• 25
    Dec
  • Influence of Age on Frequency of Vancomycin Dosing: DISCUSSION part 2

pharmacodynamics

The limitations of this study included its retrospective and observational design. Also, the study design prevented assessment of clinical outcomes. We cannot say for certain that age was the only factor influencing the need for q8h dosing. We performed basic statistical comparisons of mean age, sex, mean serum creatinine, and mean creatinine clearance (as calculated by the modified Cockcroft—Gault formula) to assess for other potential covariates, but age and mean creatinine clearance were the only 2 variables that differed significantly between the q8h and q12h groups. Of interest was the fact that serum creatinine was not statistically or clinically different between the groups. Thus, the difference in creatinine clearance was most likely the result of age differences between the groups. This finding supports the original rationale for focusing on age rather than creatinine clearance.

Although the average dose received by the q12h group was significantly higher, the clinical significance of this result is unclear. The mean difference in dose between the groups was quite small, amounting to less than the standard dose increment of 250 mg. Changes in dose generally have a smaller impact on the predose serum level of a drug than changes in dosing frequency. Thus, this small difference would not be expected to have an impact on the required dosing interval.
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Another potential limitation was the inclusion of patients with target ranges between 10 and 20 mg/L. A wide target range could make it more difficult to detect differences in the required dosing interval needed to reach specific narrower targets such as 10—15 mg/L or 15—20 mg/L. However, we do not believe that this was a large source of “noise” in our study because most patients had a target of 10-15 mg/L, and only a few (10%) had targets of 15-20 mg/L or 10-20 mg/L. In addition, this range accurately reflects local clinical practice at the time of our study with respect to desired targets for severe MRSA infections.

In conclusion, we found that a “one-regimen-fits-all” approach is not appropriate for vancomycin dosing, especially in cases of severe MRSA infection. Educational efforts should be targeted toward physicians and pharmacists to encourage initial dosing of 15 mg/kg IV q8h in adult patients with severe MRSA infections who are younger than 40 years of age and who have normal renal function. In addition, current vancomycin dosing nomograms should be re-evaluated (especially in light of new recommendations to target even higher levels of 15-20 mg/L) to ensure that q8h dosing is a standard recommendation for younger patients with normal renal function. Further research is needed to establish the most appropriate age and creatinine clearance ranges at which to recommend empiric q8h dosing with the 15-20 mg/L target.
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At a minimum, these measures would reduce workload related to ordering and interpreting unnecessary vancomycin levels. At best, earlier achievement of therapeutic levels might reduce the likelihood of clinical antibiotic failure.

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