A 23-year-old woman presents to the clinic with vaginal discharge for the past 5 days. She denies any vaginal itching, painful urination, or fever. Her last menstrual period was 10 days ago. She has recently become sexually active and uses oral contraceptive pills for contraception. Past medical history is unremarkable. She drinks a glass of wine on the weekend and does not use tobacco or any recreational drugs. Vital signs are within normal limits. Physical examination reveals malodorous, off-white thin discharge in the vaginal vault. There is no discharge from the cervical os. The uterus is small and mobile with no cervical motion tenderness. The abdomen is soft and non-tender. Microscopy of the vaginal discharge reveals multiple granular, irregular polygonal cells with numerous bacteria attached to the cell surface.
An antibiotic with which of the following mechanisms of action would be appropriate pharmacotherapy for this patient’s condition?
C) Inhibition of peptide translocation at 50S ribosomal subunit
This patient’s clinical presentation is consistent with a diagnosis of vaginitis. It is a condition characterized by inflammation of the vagina and causes symptoms such as vaginal burning, itching, and abnormal discharge. Vaginitis develops because of the disruption of the normal vaginal flora, which leads to the overgrowth of pathogenic microbes. This disruption can be due to various factors such as broad-spectrum antibiotic usage or changes in the vaginal pH (normal is 3.8-4.5) as a result of feminine hygiene products, contraceptives, or sexual intercourse. The most common subtypes of vaginitis include bacterial vaginosis, trichomoniasis, and vaginal candidiasis.
This patient has bacterial vaginosis, which is caused by Gardnerella vaginalis. It presents with a thin, malodorous off-white discharge from the vagina. Vaginal pH in these patients is increased (>4.5). The diagnosis is confirmed by microscopy of the discharge, which reveals “clue” cells. These are polygonal (epithelial) cells with numerous bacteria attached to their surface. Additionally, there is a characteristic amine (fishy) odor on adding KOH to the discharge (whiff test). Treatment is with oral or vaginal metronidazole or vaginal clindamycin (oral clindamycin is a less preferred alternative). Clindamycin is a protein synthesis inhibitor that binds to the 50S ribosomal subunit and inhibits peptide translocation. It is highly effective against anaerobic microbes. A characteristic adverse effect is pseudomembranous colitis (watery diarrhea due to disruption of gut microbiota) caused by Clostridioides difficile..
Trichomoniasis is caused by Trichomonas vaginalis. It presents with a thin, malodorous yellow-green frothy discharge from the vagina. Vaginal pH in these patients is increased (>4.5). Diagnosis is confirmed by microscopy of the discharge, which reveals motile trichomonads. In this condition, both the patient and their sexual partner need to be treated with metronidazole.
Vaginal candidiasis is most commonly caused by Candida albicans, although other Candida species have also been implicated. Broad-spectrum antibiotic usage is a risk factor for developing this infection. It often presents with vaginal itching and a thick, white “cottage cheese” discharge from the vagina. Vaginal pH is normal in these patients (3.8-4.5). Diagnosis is confirmed by microscopy of the discharge, which reveals pseudohyphae and budding yeast forms. Patients are prescribed fluconazole for treatment.
Answer choice A: Inhibition of ergosterol synthesis by inhibiting 14-⍺-demethylase, is incorrect. This is the mechanism of action of azoles (e.g., fluconazole, clotrimazole, voriconazole, ketoconazole) which are used in the treatment of local fungal infections and less serious systemic mycoses. Fluconazole is used for the treatment of vaginal candidiasis.
Answer choice B: Inhibition of folate synthesis by inhibiting dihydropteroate synthase, is incorrect. This is the mechanism of action of sulfonamides (e.g., sulfamethoxazole, sulfasalazine, dapsone) which are used for treating various gram-positive and gram-negative bacterial infections. Notable adverse effects include hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, drug-induced lupus, crystalline nephropathy, Stevens-Johnson syndrome, and kernicterus in infants.
Answer choice D: Inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV, is incorrect. This is the mechanism of action of fluoroquinolones (e.g., ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin) which are used for treating mainly gram-negative but also some gram-positive infections. They are avoided in pregnant and lactating females and in children because they may inhibit the growth of cartilage. Notable adverse effects include phototoxicity, seizures, and rashes. A rare side effect is Achilles tendinitis and tendon rupture, mostly seen in older patients.
Answer choice E: Inhibition of transpeptidase cross-linking of peptidoglycan in cell wall, is incorrect. This is the mechanism of action of the penicillin class of drugs, which are used for treating a range of bacterial infections.
Key Learning Point
Vaginitis presents with vaginal burning, itching, and abnormal vaginal discharge. Common subtypes include bacterial vaginosis (Gardnerella vaginalis), trichomoniasis (Trichomonas vaginalis), and vaginal candidiasis (Candida). Bacterial vaginosis presents with a thin, malodorous, off-white discharge with a positive whiff test and clue cells on microscopy, and is treated with metronidazole or clindamycin. Clindamycin is a protein synthesis inhibitor that binds to the 50S ribosomal subunit and inhibits peptide translocation.
