Correlation between serum linezolid concentration and the development of thrombocytopenia

Hiraki, Yoichi; Tsuji, Yasuhiro; Hiraike, Mikako; Misumi, Nobuhiro; Matsumoto, Kana; Morita, Kunihiko; Kamimura, Hidetoshi; Karube, Yoshiharu

doi:10.3109/00365548.2011.608712

Cited by 53 publications

(23 citation statements)

References 13 publications

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“…Matsumoto et al [34] reported that the trough concentration of LZD [mg/L] was 14.4–35.6 versus (vs.) 6.9–7.2 and the area under the plasma linezolid concentration–time curve for 24 h (AUC24 h) [mg h/L] was 513.1–994.6 vs. 294.3–323.6 in the thrombocytopenic vs. non-thrombocytopenic patients. In addition, several recent Japanese studies have discussed the relationship between LZD blood concentration and TP [35–37]. As mentioned above, the fact that AUC value of LZD is relatively high in low BW subjects has been previously demonstrated in the phase 3 clinical trials in Japan [24].…”

Section: Discussionmentioning

confidence: 99%

Risk factors for linezolid-associated thrombocytopenia in adult patients

Natsumoto

Yokota²,

Omata

et al. 2014

Infection

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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.

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Section: Discussionmentioning

confidence: 99%

Risk factors for linezolid-associated thrombocytopenia in adult patients

Natsumoto

Yokota²,

Omata

et al. 2014

Infection

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“…Linezolid-induced thrombocytopenia tends to occur with prolonged treatment (>2 weeks) [7][8][9] and at high serum concentrations [10]. Platelets are typically more severely affected than other cell lines.…”

Section: Non-immune Suppression Of Platelet Productionmentioning

confidence: 99%

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

Arnold

Nazi

Warkentin

et al. 2013

Transfusion Medicine Reviews

153

144

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Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is underrecognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fibandependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20 × 10 9 /L); bleeding complications; onset 5 to 10 days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and *

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“…In humans, *30 % of a linezolid dose is excreted in the urine as the parent drug [3]. However, linezolid has been reported to cause serious adverse effects such as thrombocytopenia, which can be ameliorated or prevented by coadministration of Vitamin B6 [3,8]. The other adverse effects included nausea, diarrhea, vomiting, headache, tongue discoloration and oral monilia [9].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Linezolid in Treating Gram-Positive Bacterial Infection in the Elderly: A Retrospective Study

et al. 2013

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Linezolid is commonly used for the treatment of drug-resistant Gram-positive bacterial infection. This study aimed to evaluate the efficacy and safety of linezolid in treating Gram-positive bacterial infection in the elderly from January 2010 to December 2012. Total 40 elderly patients ([60 years old) with Gram-positive bacterial infection were treated with linezolid and their demographic and clinical data were collected and analyzed. Among the 40 patients, 31 patients (77.5 %) were cured. Linezolid caused little adverse effects on liver and renal function. The main adverse effect was thrombocytopenia and its incidence was significantly associated with baseline platelet count and the duration of treatment (P \ 0.05). Logistic regression analysis showed that the baseline platelet count \200 9 10 6 /mL, but not the age, the sex, the length of hospital stay, baseline levels of hemoglobin, alanine aminotransferase, or creatinine clearance rate was significantly associated with linezolid-induced thrombocytopenia. In conclusion, linezolid is effective to cure Gram-positive bacterial infection in the elderly and causes little adverse effects on liver and renal function. Timely monitoring of baseline platelet count may be helpful to guide the use of linezolid to avoid the occurrence of thrombocytopenia.

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Correlation between serum linezolid concentration and the development of thrombocytopenia

Cited by 53 publications

References 13 publications

Risk factors for linezolid-associated thrombocytopenia in adult patients

Risk factors for linezolid-associated thrombocytopenia in adult patients

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

Efficacy and Safety of Linezolid in Treating Gram-Positive Bacterial Infection in the Elderly: A Retrospective Study

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