Aminoglycosides

A 68-year-old man with community-acquired pneumonia and renal impairment (creatinine 2.8 mg/dL) receives gentamicin 5 mg/kg as a single daily dose. After 5 days of therapy, he develops acute kidney injury with oliguria. Which nephrotoxic mechanism is most commonly responsible for aminoglycoside-induced acute tubular necrosis in this patient?

A 62-year-old man with diabetes mellitus presents with fever, dysuria, and flank pain. Urine culture grows Gram-negative rods. He has normal renal function (creatinine 0.9 mg/dL). Which aminoglycoside is the drug of choice for empirical therapy of this uncomplicated pyelonephritis?

A 62-year-old man with chronic kidney disease (eGFR 28 mL/min/1.73m²) and a urinary tract infection caused by *Pseudomonas aeruginosa* is being considered for aminoglycoside therapy. Which feature most reliably distinguishes the nephrotoxicity risk profile of tobramycin from that of gentamicin in this clinical context?

A 42-year-old woman with cystic fibrosis is admitted with acute exacerbation of Pseudomonas aeruginosa lung infection. She is prescribed tobramycin 7 mg/kg IV once daily for 14 days. Her baseline renal function is normal (serum creatinine 0.8 mg/dL, eGFR 95 mL/min/1.73m²). On day 10, she develops vertigo, nausea, and nystagmus. Audiometry shows high-frequency sensorineural hearing loss. Which of the following best describes the pharmacokinetic property of aminoglycosides that predisposes to this adverse effect, and what is the most appropriate management?

A 68-year-old man with diabetes mellitus type 2 presents with fever, dysuria, and flank pain for 3 days. Urine culture grows Gram-negative rods. Serum creatinine is 1.2 mg/dL (baseline 0.9 mg/dL), and eGFR is 58 mL/min/1.73m². The patient is started on gentamicin 5 mg/kg IV once daily. On day 5 of therapy, serum creatinine rises to 1.8 mg/dL, urine output drops to 400 mL/day, and the patient develops tinnitus. Which of the following best explains the adverse effect observed and represents the most appropriate next step?