What is the significance of clue cells on a wet mount (wet preparation)?

From the Guidelines

Clue cells on wet prep are a definitive indicator of bacterial vaginosis (BV), and treatment should be initiated promptly to alleviate symptoms and prevent complications. Bacterial vaginosis is a clinical syndrome resulting from the replacement of normal Lactobacillus sp. in the vagina with high concentrations of anaerobic bacteria, such as Prevotella sp. and Mobiluncus sp., G. vaginalis, and Mycoplasma hominis 1. The presence of clue cells on microscopic examination is one of the diagnostic criteria for BV, along with a homogeneous, white, noninflammatory discharge, a pH of vaginal fluid >4.5, and a fishy odor of vaginal discharge before or after addition of 10% KOH (i.e., the whiff test) 1.

Some key points to consider in the diagnosis and treatment of BV include:

• Clue cells are vaginal epithelial cells with bacteria adhering to their surface, giving them a stippled appearance with indistinct borders under microscopy
• Treatment typically involves oral metronidazole 500 mg twice daily for 7 days, or metronidazole gel 0.75% intravaginally once daily for 5 days, or clindamycin cream 2% intravaginally at bedtime for 7 days
• For pregnant patients, oral therapy is preferred
• Patients should abstain from alcohol during treatment with metronidazole and for 24 hours after completion due to potential disulfiram-like reactions
• Sexual partners generally don't require treatment, but condom use during treatment is recommended
• Recurrent BV may require extended or suppressive therapy
• Patients should be advised that BV can increase susceptibility to other STIs and can cause complications in pregnancy if untreated, as noted in the guidelines for sexually transmitted diseases treatment 1.

From the FDA Drug Label

A clinical diagnosis of bacterial vaginosis was based on Amsel's criteria and defined by the presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than 4. 5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains ≥20% clue cells on microscopic examination. The presence of clue cells on wet prep is one of the criteria for diagnosing bacterial vaginosis, specifically requiring ≥20% clue cells on microscopic examination 2.

• Key points:
  • Clue cells are a diagnostic criterion for bacterial vaginosis
  • The presence of ≥20% clue cells on microscopic examination is required for diagnosis
  • Tinidazole has been shown to be effective in treating bacterial vaginosis, with therapeutic cure rates ranging from 36.8% to 51.3% 2

From the Research

Clue Cells on Wet Prep

• Clue cells are an accepted clue to the diagnosis of bacterial vaginosis, characterized by epithelial cells heavily covered with adherent bacteria 3
• The exact morphologic criteria of clue cells and bacterial adherence were never elaborated, but recent studies have investigated adhesive and cohesive patterns of main microbiota groups in vaginal discharge using fluorescence in situ hybridization (FISH) 3
• True clue cells, characterized by direct cohesive adherence to the epithelial cells, were unique for Gardnerella species and observed only in 56% of the investigated samples 3
• In the remaining vaginal samples, the epithelial cells were mechanically entrapped in bacterial masses, and the composition was unrelated to the epithelial cell surface, building non-adherent pseudo clue cells 3

Diagnosis and Treatment of Bacterial Vaginosis

• Bacterial vaginosis is the commonest cause of vaginal discharge in women of childbearing age, and oral metronidazole has long been established as an effective therapy in the treatment of BV 4
• Other treatment options for bacterial vaginosis include metronidazole vaginal gel, clindamycin vaginal cream, and tinidazole, which have been shown to be effective in treating BV 4, 5, 6
• The treatment of BV is associated with high levels of failure and recurrence rates, which may be associated with antibiotic resistance, the inability to eradicate the polymicrobial biofilms, and failure to reestablish acidic pH and the lactobacillus-dominated commensal flora 7

Alternative Strategies for Treating Bacterial Vaginosis

• Alternative strategies for treating BV may include antimicrobial substances, probiotics, prebiotics, and acidifying agents, which aim to reestablish the physiologic vaginal environment and improve the local immunity response 7
• The development of formulation strategies and new dosage forms and drug delivery systems can improve treatment efficacy and overcome some limitations associated with conventional products 7