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blood loss and subsequent transfusions in field environments. of the Congressionally Directed Medical Research Programs
The findings of this study could directly impact combat ca- (CDMRP). The conduct of this study is investigator-initiated.
sualty care by providing the data needed for clinical practice The funding agency has no role in the design, interpretation,
guidelines on dosing and redosing of antibiotics for wound pro- or publication of the results.
phylaxis. This will ensure optimal antibiotic dosing for tissue
penetration without reaching supratherapeutic levels that can References
lead to toxic effects. By developing an evidence-based dosing 1. Eastridge BJ, Mabry RL, Seguin P, et al. Death on the battlefield
model that accounts for the pharmacokinetic changes caused (2001–2011): implications for the future of combat casualty
by massive blood transfusions, civilian providers will be able care. J Trauma Acute Care Surg. 2012;73(6 Suppl 5):S431–437.
doi:10.1097/TA.0b013e3182755dcc
to dose their patients more accurately and safely. Overall, the 2. Eastridge BJ, Hardin M, Cantrell J, et al. Died of wounds on the
results of the ACME study will close a critical and significant battlefield: causation and implications for improving combat
knowledge gap by providing the data necessary to revise cur- casualty care. J Trauma. 2011;71(1 Suppl):S4–8. doi:10.1097/
rent antibiotic dosing models in massive transfusions. This will TA.0b013e318221147b
lead to overall better patient outcomes, reduced infections, and 3. Shackelford SA, Del Junco DJ, Powell-Dunford N, et al. Associ-
set new care standards in civilian and military trauma settings. ation of prehospital blood product transfusion during medical
evacuation of combat casualties in Afghanistan with acute and
30-Day survival. JAMA. 2017;318(16):1581–1591. doi:10.1001/
Conclusion jama.2017.15097
4. Oliveros Rodríguez H, Ríos F, Rubio C, et al. Mortality in civil-
Our study aims to address a critical gap in trauma care by assess- ian trauma patients and massive blood transfusion treated with
ing the relationship between the pharmacokinetics of antibiotic high vs low plasma: red blood cell ratio. Systematic review and
concentration and transfusions through a multicenter, prospec- meta-analysis. Rev Colomb Anestesiol. 2020;48(3):126–137. doi:
tive, observational model. Our findings have the potential to 10.1097/CJ9.0000000000000161
significantly improve patient outcomes through evidence-based 5. Fisher AD, Lavender JS, April MD, Hill R, Bynum J, Schauer
SG. A descriptive analysis of supermassive transfusion recipi-
dosing guidelines that will ultimately enhance the effectiveness ents among US and coalition forces during combat operations
of prophylactic antibiotic therapy in trauma settings. in Afghanistan and Iraq. Mil Med. 2023;188(5–6):e1022–e1027.
doi:10.1093/milmed/usab455
Acknowledgments 6. Patil V, Shetmahajan M. Massive transfusion and massive
The authors would like to thank the Departments of Emer- transfusion protocol. Indian J Anaesth. 2014;58(5):590–595.
doi:10.4103/0019-5049.144662
gency Medicine, Surgery, and Anesthesiology at our respective 7. Young PP, Cotton BA, Goodnough LT. Massive transfusion pro-
institutions for their support of the conduct of this study. tocols for patients with substantial hemorrhage. Transfus Med
Rev. 2011;25(4):293–303. doi:10.1016/j.tmrv.2011.04.002
Author Contributions 8. Schauer SG, Naylor JF, Ahmed YM, Maddry JK, April MD. Pre-
RJH and FM contributed equally to the conception, design hospital combat wound medication pack administration in Iraq
and execution of this review. They jointly performed the litera- and Afghanistan: a Department of Defense Trauma Registry
ture search, screened and analyzed the studies and synthesized analysis. J Spec Oper Med. 2020;20(3):76–80. doi:10.55460/
X4E8-NNXE
the findings into the final manuscript. Each author contributed 9. Naylor JF, Burbank KM, April MD, Wenke J, Maddry JK, Schauer
to the drafting and critical revision of the text, ensuring accu- SG. Effects of prehospital wound prophylaxis in Iraq and Afghan-
racy and clarity throughout. istan on mortality. Journal of Trauma & Treatment. 2018;7:1–5.
doi:10.4172/2167-1222.1000424
The remaining authors provided editorial assistance, reviewed 10. Murdock J, Watson D, Dorée CJ, Blest A, Roberts MM, Brunskill
the manuscript and offered feedback that improved its clarity, SJ. Drugs and blood transfusions: dogma- or evidence-based prac-
structure and overall quality. tice? Transfus Med. 2009;19(1):6–15. doi:10.1111/j.1365-3148.
2008.00896.x
11. Vilay AM. Antibiotic dosing in chronic kidney disease and end-
Disclaimer stage renal disease: a focus on contemporary challenges. Adv
The views and information presented are those of the authors Chronic Kidney Dis. 2019;26(1):61–71. doi:10.1053/j.ackd.2018.
and do not represent the official position of the U.S. Army 10.006
Medical Center of Excellence, the U.S. Army Training and 12. Aloy B, Launay-Vacher V, Bleibtreu A, et al. Antibiotics and
Doctrine Command, the Department of the Army, the Depart- chronic kidney disease: dose adjustment update for infectious
disease clinical practice. Med Mal Infect. 2020;50(4):323–331.
ment of Defense, or the U.S. Government. doi:10.1016/j.medmal.2019.06.010
13. Chahine B. Antibiotic dosing adjustments in hospitalized pa-
Disclosures tients with chronic kidney disease: a retrospective chart review.
MDA, VSB, DAD, DJD, KRG, BJK, BJL, JKM, ACR, FLW, Int Urol Nephrol. 2022;54(1):157–163. doi:10.1007/s11255-
AAG, JAR, and SGS have received funds from the Department 021-02834-6
of Defense in the form of grants to their institution. VSB, DJD, 14. Chidambaram R. Optimal antibiotic dosage for chronic kidney
disease patient: a pharmacological manual for oral clinicians. Re-
and AAG have received funding from the National Institutes cent Pat Antiinfect Drug Discov. 2015;10(2):113–123. doi:10.21
of Health in the form of grants to their institution. AAG has 74/1574891x10666150729123754
received consulting fees from Seastar Medical. We have no 15. Grewal A, Thabet P, Dubinsky S, et al. Antimicrobial pharma-
other conflicts to report. cokinetics and dosing in critically ill adults receiving prolonged
intermittent renal replacement therapy: a systematic review. Phar-
macotherapy. 2023;43(11):1206–1220. doi:10.1002/phar.2861
Funding 16. Li AM, Gomersall CD, Choi G, Tian Q, Joynt GM, Lipman J.
This study is funded by the Department of Defense Joint Pro- A systematic review of antibiotic dosing regimens for septic pa-
gram Committee-2 (JPC-2) Military Infectious Diseases Re- tients receiving continuous renal replacement therapy: do current
search Program and the Joint Program Committee-6 (JPC-6) studies supply sufficient data? J Antimicrob Chemother. 2009;64
Combat Casualty Care Research Program through the Office (5):929–937. doi:10.1093/jac/dkp302

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