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4. Combat-Related Invasive Fungal Wound Infections

Author

Rodriguez, (Ret.) Carlos J, Ganesan, Anuradha, Shaikh, Faraz, Carson, M Leigh, Bradley, William, Warkentien, Tyler E, and Tribble, David R

Subjects
Military Personnel, Afghan Campaign 2001, Blast Injuries, Wound Infection, Public Health, Environmental and Occupational Health, Humans, Supplement Article, General Medicine, Communicable Diseases, Invasive Fungal Infections, Retrospective Studies
Abstract

Introduction During Operation Enduring Freedom in Afghanistan, an outbreak of combat-related invasive fungal wound infections (IFIs) emerged among casualties with dismounted blast trauma and became a priority issue for the Military Health System. Methods In 2011, the Trauma Infectious Disease Outcomes Study (TIDOS) team led the Department of Defense IFI outbreak investigation to describe characteristics of IFIs among combat casualties and provide recommendations related to management of the disease. To support the outbreak investigation, existing IFI definitions and classifications utilized for immunocompromised patients were modified for use in epidemiologic research in a trauma population. Following the conclusion of the outbreak investigation, multiple retrospective analyses using a population of 77 IFI patients (injured during June 2009 to August 2011) were conducted to evaluate IFI epidemiology, wound microbiology, and diagnostics to support refinement of Joint Trauma System (JTS) clinical practice guidelines. Following cessation of combat operations in Afghanistan, the TIDOS database was comprehensively reviewed to identify patients with laboratory evidence of a fungal infection and refine the IFI classification scheme to incorporate timing of laboratory fungal evidence and include categories that denote a high or low level of suspicion for IFI. The refined IFI classification scheme was utilized in a large-scale epidemiologic assessment of casualties injured over a 5.5-year period. Results Among 720 combat casualties admitted to participating hospitals (2009-2014) who had histopathology and/or wound cultures collected, 94 (13%) met criteria for an IFI and 61 (8%) were classified as high suspicion of IFI. Risk factors for development of combat-related IFIs include sustaining a dismounted blast injury, experiencing a traumatic transfemoral amputation, and requiring resuscitation with large-volume (>20 units) blood transfusions. Moreover, TIDOS analyses demonstrated the adverse impact of IFIs on wound healing, particularly with order Mucorales. A polymerase chain reaction (PCR)-based assay to identify filamentous fungi and support earlier IFI diagnosis was also assessed using archived formalin-fixed, paraffin-embedded tissue specimens. Although the PCR-based assay had high specificity (99%), there was low sensitivity (63%); however, sensitivity improved to 83% in tissues collected from sites with angioinvasion. Data obtained from the initial IFI outbreak investigation (37 IFI patients) and subsequent TIDOS analyses (77 IFI patients) supported development and refinement of a JTS clinical practice guideline for the management of IFIs in war wounds. Furthermore, a local clinical practice guideline to screen for early tissue-based evidence of IFIs among blast casualties at the Landstuhl Regional Medical Center was critically evaluated through a TIDOS investigation, providing additional clinical practice support. Through a collaboration with the Uniformed Services University Surgical Critical Care Initiative, findings from TIDOS analyses were used to support development of a clinical decision support tool to facilitate early risk stratification. Conclusions Combat-related IFIs are a highly morbid complication following severe blast trauma and remain a threat for future modern warfare. Our findings have supported JTS clinical recommendations, refined IFI classification, and confirmed the utility of PCR-based assays as a complement to histopathology and/or culture to promote early diagnosis. Analyses underway or planned will add to the knowledge base of IFI epidemiology, diagnostics, prevention, and management.

Published
2022

5. Multidrug-Resistant and Virulent Organisms Trauma Infections: Trauma Infectious Disease Outcomes Study Initiative

Author

Mende, Katrin, Akers, Kevin S, Tyner, Stuart D, Bennett, Jason W, Simons, Mark P, Blyth, Dana M, Li, Ping, Stewart, Laveta, and Tribble, David R

Subjects
TIDOS Supplement, Bacteria, Public Health, Environmental and Occupational Health, Bacterial Infections, Microbial Sensitivity Tests, General Medicine, Hospitals, Military, Communicable Diseases, United States, Anti-Bacterial Agents, Drug Resistance, Multiple, Bacterial, Gram-Negative Bacteria, Escherichia coli, Wound Infection, Humans, Enterococcus
Abstract

