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Antimicrobial Agents and Chemotherapy, January 2009, p. 210-215, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00718-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Tissue Accumulation of Cephalothin in Burns: a Comparative Study by Microdialysis of Subcutaneous Interstitial Fluid Cephalothin Concentrations in Burn Patients and Healthy Volunteers{triangledown}

Andrew J. Dalley,1,2* Jeffrey Lipman,1,3 Renae Deans,1,3 Bala Venkatesh,4 Michael Rudd,5 Michael S. Roberts,2 and Sheree E. Cross2

University of Queensland, Burns Trauma & Critical Care Research Centre, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia,1 University of Queensland, Therapeutics Research Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia,2 Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia,3 Departments of Intensive Care Medicine, Princess Alexandra and Wesley Hospitals, Brisbane, Queensland, Australia,4 Department of Surgery, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia5

Received 2 June 2008/ Returned for modification 15 August 2008/ Accepted 18 October 2008

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.

* Corresponding author. Mailing address: Burns Trauma & Critical Care Research Centre, University of Queensland Centre for Clinical Research, Royal Brisbane & Women's Hospital, Herston, Brisbane, QLD 4029, Australia. Phone: 61 7 3346 6081. Fax: 61 7 3346 5598. E-mail: a.dalley{at}uq.edu.au

{triangledown} Published ahead of print on 27 October 2008.

Antimicrobial Agents and Chemotherapy, January 2009, p. 210-215, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00718-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dalley, A. J., Deans, R., Lipman, J., Venkatesh, B., Rudd, M., Roberts, M. S., Cross, S. E. (2009). Unbound Cephalothin Pharmacokinetics in Adult Burn Patients Are Related to the Elapsed Time after Injury. Antimicrob. Agents Chemother. 53: 5303-5305 [Abstract] [Full Text]  


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