Current Fungal Infection Reports

, Volume 8, Issue 4, pp 277–286 | Cite as

Combat-Related Invasive Fungal Wound Infections

Epidemiological Aspects of Fungal Infection (T Chiller and JA Baddley, Section Editors)

Abstract

Combat-related invasive fungal (mold) wound infections (IFIs) have emerged as an important and morbid complication following explosive blast injuries among military personnel. Similar to trauma-associated IFI cases among civilian populations, as in agricultural accidents and natural disasters, these infections occur in the setting of penetrating wounds contaminated by environmental debris. Specific risk factors for combat-related IFI include dismounted (patrolling on foot) blast injuries occurring mostly in southern Afghanistan, resulting in above knee amputations requiring resuscitation with large-volume blood transfusions. Diagnosis of IFI is based upon early identification of a recurrently necrotic wound following serial debridement and tissue-based histopathology examination with special stains to detect invasive disease. Fungal culture of affected tissue also provides supportive information. Aggressive surgical debridement of affected tissue is the primary therapy. Empiric antifungal therapy should be considered when there is a strong suspicion for IFI. Both liposomal amphotericin B and voriconazole should be considered initially for treatment since many of the cases involve not only Mucorales species but also Aspergillus or Fusarium spp., with narrowing of regimen based upon clinical mycology findings.

