Polymyxins nephrotoxic effect

Parenteral nse of polymyxines is limited dne to their neuro- and nephrotoxic effects. They are the drngs of choice for some specific infections. However, they are nsed for seri-ons, life-threatening infections such as bacteremia, which are caused by some strains of P. 

Several toxic side-effects have been reported when polymyxin B and colistin are administered parenterally. Besides local irritation and pain at the site of injection in intramuscular administration, marked nephrotoxic effects are observed manifested by proteinuria, and cylindruria accompanied occasionally by an increase in white, red and epithelical cells in the urinary sediment. The neurotoxic effects of the drugs are characterized by flushing of the face, drowsiness, and a feeling of weakness and irritability. These symptoms, however, are transitory and disappear upon removal of the drug. In patients with pre-existing renal damage polymyxin and colistin should be administered in lower doses under frequent control of the renal functions. The recently available sodium sulphomethyl derivatives of polymyxin B and colistin are stated to be less toxic, yet these derivatives are also less active than their parent compounds - . ... 

On rare occasions, hepatotoxicity and toxic leukopenia have been observed during polymyxin-E (colistin) treatment, but a definite causal relationship has not been established. The most serious side effect of the polymyxins is their nephrotoxicity. Polymyxin-B is more nephrotoxic than polymyxin-E and the sulfate derivatives of both are more toxic than their corresponding methylsulfonates. The toxic effects are dose dependent and doses above the recommended range may be dangerous. The principal nephrotoxic effect of the polymyxins is on the epithelium of the renal... 

Bacitracin given parenteraHy is sufftciendy nephrotoxic that it is rarely used in human medicine for other than topical indications (80). Thus safe and effective use, especially as the zinc salt, is limited almost completely to ointments, sprays, and solutions for skin and ophthalmic use in concentrations of 250 to 1000 units per milliliter. Bacitracin is only rarely skin sensitizing. As in the case of polymyxin, bacitracin is usually combined with other antibiotics to enlarge its spectmm of activity, or with corticoids or analgesics to reUeve pain or itching. 

The antibacterial activity of five members (A to E) of the polymyxin group is of a similar nature. However, they are all nephrotoxic although this effect is much reduced with polymyxins B and E (colistin). Colistin sulphomethate sodium is the form of colistin used for parenteral administration. Sulphomyxin sodium, a mixture of sulphomethylated polymyxin B and sodium bisulphite, has the action and uses of polymyxin B sulphate, but is less toxic. 

Polymyxin B sulfate, a polypeptide antibiotic, is effective against gram-negative organisms. Hypersensitivity to topically applied polymyxin is rare. To reduce the likelihood of neurotoxicity and nephrotoxicity the total daily dose applied to the denuded skin or to open wounds should not exceed 200 mg. 

Polymyxin B and colistin (polymyxin E) (Fig. 3.9) are the least toxic of the five polymyxin antibiotics designated alphabetically A-E. Both polymyxin B and colistin are complex polypeptide compounds with specialized activity against gram-negative organisms but they are both nephrotoxic. Topical application and oral administration are more commonly used routes. Polymyxin B is used widely in ointments for topical applications and may be effective in case of mastitis, but it seldom is administered parenterally because of the possibility of renal toxicity. 

Polymyxin B is effective against many gramnegative bacteria, including E. coli, Klebsiella, and Salmonella. Systemic administration of this drug, however, is often associated with extreme nephrotoxicity. Hence, this agent is used primarily for the treatment of local, superficial infections of the skin, eyes, and mucous membranes. When applied topically for these conditions, adverse reactions are relatively rare. Polymyxin B is often combined with other antibiotics such as bacitracin and neomycin in commercial topical preparations. 

The overall sensitivity of Ps. aeruginosa to polymyxins appears unchanged for over twenty years [75] but although polymyxin E possesses reduced nephrotoxicity, this side effect is still a serious handicap. It has been suggested that polymyxins should not be used as preservatives in order to prevent any development of resistance that might occur [53]. 

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