Nephrotoxicity colistin

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

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. 

Avoid concurrent or sequential use of other neurotoxic and/or nephrotoxic drugs with streptomycin sulfate, including neomycin, kanamycin, gentamicin, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, tobramycin, and cyclosporine. 

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. 

CICLOSPORIN AMINOGLYCOSIDES, COLISTIN t risk of nephrotoxicity Additive nephrotoxic effects Monitor renal function... 

Colistin is completely excreted unchanged in the urine. It is potentially nephrotoxic and ototoxic. Respiratory paralysis due to muscle weakness is rare but cannot be reversed by neostigmine (compared with aminoglycosides). 

COLISTIN AMINOGLYCOSIDES t risk of nephrotoxicity Additive effect Renal function should be carefully monitored... 

Even in patients with normal renal function, adverse reactions have occurred in up to 25%, contributing to death in 5% (10). At therapeutically equivalent doses, suggestions of differences in nephrotoxicity or neurotoxicity between polymjTtin B and colistin are not convincing. In view of their potential for adverse effects, the poljmjodns have now been largely replaced by other antibacterial drugs. 

Nephrotoxicity occurs more often in patients with preexisting impairment of renal function. Doses must be adjusted in patients with renal insufficiency, because colistin is excreted principally by the kidneys, and raised blood concentrations can further impair renal function (21). 

Intermittent proteinuria was observed on urinalysis in 14 of 31 patients with cystic fibrosis, and one patient developed reversible, colistin-induced nephrotoxicity (14). There was no relation between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetics. 

There are few data from which to draw conclusions about the safety of other inhaled antibiotics. Aerosolized colistin has been generally well tolerated in published reports. The most frequent adverse event reported has been chest tightness associated with administration in some patients. Systemic use of colistin carries the risk for nephrotoxicity and neurotoxicity. Additional research about the safety of aerosolized colistin is warranted. 

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 - . ... 

Vancomycin is both potentially nephrotoxic and ototoxic, and its manufacturers therefore suggest that it should be used with particular care, or avoided in patients with renal impairment or deafiiess. They also advise the avoidance of other drugs that have nephrotoxic potential, because the effects could be additive. They list amphotericin B, aminoglycosides, bacitracin, colistin, poymyxin B, viomycin and cisplatin. They also list etacrynic acid and furosemide as potentially aggravating ototoxicity. 

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... 

Of 30 patients who were treated with colistin for more than 48 hours and were retrospectively reviewed, 10 developed nephrotoxicity [105 ]. Patients who were given excessive doses based on their actual body weight (as opposed to ideal body weight) were 13 times more likely to develop nephrotoxicity. Concomitant use of diuretics and/or vasopressors was also associated with nephrotoxicity. The authors concluded that it may be better to use a measure of lean body mass to calculate doses of cohstin. 

In a retrospective single-center review of 258 patients who had received colistin over 7 years there were no independent predictors of nephrotoxicity, which occurred in 26 patients [106. ... 

In a retrospective, case-matched control study of 43 patients who received aerosolized and intravenous colistin, who were matched with 43 patients who received intravenous colistin alone, eight in each group developed nephrotoxicity [107. None required renal replacement therapy or withdrawal of colistin. There were no respiratory adverse reactions in those who received aerosolized colistin. 

In a retrospective case-control study of 134 patients who received 139 courses of intravenous colistin for at least 24 hours the cumulative incidence of nephrotoxicity was 73/139 (52%) [108. Independent susceptibility factors were old age, prolonged duration of intravenous cohstin, and concomitant vancomycin therapy. 

Deryke CA, Crawford AJ, Uddin N, Wallace MR. Colistin dosing and nephrotoxicity in a large community teaching hospital. Antimicrob Agents Chemother 2010 54(10) 4503-5. 

Rattanaumpawan P, Ungprasert P, Thamlikitkul V. Risk factors for colistin-associated nephrotoxicity. J Infect 2011 62(2) 187-90. 

Intravenous and nebulized colistin in the treatment of multidrug resistant Gram-negative infections have been analysed in two retrospective chart reviews of 115 and 121 treatments [177 178 ]. There was nephrotoxicity in 8.3% and 14% respectively, and chronic renal insufficiency, diabetes mellitus, and aminoglycoside use were associated susceptibility factors. Four patients experienced neurotoxicity in one study. 

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. ... 

Hartzell JD, Neff R, Ake J, Howard R, Olson S, Paolino K, Vishnepolsky M, Weintrob A, Wortmann G. Nephrotoxicity associated with intravenous colistin (colistimethate sodium) treatment at a tertiary care medical center. Clin Infect Dis 2009 48(12) 1724-8. 

Santamaria C, Mykietiuk A, Temporiti E, Stryjewski ME, Herrera F, Bonvehi P. Nephrotoxicity associated with the use of intravenous colistin. Scand J Infect Dis 2009 41(10) 767-9. 

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 ]. 

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