Burn tissue sites are a potential source of
bacteremia during
debridement surgery.
Burn injury is likely to affect the distribution of
antibiotics to tissues, but direct evidence of this is lacking. The aim of this study was to directly evaluate the influence of
burn trauma on the distribution of
cephalothin to peripheral tissues. We used subcutaneous microdialysis techniques to monitor interstitial fluid concentrations of
cephalothin in the burnt and nonburnt tissues of adult patients with severe
burns following parenteral administration of 1 g
cephalothin for surgical prophylaxis. Analogous simultaneous studies conducted with healthy adult volunteers provided reference tissue concentration data. Equivalent tissue exposures were seen for
burn and nonburn sites, giving overall median interstitial
cephalothin concentrations (from 0 to 240 min) of 2.84 mg/liter and 3.06 mg/liter, respectively. A lower overall median interstitial
cephalothin concentration of 0.54 mg/liter was observed for healthy individuals, and the patient nonburnt tissue and volunteer control tissue
cephalothin concentrations exhibited significantly different data distributions (P < 0.001; Kolmogorov-Smirnov nonparametric test). The duration of tissue residence for
cephalothin was longer for
burn patients than for healthy volunteers. The results demonstrate the potential fallibility of using healthy population models to extrapolate tissue pharmacodynamic predictions from plasma data for
burn patients.