WBR0636
| 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 new antibiotic agent is being studied for the treatment of severe multi-drug resistant gram positive infection. The pharmaceutical company responsible for creating this drug explains that its mechanism of action involves 2 separate molecules that act synergistically at the same pathway. Which of the following combinations has a similar mechanism of action?]] |
| Answer A | AnswerA::Imipenem/cilastatin |
| Answer A Explanation | AnswerAExp::Cilastatin is used in combination with imipenem to inhibit the degradation of imipenem in the renal tubules by blocking renal dehydropeptidase 1. It has no synergistic activity with imipenem. |
| Answer B | AnswerB::Piperacillin/Tazobactam |
| Answer B Explanation | [[AnswerBExp::Since piperacillin is susceptible to penicillinase, tazobactam, an inhibitor of penicillinase (beta-lactamase) is administered in combination to increase the efficacy of the drug. Although the mechanism is synergistic, it does not act on a combined pathway.]] |
| Answer C | AnswerC::Pyrimethamine/leucovorin |
| Answer C Explanation | AnswerCExp::Leucovorin is usually co-administered with pyrimethamine to decrease the risk of myelosuppression. It has no synergistic activity. |
| Answer D | AnswerD::Izoniazid/Rifampin |
| Answer D Explanation | AnswerDExp::Izoniazid acts by inhibiting mycolic acid synthesis while rifampin inhibits the DNA dependent RNA polymerase. They do not act synergistically at the same pathway. |
| Answer E | AnswerE::Quinupristin/Dalfopristin |
| Answer E Explanation | AnswerEExp::Quinupristin and Dalfopristin act synergistically to inhibit protein synthesis by inhibiting both peptide bond formation and translocation. |
| Right Answer | RightAnswer::E |
| Explanation | [[Explanation::Quinupristin and Dalfopristin are 2 members of the streptogramin family of antibiotics that act by inhibiting protein synthesis. Streptogramins are 2 types: streptogramin A (dalfopristin) and B (quinupristin). Quinupristin binds to the 23S ribosomal unit of the 50S subunit. It acts like macrolides by blocking translocation and chain elongation. It even competes with macrolides for its binding site. Dalfopristin acts by a mechanism similar to clindamycin. It binds to the 50S ribosomal subunit and inhibits peptide bond formation by blocking peptidyltransferase. The binding of dalforpristin is facilitated by quinupristin binding. The drugs are always used in combination since alone they each exhibit weak bacteriostatic activity, while combined they are bacteriocidial. Another example of a drug combination that acts synergistically at the same pathway is TMP and SMX both of which act at the folate pathway.
Learning objective: Quinupristin and Dalfopristin act synergistically to inhibit protein synthesis by binding at the 50S ribosomal subunit. Reference:
Harms JM, Schlünzen F, Fucini P, Bartels H, Yonath A. Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin. BMC Biol. 2004;2(1):4. |
| Approved | Approved::No |
| Keyword | WBRKeyword::Antibiotics, WBRKeyword::synergy |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |