Affiliations: Texas Tech University Health Sciences Center,
University of Texas Southwestern Medical Center, Dallas, TX
Correspondence to: Ronald G. Hall II, PharmD, Texas Tech University Health Sciences Center, School of Pharmacy, 4500 Lancaster, Building 7, R 119A, Dallas, TX 75216; e-mail: firstname.lastname@example.org
We read the study by Jeffres and colleagues1 (October 2006) with interest and were intrigued with the conclusion that trough concentrations > 15 μg/mL may not offer any advantage over traditional targets. This retrospective study was not adequately powered to detect differences between traditional and aggressive trough concentrations. Therefore, a statistically insignificant result is only inconclusive and not a negative finding.
With substantial imbalances between nonsurvivors and survivors, assessments of the variable in question in both analyses are impossible. Nonsurvivors were older with higher APACHE (acute physiology and chronic health evaluation)-II scores and had greater frequencies of bacteremia, end-stage renal disease, mechanical ventilation, and vasopressors. The trough concentration ≥ 15 μg/mL group had higher APACHE-II scores and more patients receiving mechanical ventilation and vasopressors (a factor significantly associated with mortality in the multivariate analysis). Is it plausible that sicker patients receiving trough concentration ≥ 15 μg/mL have the same risk of death as less ill patients receiving lower vancomycin trough concentrations?
The unavailability of minimum inhibitory concentrations made it impossible to calculate the area under the inhibitory curve values, although the accompanying editorial2stated these were calculated. Disk diffusion does not adequately identify Staphylococcus aureus with reduced vancomycin susceptibility.3 While most isolates likely had an minimum inhibitory concentration ≤ 0.5 μg/mL, we will never know for certain. Therefore, pharmacodynamic target attainment rates cannot be compared.
While vancomycin may not display pharmacokinetic qualities of the optimal agent for methicillin-resistant S aureus pneumonia, prospective, randomized trials comparing vancomycin target concentrations will hopefully provide some definitive answers to the role of aggressive vancomycin dosing for this disease. The major issue is that vancomycin has not had a fair comparison. Unfortunately, this study had the worst possible result, as it did not definitively conclude anything.1 However, this study and the accompanying editorial suggest that the time for optimizing vancomycin dosing is over and clinicians should use “better” agents.
Dr. Hall is a member of the Speaker’s Bureau for Wyeth. Ms. Adams-Huet has no conflicts of interest to disclose.
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