What is the likely cause and treatment for a 30-year-old female with dysuria and yellow vaginal discharge, who has consistently tested negative for Urinary Tract Infection (UTI), Sexually Transmitted Infection (STI), and yeast infections?

Recurrent Dysuria and Yellow Vaginal Discharge with Negative Testing

This patient most likely has bacterial vaginosis (BV), which is the most prevalent cause of vaginal discharge and can present with dysuria despite negative standard UTI testing. 1

Most Likely Diagnosis: Bacterial Vaginosis

BV should be your primary diagnostic consideration because:

• BV is the most common cause of vaginal discharge or malodor, affecting approximately half of women who meet clinical criteria without symptoms 1
• Yellow discharge with dysuria can occur with BV, particularly when accompanied by vulvar irritation 2, 3
• Standard UTI testing misses BV because it involves anaerobic bacteria (Bacteroides, Mobiluncus, Gardnerella vaginalis, Mycoplasma hominis) rather than typical uropathogens 1
• Laboratory testing fails to identify a cause in a substantial minority of women with vaginal complaints 1, 2

Diagnostic Workup Required

Perform these specific tests at the next visit:

• Vaginal pH measurement - BV shows pH >4.5 (versus normal ≤4.5 with yeast) 1, 2
• Wet mount microscopy with saline - look for clue cells (vaginal epithelial cells with bacteria adhered creating stippled appearance and obscured borders) 1, 4, 2
• 10% KOH preparation - perform whiff test for fishy odor 1, 4
• Examine discharge character - BV produces homogeneous white discharge adhering to vaginal walls 1, 2

BV diagnosis requires 3 of 4 Amsel criteria: homogeneous white discharge, clue cells on microscopy, vaginal pH >4.5, and positive whiff test 1, 5

If wet mount is equivocal, Gram stain using Nugent criteria is the most specific procedure, showing replacement of lactobacilli by mixed anaerobic flora 2

Alternative Diagnoses to Consider

Trichomoniasis remains possible despite negative testing:

• NAAT testing is superior to wet mount due to higher sensitivity 2
• Characterized by profuse yellow-green discharge, vaginal irritation, and dysuria 6, 7
• If initial testing was wet mount only, repeat with NAAT 2

Mycoplasma genitalium should be tested if persistent urethritis or cervicitis with negative initial STI testing 7

Non-infectious causes when all testing negative:

• Mechanical or chemical irritation of the vulva from soaps, douches, or hygiene products 1
• Hypoestrogenism causing atrophic changes 8
• Interstitial cystitis presenting with dysuria without infection 8

Treatment Algorithm

If BV Confirmed (3 of 4 Amsel criteria present):

First-line treatment: Metronidazole 500 mg orally twice daily for 7 days (95% cure rate) 1, 5, 9

• Critical instruction: Avoid alcohol during treatment and for 24 hours after due to disulfiram-like reaction 1, 5
• Only treat if symptomatic - asymptomatic BV does not require treatment 1, 5

Alternative regimens if oral therapy not tolerated:

• Metronidazole gel 0.75%, one full applicator (5g) intravaginally twice daily for 5 days 1
• Clindamycin cream 2%, one full applicator (5g) intravaginally at bedtime for 7 days 1
• Warning: Clindamycin cream is oil-based and weakens latex condoms and diaphragms 5

Single-dose option when compliance is concern: Metronidazole 2g orally once (84% cure rate, lower than 7-day regimen) 1, 5

If Trichomoniasis Confirmed:

Metronidazole 2g orally as single dose for both patient and all sexual partners 9, 6

If All Testing Remains Negative:

• Trial of empiric BV treatment is reasonable given high prevalence and test limitations 1, 2
• Consider referral to gynecology for vulvoscopy to identify mechanical/chemical irritation 1
• Evaluate for interstitial cystitis if dysuria predominates without discharge 8

Critical Follow-Up Requirements

Follow-up visits are not necessary if symptoms resolve after BV treatment 1

Repeat evaluation required if:

• Symptoms persist after completing treatment 1
• Symptoms recur within 2 months 1, 3
• At that visit, repeat wet mount, pH, and whiff test 1

Recurrence is common with BV - approximately 30% recur within 3 months 1

Important Clinical Pitfalls to Avoid

Do not treat male partners - treatment of male sex partners has not been shown to alter clinical course or reduce BV recurrence rates 1, 5

Do not rely on culture for G. vaginalis - it can be isolated from vaginal cultures in half of normal women and is not specific for BV 1

Do not diagnose BV without clue cells unless confirmed by Gram stain, as this leads to treating the wrong condition 2

Recognize that VVC can occur concomitantly with other infections - evaluate for all three common causes of vaginitis (BV, candidiasis, trichomoniasis) 2, 3

Vaginal discharge decreases likelihood of UTI - when discharge is present, investigate cervicitis and vaginitis rather than pursuing repeated UTI workup 7

Avoid empiric antibiotics without proper diagnosis - this can worsen symptoms by precipitating candidal overgrowth 2