Renal toxicity colistin

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. 

PLATINUM COMPOUNDS AMINOGLYCOSIDES, CAPREOMYCIN, COLISTIN, STREPTOMYCIN, VANCOMYCIN t risk of renal toxicity and renal failure and of ototoxicity. The ototoxicity tends to occur when cisplatin is administered early during the course of aminoglycoside therapy Additive renal toxicity Monitor renal function prior to and during therapy, and ensure an intake of at least 2 L of fluid daily. Monitor serum potassium and magnesium and correct any deficiencies. Most side-effects of aminoglycosides are dose-related, and it is necessary to t interval between doses and 1 dose of aminoglycoside if there is impaired renal function... 

Four patients developed acute renal failure, which appeared to be reversible, during treatment with colistin. Three were given cefalotin concurrently and the fourth had previously been taking this antibacterial. An increase in renal toxicity associated with concurrent use has been described in another report. The reason for this reaction is not known. What is known suggests that renal function should be closely monitored if these drugs are given concurrently or sequentially. 

In a retrospective study of 66 active soldiers without previous renal replacement therapy receiving colistin mostly intravenously, 45 % had some degree of renal dysfunction and 21% stopped treatment because of nephrotoxicity. The authors concluded that the probability of renal toxicity increases with cumulative dose and duration of treatment (a fourfold increase with treatment for more than 14 days) [179. ... 

Nebulization of antibiotics in cystic fibrosis has also been reviewed (162). For P-lactams, an improvement in pulmonary function was demonstrated with carbenicillin (163). For polymyxin, colistin alone (164), or in conjunction with oral ciprofloxacin (165), there was a decrease in the rate of decline in pulmonary function and in the Ifequency of P. aeruginosa recovered from respiratory tract secretions. Antibiotics of this class have been reported to cause bronchospasm and respiratory failure (166). Aminoglycosides have been administered as aerosols since 1950, and they have demonstrated improvement of pulmonary function, decreased sputum bacterial density, no ototoxicity or renal toxicity, and according to Smith and Ramsey (162), they are of clinical benefit for patients with cystic... 

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... 

Colistin was used to treat bone and joint infections in 19 patients across eight centres in Emope. Four patients developed acute renal failure leading to cessation of treatment. One patient developed a serum creatinine level three times above baseline in association with a high colistin dose. Two patients developed an increase in blood eosinophil coxmt and a transient distal dysaesthesia developed in one subject [128. A mefa-analysis investigating the efficacy and safety of colistin compared with other standard antimicrobials found a similar safety and efficacy profile. As with other antimicrobials tested, colistin use led to an increase in nephrotoxicity (OR 1.14) and neurotoxicity (OR 1.39). Respiratory toxicity occurred in 4 of 51 subjects reviewed [129 ]. 

A multicenter, observational study investigated the effectiveness and toxicity of colistin in a paediatric intensive care setting. Seventy-nine patients were followed with a median age of 30 months. Four serious adverse events were recorded, including two of each of renal failure and seizures [134 ]. A survey study of 229 paediatric infectious disease specialists gathered data on 92 cases of colistin use in children. Twenty-two percent of children developed nephrotoxicity and four children developed reversible neurotoxicity. Concemingly development of resistance to colistin was noted in 20.5% [135 j. 

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