Department of Defense Trauma Registry Infectious Disease Module Impact on Clinical Practice

ABSTRACT

Background

The Joint Trauma System (JTS) is a DoD Center of Excellence for Military Health System trauma care delivery and the DoD’s reference body for trauma care in accordance with National Defense Authorization Act for Fiscal Year 2017. Through the JTS, evidence-based clinical practice guidelines (CPGs) have been developed and subsequently refined to standardize and improve combat casualty care. Data are amassed through a single, centralized DoD Trauma Registry to support process improvement measures with specialty modules established as the registry evolved. Herein, we review the implementation of the JTS DoD Trauma Registry specialty Infectious Disease Module and the development of infection-related CPGs and summarize published findings on the subsequent impact of the Infectious Disease Module on combat casualty care clinical practice and guidelines.

Methods

The DoD Trauma Registry Infectious Disease Module was developed in collaboration with the Infectious Disease Clinical Research Program (IDCRP) Trauma Infectious Disease Outcomes Study (TIDOS). Infection-related information (e.g., syndromes, antibiotic management, and microbiology) were collected from military personnel wounded during deployment June 1, 2009 through December 31, 2014 and medevac’d to Landstuhl Regional Medical Center in Germany before transitioning to participating military hospitals in the USA.

Results

To support process improvements and reduce variation in practice patterns, data collected through the Infectious Disease Module have been utilized in TIDOS analyses focused on assessing compliance with post-trauma antibiotic prophylaxis recommendations detailed in JTS CPGs. Analyses examined compliance over three time periods: 6 months, one-year, and 5 years. The five-year analysis demonstrated significantly improved adherence to recommendations following the dissemination of the 2011 JTS CPG, particularly with open fractures (34% compliance compared to 73% in 2013-2014). Due to conflicting recommendations regarding use of expanded Gram-negative coverage with open fractures, infectious outcomes among patients with open fractures who received cefazolin or expanded Gram-negative coverage (cefazolin plus fluoroquinolones and/or aminoglycosides) were also examined in a TIDOS analysis. The lack of a difference in the proportion of osteomyelitis (8% in both groups) and the significantly greater recovery of Gram-negative organisms resistant to aminoglycosides or fluoroquinolones among patients who received expanded Gram-negative coverage supported JTS recommendations regarding the use of cefazolin with open fractures. Following recognition of the outbreak of invasive fungal wound infections (IFIs) among blast casualties injured in Afghanistan, the ID Module was refined to capture data (e.g., fungal culture and histopathology findings, wound necrosis, and antifungal management) needed for the TIDOS team to lead the DoD outbreak investigation. These data captured through the Infectious Disease Module provided support for the development of a JTS CPG for the prevention and management of IFIs, which was later refined based on subsequent TIDOS IFI analyses.

Conclusions

To improve combat casualty care outcomes and mitigate high-consequence infections in future conflicts, particularly in the event of prolonged field care, expansion, refinement, and a mechanism for sustainability of the DoD Trauma Registry Infectious Disease Module is needed to include real-time surveillance of infectious disease trends and outcomes.

INTRODUCTION

Trauma registries were first established at civilian trauma centers in the USA during the 1970s to systematically collect data on the epidemiology of traumatic injuries.^1,2 Data documented in these trauma registries additionally support resource utilization and process improvements by identifying injury trends, as well as being used to develop and test clinical research hypotheses.^1–3 In particular, data collected through the National Trauma Data Bank (NTDB), the largest U.S. civilian trauma registry, have been used to improve patient outcomes, determine best practices, evaluate effectiveness of performance improvement initiatives, inform decision-makers, and identify populations at-risk for trauma-related complications.^4–11 As one example, data from the NTDB were utilized to examine the specificity and sensitivity of the Glasgow Coma Scale motor subscale (versus standard Glasgow Coma Scale), as well as its ability to assess trauma center needs with regards to field use as part of the National Trauma Triage Protocol.⁸ Use of NTDB data also confirmed poor prognosis with blunt carotid injury, regardless of whether treatment was open surgery or less invasive endovascular treatment.¹⁰ With regards to best practices, data from the NTDB demonstrated that patients with spinal fractures who underwent operative fixation within 3 days of injury had less complications, along with a reduction in resource needs.¹¹ These examples of evidence-based performance improvement set a standard for the best use of clinical data and underscore the importance of clinical registries.

