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Early Complications and Outcomes in Combat Injury–Related Invasive Fungal Wound Infections: A Case–Control Analysis

Lewandowski, Louis R. MD; Weintrob, Amy C. MD; Tribble, David R. MD, DrPH; Rodriguez, Carlos J. DO; Petfield, Joseph MD; Lloyd, Bradley A. DO; Murray, Clinton K. MD; Stinner, Daniel MD; Aggarwal, Deepak MSE, MSPH; Shaikh, Faraz MS; Potter, Benjamin K. MD; the Infectious Disease Clinical Research Program Trauma Infectious Disease Outcomes Study Group

Journal of Orthopaedic Trauma: March 2016 - Volume 30 - Issue 3 - p e93–e99
doi: 10.1097/BOT.0000000000000447
Original Article

Objective: Clinicians have anecdotally noted that combat-related invasive fungal wound infections (IFIs) lead to residual limb shortening, additional days and operative procedures before initial wound closure, and high early complication rates. We evaluated the validity of these observations and identified risk factors that may impact time to initial wound closure.

Design: Retrospective review and case–control analysis.

Setting: Military hospitals.

Patients/Participants: US military personnel injured during combat operations (2009–2011). The IFI cases were identified based on the presence of recurrent, necrotic extremity wounds with mold growth in culture, and/or histopathologic fungal evidence. Non-IFI controls were matched on injury pattern and severity. In a supplemental matching analysis, non-IFI controls were also matched by blood volume transfused within 24 hours of injury.

Intervention: None.

Main Outcome Measurements: Amputation revision rate and loss of functional levels.

Results: Seventy-one IFI cases (112 fungal–infected extremity wounds) were identified and matched to 160 control patients (315 non-IFI extremity wounds). The IFI wounds resulted in significantly more changes in amputation level (P < 0.001). Additionally, significantly (P < 0.001) higher number of operative procedures and longer duration to initial wound closure were associated with IFI. A shorter duration to initial wound closure was significantly associated with wounds lacking IFIs (Hazard ratio: 1.53; 95% confidence interval, 1.17–2.01). The supplemental matching analysis found similar results.

Conclusions: Our analysis indicates that IFIs adversely impact wound healing and patient recovery, requiring more frequent proximal amputation revisions and leading to higher early complication rates.

Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

*Department of Orthopaedics, Walter Reed National Military Medical Center, Bethesda, MD;

Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD;

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD;

§The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD;

Department of Orthopaedics and Rehabilitation, San Antonio Military Medical Center, JBSA Fort Sam Houston, TX;

Landstuhl Regional Medical Center, Landstuhl, Germany; and

**Infectious Disease Service, San Antonio Military Medical Center, Houston, TX (B. A. Lloyd is now with San Antonio Military Medical Center, JBSA Fort Sam Houston, TX).

Reprints: Benjamin K. Potter, MD, Department of Orthopaedics, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, America Building (19), 2nd Floor—Ortho, Bethesda, MD 20889 (e-mail: Benjamin.k.potter.mil@mail.mil).

Supported by the Infectious Disease Clinical Research Program, a DoD program executed through the Uniformed Services University of the Health Sciences. This project is funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072, and the Department of the Navy under the Wounded, Ill, and Injured Program.

A portion of these data were previously presented at the Society of Military Orthopaedic Surgeons 55th Annual Meeting, December 9–15, 2013, Vale, CO; 2014 Military Health System Research Symposium, Fort, August 18–21, 2014, Lauderdale, FL; Orthopaedic Trauma Association 30th Annual Meeting, October 15–18, 2014, Tampa, FL; and Society of Military Orthopaedic Surgeons 56th Annual Meeting, December 15–19, 2014, Scottsdale, AZ.

The authors report no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jorthotrauma.com).

The views expressed are those of the authors and do not necessarily reflect the official views or policies of the Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, the National Institutes of Health or the Department of Health and Human Services, the Department of Defense or the Departments of the Army, Navy or Air Force. Mention of trade names, commercial products, or organization does not imply endorsement by the United States Government.

The study was approved by the Infectious Disease Institutional Review Board of the Uniformed Services University of the Health Sciences (Bethesda, MD).

Accepted August 26, 2015

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