Risk factors for linezolid-associated thrombocytopenia in adult patients

Abstract

ObjectivesThrombocytopenia (TP) is a common adverse effect of linezolid (LZD). However, risk factors for LZD-associated TP have been reported in Western patients with relatively heavy body weight. The aim of this study was to determine the risk factors for LZD-associated TP in Asian population.Materials and methodsA retrospective cohort study was conducted among 101 consecutive patients who received LZD therapy (1,200 mg/day) between July 2003 and December 2013 at a tertiary referral hospital in Tokyo, Japan. The patients with obvious other causes for TP were excluded. The information of target infectious disease, patients’ age, gender, body weight, body mass index, baseline serum creatinine (SCr), baseline platelet count, and treatment duration was collected retrospectively. TP was defined as ≥50 % decrease in platelet count from baseline. Bi- and multi-variate analyses were performed.ResultsA total of 101 patients were included (mean age [SD] 64 [18]; male gender [%], 57 [56]). Median duration [range] of LZD therapy was 14 days [1–67]. LZD-associated TP was identified in 42 patients (42 %). For TP, adjusted odds ratio (OR) [95 % CI] of daily per kg dose (DPKD) and SCr was 1.14 [1.05–1.26] and 1.51 [1.01–2.50], respectively.ConclusionsHigher DPKD and elevated SCr are significantly associated with LZD-associated TP. These findings suggest that daily dose of LZD should be adjusted using body weight, as typically done in pediatrics, in adults as well. Renal function also should be considered for dose adjustment.

Linezolid-related adverse effects in clinical practice in children

“…10 Thrombocytopenia is a common adverse effect in adult patients and the incidence of linezolidrelated thrombocytopenia has been reported about 15-50%. 7,11,12 The other common drugrelated side effects reported with linezolid therapy were diarrhea, nausea, headache, neuropathy, and abnormal liver function tests. 13 These adverse effects were mostly detected in patients receiving linezolid for longer than 2 weeks.…”

“…Thrombocytopenia was defined as either a platelet count of <150 x 10 9 /L or 50% reduction in platelet count from baseline level at initiation of linezolid therapy. 7 Outcomes of the patients based on the response to linezolid treatment were defined as cure, improved or failed. Cure was defined as the resolution of clinical and laboratory findings of infection for which linezolid were administered.…”

Is Dose Adjustment Based on Several Factors of Body Size Descriptors Effective for Prevention of Thrombocytopenia by Linezolid Therapy in Hemodialysis Patients?

“…Prolonged treatment duration [7], renal insufficiencies [8], chronic liver disease [8] and lower body weight [2] have been reported as possible risk factors for linezolid-induced thrombocytopenia. Additionally, Natsumoto et al showed that both higher daily dose (mg/kg/day) (prevalence of thrombocytopenia; <17 mg/kg/day (17%), 17 -22 mg/kg/day (34%), 22 -27 mg/kg/day (48%), >27 mg/kg/day (72%)) and elevated serum creatinine were significant risk factors for linezolid-induced thrombocytopenia in non-hemodialysis patients [9]. However, we usually administer linezolid with usual dosage (600 mg q12 h) to hemodialysis patients.…”

Efectos adversos relacionados con la linezolida en la práctica clínica pediátrica

“…La trombocitopenia se definió como recuento de trombocitos de < 150 x 10 9 /l o una reducción del 50% en el recuento de trombocitos respecto del valor basal al inicio del tratamiento con linezolida. 7 Los desenlaces de los pacientes se definieron como cura, mejoría clínica o fracaso según la respuesta al tratamiento con linezolida. La cura se definió como la resolución de las manifestaciones clínicas y de laboratorio de la infección para la cual se administró la linezolida.…”

“…10 La trombocitopenia es un efecto adverso frecuente en los pacientes adultos y, según se ha señalado, la incidencia de trombocitopenia relacionada con linezolida ha sido del 15% al 50%. 7,11,12 Los otros efectos secundarios frecuentes que se publicaron en relación con el tratamiento con linezolida fueron diarrea, náuseas, cefalea, neuropatía y pruebas funcionales hepáticas anormales. 13 Estos efectos adversos se detectaron mayormente en los pacientes que recibieron linezolida durante más de dos semanas.…”