Keywords

Invasive fungal infections Combat-related trauma Invasive mold infections Wound infections Invasive mucormycosis 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Murray CK. Infectious disease complications of combat-related injuries. Crit Care Med. 2008;36 Suppl 7:S358–64.PubMedCrossRefGoogle Scholar
  2. 2.
    Murray CK, Hinkle MK, Yun HC. History of infections associated with combat-related injuries. J Trauma. 2008;64 Suppl 3:S221–31.PubMedCrossRefGoogle Scholar
  3. 3.
    Murray CK, Wilkins K, Molter NC, et al. Infections complicating the care of combat casualties during Operations Iraqi Freedom and Enduring Freedom. J Trauma. 2011;71 Suppl 1:S62–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Tribble DR, Conger NG, Fraser S, et al. Infection-associated clinical outcomes in hospitalized medical evacuees after traumatic injury: Trauma Infectious Disease Outcome Study. J Trauma. 2011;71 Suppl 1:S33–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Evriviades D, Jeffery S, Cubison T, et al. Shaping the military wound: issues surrounding the reconstruction of injured servicemen at the Royal Centre for Defence Medicine. Philos Trans R Soc Lond B Biol Sci. 2011;366:219–30.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Albrecht MC, Griffith ME, Murray CK, et al. Impact of Acinetobacter infection on the mortality of burn patients. J Am Coll Surg. 2006;203:546–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Scott P, Deye G, Srinivasan A, et al. An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex infection in the US military health care system associated with military operations in Iraq. Clin Infect Dis. 2007;44:1577–84.PubMedCrossRefGoogle Scholar
  8. 8.
    Yun HC, Branstetter JG, Murray CK. Osteomyelitis in military personnel wounded in Iraq and Afghanistan. J Trauma. 2008;64 Suppl 2:S163–8. discussion S168.PubMedCrossRefGoogle Scholar
  9. 9.
    Petersen K, Riddle MS, Danko JR, et al. Trauma-related infections in battlefield casualties from Iraq. Ann Surg. 2007;245:803–11.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Brown KV, Murray CK, Clasper JC. Infectious complications of combat-related mangled extremity injuries in the British military. J Trauma. 2010;69 Suppl 1:S109–15.PubMedCrossRefGoogle Scholar
  11. 11.
    Murray CK. Epidemiology of infections associated with combat-related injuries in Iraq and Afghanistan. J Trauma. 2008;64 Suppl 3:S232–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Murray CK, Wilkins K, Molter NC, et al. Infections in combat casualties during Operations Iraqi and Enduring Freedom. J Trauma. 2009;66 Suppl 4:S138–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Scott SG, Belanger HG, Vanderploeg RD, Massengale J, Scholten J. Mechanism-of-injury approach to evaluating patients with blast-related polytrauma. J Am Osteopath Assoc. 2006;106:265–70.PubMedGoogle Scholar
  14. 14.
    Brown KV, Guthrie HC, Ramasamy A, Kendrew JM, Clasper J. Modern military surgery: lessons from Iraq and Afghanistan. J Bone Joint Surg (Br). 2012;94:536–43.CrossRefGoogle Scholar
  15. 15.
    Krueger CA, Wenke JC, Ficke JR. Ten years at war: comprehensive analysis of amputation trends. J Trauma Acute Care Surg. 2012;73 Suppl 5:S438–44.PubMedCrossRefGoogle Scholar
  16. 16.
    Andersen RC, Fleming M, Forsberg JA, et al. Dismounted complex blast injury. J Surg Orthop Adv. 2012;21:2–7.PubMedGoogle Scholar
  17. 17.
    Fleming M, Waterman S, Dunne J, D’Alleyrand JC, Andersen RC. Dismounted complex blast injuries: patterns of injuries and resource utilization associated with the multiple extremity amputee. J Surg Orthop Adv. 2012;21:32–7.PubMedGoogle Scholar
  18. 18.
    Ficke JR, Eastridge BJ, Butler F, et al. Dismounted complex blast injury report of the Army Dismounted Complex Blast Injury Task Force. J Trauma Acute Care Surg. 2012;73 Suppl 5:S520–34.CrossRefGoogle Scholar
  19. 19.
    Flow Investigators, Petrisor B, Sun X, et al. Fluid lavage of open wounds (FLOW): a multicenter, blinded, factorial pilot trial comparing alternative irrigating solutions and pressures in patients with open fractures. J Trauma. 2011;71:596–606.Google Scholar
  20. 20.
    Owens BD, White DW, Wenke JC. Comparison of irrigation solutions and devices in a contaminated musculoskeletal wound survival model. J Bone Joint Surg Am. 2009;91:92–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Fleming ME, Watson JT, Gaines RJ, O’Toole RV, Extremity War Injuries VIIRP. Evolution of orthopaedic reconstructive care. J Am Acad Orthop Surg. 2012;20 Suppl 1:S74–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Gordon G, Indeck M, Bross J, Kapoor DA, Brotman S. Injury from silage wagon accident complicated by mucormycosis. J Trauma. 1988;28:866–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Skiada A, Petrikkos G. Cutaneous zygomycosis. Clin Microbiol Infect. 2009;15 Suppl 5:41–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Andresen D, Donaldson A, Choo L, et al. Multifocal cutaneous mucormycosis complicating polymicrobial wound infections in a tsunami survivor from Sri Lanka. Lancet. 2005;365:876–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Kontogiorgi M, Floros I, Koroneos A, et al. Fatal post-traumatic zygomycosis in an immunocompetent young patient. J Med Microbiol. 2007;56:1243–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Taams M, Bade PG, Thomson SR. Post-traumatic abdominal mucormycosis. Injury. 1992;23:390–2.PubMedCrossRefGoogle Scholar
