WBR0643

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Infectious Disease
Prompt	[[Prompt::A 68-year-old woman with past history of Parkinson's disease presents to the emergency department for 12 hours of high grade fever and several episodes of chills. On admission the patient's pulse is 121/min, her blood pressure is 98/66 mm Hg, and temperature is 39.5 ᵒC (103 ᵒF). You draw 2 sets of blood cultures and initiate broad spectrum coverage with vancomycin and piperacillin/tazobactam. Two days later, the patient does not seem be improving and blood culture results reveal gram negative rods resistant to piperacillin/tazobactam. You decide to switch the patient to another antibiotic that covers gram-negative rods. After less than 24 hours on the new medication, the patient experiences a tonic-clonic seizure lasting 4 minutes and requiring sedation. What is the mechanism of action of the drug used in this patient?]]
Answer A	AnswerA::Block peptide bond formation by inhibiting peptidyltransferase
Answer A Explanation	AnswerAExp::This is the mechanism of action of clindamycin and chloramphenicol.
Answer B	AnswerB::Inhibit protein synthesis by inhibiting translocation of growing peptide
Answer B Explanation	AnswerBExp::This is the mechanism of action of macrolides.
Answer C	AnswerC::Inhibit tRNA binding to ribosome
Answer C Explanation	AnswerCExp::This is the mechanism of action of tetracyclines.
Answer D	AnswerD::Interfere with cell wall synthesis by blocking cross-linking
Answer D Explanation	AnswerDExp::This is the mechanism of action of all penicillins including carbapenems like imipenem.
Answer E	AnswerE::Interferes with cell membrane leading to postassium leak and depolarization.
Answer E Explanation	AnswerEExp::This is the mechanism of action of daptomycin used in MRSA infections.
Right Answer	RightAnswer::D
Explanation	[[Explanation:: Imipenem is an antimicrobial agent from the carabpenem class of antibiotics, newer beta-lactamase resistant derivatives of penicillin. Carbapenems act by the same mechanism as penicillins, interfering with cell wall synthesis by inhibiting peptidoglycan cross-linking. Imipenem is usually used in patients with severe gram-negative infections that are usually resistant to other drugs and/or produce extended spectrum beta-lactamase (ESBL). It is usually administered in combination with cilastatin an inhibitor of renal dehydropeptidase I which inactivates the drug in the renal tubules. Imipenem is known to decrease the seizure threshold with approximately 0.5-1% of patients suffering from drug related seizures. The mechanism of seizures in imipenem is postulated to be related to the structure of the B-lactam ring that resembles that of GABA and acts as an antagonist at the GABA receptor site. Patients with renal insufficiency should receive tailored doses of imipenem/cilastatin to decrease the risk of seizures. Educational Objective: Imipenem is a carbapenem used in resistant gram negative infections that can cause an increase in the risk of seizures. Carbapenems are β-lactams that act by blocking peptidoglycan cross-linking thus interfering with cell wall synthesis. References: De sarro A, De sarro GB, Ascioti C, Nisticó G. Epileptogenic activity of some beta-lactam derivatives: structure-activity relationship. Neuropharmacology. 1989;28(4):359-65. Rodloff AC, Goldstein EJ, Torres A. Two decades of imipenem therapy. J Antimicrob Chemother. 2006;58(5):916-29.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Carbapenems, WBRKeyword::Imipenem, WBRKeyword::Mechanism of action, WBRKeyword::Antibiotics
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Order in Linked Questions	LinkedOrder::