Introduction During the wars in Iraq and Afghanistan, increased incidence of multidrug-resistant (MDR) organisms, as well as polymicrobial wounds and infections, complicated the management of combat trauma–related infections. Multidrug resistance and wound microbiology are a research focus of the Trauma Infectious Disease Outcomes Study (TIDOS), an Infectious Disease Clinical Research Program, Uniformed Services University, research protocol. To conduct comprehensive microbiological research with the goal of improving the understanding of the complicated etiology of wound infections, the TIDOS MDR and Virulent Organisms Trauma Infections Initiative (MDR/VO Initiative) was established as a collaborative effort with the Brooke Army Medical Center, Naval Medical Research Center, U.S. Army Institute of Surgical Research, and Walter Reed Army Institute of Research. We provide a review of the TIDOS MDR/VO Initiative and summarize published findings. Methods Antagonism and biofilm formation of commonly isolated wound bacteria (e.g., ESKAPE pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), antimicrobial susceptibility patterns, and clinical outcomes are being examined. Isolates collected from admission surveillance swabs, as part of infection control policy, and clinical infection workups were retained in the TIDOS Microbiological Repository and associated clinical data in the TIDOS database. Results Over the TIDOS study period (June 2009 to December 2014), more than 8,300 colonizing and infecting isolates were collected from military personnel injured with nearly one-third of isolates classified as MDR. At admission to participating U.S. military hospitals, 12% of wounded warriors were colonized with MDR Gram-negative bacilli. Furthermore, 27% of 913 combat casualties with ≥1 infection during their trauma hospitalization had MDR Gram-negative bacterial infections. Among 335 confirmed combat-related extremity wound infections (2009–2012), 61% were polymicrobial and comprised various combinations of Gram-negative and Gram-positive bacteria, yeast, fungi, and anaerobes. Escherichia coli was the most common Gram-negative bacilli isolated from clinical workups, as well as the most common colonizing MDR secondary to extended-spectrum β-lactamase resistance. Assessment of 479 E. coli isolates collected from wounded warriors found 188 pulsed-field types (PFTs) from colonizing isolates and 54 PFTs from infecting isolates without significant overlap across combat theaters, military hospitals, and study years. A minority of patients with colonizing E. coli isolates developed subsequent infections with the same E. coli strain. Enterococcus spp. were most commonly isolated from polymicrobial wound infections (53% of 204 polymicrobial cultures). Patients with Enterococcus infections were severely injured with a high proportion of lower extremity amputations and genitourinary injuries. Approximately 65% of polymicrobial Enterococcus infections had other ESKAPE organisms isolated. As biofilms have been suggested as a cause of delayed wound healing, wound infections with persistent recovery of bacteria (isolates of same organism collected ≥14 days apart) and nonrecurrent bacterial isolates were assessed. Biofilm production was significantly associated with recurrent bacteria isolation (97% vs. 59% with nonrecurrent isolates; P Conclusions The TIDOS MDR/VO Initiative provides comprehensive and detailed data of major microbial threats associated with combat-related wound infections to further the understanding of wound etiology and potentially identify infectious disease countermeasures, which may lead to improvements in combat casualty care.

Published
2022

20. Treatment of Suspected Invasive Fungal Infection in War Wounds

Author

Rodriguez, Carlos J, primary, Tribble, David R, additional, Malone, Debra L, additional, Murray, Clinton K, additional, Jessie, Elliot M, additional, Khan, Mansoor, additional, Fleming, Mark E, additional, Potter, Benjamin K, additional, Gordon, Wade T, additional, and Shackelford, Stacy A, additional

Published
2018
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30. Antimicrobial Prophylaxis with Combat-Related Open Soft-Tissue Injuries.

