Influence of Age on Frequency of Vancomycin Dosing: METHODS
A retrospective unmatched case—control study was conducted to examine vancomycin dosing frequency as a function of age. The study was conducted at St Paul’s Hospital, a 520-bed acute care teaching hospital located in downtown Vancouver. The pharmacy’s computer system was used to identify patients admitted to the hospital between October 2002 and August 2006 for whom vancomycin was prescribed. Candidate charts were then screened for inclusion and exclusion criteria. For patients with multiple eligible admissions, only the most recent admission was included in the study.
The major inclusion criteria were severe infection, including suspected or confirmed osteomyelitis, sepsis, bacteremia, pneumonia, endocarditis, or meningitis; MRSA as the suspected or confirmed causative pathogen; normal renal function, defined as creatinine clearance above 90 mL/min per 70 kg, measured within 48 h of starting vancomycin; vancomycin therapy for more than 2 days, with a dosing regimen of either q12h or q8h; and age above 18 years. The appropriateness of the regimen had to have been confirmed by a predose serum concentration of vancomycin within the target range. When this study was conducted, the most commonly accepted target at the institution was 10-15 mg/L.
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At the time of this study, physicians at the study institution ordered the initial vancomycin regimen, after which pharmacists provided pharmacokinetic monitoring and adjusted the vancomycin dose and/or dosing interval as required. For the severe infections listed above, the pharmacists would typically order measurement of a predose serum level within the first few days of therapy to confirm therapeutic efficacy.
The major exclusion criteria were infection at a site not described as being included, duration of vancomycin therapy less than 2 days, serum creatinine level not available, and cystic fibrosis.
Cases were defined as patients who were confirmed as requiring q8h dosing. Controls were patients who were confirmed as requiring q12h dosing. The intended enrolment was 2 controls for each case.
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The primary outcome was the odds ratio (OR) of patients less than 40 years of age requiring more frequent vancomycin dosing (specifically q8h dosing instead of q12h) relative to patients 40 years or older. The influence of other variables, including concurrent nephrotoxic drugs, diabetes mellitus, and sex, on the vancomycin regimen was also explored.
Additional secondary outcomes were empiric dosing regimen, average vancomycin dose, regimen required by age group, time until first therapeutic level, frequency of creatinine increase by greater than 30% above baseline during vancomycin therapy, frequency of regimen change due to a high predose serum level or creatinine increase by greater than 30% above baseline during vancomycin therapy, and professional responsible for making the dosing change.
The study was conducted with ethics approval from the University of British Columbia – Providence Health Care Research Ethics Board.