Linezolid-Associated Thrombocytopenia More Frequent in Children with Baseline Renal Impairment

SAN FRANCISCO, CA—Linezolid-associated thrombocytopenia was associated with baseline renal impairment and low platelet values in children, underscoring the need “for a diligent risk-benefit assessment” in this population prior to initiation of therapy, a retrospective cohort study reported at IDWeek 2013.

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Linezolid-associated thrombocytopenia has been shown to occur in up to 12.9% of children compared with 3% of adults; however, independent risk factors, such as those identified for adults, are lacking for pediatric patients. For example, in adults, end-stage renal disease, pretreatment disease severity score, catheter-related infection, duration of linezolid therapy ≥14 days, creatinine clearance <50mL/min/1.73m2, and respiratory tract infection have been associated with thrombocytopenia.

For this reason, Chad Knoderer, PharmD, of Butler University College of Pharmacy and Health Sciences, Indianapolis, IN, and colleagues reviewed electronic medical records of 170 children with a median age of 9 (range, 3–14 years) who received linezolid between January 1, 2007, and March 31, 2012, to evaluate and compare the rate of linezolid-associated thrombocytopenia in pediatric patients with and without renal impairment.

Patients with a documented serum creatinine levels and height were included in the study. Also captured were demographic data, baseline serum creatinine, baseline platelet count, indication for linezolid therapy (including cultures and susceptibility data), dosing, and duration of therapy. The investigators defined renal impairment as an estimated creatinine clearance (CrCl) <60mL/min/1.73m2. Thrombocytopenia was defined as <100 x 103 platelets/mm3 or ≥30% reduction from baseline.

Of the 170 children, 22% had baseline renal impairment, and it was among these children that thrombocytopenia was found to occur significantly more frequently (57%) compared with those without such impairment (21%; P<0.05).

Among children who developed thrombocytopenia, baseline estimated CrCl (mL/min/1.73m2) was significantly lower (median 66 [39–125] vs. 99 [78–130], P=0.004).

Of children with a low baseline platelet count (<170,000 platelets/mm3) at initiation, significantly more experienced thrombocytopenia compared with those with normal to high baseline platelet counts, 75% vs. 12.1% (P<0.05).

Dr. Knoderer and his team added that “additional studies are needed to determine if dose modifications are warranted for children receiving linezolid with renal impairment.” 

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