Pharmacology · Year 2 · from Pharmacology
Case 2: Aminoglycoside Nephrotoxicity and Ototoxicity
Clinical Scenario
A 72-year-old male being treated for gram-negative sepsis develops rising creatinine and hearing loss while on gentamicin.
Patient Demographics
- Age: 72 years
- Sex: Male
- Weight: 70 kg
Chief Complaint
"I can't hear my wife talking" and decreased urine output
History of Present Illness
The patient was admitted 12 days ago with Pseudomonas aeruginosa bacteremia from a urinary source. He was treated with piperacillin-tazobactam plus gentamicin 5 mg/kg/day (extended-interval dosing). Blood cultures cleared after 3 days, but the infectious disease consultant recommended completing 14 days of combination therapy. Over the past 3 days, his creatinine has risen from 1.2 to 2.8 mg/dL, and he has noticed difficulty hearing conversations.
Physical Examination
- Vital Signs: BP 138/82 mmHg, HR 76 bpm, RR 16, T 37.0C
- General: Improved from admission, conversant
- HEENT: Hearing grossly diminished bilaterally; Weber lateralizes to neither side; Rinne: air > bone bilaterally
- Cardiovascular: Regular, no murmurs
- Abdominal: Soft, mild suprapubic tenderness
- Neurological: Mild unsteadiness on standing
Workup and Results
| Test | Result | Reference Range |
|---|---|---|
| Creatinine (Day 1) | 1.0 mg/dL | 0.6-1.2 mg/dL |
| Creatinine (Day 8) | 1.2 mg/dL | - |
| Creatinine (Day 12) | 2.8 mg/dL | - |
| Gentamicin trough | 1.8 mcg/mL | <1 mcg/mL |
| BUN | 45 mg/dL | 7-20 mg/dL |
| Urinalysis | Granular casts, low-grade proteinuria | - |
Audiometry: Bilateral high-frequency sensorineural hearing loss (4000-8000 Hz)
Diagnosis
Aminoglycoside-induced nephrotoxicity and ototoxicity - elevated trough indicates accumulation
Antimicrobial Pharmacology Principles Illustrated
- Concentration-dependent killing: Aminoglycosides are more effective at higher peak concentrations (Cmax/MIC ratio).
- Trough-related toxicity: Nephrotoxicity and ototoxicity correlate with elevated trough levels and prolonged exposure.
- Renal accumulation: Aminoglycosides accumulate in proximal tubular cells, causing acute tubular necrosis.
- Cochlear toxicity: Destroys hair cells in the organ of Corti; irreversible.
- Extended-interval dosing rationale: High peaks (efficacy) with drug-free intervals (reduced toxicity).
- Risk factors: Age, baseline renal impairment, prolonged therapy, concurrent nephrotoxins.
Treatment
- Discontinue gentamicin immediately
- Continue piperacillin-tazobactam alone to complete therapy if cultures remain negative
- Supportive care for AKI:
- IV fluids if not volume overloaded
- Avoid additional nephrotoxins (NSAIDs, contrast, etc.)
- Monitor for hyperkalemia
- Audiology follow-up: Serial audiograms to document extent of hearing loss
- Vestibular assessment: If symptoms of imbalance persist
- Patient education: Hearing loss likely permanent; kidney function may recover
Clinical Image
Pseudomonas aeruginosa, a gram-negative bacterium that frequently requires aminoglycoside therapy, particularly for serious infections and in combination with beta-lactam antibiotics for synergy.
Image Source: Wikimedia Commons License: Public Domain URL: https://commons.wikimedia.org/wiki/File:Pseudomonas_aeruginosa_01.jpg