Early lactic acidosis associated with linezolid therapy in paediatric patients

Linezolid, an oxazolidinone class antibiotic, is used to treat Gram-positive infections, including those due to meticillin-resistant staphylococci and vancomycin-resistant enterococci. In paediatric clinical trials, the frequency of possible linezolid-related adverse events ranged from 18.8% to 25.6%. The most commonly reported side effects are gastrointestinal disturbances, headache, rash and liver function alterations. Lactic acidosis has been reported as a side effect of linezolid treatment, and limited data suggest it may be more common in children. We report on our experience of treating 50 children aged 1 month to years with linezolid. Eight patients (16%) developed lactic acidosis and another eight (16%) had lactic acidaemia without acidosis. Onset of lactic acidaemia (median 1.5 days; range 1-72 days) and lactic acidosis (median 2 days; range 1-13 days) tended to be early. Being an ICU patient and requiring mechanical ventilation significantly increased the risk of lactic acidaemia or acidosis (OR=22.75, 95% CI 4.24-122.09; OR=32.67, 95% CI 5.83-183.19, respectively; P<0.001). All 16 patients were able to continue linezolid treatment. Linezolid therapy was effective (microbiologic and/or clinical cure) in 39 patients (78%). Nine patients died whilst receiving linezolid treatment; the deaths were not considered to be a result of linezolid treatment failure. Two patients who did not respond clinically to linezolid recovered after their treatment was changed to vancomycin. Linezolid use in children appears to be as safe and effective as in adults. However, lactic acidosis appears to be more common, and occur earlier, in children.