Although trauma registry data have been used to support process improvements and advancements in trauma care,¹² their utility is dependent on the completeness and accuracy of the medical records and the data entered into the registry. Another limitation is that trauma registries primarily collect data at the time of hospital admission, thus, information on outcomes are frequently not available for evaluation, unless the trauma programs participate holistically in the larger quality improvement programs, such as Trauma Quality Improvement Programs, run by the American College of Surgeons.¹ In addition, typically, data collected through registries directly pertain to the injury, so information on preexisting comorbid conditions may not be captured. Furthermore, rates of complications (e.g., sepsis) resulting from traumatic injuries are underreported.¹

Along with the numerous national/regional civilian trauma registries, there are also registries focused on trauma sustained by military personnel. One such military registry is the Joint Theatre Trauma Registry of the U.K. Defence Medical Services, which has collected and analyzed trauma data from wounded personnel since 1999.^13–16 The criterion for inclusion in the U.K. Joint Theatre Trauma Registry is the triggering of a trauma team call at a deployed U.K. field hospital or a primary casualty receiving facility afloat.¹⁴ There is also a Battlefield Casualties Database of the Dutch Armed Forces, which has been utilized to support military trauma research in the Netherlands.¹⁷

Within the USA, there is a large centralized registry of data collected from wounded service members: the Joint Trauma System (JTS; https://jts.amedd.army.mil/) Department of Defense Trauma Registry (DoDTR).¹⁸ Herein, we review the history and application of the DoDTR in relation to supporting research and process improvements with infections complicating deployment-related trauma, including the development of clinical practice guidelines (CPGs) for infection prevention. The development of the specialty Infectious Disease (ID) Module of the DoDTR and its impact on combat casualty clinical practice is also discussed.

JOINT TRAUMA SYSTEM DEPARTMENT OF DEFENSE TRAUMA REGISTRY

The JTS is a DoD Center of Excellence for Military Health System trauma care delivery. Established in 2004 (as the Joint Theater Trauma System) and based on civilian trauma systems, the JTS was established as a collaborative effort involving personnel from each Service, Surgeon Generals of the U.S. military, the U.S. Army Institute of Surgical Research, the Surgeons’ General of the Combatant Command, and the American College of Surgeons Committee on Trauma to evolve combat casualty care into a trauma care system.^19–21 In 2018, in accordance with the National Defense Authorization Act for Fiscal Year 2017, the JTS migrated from the U.S. Army Institute of Surgical Research to the Defense Health Agency. The overall purpose of the JTS is to provide a systematic and integrated approach related to coordinating combat casualty care with the objective of providing the right care to the right patient at the right time and to provide evidence-based guidelines through the performance improvement process of analyzing trauma care delivery and determining best practices.^21–23 Built on the ideas of prevention, prehospital integration, education, leadership and communication, evidence-based performance improvement, research, and information systems,²³ the overall mission of the JTS is to advance trauma readiness and improve outcomes of wounded warriors (Fig. 1). The vision of the JTS is that every Soldier, Sailor, Airman, and Marine injured on the battlefield or in any theater of operations will be provided with the optimum chance for survival and maximum potential for functional recovery.

FIGURE 1.

The operational cycle of the Joint Trauma System for bold, responsible practice of battlefield medicine to support its vision and mission (https://jts.amedd.army.mil/index.cfm/about/vision).

A critical component of the JTS is the DoDTR (previously known as the Joint Theater Trauma Registry), which was created in 2004 by the Assistant Secretary of the Defense for Health Affairs to collect data from injured service members.¹⁸ The DoDTR was developed based on the NTDB and collects data from wounded military personnel across different levels of care (e.g., support hospitals within combat zones, regional military hospitals, and tertiary military hospitals within the USA) via specialty modules related to patient’s characteristics and management. Included in the DoDTR are more than 700 unique variables on demographics, mechanisms and circumstances of injury, protective equipment, injury severity, initial trauma care, clinical characteristics, surgical treatment, and selected (often short-term) outcomes.^{17,18,21,24,25} The information is collected from patient medical records and entered into the DoDTR database by trained trauma registrars. Initially, trauma registrars were located at military treatment facilities receiving combat trauma patients to include CSHs in theater through medical care at Landstuhl Regional Medical Center (LRMC) in Germany to receiving hospitals in the CONUS. Beginning in 2014, the trauma registrar elements of the JTS were consolidated in San Antonio, Texas. Database fields are a combination of predefined selections in drop-down menus and free-text fields depending on the variables. Information considered to be less systematic and highly variable, such as clinical provider notes, is typically not included in the database, but can be searched for future use.²⁶ The DoDTR also now captures prehospital data related to care of wounded service members in the austere environment before admission at a hospital. These data can be vitally important as the time from injury to admission at the regional military hospital following medical evacuation may be days compared to minutes for civilian patients.^17,25