  27. 27.
    Vitrat-Hincky V, Lebeau B, Bozonnet E, et al. Severe filamentous fungal infections after widespread tissue damage due to traumatic injury: six cases and review of the literature. Scand J Infect Dis. 2009;41:491–500.PubMedCrossRefGoogle Scholar
  28. 28.
    Patino JF, Castro D, Valencia A, Morales P. Necrotizing soft tissue lesions after a volcanic cataclysm. World J Surg. 1991;15:240–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Horvath EE, Murray CK, Vaughan GM, et al. Fungal wound infection (not colonization) is independently associated with mortality in burn patients. Ann Surg. 2007;245:978–85.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Cocanour CS, Miller-Crotchett P, Reed 2nd RL, Johnson PC, Fischer RP. Mucormycosis in trauma patients. J Trauma. 1992;32:12–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Hajdu S, Obradovic A, Presterl E, Vecsei V. Invasive mycoses following trauma. Injury. 2009;40:548–54.PubMedCrossRefGoogle Scholar
  32. 32.
    Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634–53.PubMedCrossRefGoogle Scholar
  33. 33.
    Neblett Fanfair R, Benedict K, Bos J, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med. 2012;367:2214–25.PubMedCrossRefGoogle Scholar
  34. 34.
    Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000;13:236–301.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Tully CC, Romanelli AM, Sutton DA, Wickes BL, Hospenthal DR. Fatal Actinomucor elegans var. kuwaitiensis infection following combat trauma. J Clin Microbiol. 2009;47:3394–9.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.•
    Paolino KM, Henry JA, Hospenthal DR, Wortmann GW, Hartzell JD. Invasive fungal infections following combat-related injury. Mil Med. 2012;177:681–5. Description of six invasive fungal wound infections among military personnel with injuries sustained in Iraq. Provides data on the observed incidence of invasive fungal wound infections in Iraq and the significant mortality and morbidity associated with the disease.PubMedCrossRefGoogle Scholar
  37. 37.•
    Weintrob AC, Weisbrod AB, Dunne JR, et al. Combat trauma-associated invasive fungal wound infections: epidemiology and clinical classification. Epidemiol Infect. 2014. doi:10.1017/S095026881400051X. Descriptions of a trauma-related invasive fungal infection classification scheme. The scheme is an effective tool for clinical and epidemiological surveillance/research.
  38. 38.
    Skiada A, Rigopoulos D, Larios G, Petrikkos G, Katsambas A. Global epidemiology of cutaneous zygomycosis. Clin Dermatol. 2012;30:628–32.PubMedCrossRefGoogle Scholar
  39. 39.
    De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.••
    Rodriguez C, Weintrob AC, Shah J, et al. Risk factors associated with invasive fungal Infections in combat trauma. Surg Infect (Larchmt). 2014. doi:10.1089/sur.2013.123. Case–control analysis of risk factors for the development of combat-related invasive fungal wound infections. Determined that blast injuries sustained while dismounted, resulting in above knee amputations and requiring large volume blood product transfusions within 24 hours of injury are independent risk factors.
  41. 41.
    Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards Jr J, Ibrahim AS. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis. 2009;48:1743–51.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Taylor RW, Manganaro L, O’Brien J, et al. Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient. Crit Care Med. 2002;30:2249–54.PubMedCrossRefGoogle Scholar
  43. 43.
    Ibrahim AS, Spellberg B, Edwards Jr J. Iron acquisition: a novel perspective on mucormycosis pathogenesis and treatment. Curr Opin Infect Dis. 2008;21:620–5.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis. 2012;54 Suppl 1:S16–22.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Spellberg B, Edwards Jr J, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18:556–69.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Tarrand JJ, Lichterfeld M, Warraich I, et al. Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination. Am J Clin Pathol. 2003;119:854–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Vainrub B, Macareno A, Mandel S, Musher DM. Wound zygomycosis (mucormycosis) in otherwise healthy adults. Am J Med. 1988;84:546–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Owens BD, Kragh Jr JF, Macaitis J, Svoboda SJ, Wenke JC. Characterization of extremity wounds in Operation Iraqi Freedom and Operation Enduring Freedom. J Orthop Trauma. 2007;21:254–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Kordy FN, Al-Mohsen IZ, Hashem F, et al. Successful treatment of a child with posttraumatic necrotizing fasciitis caused by Apophysomyces elegans: case report and review of literature. Pediatr Infect Dis J. 2004;23:877–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Blair JE, Fredrikson LJ, Pockaj BA, Lucaire CS. Locally invasive cutaneous Apophysomyces elegans infection acquired from snapdragon patch test. Mayo Clin Proc. 2002;77:717–20.PubMedCrossRefGoogle Scholar
