• Vlado Antonic, Venkatasivasaisujith Sajja, Jason Sousa, Ken Nguyen, Yonas Alamneh, Brittany Garry, Maria Medina-Rojas, Donna Wilder, Chau Vuong, Brittney Potter, Daniel Zurawski, Jonathan Shearer, Chad Black, Samandra Demons, Joseph Long, and Stuart Tyner.
• CCCRP, 722 Doughten Street, Fort Detrick, MD 21702.
• Mil Med. 2020 Jan 7; 185 (Suppl 1): 256-262.

ObjectiveInfection as sequelae to explosion-related injury is an enduring threat to our troops. There are limited data on the effects of blast on antibiotic pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. The observational study presented here is our Institute's first attempt to address this issue by combining our existing interdepartmental blast, infection modeling, and in vivo PK/PD capabilities and was designed to determine the PK effects of blast on the first-line antibiotic, cefazolin, in an in vivo mouse model.MethodsA total of 160 male BALB/c mice were divided to sham and blast (exposed to blast overpressure of 19 psi) in two biological replicates. At 1 hour after blast/sham exposure, the animals received IV injection of cefazolin (328 mg/kg). Animals were euthanized at 3 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, or 10 hours after the injection. Plasma and liver were analyzed for concentration of cefazolin using mass-spectrometry.ResultsWe observed increases in the concentration of cefazolin in the plasma and liver of blast exposed animals at later time points and increase in elimination half-life.ConclusionOur results indicate that blast-induced physiologic changes significantly influence cefazolin PK and suggest that efficacy could be affected in the context of the blast; assessment of efficacy and PD effects require further investigation. Metabolic changes resulting from blast may influence other classes of antibiotics and other therapeutics used with these injuries. Therefore, this may have important treatment considerations in other areas of military medicine.© Association of Military Surgeons of the United States 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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