What is the diagnosis and treatment for a condition characterized by the presence of clue cells?

Clue Cells: Diagnosis and Treatment of Bacterial Vaginosis

What Are Clue Cells?

Clue cells are vaginal epithelial cells with bacteria adhered to their surface, creating a stippled appearance with obscured cell borders when viewed under microscopy, and they are the hallmark diagnostic finding for bacterial vaginosis (BV). 1

• Clue cells are easily identified in saline wet mount preparations at low- and high-dry microscopic power 2
• They represent one of the four Amsel criteria used to diagnose BV 1

Diagnosis of Bacterial Vaginosis

BV is diagnosed when at least 3 of the following 4 Amsel criteria are present: 2, 1

• Homogeneous, white, non-inflammatory discharge that smoothly coats the vaginal walls 2
• Presence of clue cells on microscopic examination 2
• Vaginal pH greater than 4.5 2
• Positive whiff test (fishy odor before or after addition of 10% KOH) 2

Diagnostic Pitfalls to Avoid

• Do not diagnose BV without clue cells unless confirmed by Gram stain (Nugent criteria), as this may lead to treating the wrong condition 1
• Culture of Gardnerella vaginalis is not recommended as a diagnostic tool because it is not specific 2
• Wet mount sensitivity is only 40-80%, so consider quantitative Gram stain when wet mount is equivocal 1

Treatment Recommendations

Who Requires Treatment

All women with symptomatic BV require treatment, regardless of pregnancy status, with the principal goal being relief of vaginal symptoms and signs of infection. 2, 3

First-Line Treatment Regimen

Metronidazole 500 mg orally twice daily for 7 days is the recommended first-line treatment, achieving a 95% cure rate. 1, 3, 4

Alternative Treatment Options

• Metronidazole gel 0.75%, one full applicator (5g) intravaginally once daily for 5 days 3
• Clindamycin cream 2%, one full applicator (5g) intravaginally at bedtime for 7 days 3
• Metronidazole 2g orally as a single dose (84% cure rate) - useful when compliance is a concern 1, 3
• Clindamycin 300 mg orally twice daily for 7 days 3
• Tinidazole 2g once daily for 2 days or 1g once daily for 5 days 5

Critical Treatment Warnings

• Patients using metronidazole must avoid alcohol during treatment and for 24 hours afterward due to potential disulfiram-like reaction 3, 4
• Clindamycin cream is oil-based and might weaken latex condoms and diaphragms 3
• Treatment of male sex partners has not been shown to alter clinical course or reduce recurrence rates 3, 4

Special Clinical Situations Requiring Treatment

Before Invasive Procedures

Treatment of BV with metronidazole before surgical abortion procedures substantially reduces post-abortion pelvic inflammatory disease (PID). 2, 1, 4

• BV bacteria have been recovered from the endometria and fallopian tubes of women with PID 2, 4
• BV is associated with endometritis, PID, and vaginal cuff cellulitis after invasive procedures including endometrial biopsy, hysterectomy, hysterosalpingography, IUD placement, cesarean section, and uterine curettage 2
• Consider treatment before hysterectomy or other invasive gynecological procedures due to increased risk for postoperative infectious complications 3

Pregnancy Considerations

• High-risk pregnant women (those with history of preterm delivery) may benefit from treatment, as it may reduce risk of prematurity 2, 3
• BV during pregnancy is associated with adverse pregnancy outcomes 2

Clinical Course and Follow-Up

• BV has a high recurrence rate of 50-80% within one year, which may necessitate repeated evaluations 1, 6
• Follow-up visits are not necessary if symptoms resolve 4
• For recurrent BV, extended metronidazole treatment (500 mg twice daily for 10-14 days) is recommended 6
• If extended treatment is ineffective, metronidazole vaginal gel 0.75% for 10 days, followed by twice weekly for 3-6 months, is an alternate regimen 6

Pathophysiology

BV results from replacement of normal H₂O₂-producing Lactobacillus species in the vagina with high concentrations of anaerobic bacteria (e.g., Prevotella sp. and Mobiluncus sp.), G. vaginalis, and Mycoplasma hominis 2. Half of women meeting clinical criteria for BV are asymptomatic 2.