Linezolid-Associated Thrombocytopenia in Children with Renal Impairment

Background: Linezolid-associated thrombocytopenia occurs in up to 12.9% of children compared to 3% of adults. Independent risk factors for linezolid-associated thrombocytopenia are identified in adults, although similar data is lacking in pediatric patients.   End-stage renal disease, pretreatment disease severity score, catheter-related infection, duration of linezolid therapy greater than or equal to 14 days, creatinine clearance less than 50mL/min/1.73m², and respiratory tract infection have been associated with thrombocytopenia.  The objectives of this study were to evaluate and compare the rate of linezolid-associated thrombocytopenia in pediatric patients with and without renal impairment.

Methods: This was a retrospective cohort study of patients less than 18 years who received linezolid between January 1, 2007 and March 31, 2012 and had a documented serum creatinine and height.  Patients’ electronic medical records were reviewed to capture demographic data, baseline serum creatinine, baseline platelet count, indication for linezolid therapy (including cultures and susceptibility data), dosing, and therapy duration.  Renal impairment was defined as an estimated creatinine clearance  (CrCl) less than 60 mL/min/1.73m².  Thrombocytopenia was defined as less than 100 x 10³ platelets/mm³ or ≥ 30% reduction from baseline.

Results: One hundred seventy children with a median (IQR) age of 9 (3 – 14) years were included, and 22% of these had baseline renal impairment.  Thrombocytopenia occurred more frequently in patients with baseline renal impairment (57% vs. 21%, p < 0.05).  Baseline estimated CrCl (mL/min/1.73m²) was significantly lower in patients who developed thrombocytopenia (median [IQR]: 66 [39 – 125] vs. 99 [78 – 130], p = 0.004).  Seventy-five percent of patients with a low baseline platelet count (<170,000 platelets/mm³) at initiation experienced thrombocytopenia versus 12.1% of patients with normal to high baseline platelet count (p <0.05).

Conclusion: Linezolid-associated thrombocytopenia in this pediatric cohort was associated with renal impairment and low platelet values upon therapy initiation.  These findings illustrate the need for a diligent risk-benefit assessment prior to the initiation of linezolid therapy for children.