Although the DoDTR was not created to be a research database, information collected through the registry and its specialty modules can be utilized for retrospective research to continue to adapt and improve battlefield trauma care delivery.²⁵ The primary function of data captured through the DoDTR is for identifying trends and assessing application of resources, as well as developing benchmark metrics, performance improvements, and CPGs.^25,26 In one example, data from the DoDTR identified a change in combat-related injury patterns in 2010 as a greater number of military personnel transitioned to Afghanistan. Specifically, there was an increased proportion of traumatic limb amputations along with genitourinary injuries among personnel with blast injuries sustained while dismounted. Identification of this increasing trend led to the development of a Task Force to fully characterize the dismounted complex blast injury pattern and provide recommendations for care.^18,27 The DoDTR has also been employed to track trauma complications, such as venous thromboembolism in amputation patients, extremity compartment syndrome, and ventilator-associated pneumonia, which resulted in performance improvement initiatives and a reduction in the rate of such complications.²²

Trauma Infectious Disease Outcomes Study (TIDOS)

Common to every war has been the occurrence of infections complicating war wounds with substantial associated morbidity and mortality.^28,29 During Operations Iraqi Freedom and Enduring Freedom, survivability of severe battlefield trauma increased as the result of advancements in personal protection equipment and improvements in combat casualty care through the establishment of the JTS. With more wounded warriors surviving severe injuries, a rise in the rate of infectious complications was also noted.^28,30–34 The challenge of managing these infections became apparent early on as outbreaks of bloodstream infections with multidrug-resistant Acinetobacter baumannii-calcoaceticus complex were reported among service members injured in Iraq. These outbreaks prompted concerns related to infection control and the threat of transmission of multidrug-resistant organisms through the combat casualty care pathway.^35–38

Although at the time, the DoDTR was collecting wide-ranging data from combat casualties on trauma characteristics and management, information on infectious complications and their management was not included and that significant knowledge gap needed to be addressed. The multicenter DoD—Department of Veterans Affairs Trauma Infectious Disease Outcomes Study (TIDOS) of the Infectious Disease Clinical Research Program (IDCRP, Uniformed Services University of the Health Sciences) was established to investigate the short- and long-term infectious complications of deployment-related injuries.^39,40 Patients were considered eligible for inclusion in TIDOS if they were active duty personnel at least 18 years of age, wounded during deployment, and required medical evacuation to LRMC in Germany before being transitioned to a participating military hospital in the USA (June 1, 2009 to December 31, 2014).

DoDTR infectious disease module

To collect infection-related data throughout multiple levels of care, a supplemental specialty ID Module was developed in collaboration between the TIDOS investigative team and the JTS to augment the DoDTR. The type of information captured through the ID Module included infection diagnoses, antimicrobial treatment, microbiology findings, and outcomes related to specific infection syndromes (i.e., skin and soft-tissue, bloodstream, central nervous system, sepsis, osteomyelitis, intrathoracic/pulmonary, and intra-abdominal).^39,40 The ID events are identified through review of medical records for clinical findings and laboratory test results and classified based upon the National Healthcare Safety Network standardized definitions for healthcare-associated infections.⁴¹ In addition, ID events were included if, in the absence of meeting the predefined a priori criteria, there was a clinical diagnosis with directed antimicrobial therapy that was continued for more than 5 days. If medical record review provided an alternative diagnosis and antimicrobial treatment was terminated, the ID event was excluded.