Author

Lloyd, Bradley A, Murray, Clinton K, Shaikh, Faraz, Carson, M Leigh, Blyth, Dana M, Schnaubelt, Elizabeth R, Whitman, Timothy J, and Tribble, David R

Abstract

All Department of Defense (DoD) guidance documents recommend cefazolin or clindamycin as post-trauma antibiotic prophylaxis for open soft-tissue injuries. Although not advocated, some patients with open soft-tissue injuries also received expanded Gram-negative coverage (EGN) prophylaxis based on the judgment of front-line trauma providers. During the study period, revised guidelines in 2011/2012 re-emphasized recommendations for using cefazolin or clindamycin, and stewardship efforts in the DoD trauma community aimed to reduce the practice of adding EGN to guideline-recommended antibiotic prophylaxis. Our objective was to examine antibiotic utilization among wounded military personnel with open extremity soft-tissue injuries over a 5-yr period and assess the impact on infectious outcomes in patients who received EGN prophylaxis versus guideline-directed prophylaxis.

Published
2018
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31. Adherence to Published Antimicrobial Prophylaxis Guidelines for Wounded Service Members in the Ongoing Conflicts in Southwest Asia

Author

Lloyd, Bradley A., primary, Weintrob, Amy C., additional, Hinkle, Mary K., additional, Fortuna, Gerald R., additional, Murray, Clinton K., additional, Bradley, William, additional, Millar, Eugene V., additional, Shaikh, Faraz, additional, Vanderzant, Kristen, additional, Gregg, Stacie, additional, Lloyd, Gina, additional, Stevens, Julie, additional, Carson, M. Leigh, additional, Aggarwal, Deepak, additional, and Tribble, David R., additional

Published
2014
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41. Prevalence of Staphylococcus aureus Colonization and Risk Factors for Infection Among Military Personnel in a Shipboard Setting.

Author

Curry, Jennifer A, Maguire, Jason D, Fraser, Jamie, Tribble, David R, Deiss, Robert G, Bryan, Coleman, Tisdale, Michele D, Crawford, Katrina, Ellis, Michael, and Lalani, Tahaniyat

Abstract

Staphylococcal skin and soft tissue infections (SSTIs), especially those due to methicillin-resistant Staphylococcus aureus (MRSA) are an important public health issue for the military. Limited data exist regarding the prevalence of S. aureus colonization in the shipboard setting. We conducted a cross-sectional, observational study to determine the point prevalence of S. aureus colonization among military personnel onboard a naval vessel. Asymptomatic active duty personnel completed a survey for risk factors associated with colonization and SSTIs. Culture specimens were obtained from the anterior nares, pharynx, groin, and perirectal regions. MRSA isolates underwent testing for antimicrobial resistance, virulence factors, and pulsed-field type. 400 individuals were enrolled, 198 (49.5%) of whom were colonized with S. aureus, with MRSA identified in 14 participants (3.5%). No significant risk factors were associated with MRSA colonization. USA800 was the most common colonizing MRSA strain in the cohort and was detected in 10 participants (71%). Two participants (14%) were colonized with USA300 MRSA. In this first report of S. aureus epidemiology in a shipboard setting, we observed high rates of S. aureus and MRSA colonization. Longitudinal studies are needed to document the incident rates of S. aureus colonization during shipboard deployment and its impact on SSTI risk.

Published
2016
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43. Healthcare-associated pneumonia among U.S. combat casualties, 2009 to 2010.

Author

Yun, Heather C, Weintrob, Amy C, Conger, Nicholas G, Li, Ping, Lu, Dan, Tribble, David R, and Murray, Clinton K

Abstract

Although there is literature evaluating infectious complications associated with combat-related injuries from Iraq and Afghanistan, none have evaluated pneumonia specifically. Therefore, we assessed a series of pneumonia cases among wounded military personnel admitted to Landstuhl Regional Medical Center, and then evacuated further to participating U.S. military hospitals. Of the 423 casualties evacuated to the United States, 36 developed pneumonia (8.5%) and 30 of these (83.3%) were ventilator-associated. Restricting to 162 subjects admitted to intensive care, 30 patients had pneumonia (18.5%). The median Injury Severity Score was higher among subjects with pneumonia (23.0 vs. 6.0; p < 0.01). There were 61 first-isolate respiratory specimens recovered from 31 pneumonia subjects, of which 56.1% were gram-negative, 18.2% were gram-positive, and 18.2% were fungal. Staphylococcus aureus and Pseudomonas aeruginosa were most commonly recovered (10.6%, and 9.1%, respectively). Thirteen bacterial isolates (26.5%) were multidrug-resistant. Outcome data were available for 32 patients, of which 26 resolved their infection without progression, 5 resolved after initial progression, and 1 died. Overall, combat-injured casualties suffer a relatively high rate of pneumonia, particularly those requiring mechanical ventilation. Although gram-negative pathogens were common, S. aureus was most frequently isolated. Continued focus on pneumonia prevention strategies is necessary for improving combat care.

