How to manage polymyxin (antibiotic)-associated Acute Kidney Injury (AKI)?

Management of Polymyxin-Associated Acute Kidney Injury (AKI)

For patients with polymyxin-associated AKI, switching to polymyxin B from colistin (if applicable), dose adjustment based on renal function, discontinuation of concurrent nephrotoxic agents, and close monitoring of renal parameters are the recommended management strategies. 1, 2

Risk Assessment and Prevention

• Polymyxin-associated AKI is common with an incidence of approximately 60% in patients receiving polymyxin B therapy 3

• Key risk factors for polymyxin-associated AKI include:

  • Abnormal baseline serum creatinine 4
  • Need for vasoactive drugs 4
  • Infection site (abdomen, blood, or catheter) 4
  • Higher BMI 3
  • Concomitant use of other nephrotoxic agents, particularly vancomycin 3
  • Higher cumulative doses of polymyxins 3, 5

• Preventive measures include:

  • Avoiding concurrent use of other nephrotoxic medications when possible 1, 5
  • Careful dose selection, particularly in high-risk patients 2
  • Discontinuation of NSAIDs, which can exacerbate kidney injury 1, 6

Diagnosis of Polymyxin-Associated AKI

• AKI should be diagnosed when serum creatinine increases by ≥0.3 mg/dL within 48 hours or ≥50% from baseline, or when urine output is reduced below 0.5 mL/kg/h for >6 hours 1
• Monitor for early signs of nephrotoxicity:
  • Albuminuria
  • Cellular casts
  • Azotemia
  • Diminishing urine output
  • Rising BUN 2

Management Strategies

Medication Adjustments

• Immediately discontinue all potentially nephrotoxic medications 6, 5
• Consider switching from colistin to polymyxin B if the patient is on colistin, as polymyxin B has been associated with lower incidence of renal failure 1
• Adjust polymyxin B dosing based on renal function:
  • Normal renal function: 15,000 to 25,000 units/kg/day
  • Impaired renal function: Reduce from 15,000 units/kg downward 2
  • Avoid exceeding 25,000 units/kg/day total daily dose 2

Dosing Optimization

• Use loading doses to achieve therapeutic concentrations quickly:
  • For polymyxin B, a loading dose of 2-2.5 mg/kg is recommended 1
  • Maintenance dose should be 1.5-3 mg/kg/day 1
• Recent evidence suggests that twice-daily dosing may be less nephrotoxic than more frequent dosing regimens 7
• Higher doses (150 mg loading, 75 mg every 12 hours) may improve long-term survival despite increased AKI risk, suggesting a need to balance efficacy and toxicity 8

Renal Replacement Therapy Considerations

• For patients on continuous renal replacement therapy:
  • Dose adjustment is not necessary for polymyxin B 1
  • A dose of at least 9 million IU/day is suggested for colistin 1
• For patients on intermittent hemodialysis:
  • Administer 2 million IU colistimethate sodium (CMS) every 12 hours with a normal loading dose
  • Schedule dialysis toward the end of a CMS dosage interval 1

Monitoring

• Monitor renal function closely during polymyxin therapy 6, 5
• Assess urine output, vital signs, and when indicated, use echocardiography or CVP to monitor fluid status 1
• Consider therapeutic drug monitoring (TDM) to maintain area under the concentration-time curve across 24h (ssAUC0-24) of 50-100 mg h/L, as this may help prevent AKI 8

Special Considerations

• If the patient has a concurrent infection requiring antibiotics, obtain cultures before starting therapy to guide definitive treatment 6
• For patients with suspected UTI and AKI, avoid antibiotics with known nephrotoxic potential when alternatives are available 6
• Do not treat asymptomatic bacteriuria in patients with AKI 6

Pitfalls to Avoid

• Avoid the combination of NSAIDs, diuretics, and ACE inhibitors/ARBs during polymyxin treatment as this dramatically increases AKI risk 6
• Avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with polymyxin B, particularly bacitracin, streptomycin, neomycin, kanamycin, gentamicin, tobramycin, amikacin, cephaloridine, paromomycin, viomycin, and colistin 2
• Avoid polymyxin B in patients with pre-existing severe renal impairment unless benefits outweigh risks 2, 5