What is the appropriate next step in evaluating a woman with normal‑appearing vaginal discharge and negative bacterial vaginosis and Candida test results?

Evaluation of Vaginal Discharge with Negative BV and Candida Testing

When bacterial vaginosis and candidiasis have been ruled out, you must test for trichomoniasis using nucleic acid amplification testing (NAAT), because wet mount microscopy misses 20–60% of infections, and consider testing for gonorrhea and chlamydia if the patient has cervical involvement or risk factors. 1, 2

Immediate Diagnostic Steps

Order NAAT for Trichomonas vaginalis

• Microscopy for trichomonads has a sensitivity of only 40–80%, so a negative wet mount does not exclude trichomoniasis. 3, 1
• NAAT is the CDC-recommended diagnostic method and should be ordered in any woman with persistent vaginal discharge when initial testing is negative. 1, 2
• Culture for T. vaginalis is more sensitive than microscopy but still inferior to NAAT. 3

Test for Cervicitis

• Obtain NAAT for Neisseria gonorrhoeae and Chlamydia trachomatis from a vaginal or cervical swab, because mucopurulent cervicitis can present as vaginal discharge. 3, 1
• Look specifically for cervical friability, hyperemia, or easily induced bleeding on speculum examination. 1

Re-verify Your Initial Testing

• Confirm that vaginal pH was measured with narrow-range pH paper—a pH >4.5 suggests BV or trichomoniasis, while pH <4.5 suggests candidiasis. 1, 4
• Re-examine the wet mount for clue cells, as the absence of clue cells makes BV unlikely unless confirmed by Gram stain. 1, 4
• Consider Gram stain of vaginal fluid if Amsel criteria were borderline, as this provides definitive BV diagnosis. 5, 4
• Order Candida culture if clinical suspicion remains high, because KOH microscopy can miss non-albicans species like Candida glabrata. 6, 2

Consider Non-Infectious Causes

Evaluate for Physiologic Discharge

• Normal vaginal discharge is clear to white, has no odor, maintains pH <4.5, and shows only epithelial cells and lactobacilli on microscopy. 3
• If the discharge appears normal and all testing is negative, reassure the patient that physiologic discharge requires no treatment. 1

Assess for Irritant or Allergic Vaginitis

• The presence of external vulvar inflammation with minimal discharge and no identified pathogens suggests mechanical, chemical, or allergic irritation. 3
• Ask specifically about new soaps, detergents, douches, lubricants, or latex condom use. 7, 8

Screen for Atrophic Vaginitis

• In perimenopausal or postmenopausal women, estrogen deficiency causes vaginal dryness, irritation, and thin discharge. 6, 2
• Examination reveals pale, thin vaginal mucosa with petechiae; pH is typically elevated (>5.0). 6

Empiric Treatment Considerations

When to Treat Empirically for Trichomoniasis

• If the discharge is green, copious, and frothy, the American Academy of Family Physicians recommends empiric metronidazole 2 g single dose or 500 mg twice daily for 7 days while awaiting NAAT results. 1
• Treat sexual partners simultaneously with metronidazole 2 g single dose to prevent reinfection. 1, 5

When to Avoid Empiric Treatment

• Do not treat empirically based on discharge appearance alone, as clinical characteristics are unreliable for distinguishing causes. 1
• Laboratory testing fails to identify a cause in a minority of women, and empiric treatment without diagnosis leads to inappropriate antibiotic use. 3

Critical Pitfalls to Avoid

• Never diagnose BV without clue cells unless confirmed by Gram stain—treating the wrong condition worsens outcomes. 1
• Do not assume negative culture rules out trichomoniasis—NAAT remains the gold standard. 1
• Do not culture Gardnerella vaginalis for BV diagnosis—it is isolated from 50% of asymptomatic women and lacks specificity. 1, 5
• Consider mixed infections, as multiple pathogens may coexist and require combined treatment approaches. 1

Follow-Up Strategy

• Reassess if symptoms persist after completing any empiric therapy—ongoing symptoms may signal reinfection from an untreated partner or resistant organisms. 1
• If all testing returns negative and symptoms continue, refer to gynecology for consideration of desquamative inflammatory vaginitis or other rare conditions. 2, 8