Low-dose vitamin K to augment anticoagulation control.

STUDY OBJECTIVES: To determine the effect of daily low-dose oral vitamin K supplementation on reducing variations in the international normalized ratios (INRs) in patients taking warfarin. DESIGN: Retrospective analysis. SETTING: Anticoagulation clinic in a large, private-practice hematology group. PATIENTS: Eight motivated patients (three men, five women), aged 45-79 years, receiving anticoagulant therapy with warfarin, whose INRs had been fluctuating for reasons not associated with identifiable changes in diet, warfarin dosage, activity level, illness, or changes in drug therapy. INTERVENTION: Daily supplementation with oral vitamin K, starting with 100 microg/day MEASUREMENTS AND MAIN RESULTS: Anticoagulation providers monitored INR responses; all documented INR values were included in the analysis, even those intentionally allowed outside the therapeutic range when dosages were adjusted for procedures. After dietary vitamin K supplementation, INR fluctuations diminished in nearly all patients. Overall, a significant decrease was noted in the INR standard deviation (p<0.05), and more INRs were in the therapeutic range after the start of supplementation. Allowing for small fluctuations on either side of the target range, the number of INRs within 0.2 units of the target range increased from 32% to 57% (relative increase 76%). Time in range also increased by a similar degree. CONCLUSION: Supplementation with daily low-dose oral vitamin K significantly increased the number of INRs in range as well as the time in range, and decreased INR fluctuation in this small series of selected patients.

Pharmacodynamics of intermittent and continuous infusion piperacillin/tazobactam and cefepime against extended-spectrum beta-lactamase-producing organisms.

The pharmacodynamics of piperacillin/tazobactam and cefepime were evaluated against extended-spectrum beta-lactamase (ESBL)-producing organisms. Ten thousand patients were simulated based on ESBL minimum inhibitory concentrations (MICs) from our laboratory (N=39) and on pharmacokinetic data from peer-reviewed literature. The desired proportion of the dosing interval that the concentration remains above the MIC (%T>MIC) for the intermittent bolus regimens was >/=40% for piperacillin/tazobactam and >/=60% for cefepime. The desired C(ss)/MIC ratio (where C(ss) is the concentration at steady state) was >/=2 for all continuous infusion (CI) regimens. MIC(50), MIC(90) and %S were, respectively, 64/4mug/mL, 1024/4mug/mL and 33% for piperacillin/tazobactam and 8mug/mL, 16mug/mL and 0% for cefepime. For piperacillin/tazobactam, 3.375g every 4h (q4h) achieved the highest probability of target attainment (43%), followed by 13.5g CI (31%), 3.375g q6h (27%), 4.5g q8h (17%) and 6.75g CI (10%). However, for cefepime, 4g CI had the highest probability of target attainment (77%), followed by 1g q8h (65%), 2g q12h (58%), 3g CI (46%) and 1g q12h (27%). Although the probabilities of target attainment for cefepime were higher than for piperacillin/tazobactam, neither agent achieved a high probability of target attainment and should not be used routinely for the treatment of ESBL infections.