Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory

被引:8
|
作者
Belley, Adam [1 ]
Robson, Richard [2 ]
Francis, John L. [3 ]
Adcock, Dorothy M. [4 ]
Tiefenbacher, Stefan [4 ]
Rubino, Christopher M. [5 ]
Moeck, Greg [1 ]
Sylvester, David [1 ]
Dudley, Michael N. [1 ]
Loutit, Jeffery [1 ]
机构
[1] Medicines Co, Parsippany, NJ 07054 USA
[2] Christchurch Clin Studies Trust, Christchurch, New Zealand
[3] Florida Hosp Ctr Thrombosis Res, Winter Pk, FL USA
[4] Colorado Coagulat, Lab Corp Amer Holdings, Englewood, CO USA
[5] Inst Clin Pharmacodynam, Latham, NY USA
关键词
oritavancin; coagulation; hemostasis; ABSSSI; antibiotic; lipoglycopeptide; SINGLE-DOSE ORITAVANCIN; ACUTE BACTERIAL SKIN; TELAVANCIN; DAPTOMYCIN;
D O I
10.1128/AAC.01968-16
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Previous studies have shown that some lipoglycopeptide and lipopep-tide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic antifactor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing.
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页数:9
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