Colistin neurotoxicity

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. 

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. 

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. 

During treatment with any of the polymyxins, neurotoxicity can occur in up to 7% of patients with normal renal function. Circumoral paresthesia, vasomotor instability, ataxia, dizziness, convulsions of varying severity, and apnea have been reported. Of 31 patients with cystic fibrosis 21 had one or more adverse effects attributed to colistin (14). The most common reactions involved reversible neurological effects, including oral and perioral paresthesia (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these effects, although bothersome, were benign and reversible. 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 - . ... 

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. 

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 75-year-old man developed flaccid paralysis, dyspnoea, tachypnoea and hypokalaemia 36h after being treated with 6mg/kg per day of intravenous colistin. Twelve hours following his final dose he became apnoeic necessitating endotracheal intubation. The recommended dose for colistin is 5mg/kg per day. The proposed mechanism for neurotoxicity is presynaptic blockade of acetylcholine release [133 ]. 

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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