Tissue accumulation of cephalothin in burns: a comparative study by microdialysis of subcutaneous interstitial fluid cephalothin concentrations in burn patients and healthy volunteers.
(2008)
Journal - Antimicrobial agents and chemotherapy (United States )
Abstract :
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.
Inadequate antimicrobial prophylaxis during surgery: a study of beta-lactam levels during burn debridement.
(2007)
Journal - The Journal of antimicrobial chemotherapy (England )
Abstract :
OBJECTIVES: To determine how long single-dose prophylactic antibiotic regimens for burns surgery maintained plasma concentrations above the MICs for target organisms during surgery. PATIENTS AND METHODS: We monitored antibiotic plasma concentrations in 12 patients (mean +/- SD 43 +/- 12% total burn surface area) throughout debridement surgery after administration of the standard prophylactic antibiotic dosing regimens of either 1 g of intravenous cefalotin or 4.5 g of intravenous piperacillin/tazobactam. RESULTS: The eschar debridement and grafting procedures ranged in duration from 2.25 to over 8.5 h. The duration of total plasma cefalotin concentration above an MIC of 0.2 mg/L for Staphylococcus aureus was 6.49 +/- 2.85 h, whereas the mean duration of total plasma piperacillin concentration above an MIC of 64 mg/L for Pseudomonas aeruginosa was only 1.15 +/- 0.59 h. None of the patients dosed with piperacillin/tazobactam was adequately protected for the duration of their surgery and adequate prophylaxis was only evident in four of the nine patients administered cefalotin. CONCLUSIONS: These results suggest a need to review antibiotic prophylaxis dosage regimens for burns surgery and the adoption of regimens that will minimize the risk of infection in this high-risk patient group. It is suggested that the antibiotic prophylaxis guideline for burn debridement surgery be modified to include re-dosing or a continuous infusion of beta-lactam antibiotics.
| ISSN : | 0305-7453 |
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| Mesh Heading : | Adult Bacterial Infections Burns Cephalothin Debridement Drug Administration Schedule Drug Therapy, Combination Humans Penicillanic Acid Piperacillin Pseudomonas aeruginosa Staphylococcus aureus administration & dosage pharmacokinetics therapeutic use microbiology administration & dosage pharmacokinetics therapeutic use administration & dosage analogs & derivatives pharmacokinetics therapeutic use administration & dosage pharmacokinetics therapeutic use drug effects drug effects administration & dosage pharmacokinetics therapeutic use |
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| Mesh Heading Relevant : | Anti-Bacterial Agents Antibiotic Prophylaxis beta-Lactams prevention & control surgery adverse effects |
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Tissue Accumulation of Cephalothin in Burns: a Comparative Study by Microdialysis of Subcutaneous Interstitial Fluid Cephalothin Concentrations in Burn Patients and Healthy Volunteers
(2009)
Journal - Antimicrobial Agents and Chemotherapy
Abstract :
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.