WBR0643

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
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 bpm, her blood pressure is 98/66 mmHg, and temperature is 39.5 C (103 F). 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 that are 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. Although rare, imipenem is known to decrease the seizure threshold with 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. Learning objective: Imipenem is a carbapenem used in resistant gram negative infections that can cause an increase in the risk of seizures. 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. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Carbapenems, WBRKeyword::Imipenem, WBRKeyword::Mechanism of Action
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::