Gentamicin Dosing in a Patient with Changing Renal Function
A 70-year-old man weighing 80 kg is treated for a serious Gram-negative infection with intravenous gentamicin 5 mg/kg once daily (400 mg). His serum creatinine has risen from 90 to 180 micromol/L over three days, and his urine output is falling. The ward pharmacist notes that the trough gentamicin concentration is 3.2 mg/L (target usually below 1 mg/L for once-daily dosing) and the peak, taken one hour after the dose, is 12 mg/L. He is also receiving furosemide and vancomycin. The prescriber asks whether the dose can simply be increased because the infection is not improving.
1. Interpret the concentrations and explain why increasing the dose would be unsafe.
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The trough of 3.2 mg/L is well above the usual once-daily target of below about 1 mg/L, indicating accumulation and a high risk of nephrotoxicity and ototoxicity. The peak of 12 mg/L is within a reasonable range for many Gram-negative infections, so the problem is not underdosing but impaired clearance. The rising creatinine and falling urine output indicate acute kidney injury, which reduces gentamicin elimination because the drug is cleared almost entirely unchanged by glomerular filtration. Increasing the dose would raise both peak and trough and accelerate tubular and cochlear damage without improving efficacy. The correct response is to hold or extend the interval, re-dose according to renal function and measured concentrations, and consider a less nephrotoxic alternative guided by culture results. Concomitant furosemide and vancomycin add to the risk of nephrotoxicity.
2. Outline a monitoring and adjustment plan, including how you would individualise the regimen.
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Obtain cultures and sensitivities before changes, and review whether gentamicin is still needed. Estimate creatinine clearance using the Cockcroft–Gault equation with current creatinine, recognising that in acute kidney injury it overestimates function; consider measured clearance or a validated nomogram. Hold the next dose until concentrations fall, then use extended-interval dosing with a reduced dose or prolonged interval based on renal function, and recheck peak and trough around the third dose. Monitor daily creatinine, urine output, electrolytes, and hearing and balance symptoms; keep the course as short as possible. Avoid or minimise other nephrotoxins, review furosemide and vancomycin with the prescriber, and ensure adequate hydration. Document the rationale, and counsel the patient to report tinnitus, hearing loss, dizziness or reduced urine output immediately.