In the Literature Can We Prevent Linezolid - Associated Anemia and Thrombocytopenia ?

The most frequently encountered adverse effects of linezolid therapy are anemia and thrombocytopenia, both of which are observed mostly in individuals receiving the drug for 12 weeks, and both of which are generally reversible after discontinuation of treatment. This effect appears to be the result of bone marrow suppression, possibly as a consequence of inhibition of mitochondrial protein synthesis resulting in impairment of cellular proliferation [1]. The finding of ringed sideroblasts in the bone marrow of some patients with linezolid-associated anemia has raised the consideration that pyridoxine, which has a putative role in mitochondrial function, may play a preventive or therapeutic role. Such a role of pyridoxine supplementation was suggested by a report of reversal of anemia and thrombocytopenia in 2 patients who were given this B complex vitamin [2]. A subsequent uncontrolled, retrospective cohort study, however, found a high incidence of both anemia and thrombocytopenia, despite administration of pyridoxine, in 24 patients with osseous infections who received therapy for a median period of 3.5 weeks [3]. Soriano and colleagues have now examined the effect of pyridoxine and other factors on linezolid-associated hematological toxicity in a prospective, nonrandomized, cohort controlled study. All 52 of the patients who were studied, most of whom had osseous infection, were treated with standard doses of linezolid. The first 24 patients receiving linezolid alone, and the next 28 received linezolid plus pyridoxine (200 mg daily). The 2 treatment groups were comparable at baseline. The median durations of linezolid administration were 55.5 days and 50.8 days, respectively, in the 2 groups. A baseline glomerular filtration rate!50 mL/ min was associated with an increased risk of thrombocytopenia ( ). PyridoxP p .02 ine administration was not demonstrated to provide a benefit; the cumulative probabilities of thrombocytopenia and anemia did not significantly differ between the groups. Linezolid treatment was discontinued because of the occurrence of a platelet count ! platelets/L in 9 100 10 12.5% of those who received the antibiotic alone and in 14.2% of those who received it with pyridoxine. Linezolid treatment was discontinued because of severe anemia (hemoglobin concentration, !8 g/L) in 12.5% and 3.5% of patients, respectively ( ). Thus, the accumulated eviP p .24 dence suggests that pyridoxone supplementation does not reduce the risk of the hematologic toxicity of linezolid. On the other hand, rifampin treatment may play a protective role. Seventeen of the 52 patients received rifampin with linezolid for treatment of retained infected orthopedic implants. Cox regression analysis identified concomitant rifampin use as the only factor independently associated with a reduced risk of thrombocytopenia (hazard ratio, 0.37; 95% CI, 0.14–0.98). No factor was identified in association with anemia. The reason for the apparent protective effect of rifampin is unknown, but it has been speculated to be associated with a proposed rifampin-enhanced transport of linezolid [4]. Thus, although rifampin may provide protection from adverse hematologic effects, it may do so by reducing exposure to linezolid, with a consequent potential reduction in antibacterial efficacy.