JOINT TRAUMA SYSTEM CLINICAL PRACTICE GUIDELINES

A major component of effective trauma care systems is the development and subsequent refinement of evidence-based CPGs, supporting a dynamic evidence-based “learning healthcare system.” Implementation of such a system has the potential to reduce practice variation, enhance antibiotic stewardship, and, most importantly, improve patient outcomes. Adherence to guideline recommendations has been shown to have a demonstrable benefit on clinical outcomes. In an observational study of 3,867 patients with moderate to severe injuries at five Level 1 civilian trauma centers, compliance with a range of clinical guidelines (e.g., thoracotomy, preoperative antibiotics prior to laparotomy, and intravenous antibiotics with open fractures) ranged from 13% to 94%. After adjusting for demographics and injury severity, the risk of mortality decreased by 14% with every 10% increase in compliance with the recommended practices.⁴²

Recognizing the benefit of clinical guidance, one of the initial recommendations to advance the JTS was to develop and implement evidence-based CPGs related to combat casualty care to reduce practice variation, improve quality of care, measure outcomes, and evaluate risk-benefits of specific interventions.^21,43 Presently, the JTS has produced 71 evidence-based CPGs on topics ranging from airway management to burn care to the prevention of combat trauma-related infections (https://jts.amedd.army.mil/index.cfm/PI_CPGs/cpgs).

Following JTS implementation in 2004, the components and limitations of the existing trauma system infrastructure within the combat zones were assessed and a formal process for performance improvement was established. Changes needed to improve the trauma care system that were identified included the development of a clinical information scheme, implementation of a system for continuous performance improvement, and preparation of a resource detailing optimal care of combat casualties. It was also mandated that the DoDTR, morbidity and mortality reports circulated between facilities, and operative case reports be reviewed and maintained. Additional recommendations included the development of triage criteria for casualty evacuation, placement of surgical assets within the combat zone, and a decrease in the number of surgical sites within the combat zone.²¹ Lastly, it was recognized that there was a clear need for military-specific CPGs to improve and standardize the care of combat casualties.

To develop the trauma-related infection CPGs, committees of civilian and military subject-matter experts were formed with expertise ranging from infection control to surgical specialties. The members of the committees were tasked with reviewing relevant literature prior to conferences where the guidelines would be drafted. Owing to the lack of high-quality clinical trials conducted in the military setting, the civilian experience was heavily relied upon during the development of the military-specific CPGs.

Recommendations for Prevention of Combat Trauma-Related Infections

The first JTS evidence-based CPG for the prevention of infections following combat-related injury was published in 2008.⁴⁴ To develop the guidelines, a panel of military and civilian subject-matter experts comprehensively reviewed relevant literature to provide recommendations for a clinical pathway to manage combat casualties. This included Cochrane reviews and guidelines or recommendations published by civilian organizations, such as the Surgical Infection Society (SIS), Eastern Association for the Surgery of Trauma (EAST), and the Infectious Diseases Society of America (IDSA).^32,44,45 Recommendations were evaluated based on the strength of the recommendation and quality of evidence using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system (www.gradeworkinggroup.org). Nevertheless, there were limitations in the grading system that were noted early on during the review process, particularly the lack of randomized controlled trials in combat zones. While evaluation of articles on military trauma was prioritized, there was a need to supplement with peer-reviewed articles providing data from civilian trauma studies. Generalizing civilian trauma data to battlefield care were difficult due to differences in injury severity, mechanism of injury, and evacuation time, as well as the diagnostic capabilities and the austere nature of military support hospitals within the combat zone.

In 2011, the CPG was revised and updated based on evidence made available after the publication of the 2008 CPG related to injuries of the extremities, central nervous system, eye, maxillofacial area, neck, thoracic region, and abdominal cavity, as well as burns.^46,47 The revised 2011 CPG was endorsed by the IDSA Standards and Practice Guideline Committee, the IDSA Board of Directors, and the Executive Council of the SIS.⁴⁷ As part of the revision, civilian guidelines related to trauma-related infections published by the CDC, Society for Healthcare Epidemiology of America, Association for Professionals in Infection Control and Epidemiology, SIS, EAST, and the IDSA were comprehensively reviewed.⁴⁷

With a shift in wound microbiology from infections with multidrug-resistant Acinetobacter spp. from casualties injured in Iraq to other multidrug-resistant Gram-negative bacilli (e.g., extended-spectrum β-lactamase-producing Escherichia coli), further evaluation of post-trauma antibiotic prophylaxis was needed in the 2011 revision.⁴⁶ Along with initial combat casualty care recommendations (e.g., use of negative pressure wound treatment and oxygen supplementation during aeromedical evacuation), the revised injury-specific recommendations included use of high-dose cefazolin as the foundation of post-trauma antibiotic prophylaxis with adjusted dosages from the 2008 CPGs, as well as a modified listing of alternative agents (Table I). While the 2008 CPG did not advocate use of expanded Gram-negative coverage with open fractures and maxillofacial injuries, there were other guidelines published during the same timeframe with conflicting recommendations.⁴⁸ Therefore, the 2011 CPG strongly emphasized that use of expanded Gram-negative coverage with open fracture and maxillofacial injuries was not recommended.⁴⁷ The CPG was most recently revised in 2021 with minor changes to recommendations for the duration of the post-trauma antibiotic prophylaxis with extremity wounds (changed from 1-3 to 24 hours with skin and soft-tissue wounds and 24 hours initially and repeated with each subsequent irrigation and debridement until soft-tissue coverage for open fracture).⁴⁹

TABLE I.

