What are examples of commonly prescribed nephrotoxic, cardiotoxic, and hepatotoxic antibiotics?

Commonly Prescribed Nephrotoxic, Cardiotoxic, and Hepatotoxic Antibiotics

Aminoglycosides are the most nephrotoxic antibiotics commonly prescribed, with gentamicin showing significantly higher nephrotoxicity rates (26-55%) compared to tobramycin (12-23%) and amikacin (25%). 1, 2, 3, 4

Nephrotoxic Antibiotics

Aminoglycosides

• Gentamicin: Highest nephrotoxicity rate (26-55%)
• Tobramycin: Moderate nephrotoxicity (12-23%)
• Amikacin: Moderate nephrotoxicity (approximately 25%)
• Streptomycin: Alternative when other aminoglycosides cannot be used

Mechanism of Nephrotoxicity

Aminoglycosides accumulate in renal proximal tubular cells (approximately 10% of administered dose), bind to acidic phospholipids and megalin receptors, and remain in the kidney for prolonged periods, causing direct tubular damage 5.

Risk Factors for Aminoglycoside Nephrotoxicity

• Pre-existing renal impairment
• Prolonged therapy (>7 days)
• Higher doses
• Concomitant nephrotoxic medications
• Advanced age
• Dehydration

Other Nephrotoxic Antibiotics

• Vancomycin: Especially at high trough levels (>20 μg/mL)
• Polymyxins (colistin)
• Amphotericin B: Conventional formulation more nephrotoxic than lipid formulations
• Sulfonamides (including sulfamethoxazole in co-trimoxazole)

Cardiotoxic Antibiotics

QT Interval Prolongation

• Fluoroquinolones:
  • Moxifloxacin (highest risk)
  • Levofloxacin
  • Ciprofloxacin (lower risk)

Direct Myocardial Toxicity

• Daptomycin: Can cause myopathy with elevated CPK levels
• Amphotericin B: Can cause arrhythmias, especially with rapid infusion
• Macrolides (erythromycin, clarithromycin, azithromycin): QT prolongation

Hepatotoxic Antibiotics

Commonly Hepatotoxic

• Rifampin: Increases hepatic metabolism of many drugs, can cause hepatitis
• Isoniazid: Direct hepatocellular injury
• Amoxicillin-clavulanate: Most common cause of drug-induced liver injury among antibiotics
• Flucloxacillin: Cholestatic hepatitis
• Nitrofurantoin: Chronic use associated with hepatotoxicity

Less Commonly Hepatotoxic

• Tetracyclines: Especially at high doses
• Sulfonamides: Hypersensitivity reactions affecting the liver
• Macrolides: Cholestatic hepatitis (especially erythromycin)

Monitoring Recommendations

For Nephrotoxic Antibiotics

• Baseline renal function before starting therapy
• Regular monitoring of serum creatinine (at least twice weekly)
• For aminoglycosides: Therapeutic drug monitoring
  • Gentamicin/Tobramycin: Trough levels <1 μg/mL
  • Amikacin: Trough levels <4-5 μg/mL
  • Single daily dosing preferred to reduce nephrotoxicity 1

For Cardiotoxic Antibiotics

• Baseline ECG before starting therapy
• Regular ECG monitoring for QT prolongation
• Avoid combinations of QT-prolonging medications
• For daptomycin: Monitor CPK levels at least weekly 1

For Hepatotoxic Antibiotics

• Baseline liver function tests
• Regular monitoring of liver enzymes
• Rifampin requires monitoring of drug interactions due to hepatic enzyme induction 1

Special Considerations

• When treating serious infections like endocarditis, the benefit of using potentially toxic antibiotics often outweighs the risks
• For patients with prosthetic valves, combination therapy with rifampin and gentamicin is recommended despite potential toxicity 1
• In patients with renal impairment, dose adjustments are critical to minimize toxicity while maintaining efficacy
• Consider alternative antibiotics in patients with multiple risk factors for specific organ toxicity

By understanding the toxicity profiles of commonly prescribed antibiotics, clinicians can make informed decisions to minimize adverse effects while effectively treating infections.