WBR0252

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [2])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Genitourinary
Prompt	[[Prompt::A 28-year-old woman presents to the physician's office with complaints of vaginal odor and discharge. A thin, homogeneous, greyish-white fluid that is adherent to the vaginal mucosa is observed on physical examination. The labia, introitus, cervix, and cervical discharge appear normal. Microscopic examination of the discharge demonstrates a pH = 5 and clue cells. The physician decides to prescribe an antimicrobial agent to treat this patient's condition. What is the mechanism of action of the prescribed antimicrobial agent?]]
Answer A	AnswerA::Inhibits ergosterol synthesis
Answer A Explanation	[[AnswerAExp::Azoles, such as fluconazole, inhibit fungal ergosterol synthesis by blocking the conversion from lanosterol to ergosterol. Fluconazole is prescribed for vaginal candidiasis, which is in the differential diagnosis of bacterial vaginosis. Vaginal candidiasis is caused by the fungus Candida albicans. It manifests as vaginal inflammation with pruritus, along with the presence of a thick, cottage-cheese, white discharge that typically has no odor. Vaginal pH is typically between 4 and 4.5, and vaginal smear shows pseudohyphae.]]
Answer B	AnswerB::Binds ergosterol and forms membrane pores that leak electrolytes
Answer B Explanation	AnswerBExp::Amphotericin B binds ergosterol and forms membrane pores that leak electrolytes.
Answer C	AnswerC::Inhibits dihydrofolate reductase
Answer C Explanation	AnswerCExp::Trimethoprim is a bacteriostatic agent that inhibits bacterial dihydrofolate reductase.
Answer D	AnswerD::Forms free radical toxic metabolites
Answer D Explanation	AnswerDExp::Metronidazole forms free radical toxic metabolites that cause DNA injury in the bacterial cell. Metronidazole is the first line antimicrobial therapy to treat bacterial vaginosis.
Answer E	AnswerE::Inhibits DNA gyrase
Answer E Explanation	AnswerEExp::Fluoroquinolones inhibit DNA gyrase (topoisomerase II) and topoisomerase IV.
Right Answer	RightAnswer::D
Explanation	[[Explanation::Bacterial vaginosis is a polymicrobial non-sexually-transmitted disease that is caused by the replacement of the normal vaginal flora (Lactobacilli) with other anaerobic bacteria. Gardnerella vaginalis is a facultative anaerobic, gram-negative (pleomorphic) rod, which is both catalase- and oxidase-negative. It is usually the causative agent responsible for the majority of cases of bacterial vaginosis. Infection by G. vaginalis may follow menses or antibiotic therapy. Bacterial vaginosis is frequently treated with metronidazole (forms free radical toxic metabolites that cause DNA injury in the bacterial cell) or clindamycin (blocks peptide translocation at 50S ribosomal subunit). Although 50% of women with bacterial vaginosis remain asymptomatic, manifestations of bacterial vaginosis include suprapubic pain, inter-menstrual spotting, abnormal menses, and malodorous vaginal discharge that produces a characteristic fishy smell upon addition of 10% KOH. The diagnostic criteria for bacterial vaginosis are: Presence of thin, homogeneous, adherent, greyish-white vaginal discharge Vaginal pH > 4.5 Fishy amine odor upon addition of 10% KOH At least 20% clue cells on microscopic exam of vaginal smear. Clue cells are defined as epithelial cells whose borders are covered by bacteria Educational Objective: Metronidazole forms free radical toxic metabolites that cause DNA injury in the bacterial cell. Metronidazole is the first line antimicrobial therapy to treat bacterial vaginosis. References: Morris M, Nicoll A, Simms I, et al. Bacterial vaginosis: a public health review. BJOG. 2001;108(5):439-50. First Aid 2014 page 143]]
Approved	Approved::Yes
Keyword	WBRKeyword::Clue cells, WBRKeyword::Bacterial vaginosis, WBRKeyword::Gardnerella vaginalis, WBRKeyword::Metronidazole, WBRKeyword::Mechanism of action, WBRKeyword::Antibiotics, WBRKeyword::Vaginal smear
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