Post-Injury Antimicrobial Agent Selection and Duration Based upon Injury Pattern. Reprinted with Permission from Hospenthal et al. 2011⁴⁷

Injury	Preferred agent(s)a	Alternate agent(s)a	Duration
Extremity wounds (includes skin, soft tissue, bone)
Skin, soft tissue, no open fractures	Cefazolin, 2 gm IV q6-8 hoursb,c	Clindamycin (300-450 mg PO TID or 600 mg IV q8 hours)	1-3 days
Skin, soft tissue, with open fractures, exposed bone, or open joints	Cefazolin 2 gm IV q6-8 hoursb,c,d	Clindamycin 600 mg IV q8 hours	1-3 days
Thoracic wounds
Penetrating chest injury without esophageal disruption	Cefazolin, 2 gm IV q6-8 hoursb,c	Clindamycin (300-450 mg PO TID or 600 mg IV q8 hours)	1 day
Penetrating chest injury with esophageal disruption	Cefazolin 2 gm IV q6-8 hoursb,c PLUS metronidazole 500 mg IV q8-12 hours	Ertapenem 1 gm IV × 1 dose, OR moxifloxacin 400 mg IV × 1 dose	1 day after definitive washout
Abdominal wounds
Penetrating abdominal injury with suspected/ known hollow viscus injury and soilage; may apply to rectal/perineal injuries as well	Cefazolin 2 gm IV q 6-8 hoursb,c PLUS metronidazole 500 mg IV q8-12 hours	Ertapenem 1 gm IV × 1 dose, OR moxifloxacin 400 mg IV × 1 dose	1 day after definitive washout
Maxillofacial and neck wounds
Open maxillofacial fractures, or maxillofacial fractures with foreign body or fixation device	Cefazolin 2 gm IV q6-8 hoursb,c	Clindamycin 600 mg IV q8 hours	1 day
Central nervous system wounds
Penetrating brain injury	Cefazolin 2 gm IV q6-8 hoursb,c Consider adding metronidazole 500 mg IV q8–12 hours if gross contamination with organic debris	Ceftriaxone 2 gm IV q24 hours. Consider adding metronidazole 500 mg IV q8–12 hours if gross contamination with organic debris. For penicillin allergic patients, vancomycin 1 gm IV q12 hours PLUS ciprofloxacin 400 mg IV q8–12 hours	5 days or until CSF leak is closed, whichever is longer
Penetrating spinal cord injury	Cefazolin 2 gm IV q6-8 hoursb,c ADD metronidazole 500 mg IV q8–12 hours if abdominal cavity is involved	As above. ADD metronidazole 500 mg IV q8–12 hours if abdominal cavity is involved	5 days or until CSF leak is closed, whichever is longer
Eye wounds
Eye injury, burn, or abrasion	Topical: Erythromycin or Bacitracin ophthalmic ointment QID and PRN for symptomatic relief. Systemic: No systemic treatment required	Fluoroquinolone 1 drop QID	Until epithelium healed (no fluorescein staining)
Eye injury, penetrating	Levofloxacin 500 mg IV/PO once daily. Prior to primary repair, no topical agents should be used unless directed by ophthalmology		7 days or until evaluated by an ophthalmologist
Burns
Superficial burns	Topical antimicrobials with twice daily dressing changes (include mafenide acetatee or silver sulfadiazine; may alternate between the two), OR silver impregnated dressing changed q3–5 days, OR Biobrane	Silver nitrate solution applied to dressings	Until healed
Deep partial thickness burns	Topical antimicrobials with twice daily dressing changes, OR silver impregnated dressing changed q3–5 days, PLUS excision and grafting	Silver nitrate solution applied to dressings PLUS excision and grafting	Until healed or grafted
Full thickness burns	Topical antimicrobials with twice daily dressing changes PLUS excision and grafting	Silver nitrate solution applied to dressings PLUS excision and grafting	Until healed or grafted
Point of injury delayed evacuationf
Expected delay to reach surgical care	Moxifloxacin 400 mg PO × 1 dose. Ertapenem 1 g IV or IM if penetrating abdominal injury, shock, or unable to tolerate PO medications	Levofloxacin 500 mg PO × 1 dose. Cefotetan 2 g IV or IM q12 hours if penetrating abdominal injury, shock, or unable to tolerate PO medications	Single dose therapy

