Page 68 - JSOM Fall 2025

Antibiotic Concentrations After Massive Transfusion (ACME) Study

A Review of the Literature on Antibiotic Dosing
During Transfusion and Study Protocol

2a
1a
Rocio J. Huaman, BS ; Fabiola Mancha, MS ; Erin L. Anderson, RN ;
3
Michael D. April, MD, DPhil, MSc ; Vikhyat S. Bebarta, MD ; Marisol S. Castaneto, PhD ;
4
5
6
Uwe Christians, MD, PhD ; Daniel N. Darlington, PhD ; David J. Douin, MD, MSc ;
7
8
9
13
Keith R. Glenn, MD ; Pucheng Ke, PhD ; Brian J. Kirkwood, DDS, MS ; Brit J. Long, MD ;
12
11
10
16
15
Joseph K. Maddry, MD ; Jessica Mendez, MS ; Allyson A. Mireles, PhD ;
14
18
17
19
Anne C. Ritter, DrPH, MPH ; Kristine E. Schauer, MBA, RN ; Annabel L. Schumaker, PharmD ;
21
Matthew D. Smith, MD ; Franklin L. Wright, MD ; Adit A. Ginde, MD, MPH ;
20
22
23
Julie A. Rizzo, MD ; Steven G. Schauer, DO, MS *
24
ABSTRACT
Background: Trauma in combat or civilian settings often in- that could potentially lead to optimized antibiotic dosing and
volves severe hemorrhage and open wounds, which carry a improved outcomes for trauma patients.
high risk of infection. Current clinical guidelines recommend
prophylactic antibiotics for high-risk wounds. Adequate Keywords: antibiotic; concentration; drug; massive antibiotic;
plasma antibiotic concentrations are necessary for tissue blood; blood transfusion; hemorrhage; anti-bacterial agents;
penetration, particularly into injured tissue. Blood loss from wounds and injuries
traumatic hemorrhage may impact plasma antibiotic concen-
trations. However, the association between blood loss, subse-
quent blood product transfusion, and antibiotic concentrations Introduction
remains unclear. We hypothesize that antibiotic concentrations
decrease in proportion to the volume of blood transfused, po- Traumatic injury, whether in military or civilian settings, often
tentially leading to insufficient antibiotic concentrations, plac- leads to hemorrhage, which is a leading cause of potentially pre-
ing the injured patient at increased infection risk. Methods: ventable death on the battlefield. Studies indicate that early
1,2
We are conducting a prospective, multicenter study that will blood transfusions can significantly improve survival rates in
enroll trauma patients from two large trauma centers: Brooke both settings. Additionally, casualties often require extensive
3,4
Army Medical Center and the University of Colorado Hospi- volumes of blood products, with 23% of combat casualties re-
tal. We will enroll participants receiving antibiotics for wound ceiving any volume of blood products, and nearly 3% reaching
prophylaxis and three or more units of blood products. We supermassive transfusion. Casualties receiving transfusions
5–7
will also enroll a control arm comprised of participants re- frequently have open wounds, which confer a significant risk of
ceiving the same antibiotics who receive two or fewer units infection. Although these open wounds may not result in immedi-
of blood. Blood samples will be collected from participants at ate death, infections can cause delayed morbidity and mortality.
predetermined time intervals after antibiotic infusion to assess To mitigate this risk and prevent such infections, administration
antibiotic concentrations. Our statistical analysis will focus of antibiotics during the early phases of care is recommended by
on the relationship between the volume of blood products ad- several guidelines, including the Committee on Tactical Combat
ministered and antibiotic concentrations. Results will inform Casualty Care (CoTCCC) guidelines and Joint Trauma System
the development of antibiotic dosing models for clinicians that guidelines. However, there is insufficient data guiding clini-
8,9
adjust for the effects of blood transfusion. Conclusion: The cians on initial dosing and potential redosing of antibiotics in
goal of this study is to fill a significant gap in trauma care cases of blood loss and subsequent blood transfusions.
*Correspondence to steven.g.schauer.mil@army.mil
a These two authors contributed equally to the work.
12
1 Rocio J. Huaman, Fabiola Mancha, Dr. Daniel N. Darlington, LTC Brian J. Kirkwood, Jessica Mendez, and LTC Steven G. Schauer
24
8
15
2
are affiliated with the U.S. Army Institute of Surgical Research (USAISR), Joint Base San Antonio–Fort Sam Houston (JBSA–FSH), TX.
1 Rocio J. Huaman, Fabiola Mancha, Jessica Mendez, and Dr. Allyson A. Mireles are affiliated with the Metis Foundation, San Antonio,
2
15
16
22
TX. Erin L. Anderson, Col Vikhyat S. Bebarta, Dr. Anne C. Ritter, Kristine E. Schauer, and Dr. Adit A. Ginde are affiliated with the De-
17
3
18
5
partment of Emergency Medicine, University of Colorado School of Medicine (CU SOM), Aurora, CO. LTC Michael D. April, MAJ Brit J.
13
4
24
14
Long, Col Joseph K. Maddry, and LTC Steven G. Schauer are affiliated with the Department of Emergency Medicine, Brooke Army Medical
5
Center (BAMC), JBSA–FSH, TX. Col Vikhyat S. Bebarta is affiliated with the Center for Combat and Battlefield (COMBAT) Research, Aurora,
CO. LTC Marisol S. Castaneto is affiliated with the Army Forensic Toxicology Program, JBSA–FSH, TX. Dr. Uwe Christians and Dr. David
7
9
6
J. Douin are affiliated with the Department of Anesthesiology, CU SOM, Aurora, CO. MAJ Keith R. Glenn is affiliated with the Department
10
of Medicine, BAMC, JBSA–FSH, TX. MAJ Pucheng Ke is affiliated with the Forensic Toxicology Drug Testing Laboratory, Fort Meade, MD.
11
19 Dr. Annabel L. Schumaker is affiliated with the Department of Pharmacy, BAMC, JBSA–FSH, TX. MAJ Matthew D. Smith is affiliated with the
20
Department of Anesthesiology, BAMC, JBSA–FSH, TX. Dr. Franklin L. Wright is affiliated with the Department of Surgery, CU SOM, Aurora,
21
23
CO. LTC Julie A. Rizzo is affiliated with the Department of Surgery, BAMC, JBSA–FSH, TX.
66