655. Plasma Linezolid Concentrations Are Correlated with Thrombocytopenia and Anemia
Session: Poster Abstract Session: Pharmacokinetics and Adverse Drug Reactions
Friday, October 21, 2011
Room: Poster Hall B1
Background: Currently, it is thought that drug monitoring and dose adjustment are not required during therapy with linezolid (LZD). However, cytopenia is sometimes observed during LZD therapy. This study aimed to investigate the correlation between plasma LZD concentration and cytopenia.

Methods: Between October 2009 and February 2011, 35 adult patients (men, 26; mean age, 50.8 years) were administered LZD at the University of Tokyo Hospital. On days 3, 7,and 14 after the initial administration and on the day that adverse events occurred, venous blood samples were drawn just before the next dose of LZD was administered. The plasma LZD concentrations were measured by high-performance liquid chromatography. In addition, the clinical symptoms and laboratory findings associated with the adverse effects were also monitored.

Results: The conditions for which the patients in the study population required LZD therapy were as follows: bacteremia (n = 15), mediastinitis (n = 8), wound infection (n = 6), pneumonia (n = 3), and others (n = 3). Thrombocytopenia occurred in 15 patients (42.8%). Univariate analysis showed that age and renal insufficiency were dependent risk factors that were associated with thrombocytopenia (P < 0.001). The high plasma LZD concentration on day 3 was strongly correlated with the decreasing creatinine clearance level (r = 0.750). The median plasma LZD concentration for thrombocytopenic patients was significantly higher than that for nonthrombocytopenic patients (day 3, 16.2 ± 5.8  vs. 4.5 ± 2.3 μg/mL; day 7, 18.1 ± 6.9 vs. 4.7 ± 3.0 μg/mL; day 14, 18.3 ± 5.5 vs. 6.5 ± 3.1 μg/mL; P < 0.001). Among thrombocytopenic patients, the platelet level rapidly decreased to 89.4%, 75.0%, and 51.0% on days 3, 7, and 14, respectively. The platelet and hemoglobin levels decreased with increase in the LZD concentrations, and these changes were significantly correlated (r = 0.634 and r = 0.551, respectively).

Conclusion: The plasma LZD concentration correlated with thrombocytopenia and anemia in a concentration-dependent manner, especially in the elderly and in patients with renal insufficiency. These findings indicate that careful monitoring and dose adjustment may be necessary during LZD therapy for such patients.


Subject Category: C. Clinical studies of bacterial infections and antibacterials including sexually transmitted diseases and mycobacterial infections (surveys, epidemiology, and clinical trials)

Yoko Nukui, MD, PhD1, Shuji Hatakeyama, MD, PhD2, Koh Okamoto, MD2, Takehito Yamamoto, MS3, Akihiro Hisaka, PhD4, Hiroshi Suzuki, PhD3, Hiroshi Yotsuyanagi, MD, PhD2 and Kyoji Moriya, MD, PhD1, (1)Department of Infection Control and Prevention, University of Tokyo Hospital, Tokyo, Japan, (2)Department of Infectious Diseases, University of Tokyo Hospital, Tokyo, Japan, (3)Department of Pharmacy, University of Tokyo Hospital, Tokyo, Japan, (4)Pharmacology and Pharmacokinetics, 22nd Century Medical and Research Center, University of Tokyo Hospital, Tokyo, Japan

Disclosures:

Y. Nukui, None

S. Hatakeyama, None

K. Okamoto, None

T. Yamamoto, None

A. Hisaka, None

H. Suzuki, None

H. Yotsuyanagi, None

K. Moriya, None

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