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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Ochuko}} {{Alison}}
|QuestionAuthor={{Ochuko}} (Reviewed by {{YD}} and {{AJL}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|MainCategory=Microbiology
|MainCategory=Pharmacology
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|MainCategory=Microbiology
|MainCategory=Pharmacology
|MainCategory=Microbiology
|MainCategory=Pharmacology
|SubCategory=Infectious Disease
|SubCategory=Genitourinary
|Prompt=A 28-year-old female presents to the physicians office with complaints of vaginal odor, itching, pain, and discharge. A thin gray homogeneous fluid that is adherent to the vaginal mucosa is observed during physical examination. The labia, introitus, cervix, and cervical discharge appear normal. Microscopic examination of the discharge demonstrates clue cells, with a PH greater than 5 and dominant gram-negative cells. Which of the following is the likely etiologic agent?
|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?
|Explanation=The patient in this scenario has [[Bacterial vaginosis]], caused by ''[[Gardnerella vaginalis]]''. ''[[Gardnerella vaginalis]]'' is a facultative anaerobic gram-negative (pleomorphic) rod, which is [[catalase]] and [[oxidase]] negative. It works synergistically with other normal flora organisms such as ''[[lactobacillus]]'', ''mobiluncus'', ''[[bacteroides]]'' and ''[[peptostreptococcus]]''. ''[[Gardnerella vaginalis]]'' flourishes with an increased vaginal pH of > 4.5. Diagnostic indications include clue cells (epithelial cells covered with bacteria), a vaginal pH > 4.5, gray homogenous discharge, and upon a Whiff test with KOH, a “fishy” amine odor. Infection may follow menses or antibiotic therapy. [[Bacterial vaginosis]] is frequently treated with [[Metronidazole]] or [[Clindamycin]].
|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:
|AnswerA=''Gardnerella vaginalis''
*Presence of thin, homogeneous, adherent, greyish-white vaginal discharge
|AnswerAExp=''[[Gardnerella vaginalis]]'' is the causative agent of [[bacterial vaginosis]] presenting as a gray vaginal discharge with a fishy smell, clue cells, and a vaginal pH greater than 4.5.
*Vaginal pH > 4.5
|AnswerB=''Candida albicans''
*Fishy amine odor upon addition of 10% KOH
|AnswerBExp=''[[Candida albicans]]'' are yeasts with pseudohyphae and hyphae that form germ tubes at 37 °C in serum.
*At least 20% clue cells on microscopic exam of vaginal smear. Clue cells are defined as epithelial cells whose borders are covered by bacteria
|AnswerC=''Trichomonas vaginalis''
 
|AnswerCExp=''[[Trichomonas vaginalis]]'', often sexually transmitted, may cause foul-smelling greenish discharge, itching, and burning. ''[[Trichomonas vaginalis]]'' is displayed as motile trophozoites in a methylene blue wet mount, and demonstrates corkscrew motility.
|AnswerA=Inhibits ergosterol synthesis
|AnswerD=''Neisseria gonorrhea''
|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.
|AnswerDExp=''[[Neisseria gonorrhea]]'' is a gram-negative, kidney bean-shaped diplococci that can cause creamy purulent  vaginal discharge.
|AnswerB=Binds ergosterol and forms membrane pores that leak electrolytes
|AnswerE=''Chlamydia trachomatis''
|AnswerBExp=Amphotericin B binds ergosterol and forms membrane pores that leak electrolytes.  
|AnswerEExp=''[[Chlamydia trachomatis]]'', an obligate intracellular bacterium that cannot make ATP, is gram-negative. In adults, it often causes [[urethritis]], [[cervicitis]], [[pelvic inflammatory disease]], and inclusion conjunctivitis, while in neonates, it causes inclusion conjunctivitis and neonatal pneumonia.
|AnswerC=Inhibits dihydrofolate reductase
|EducationalObjectives=''[[Gardnerella vaginalis]]'', a gram-negative rod,  is the causative agent of [[bacterial vaginosis]], which presents as a thin, gray, homogenous fluid with clue cells and a vaginal pH greater than 4.5.
|AnswerCExp=Trimethoprim is a bacteriostatic agent that inhibits bacterial dihydrofolate reductase.
|References=First Aid 2014 page 143
|AnswerD=Forms free radical toxic metabolites
|RightAnswer=A
|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.  
|WBRKeyword=Clue cells, Bacteria, STI, STD, Vagina, Microbiology, Infection, Genital
|AnswerE=Inhibits DNA gyrase
|AnswerEExp=Fluoroquinolones inhibit DNA gyrase (topoisomerase II) and topoisomerase IV.
|EducationalObjectives=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.<br>
First Aid 2014 page 143
|RightAnswer=D
|WBRKeyword=Clue cells, Bacterial vaginosis, Gardnerella vaginalis, Metronidazole, Mechanism of action, Antibiotics, Vaginal smear
|Approved=Yes
|Approved=Yes
}}
}}

Revision as of 15:19, 10 November 2014

 
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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