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Vancomycin Tissue Pharmacokinetics in Patients with Lower-Limb Infections via In Vivo Microdialysis

Seth T. Housman PharmD, MPA1, Amira A. Bhalodi PharmD1, Ashley Shepard DPM2, James Nugent DPM2, and David P. Nicolau PharmD3
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  • 1 Center for Anti-infective Research and Development, Hartford Hospital, Hartford, CT.
  • | 2 Hartford Healthcare Medical Group, Hartford Hospital, Hartford, CT.
  • | 3 Department of Medicine, Division of Infectious Diseases, Hartford Hospital, Hartford, CT.
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Background

Vancomycin is a common treatment option for skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Given the increasing prevalence of MRSA, vancomycin is widely used as empirical therapy. In patients with lower-limb infections, antimicrobial penetration is often reduced because of decreased vascular perfusion. In this study, we evaluated the tissue concentrations of vancomycin in hospitalized patients with lower-limb infections.

Methods

An in vivo microdialysis catheter was inserted near the margin of the wound and was perfused with lactated Ringer's solution. Tissue and serum samples were obtained after steady state for one dosing interval. Tissue concentrations were corrected for percentage of in vivo recovery using the retrodialysis technique.

Results

Nine patients were enrolled (mean ± SD: age, 54 ± 19 years; weight, 105.6 ± 31.5 kg). Patients received a mean of 12.8 mg/kg of vancomycin every 12 hours (n = 7), every 8 hours (n = 1), or every 24 hours (n = 1). Mean ± SD steady-state trough vancomycin concentrations in serum and tissue were 11.1 ± 3.3 and 6.0 ± 2.6 μg/mL. The mean ± SD 24-hour free drug areas under the curve for serum and wound were 283.7 ± 89.4 and 232.8 ± 75.7 μg*h/mL, respectively. The mean ± SD tissue penetration ratio was 0.8 ± 0.2.

Conclusions

These data suggest that against MRSA with minimum inhibitory concentrations of 1 μg/mL or less, vancomycin achieved blood pharmacodynamic targets required for the likelihood of success. Reduced concentrations may contribute to poor outcomes and the development of resistance. As other literature suggests, alternative agents may be needed when the pathogen of interest has a minimum inhibitory concentration greater than 1 μg/mL.

Corresponding author: David P. Nicolau, PharmD, Department of Medicine, Division of Infectious Diseases, Hartford Hospital, 80 Seymour St, Hartford, CT 06102. (E-mail: david.nicolau@hhchealth.org)