Renal function as a predictor of linezolid-induced thrombocytopenia

Matsumoto, Kazuaki; Takeda, Yasuo; Takeshita, Ayumi; Fukunaga, Naoko; Shigemi, Akari; Yaji, Keiko; Shimodozono, Yoshihiro; Yamada, Katsushi; Ikawa, Kazuro; Morikawa, Norifumi

doi:10.1016/j.ijantimicag.2008.07.002

Cited by 51 publications

(34 citation statements)

References 7 publications

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“…However, thrombocytopenia and anemia are adverse effects of LZD [6,7], and have also been reported after LZD administration in patients with renal dysfunction compared to those in patients with normal renal function [8,9]. We also observed the development of pancytopenia in the presence of a high blood LZD concentration in patients undergoing hemodialysis treatment for MRSA infection [10].…”

Section: Introductionsupporting

confidence: 63%

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Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction

Tsuji

Hiraki

Matsumoto

et al. 2011

Journal of Infection and Chemotherapy

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Section: Introductionsupporting

confidence: 63%

“…LZD was administered for seven days or longer to patients with a glomerular filtration rate (GFR) of \60 (renal dysfunction group) [9,11] before LZD treatment. Those who developed thrombocytopenia or anemia that was thought to be caused by LZD were selected as subjects for the study.…”

Section: Subjectsmentioning

confidence: 99%

Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction

Tsuji

Hiraki

Matsumoto

et al. 2011

Journal of Infection and Chemotherapy

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“…The incidence of LZD-induced thrombocytopenia varies from 2.4 to 64.7% (3,6,14,22,28,30,34), and little is known about the mechanism responsible. Recent studies, however, have shown the incidence of LZD-induced thrombocytopenia to be significantly higher in patients treated long term (Ͼ14 days) (16) or with insufficient renal function (22,25,34), and it is lower in patients coadministered rifampin, which significantly reduced the area under the curve (AUC) of LZD (34,12). Given these findings, the development of thrombocytopenia may depend on the degree of exposure to LZD; however, few studies have examined the relationship between exposure to LZD and the incidence of thrombocytopenia quantitatively.…”

mentioning

confidence: 99%

Population Pharmacokinetic and Pharmacodynamic Analysis of Linezolid and a Hematologic Side Effect, Thrombocytopenia, in Japanese Patients

Sasaki

Takane

Ogawa

et al. 2011

Antimicrob Agents Chemother

119

147

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Linezolid is an antimicrobial agent to treat infections by Gram-positive pathogens, including methicillinresistant Staphylococcus aureus (MRSA). While effective, linezolid treatment frequently is associated with hematological side effects, especially thrombocytopenia. However, little is known about the mechanism of this side effect and the exposure-response relationship. The present population pharmacokinetic/pharmacodynamic (PPK/PD) study was undertaken to elucidate the factors that determine linezolid levels, the relationship between exposure to linezolid and a decrease in platelet counts, and appropriate dosage adjustments based on exposure levels. In total, 50 patients (135 plasma samples) were used for the PPK analysis. The PPK analysis revealed that renal function and severe liver cirrhosis (Child Pugh grade C) significantly affect the pharmacokinetics of linezolid according to the equation clearance (liter/h) ‫؍‬ 2.85 ؋ (creatinine clearance/60.9) 0.618 ؋ 0.472 CIR (CIR indicates cirrhosis status; 0 for noncirrhosis, 1 for cirrhosis patients). Using 603 platelet counts from 45 patients, a PPK/PD analysis with a semimechanistic pharmacodynamic model described the relationship between linezolid exposure and platelet counts quantitatively, and the newly constructed model was validated using external data (776 platelet counts from 60 patients). Simulation indicated considerable risks in patients with insufficient renal function (creatinine clearance, <30 ml/min) or severe liver cirrhosis. For these patients, a reduced dosage (600 mg/day) would be recommended for sufficient efficacy (area under the concentration-time curve over 24 h in the steady state divided by the MIC, >100) and safety.

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“…Therefore, special attention to thrombocytopenia has been recommended when linezolid is administered to patients with creatinine clearance <60 ml/min and/or a blood urea nitrogen value >23 mg/dl [22]. Renal dysfunction has been reported to increase trough linezolid concentrations and areas under the curves, with higher drug exposures inducing thrombocytopenia [23,24].…”

Section: Discussionmentioning

confidence: 99%

Impact of Vancomycin or Linezolid Therapy on Development of Renal Dysfunction and Thrombocytopenia in Japanese Patients

Fujii¹,

Takahashi²,

Makino³

et al. 2013

Chemotherapy

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Background: Vancomycin and linezolid therapies are associated with renal dysfunction and thrombocytopenia, respectively. Methods: We retrospectively investigated Japanese patients with renal dysfunction or thrombocytopenia possibly associated with vancomycin and linezolid therapies, including 235 patients treated with parenteral vancomycin and 178 treated with parenteral linezolid. Results: Renal dysfunction occurred more frequently in patients receiving vancomycin (24%) than in those receiving linezolid (13%; p = 0.032), whereas thrombocytopenia occurred more frequently in linezolid-treated patients (41%) than in vancomycin-treated patients (17%; p < 0.001). Controlling trough vancomycin concentrations (<20 μg/ml) protects against renal dysfunction, but thrombocytopenia may occur after >7.5 days of linezolid treatment. Conclusion: Controlling trough vancomycin concentrations to <20 μg/ml protects Japanese patients against renal dysfunction. Linezolid is an appropriate initial therapy for severe infections in patients with acute renal dysfunction, but monitoring of platelet counts is essential after initiation of therapy.

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Renal function as a predictor of linezolid-induced thrombocytopenia

Cited by 51 publications

References 7 publications

Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction

Thrombocytopenia and anemia caused by a persistent high linezolid concentration in patients with renal dysfunction

Population Pharmacokinetic and Pharmacodynamic Analysis of Linezolid and a Hematologic Side Effect, Thrombocytopenia, in Japanese Patients

Impact of Vancomycin or Linezolid Therapy on Development of Renal Dysfunction and Thrombocytopenia in Japanese Patients

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