Published
2015
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44. Self-reported incidence of snake, spider, and scorpion encounters among deployed U.S. military in Iraq and Afghanistan.

Author

Riddle MS, Shiau DT, Sanders JW, Putnam SD, Buff A, Beasley W, Tribble DR, Shiau, Danny T, Sanders, John W, Putnam, Shannon D, Buff, Ann, Beasley, William, Tribble, David R, and Riddle, Mark S

Abstract

Much has been written about injury, diarrhea, and respiratory cases but less is known about other threats, specifically snake, scorpion, and spider encounters. To examine the risk from local fauna, a cross-sectional study using an anonymous survey was conducted among U.S. troops in Southwest Asia between January 2005 and May 2006. Among 3,265 troops, 9 cases (0.3%) of snakebites and 85 cases (2.6%) of spider stings and scorpion bites were reported, equating to an incidence of 46.1 per 10,000 person-months for scorpion/spider encounters and 4.9 per 10,000 person-months for snakebites. There was a significant association with service branch and toileting facilities for snakebites. Season, deployment location, rank, and toileting facilities were associated with differential risk of scorpion/spider encounters. Troops are at risk for local fauna encounters while deployed in the current operational environment. The potential morbidity, mortality, and operational impact of these health hazards need to be considered. [ABSTRACT FROM AUTHOR]

Published
2007

45. Knowledge, attitudes, and practices regarding epidemiology and management of travelers' diarrhea: a survey of front-line providers in Iraq and Afghanistan.

Author

Sanders JW, Riddle MS, Tribble DS, Jobanputra NK, Jones JJ, Putnam SD, Frenck RW, Riddle, Mark S, Tribble, David R, Jobanputra, Nishith K, Jones, James J, Putnam, Shannon D, Frenck, Robert W, and Sanders, John W

Abstract

To evaluate the relationship between medical knowledge and clinical practice, a survey on travelers' diarrhea was administered to military health care providers attending a professional development and trauma management conference. The survey was administered at the beginning of the conference and 58 of the 76 attendees participated by completing a questionnaire. Respondents were aware of the standard definition of travelers' diarrhea; however, their knowledge about the epidemiology and management of travelers' diarrhea was low. Less than one-third correctly answered questions on etiology and more than two-thirds made incorrect management choices in treatment of mild to moderate watery diarrhea and dysentery. Important knowledge gaps about gastroenteritis were identified and should serve as a basis to develop military-specific clinical guidelines and training programs. [ABSTRACT FROM AUTHOR]

Published
2005

46. History of U.S. military contributions to the study of diarrheal diseases.

Author

Bavaro MF, Kelly DJ, Dasch GA, Hale BR, Olson P, Lim, Matthew L, Murphy, Gerald S, Calloway, Margaret, and Tribble, David

Abstract

Diarrhea, a scourge upon humanity since preliterate times, has been the particular nemesis of military forces. The Armed Forces of the United States have been in the forefront in the diagnosis, treatment, and prevention of diarrheal illness. U.S. military scientists and physicians implemented the first mandatory typhoid inoculation program, contributed to advances in water chlorination, and pioneered the use of antibiotics for typhoid fever. U.S. Navy physicians refined the intravenous treatment of cholera, reducing the death rate from 20% to less than 1%. Their studies of electrolyte and fluid balance in cholera, and the subsequent development of oral rehydration therapy for cholera and other diarrheal illness, have saved millions of lives worldwide. U.S. Army researchers refuted the desquamation theory of cholera pathogenesis, isolated the cholera exotoxin, and developed improved cholera vaccines. U.S. Army and Navy researchers pioneered the use of antibiotics for the treatment of typhoid fever, made major contributions to the treatment of dysentery, developed algorithms for the treatment of traveler's diarrhea, and continue active development of traveler's diarrhea and dysentery vaccines. U.S. military diarrheal research has directly contributed to the welfare of hundreds of millions of people. [ABSTRACT FROM AUTHOR]

Published
2005
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