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  • Influence of Age on Frequency of Vancomycin Dosing: DISCUSSION

This study was undertaken to determine whether age less than 40 years predicts the need for more frequent vancomycin dosing. In the study population, patients under the age of 40 were 3 times more likely than older patients to require q8h dosing instead of q12h dosing.

Of the covariates studied, only a concurrent prescription for aminoglycoside seemed to predict q8h dosing. A likely explanation for this finding is that aminoglycosides were commonly prescribed for synergy with other antibiotics for endocarditis. Thus, aggressive vancomycin dosing in endocarditis was associated with, not caused by, aminoglycoside use. In addition, given the unclear evidence for synergy between aminoglycosides and vancomycin, it is likely that this combination was prescribed preferentially for younger patients who might better tolerate this nephrotoxic combination. cialis professional

Another important finding was that 60% of patients less than 40 years of age ultimately required q8h dosing to achieve the desired predose vancomycin levels. In addition, for those patients who required q8h dosing it took 1.5 times as long to achieve a therapeutic predose level as for patients who required q12h dosing. This delay probably represented the time needed to achieve a steady-state predose level and to determine that the q12h regimen was inadequate. Given that q8h dosing was prescribed empirically in only 5% of cases, it could be expected that a majority of younger patients with severe MRSA infec­tions would experience this delay.
There is ample evidence to suggest that delays in achieving optimal antibiotic dosing can affect outcomes. Previous studies have shown that a delay in initiating appropriate antibiotic therapy in cases of ventilator-associated pneumonia and S. aureus bacteremia was associated with higher in-hospital mortality. Similarly, it has been demonstrated that appropriate antibiotic therapy within the first hour of sepsis increases survival. Although Jeffres and others found that higher trough levels or area-under-the-curve values did not correlate with improved hospital outcome, these authors also admitted that they did not investigate the effect of time to achieve therapeutic levels on patient outcomes.

Although the current study focused on the effects of altered dosing frequency on achieving target predose serum levels of vancomycin, giving an initial loading dose of the drug is also an efficient way to improve serum concentrations early in therapy. However, it will still be through appropriate dosing frequency that adequate steady-state predose levels are maintained.
The relatively high frequency of increased serum creatinine in both groups during vancomycin therapy was most likely a result of the severity of illness in these patients rather than a result of the vancomycin therapy. However, it is possible that the intensity of vancomycin dosing was a contributing factor. Another retrospective study suggested that higher trough levels and prolonged exposure to vancomycin may increase the risk of nephrotoxicity. However, the patients in that study who were experiencing renal toxicity also had higher Acute Physiology and Chronic Health Evaluation II scores, which made it difficult to differentiate the effect of the underlying disease process on renal function. Another recent study found increased occurrence of nephrotoxicity among patients receiving vancomycin at a dose of 4 g/day or above. However, the effects of receiving at least 4 g/day were studied in only a small number of patients. Nevertheless, the current findings underscore the importance of regular monitoring of serum creatinine and judicious ordering of predose drug levels during vancomycin therapy. discount drugs canda

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