WBR0634

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pharmacology
Sub Category	SubCategory::Infectious Disease
Prompt	[[Prompt::A 57 year old man with history of poorly controlled diabetes and hypertension presents to the emergency department for 2 days of high grade fever and chills. On admission, his heart rate is 122 bpm and blood pressure 100/78. He is admitted to the intensive care unit and stabilized with empiric antibiotic therapy initiated. Two days later, blood cultures drawn grow resistant gram negative rods. You decide to switch the patient to amikacin but consider the need for dual coverage. Which of the following add-on antibiotics would you try to avoid in this patient considering the organism is sensitive to all?]]
Answer A	AnswerA::Aztreonam
Answer A Explanation	AnswerAExp::Aztreonam is actually a good alternative for aminoglycosides in patients with renal disease because it is considered relatively safe. It does not interact with aminoglycosides.
Answer B	AnswerB::Imipenem
Answer B Explanation	AnswerBExp::Imipenem does not interact with aminoglycosides. It can be used as an alternative or in combination. Major side effects include seizures, GI distress, and rash.
Answer C	AnswerC::Piperacillin/Tazobactam
Answer C Explanation	AnswerCExp::Pip/Tazo is an extended spectrum antibiotic that can be used in gram negative infections. Piperacillin is penicillinase sensitive, so tazobactam is added to inhibit the beta-lactamase. Pip/Tazo doesn't interact with aminoglycosides.
Answer D	AnswerD::Amoxicillin/clavulanic acid
Answer D Explanation	AnswerDExp::Amoxicillin/clavulanic acid is a wide spectrum antibiotic with gram positive and gram negative coverage. Its use with aminoglycosides does not increase the risk for renal injury.
Answer E	AnswerE::Ceftriaxone
Answer E Explanation	AnswerEExp::Cephalosporins are associated with increased nephrotoxicity when used with aminoglycosides.
Right Answer	RightAnswer::E
Explanation	[[Explanation::In this vignette, the patient is put on Amikacin, an aminoglycoside antibiotic. A reported class effect of cephalosporins is the synergistic effect on nephrotoxicity when combined with aminoglycosides. Initially, the strongest evidence came from the combination of cephalothin and gentamicin or tobramycin. The increased risk of renal dysfunction with this combination is seen mostly in critically ill patients and those with pre-existing renal disease. Large doses of cephalosporins have also been associated with increased risk for nephrotoxicity. Despite initial reports of aminoglycoside toxicity being potentiated by cephalosporins, animal studies have shown the opposite. The exact mechanism of synergistic kidney toxicity is not known. Still, it is best to avoid using this combination of antibiotics unless clinically indicted with no other alternatives. Educational Objective: The combination of cephalosporins and aminoglycosides should be avoided due to the synergistic effect on nephrotoxicity. References: Rankin GO, Sutherland CH. Nephrotoxicity of aminoglycosides and cephalosporins in combination. Adverse Drug React Acute Poisoning Rev. 1989;8(2):73-88. First Aid 2015 page 182 (Cephalosporins) First Aid 2015 page 184 (Aminoglycosides)]]
Approved	Approved::Yes
Keyword	WBRKeyword::Drug interactions, WBRKeyword::Cephalosporins, WBRKeyword::Aminoglycosides, WBRKeyword::Antibiotics, WBRKeyword::Bacteria, WBRKeyword::Gram negative
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