IV, intravenous; PO, orally; IM, intramuscularly; TID, three times daily; QID, four times daily; PRN, as needed; CSF, cerebrospinal fluid.

^aPost-injury antimicrobial agents are recommended to prevent early post-traumatic infectious complications, including sepsis, secondary to common bacterial flora. Selection is based on narrowest spectrum and duration required to prevent early infections prior to adequate surgical wound management. This narrow spectrum is selected to avoid selection of resistant bacteria. The antimicrobials listed are not intended for use in established infections, where multidrug-resistant (MDR) or other nosocomial pathogens may be causing infection.

^bCefazolin may be dosed based on body mass: 1 gram if weight <80 kg (176 lbs), 2 grams if weight 81-160 kg (177-352 lbs), 3 grams if weight > 160 kg (>352 lbs); doses up to 12 grams daily are supported by FDA-approved package insert.

^cPediatric dosing: cefazolin, 20-30 mg/kg IV q6–8 h (maximum, 100 mg/kg/d); metronidazole, 7.5 mg/kg IV q6h; clindamycin 25-40 mg/kg/d IV divided q6–8 h; ertapenem, 15 mg/kg IV or IM q12 (children up to 12 years) or 20 mg/kg IV or IM once daily (children over 12 years; maximum, 1 gm/d); ceftriaxone, 100 mg/kg/d IV divided q12–24 h (dosing for CNS injury); levofloxacin, 8 mg/kg IV or PO q12h (levofloxacin is only FDA-approved in children for prophylaxis of inhalational anthrax in children >6 months of age, but this dose is commonly used for other indications); vancomycin 60 mg/kg/d IV divided q6h (dosing for CNS injury); ciprofloxacin, 10 mg/kg IV (or 10-20 mg/kg PO) q12h.

^dThese guidelines do not advocate adding enhanced gram-negative bacteria coverage (i.e., addition of fluoroquinolone or aminoglycoside antimicrobials) in type III fractures.

^eMafenide acetate is contraindicated in infants less than 2 months of age.

^fPost-injury antimicrobial therapy as suggested by the Tactical Combat Casualty Care Committee.

CLINICAL IMPACT OF DoDTR ID MODULE

Through use of data collected through the DoDTR ID Module, multiple TIDOS analyses related to infectious complications of deployment trauma have been completed, adding to the knowledge base to improve the prevention and management of these serious infections. See Petfield et al.,⁵⁰ Rodriguez et al.,⁵¹ and Mende et al.⁵² within this supplement for further information on these analyses. As part of the effort to support process improvement, data captured through the DoDTR ID Module were also utilized to assess adherence to post-trauma antibiotic prophylaxis recommendations and the effectiveness of different antibiotic regimens with regard to infectious outcomes in multiple analyses.^48,53–56 Furthermore, findings from TIDOS analyses conducted using DoDTR ID Module data also supported the refinement of the JTS CPG for the prevention of combat-related infections.⁴⁹

Adherence with JTS Post-Trauma Antibiotic Prophylactic Recommendations

A fundamental principle of effective practice guidance implementation is CPG training and dissemination followed by tracking adherence to key clinical and operational metrics. Each CPG concludes with adherence measures, which are tracked in the DoDTR. In addition, it is also imperative to analyze health outcomes to assure recommendations work as intended. The JTS operational cycle demonstrates this iterative performance improvement process (Fig. 1).

