What does the presence of clue cells on a vaginal sample indicate in a woman of reproductive age?

Clue Cells Indicate Bacterial Vaginosis

The presence of clue cells on vaginal microscopy is the single most reliable diagnostic indicator of bacterial vaginosis (BV), representing vaginal epithelial cells heavily coated with adherent bacteria, primarily Gardnerella vaginalis. 1, 2

What Clue Cells Are

• Clue cells are vaginal epithelial cells with their surfaces obscured by dense adherence of gram-negative bacteria, giving them a stippled or granular appearance with indistinct borders 1
• Immunofluorescence studies confirm that Gardnerella vaginalis is the predominant bacteria adhering to clue cell surfaces, though other anaerobes may be present 3
• Clue cells are identified on saline wet mount microscopy at low- and high-dry power magnification 1

Diagnostic Significance

Clue cells have the highest diagnostic accuracy of any single parameter for BV, with 98.2% sensitivity, 94.3% specificity, 89.9% positive predictive value, and 99.0% negative predictive value. 2

• The CDC diagnostic criteria (Amsel criteria) require three of four findings: homogeneous white discharge coating vaginal walls, clue cells on microscopy, vaginal pH >4.5, and positive whiff test (fishy odor with KOH) 1, 4
• When combined with the whiff test, clue cells achieve 99.5% sensitivity and 98.8% positive predictive value for BV diagnosis 2
• Recent research distinguishes "true clue cells" (bacteria directly adherent to epithelial surfaces, unique to Gardnerella) from "pseudo clue cells" (epithelial cells mechanically entrapped in bacterial masses), though this distinction is primarily of research interest 5

Clinical Context of BV

• BV results from replacement of normal H₂O₂-producing Lactobacillus species with high concentrations of anaerobic bacteria including Prevotella, Mobiluncus, Gardnerella vaginalis, and Mycoplasma hominis 1
• Up to 50% of women meeting diagnostic criteria for BV are asymptomatic, so clue cells may be found incidentally 1
• BV is associated with serious complications including pelvic inflammatory disease, endometritis, vaginal cuff cellulitis after invasive procedures, and adverse pregnancy outcomes (preterm birth, premature rupture of membranes, postpartum endometritis) 1

Treatment Implications

When clue cells are identified, treatment with metronidazole 500 mg orally twice daily for 7 days is indicated for symptomatic women. 1, 6

• Patients must avoid alcohol during metronidazole treatment and for 24 hours after completion to prevent disulfiram-like reactions 6
• Treatment of male partners does not reduce recurrence rates and is not recommended 1, 6
• Consider treating asymptomatic BV before surgical abortion or other invasive gynecologic procedures to reduce infectious complications 1

Common Diagnostic Pitfalls

• Do not rely on discharge characteristics alone—homogeneous discharge has poor diagnostic value compared to clue cells 2
• Gram stain morphotype scoring is less accurate than wet mount identification of clue cells (sensitivity 97.0% vs 98.2%, specificity 66.2% vs 94.3%) 2
• Culture for G. vaginalis is not recommended because it lacks specificity—this organism can be isolated from 50% of normal women 1
• Cervical Pap tests have limited utility for BV diagnosis due to low sensitivity 1