Polymyxin B and Renal dysfunction

Parenteral use of polymyxin antibiotics may be associated with dose-related neuro- and nephrotoxic effects. Neurotoxicity may manifest as dizziness, drowsiness, confusion, irritability, nystagmus, muscle weakness, circumoral paresthesia, numbness of the extremities, slurred speech, ataxia, coma, seizures, and respiratory paralysis. Nephrotoxicity is usually evidenced by albuminuria, cellular casts, azotemia, increased serum concentrations of creatinine and BUN, and elevated drug levels without an increase in dose. Although mild nephrotoxicity is generally reversible following discontinuation of the drug, renal failure and acute tubular necrosis have occurred. Therapy with polymyxin antibiotics should be administered cautiously at reduced dosages in patients with renal impairment, since they may be at increased risk for neuro- and nephrotoxicity due to drug accumulation. To minimize the risk of toxicity, the usual dosage should not be exceeded, use with other neuro- and nephrotoxic agents should be avoided, and serum drug concentrations should be periodically determined and dosage adjusted to maintain desired levels. Renal function should be closely monitored, and the dosage reduced or therapy withdrawn if toxicity develops. Diminishing urinary output, rising BUN or serum creatinine, and/or signs of respiratory paralysis are indications for discontinuing therapy.