Following publication of the JTS CPG in 2008, the first TIDOS analysis examined antimicrobial prescribing patterns for combat trauma-related injuries over a 6-month period (June–November 2009).⁵³ Compliance differed between injury patterns with adherence ranging from 10% with penetrating abdominal injuries to 73% with maxillofacial injuries. For open fractures, 35% were compliant with the 2008 CPG guidelines as 44% of the patients received expanded Gram-negative coverage (not recommended in the 2008 CPG; however, was recommended in other guidelines circulated in the same timeframe) and 15% received other antibiotics. Regarding closed injuries, 48% received antibiotics in contrast to the recommendations.⁵³ The second TIDOS assessment examined prescribing patterns over a one-year period (June 2009–May 2010).⁵⁴ Overall compliance with the CPG recommendations was 75% and, as with the 6-month assessment, noncompliance primarily resulted from use of antibiotics other than recommended, including expanded Gram-negative coverage with open fractures (received by 48% of patients) and maxillofacial injuries (received by 27% of patients).⁵⁴ The JTS Operational Cycle capitalizes on the Hawthorne effect, which refers to when individuals modify their behavior in response to their awareness of being observed; through the performance improvement process and tracking metric adherence, compliance with the CPGs has improved.

In a TIDOS assessment of post-trauma antibiotic prophylaxis prescribed over a five-year period (June 2009–May 2014), adherence to the 2011 CPG was examined.⁵⁵ The findings demonstrated an increasing trend toward compliance with the CPG recommendations over the study years. In particular, adherence with antibiotic prophylaxis following open fractures showed a significant improvement from 34% compliance in 2009-2010 to 73% in 2013-2014 (53% compliance overall). The increased adherence with open fracture antibiotic prophylaxis was largely the result of a significant decrease in use of expanded Gram-negative coverage from >50% between June 2009 and May 2011 to ≤5% from June 2011 to December 2014 (Fig. 2). Reduced use of expanded Gram-negative coverage with maxillofacial injuries also resulted in compliance improving from 50% in 2009-2010 to 76% in 2013-2014. For penetrating abdominal injuries, use of levofloxacin/ciprofloxacin decreased from 42% in 2010-2011 to zero in 2013-2014.⁵⁵

FIGURE 2.

Proportion of wounded military personnel who received expanded Gram-negative coverage by injury pattern. Each time period began in June and ended in May. Overall total patients who received expanded Gram-negative coverage per injury pattern was: open fractures = 703; skin and soft-tissue injuries = 175; closed = 18; and maxillofacial = 133. All injury patterns had significant differences in proportions across the study years with P-values of <0.001 for skin and soft-tissue injuries and open fractures, P = 0.007 for closed injuries, and P = 0.001 for maxillofacial injuries. The 2008 CPG did not recommend use of Gram-negative agents in open fractures or maxillofacial injuries. The 2010 JTS guidance document recommended use of Gram-negative agents in contaminated open fractures and some maxillofacial injuries. The 2011 CPG recommended against use of Gram-negative coverage in all injuries except for penetrating abdomen where cefazolin/metronidazole or ertapenem was recommended. Reprinted from Lloyd et al. 2017⁵⁵ with permission from Oxford Press.

Due to the conflicting guidance regarding use of expanded Gram-negative coverage with open fractures, a TIDOS analysis examined infectious outcomes with open fractures based on the type of prophylactic regimen received (i.e., JTS recommended narrow-spectrum antibiotic [cefazolin] versus a narrow-spectrum regimen with the addition of fluoroquinolones and/or aminoglycosides as expanded Gram-negative coverage). While there was a reduction in the occurrence of skin and soft-tissue infections with use of expanded Gram-negative coverage, there was no difference in the proportion of osteomyelitis between the comparator groups (8% in both regimen groups). In addition, there was an adverse effect of greater recovery of organisms resistant to fluoroquinolones and aminoglycosides being isolated from patients who received expanded Gram-negative coverage.⁴⁸ Similar results were reported in a TIDOS analysis assessing open extremity soft-tissue injuries.⁵⁶ The findings of these two analyses support the current JTS CPG recommendations regarding use of a narrow-spectrum antibiotic prophylactic regimen with open extremity trauma.^48,56

Prevention and Management of Invasive Fungal Wound Infections

Since inception, the DoDTR ID Module has continued to evolve in response to the needs of the Military Health System. One example is the outbreak of invasive fungal wound infections (IFIs) among service members injured in Afghanistan. Once the IFI outbreak was recognized, the ID Module was modified to include variables related to mycology, wound necrosis, antifungal use, and IFI diagnosis in order to conduct the outbreak investigation. Owing to the complexity of these serious infections, the ID Module was also modified to capture data on wound outcomes (e.g., time to closure and amputation revisions) to further understand the impact of IFIs and other wound infections on wound healing and assess management approaches. For more information on IFIs, see Rodriguez et al.⁵¹ within this supplement.

