WBR0463

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Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Microbiology
Sub Category SubCategory::Dermatology, SubCategory::General Principles, SubCategory::Infectious Disease
Prompt [[Prompt::A 15-year-old girl is brought to the physician’s office with low-grade fever and rash for the past 2 days. Upon further questioning, the patient informs the physician that she went camping in southeast USA one week ago and was bitten by ticks. Prior to the onset of fever and rash, she was complaining of nausea, anorexia, and myalgias. On physical examination, the physician notes several blanching maculopapular spots of 1-5 mm on her palms and soles. The physician then prescribes a course of antibiotics to treat the patient's condition. What is the mechanism of action of the most likely prescribed antibiotic agent?]]
Answer A AnswerA::A bacteriostatic agent that inhibits the attachment of aminoacyl t-RNA by binding to the 30S ribosomal subunit
Answer A Explanation [[AnswerAExp::Doxycyline is a tetracycline that inhibits the attachment of aminoacyl-tRNA by binding to the 30S ribosomal subunit. Doxycycline is the first line antibiotic therapy for patients with rickettsial infections.]]
Answer B AnswerB::A bacteriostatic agent that inhibits the translocaton during protein synthesis by binding to the 50S ribosomal subunit
Answer B Explanation [[AnswerBExp::Macrolides are bacteriostatic antibiotics that inhibit translocation during protein synthesis by binding to the 23S rRNA of the 50S ribosomal subunit. Macrolides are not prescribed to treat rickettsial infections.]]
Answer C AnswerC::A bactericidal agent that inhibits the attachment of aminoacyl t-RNA by binding to the 50S ribosomal subunit.
Answer C Explanation [[AnswerCExp::Tetracyclines do not act on the 50S ribosome. Tetracyclines inhibit the attachment of aminoacyl-tRNA by binding to the 30S ribosomal subunit.]]
Answer D AnswerD::A bactericidal agent that inhibits the translocation during protein synthesis by binding to the 50S ribosomal subunit
Answer D Explanation [[AnswerDExp::Macrolides are bacteriostatic agents that are not usually prescribed to treat rickettsial infections.]]
Answer E AnswerE::A bactericidal agent that activates the attachment of aminoacyl-tRNA by binding to 30S ribosomal subunit
Answer E Explanation AnswerEExp::Activation of the aminoacyl t-RNA attachment is not the mechanism of action of any antibiotic agent.
Right Answer RightAnswer::A
Explanation [[Explanation::Rocky mountain spotted fever (RMSF) is caused by Rickettsia rickettsii, an obligate intracellular bacteria that is carried by ticks (eg. wood tick or American dog Dermacentor variabilis tick) and spread to humans by tick bites. Despite its name, RMSF is common in southeastern and southcentral USA (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri) especially during the spring and summer. The disease is often characterized by a prodrome of non-specific GI symptoms, headaches, and myalgias followed by a fever and a rash. The rash has a centripetal distribution, where it initially manifests as small, blanching, maculopapular lesions over the distal upper and lower extremities (wrists and ankles) with involvement of the palms and soles and then progresses centrally to include the trunk with petechial, hemorrhagic, and non-blanching features. RMSF may be associated with severe neurological complications, including seizures and meningismus, cardiopulmonary disease, and disseminated intravascular coagulopathy (DIC). If left untreated, the rate of death may be as high as 20%. Accordingly, the administration of antibiotics empirically is necessary upon high clinical suspicion even in the absence of the characteristic rash. Work-up results may be delayed up to 2 weeks of infection and may include anemia, leukopenia, thrombocytopenia, hyponatremia with elevated liver enzymes. Although Weil-Felix and complement-fixation reaction assays may be helpful, they are often not sensitive. Accordingly, latex agglutination, hemagglutination, microimmunofluorescence, and ELISA are superior for the diagnosis of RMSF but often unnecessary. Doxycycline is the fist-line antibiotic therapy for RMSF and may be prescribed empirically upon clinical suspicion. Doxycyline inhibits the attachment of aminoacyl-tRNA by binding to the 30S ribosomal subunit. Doxycycline is contraindicated in pregnant women and children < 8 years of age; these patients are often prescribed amoxicillin instead.

Educational Objective: Doxycycline is the fist-line antibiotic therapy for RMSF. Doxycyline inhibits the attachment of aminoacyl-tRNA by binding to 30S ribosomal subunit. Doxycycline is contraindicated in pregnant women and children < 8 years of age.
References: Abramson JS, Laurence GB. Rocky mountain spotted fever. Ped Infect Dis J. 1999;18(6):539-40.
First Aid 2014 page 144]]

Approved Approved::Yes
Keyword WBRKeyword::Rocky Mountain spotted fever, WBRKeyword::RMSF, WBRKeyword::Doxycycline, WBRKeyword::Tetracycline, WBRKeyword::Antibiotic, WBRKeyword::Tick, WBRKeyword::Antibiotics, WBRKeyword::Mechanism of action, WBRKeyword::Tick bite, WBRKeyword::Tickborne disease, WBRKeyword::Dermacentor variabilis, WBRKeyword::American dog tick, WBRKeyword::Infection
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