Abstract
BackgroundSeveral studies have reported that daptomycin induced artificial prolongation of prothrombin time (PT) in some test reagents, particularly in warfarin users. However, it remains unknown whether the artificial prolongation can be affected by coagulation abnormalities other than the use of warfarin. Thus, we investigated the effect of daptomycin on PT with two types of coagulation abnormalities.MethodsPlasma samples were pooled by four groups: healthy volunteers (Plasma A), warfarin users with a PT-international normalized ratio (INR) of approximately 2.0 (Plasma B) or 3.0 (Plasma C), and patients with liver cirrhosis with a PT-INR of approximately 2.0 (Plasma D). Plasma A was composed of plasma from two healthy individuals (9 mL from each individual). Plasma B, C, and D were composed of plasma from 36 patients (0.5 mL from each patient). Daptomycin was added to each sample to create solutions with several concentrations (0–150 μg/mL). The PT-INR for each solution was measured with three PT reagents. Linear regression analyses were used to determine the association between daptomycin concentration and PT-INR. The relative change in PT-INR due to daptomycin concentrations was calculated.ResultsStrong linear correlations were observed between daptomycin concentrations and PT-INR for all the plasma groups and reagents (R2 > 0.7, P < 0.01). At a daptomycin concentration of 150 μg/mL, the relative increase of PT-INR was ≥10% in the majority of the plasma groups with an elevated baseline PT-INR in all reagents tested.ConclusionsDaptomycin induced the artificial prolongation of PT-INR in a concentration-dependent manner, particularly in plasma samples with an elevated baseline PT-INR. PT should be evaluated at the trough levels of daptomycin.
Highlights
Several studies have reported that daptomycin induced artificial prolongation of prothrombin time (PT) in some test reagents, in warfarin users
PT prolongation was concentration dependent, and the Food and Drug Administration (FDA) suggests that PT should be evaluated at the trough levels of daptomycin [6]
When the daptomycin concentration was 100 μg/mL, the PT-international normalized ratio (INR) was prolonged by more than 10% in Plasma C using Reagent 1 and Plasma B, C, and D, respectively, using Reagent 3 (Table 2)
Summary
Several studies have reported that daptomycin induced artificial prolongation of prothrombin time (PT) in some test reagents, in warfarin users It remains unknown whether the artificial prolongation can be affected by coagulation abnormalities other than the use of warfarin. Daptomycin is a cyclic lipopeptide antibiotic that is used to treat Gram-positive bacteria, such as methicillinresistant Staphylococcus aureus (MRSA) [1] It is inserted into the cytoplasmic membrane of Grampositive bacteria and disrupts the membrane, Some studies have reported the prolongation of prothrombin time (PT) in daptomycin users [3,4,5]. In vitro studies in a more controlled condition should be conducted to verify the results of our in vivo study It remains unknown whether this prolongation is observed in patients with other coagulation disorders, such as liver cirrhosis. We conducted an in vitro study to determine whether daptomycin affects the PTinternational normalized ratio (INR) in patients with coagulation abnormalities in addition to warfarin users
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