The JTS developed a CPG for the prevention and management of IFIs, which was first published in November 2012 and later superseded by revised guidelines in 2016. To develop the initial 2012 CPG, the JTS utilized findings from the IDCRP TIDOS IFI Outbreak Investigation Technical Report.⁵⁷ The CPG focused recommendations on the early detection of IFI, risk stratification, wound care, and prompt antifungal and surgical treatment of suspected infections. Potential IFI risk factors identified in the CPG were based on the characteristics common to the IFI patients detailed in the TIDOS IFI Outbreak Investigation Technical Report,⁵⁷ such as being injured via a blast injury while dismounted; sustaining a traumatic above knee amputation; extensive perineal, genitourinary, or rectal injury; and receipt of massive transfusion of >25 units of blood within 24 hours post-injury. The JTS CPG emphasized early and aggressive surgical debridements and advocated use of antifungal topical therapy. Dual antifungal therapy was recommended when there was significant progressive tissue necrosis on two consecutive debridements (not including the first two debridements frequently occurring in the combat zone). A “blast protocol” was implemented at LRMC, which is the first military treatment facility along the continuum of casualty care that had a reliable capability to perform histopathology.⁵⁸ Based on the results of the laboratory and histopathology examination, antifungal treatment (frequently dual) was initiated with the combat casualties. Collection of tissue specimens was recommended for patients with ≥3 of the potential IFI risk factors at LRMC and for patients with ≥3 risk factors and a suspicious wound (i.e., appearance indicative of a necrotic wound infection) following admission to military hospitals in the USA.

The preliminary risk factors detailed in the 2012 JTS CPG were assessed in a TIDOS analysis utilizing data from the ID Module. Except for extensive perineal, genitourinary, or rectal injury, all the risk factors were confirmed as independent predictors of an IFI; however, the volume of blood transfusion within 24 hours of injury was modified from 25 units to 20 units.⁵⁹ Subsequent TIDOS analyses further evaluated IFI epidemiology, diagnostic methods, wound microbiology, and clinical outcomes.^51,60,61 Findings from these analyses were utilized to refine the JTS CPG for the management of IFI in war wounds in 2016.⁶² Along with the refined risk factors, the 2016 CPG also included diagnostic criteria for an IFI, visual examples of a suspicious wound indicative of an IFI, an adjusted concentration for Dakins solution for topical antifungal therapy, timing of debridements, and inclusion of posaconazole as an alternative to voriconazole for antifungal therapy.⁶²

FUTURE PLANS

The dissemination of the JTS CPG on the prevention of combat trauma-related infections reduced variation in antibiotic prescribing patterns, including use of broad-spectrum antibiotics, there remained substantial variation with regards to the antibiotic treatment of combat-related infections. As such, an evidence-based CPG focused on the treatment of combat-related infections, particularly extremity wound infections is needed. Presently, TIDOS analyses examining clinical outcomes with regards to different treatment regimens are underway. These findings will lay the groundwork to support the development of an evidence-based CPG for the treatment of combat-related infections.

Future conflicts require timely capture and analysis of critical data elements that provide information on injury circumstances, wounding patterns, early and continued approaches to surgical and medical care, post-trauma complications such as highly prevalent infections, and importantly, clinical outcomes. Conflicts over the last 20 years generated modest casualty volumes, and it can be anticipated that in future conflicts, the volume and acuity of combat casualties will be dramatically increased. Additionally, there is the potential for casualties being in prolonged hold scenarios if air evacuation is delayed. It is important during peacetime to critically review the tools that were successful during the recent conflicts and improve their throughput, as well as enhance capabilities to best respond to future emergent threats and rapidly adapt prevention and treatment approaches using best available evidence. The uniqueness of modern warfare and the challenges in extrapolating civilian evidence to the battlefield highlight the importance of military registry-based systems in assuring best care for the warfighter.

FUNDING

This work was conducted by the Infectious Disease Clinical Research Program, a DoD program executed by USU, through a cooperative agreement with The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been supported with federal funds from the National Institute of Allergy and Infectious Diseases, NIH, under Inter-Agency Agreement Y1-AI-5072, the Defense Health Program, U.S. DoD, under award HU0001190002, the Department of the Navy under the Wounded, Ill, and Injured Program, Defense Medical Research and Development Program, and the Military Infectious Diseases Research Program.

CONFLICT OF INTEREST

None declared.