosis

Asymptomatic Bacteriuria

• ≥10⁵ CFU/mL of a single uropathogen on two consecutive midstream clean-catch urine cultures (or one catheter specimen)
• No urinary symptoms

Acute Cystitis

• Symptoms: dysuria, frequency, urgency, suprapubic pain, haematuria
• Urinalysis: pyuria (≥10 WBC/hpf), bacteriuria, ± haematuria
• Urine culture: ≥10³–10⁵ CFU/mL (lower threshold than non-pregnant)

Acute Pyelonephritis

• Symptoms: fever (>38°C), rigors, flank/loin pain, CVAT, nausea/vomiting ± lower urinary symptoms
• Labs: urine culture, CBC (leukocytosis), CRP, blood cultures (in febrile/toxic patients), renal function, electrolytes
• Imaging: renal USS if no improvement after 48–72h (to exclude obstruction, abscess, calculi)
• Most common in 2nd trimester; right side more commonly affected

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Step 3: Common Pathogens

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Step 4: Treatment — Antibiotic Selection

Safety Framework by Trimester

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Treatment by Syndrome

Asymptomatic Bacteriuria / Acute Cystitis (Oral, 5–7 days)

Single-dose therapy has lower cure rates in pregnancy — 7-day courses are preferred over single-dose for most regimens (except fosfomycin).

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Acute Pyelonephritis

• All pyelonephritis in pregnancy should be admitted (high risk of sepsis, preterm labour)
• Particularly: fever >39°C, vomiting, signs of sepsis, inability to take oral fluids

• Based on culture and sensitivity results
• Cefalexin or amoxicillin-clavulanate most commonly used

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Step 5: Follow-Up Culture (Test of Cure)

• Mandatory in pregnancy — unlike non-pregnant patients
• Perform urine culture 1 week after completing treatment for all UTI types
• Then monthly urine cultures for the remainder of pregnancy

This is unique to pregnancy; persistent bacteriuria after treatment requires retreatment with an alternative antibiotic.

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Step 6: Recurrent UTI in Pregnancy

Per Urinary Tract Infections in Pregnant Individuals (p. 3): "After treating a recurrent acute infection, clinicians may consider initiating antimicrobial urinary suppression for the remainder of the pregnancy, preferably using a lower single daily dose of an antibacterial drug to which the bacterium isolated was susceptible."

• Suppressive therapy options (low-dose nocturnal):
  • Cefalexin 125–250mg OD at night
  • Nitrofurantoin 50–100mg OD at night (avoid in 1st trimester and ≥36 weeks)
  • Trimethoprim 100mg OD at night (mid-trimester only)

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Step 7: Complications if Untreated

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Step 8: GBS-Specific Consideration

• GBS (Group B Strep) bacteriuria at any count (even <10⁵ CFU/mL) in pregnancy:
  • Treat during pregnancy (indicates heavy GBS colonisation)
  • Flag for intrapartum antibiotic prophylaxis (IV penicillin in labour)
  • Do NOT rely on routine vaginal-rectal GBS swab at 35–37 weeks — bacteriuria = automatic indication

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Summary Algorithm

Pregnant woman at first prenatal visit
         ↓
Urine culture (screening)
         ↓
┌──────────────────┬───────────────────┐
│  ASB (no Sx)     │  Symptomatic UTI  │
└──────────────────┴───────────────────┘
         ↓                   ↓
     TREAT (7d)        Lower (cystitis) vs Upper (pyelonephritis)?
         ↓                   ↓
Test of cure 1wk      Lower: oral 7d → ToC 1wk → monthly cultures
                       Upper: ADMIT → IV abx → step down oral → 14d total
                                ↓
                      Recurrent? → Suppressive therapy rest of pregnancy

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Key Points to Remember

• Screen all pregnant women for ASB with urine culture — treat even if asymptomatic
• Always treat UTI in pregnancy regardless of severity
• Culture-guided therapy is mandatory — empirical choices must be trimester-appropriate
• Test of cure after every UTI in pregnancy (not done in non-pregnant patients)
• GBS bacteriuria = treat + intrapartum prophylaxis
• Admit all pyelonephritis in pregnancy
• Avoid: fluoroquinolones, tetracyclines, nitrofurantoin at term, trimethoprim in 1st trimester