TY - JOUR
T1 - Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with Gram-positive infections
AU - Cattaneo, Dario
AU - Orlando, Giovanna
AU - Cozzi, Valeria
AU - Cordier, Laura
AU - Baldelli, Sara
AU - Merli, Stefania
AU - Fucile, Serena
AU - Gulisano, Cecilia
AU - Rizzardini, Giuliano
AU - Clementi, Emilio
PY - 2013/6
Y1 - 2013/6
N2 - Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (Cmin values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ Cmin values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ Cmin values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ Cmin evaluations, were considered. All patients (n = 9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ Cmin values during the first week of therapy (9.0 ± 6.4 mg/L vs. 4.9 ± 3.7 mg/L; P <0.01) and thereafter (9.3 ± 5.4 mg/L vs. 4.4 ± 3.4 mg/L; P <0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy.
AB - Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (Cmin values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ Cmin values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ Cmin values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ Cmin evaluations, were considered. All patients (n = 9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ Cmin values during the first week of therapy (9.0 ± 6.4 mg/L vs. 4.9 ± 3.7 mg/L; P <0.01) and thereafter (9.3 ± 5.4 mg/L vs. 4.4 ± 3.4 mg/L; P <0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy.
KW - Gram-positive infections
KW - Haematological toxicity
KW - Linezolid
KW - Therapeutic drug monitoring
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U2 - 10.1016/j.ijantimicag.2013.02.020
DO - 10.1016/j.ijantimicag.2013.02.020
M3 - Article
C2 - 23562639
AN - SCOPUS:84877705625
VL - 41
SP - 586
EP - 589
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
SN - 0924-8579
IS - 6
ER -