  51. 51.
    Gettleman LK, Shetty AK, Prober CG. Posttraumatic invasive Aspergillus fumigatus wound infection. Pediatr Infect Dis J. 1999;18:745–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Demirel R, Ilhan S, Asan A, Kinaci E, Oner S. Microfungi in cultivated fields in Eskisehir province (Turkey). J Basic Microbiol. 2005;45:279–93.PubMedCrossRefGoogle Scholar
  53. 53.
    Chakrabarti A, Kumar P, Padhye AA, et al. Primary cutaneous zygomycosis due to Saksenaea vasiformis and Apophysomyces elegans. Clin Infect Dis. 1997;24:580–3.PubMedCrossRefGoogle Scholar
  54. 54.
    Radowsky JS, Strawn AA, Sherwood J, Braden A, Liston W. Invasive mucormycosis and aspergillosis in a healthy 22-year-old battle casualty: case report. Surg Infect (Larchmt). 2011;12:397–400.CrossRefGoogle Scholar
  55. 55.
    Lloyd B, Weintrob A, Rodriguez C, et al. Effect of early screening for invasive fungal infections in U.S. service members with explosive blast injuries. Surg Infect (Larchmt). 2014. doi:10.1089/sur2012.245.Google Scholar
  56. 56.••
    Warkentien T, Rodriguez C, Lloyd B, et al. Invasive mold infections following combat-related injuries. Clin Infect Dis. 2012;55:1441–9. Initial case investigation of 37 military personnel with invasive fungal wound infections. Provides first data on clinical characteristics, injury patterns, and outcomes associated with the disease.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47:364–71.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Walsh TJ, Hiemenz JW, Seibel NL, et al. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin Infect Dis. 1998;26:1383–96.PubMedCrossRefGoogle Scholar
  59. 59.
    Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of Aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60.PubMedCrossRefGoogle Scholar
  60. 60.
    Meletiadis J, Antachopoulos C, Stergiopoulou T, et al. Differential fungicidal activities of amphotericin B and voriconazole against Aspergillus species determined by microbroth methodology. Antimicrob Agents Chemother. 2007;51:3329–37.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Luke DR, Tomaszewski K, Damle B, Schlamm HT. Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci. 2010;99:3291–301.PubMedCrossRefGoogle Scholar
  62. 62.
    Neofytos D, Lombardi LR, Shields RK, et al. Administration of voriconazole in patients with renal dysfunction. Clin Infect Dis. 2012;54:913–21.PubMedCrossRefGoogle Scholar
  63. 63.
    Greenberg RN, Mullane K, van Burik JA, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. 2006;50:126–33.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42:e61–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Sealy PI, Nguyen C, Tucci M, Benghuzzi H, Cleary JD. Delivery of antifungal agents using bioactive and nonbioactive bone cements. Ann Pharmacother. 2009;43:1606–15.PubMedCrossRefGoogle Scholar
  66. 66.
    Barret JP, Ramzy PI, Heggers JP, et al. Topical nystatin powder in severe burns: a new treatment for angioinvasive fungal infections refractory to other topical and systemic agents. Burns. 1999;25:505–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Hirsch EF. “The treatment of infected wounds,” Alexis Carrel’s contribution to the care of wounded soldiers during World War I. J Trauma. 2008;64 Suppl 3:S209–10.PubMedCrossRefGoogle Scholar
  68. 68.
    Lewandowski L, Purcell R, Fleming M, Gordon WT. The use of dilute Dakin’s solution for the treatment of angioinvasive fungal infection in the combat wounded: a case series. Mil Med. 2013;178:e503–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Segal BH, Almyroudis NG, Battiwalla M, et al. Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Clin Infect Dis. 2007;44:402–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007;356:335–47.PubMedCrossRefGoogle Scholar
  71. 71.
    Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348–59.PubMedCrossRefGoogle Scholar
  72. 72.
    De Laurenzi A, Matteocci A, Lanti A, et al. Amphotericin B prophylaxis against invasive fungal infections in neutropenic patients: a single center experience from 1980 to 1995. Infection. 1996;24:361–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Perfect JR, Klotman ME, Gilbert CC, et al. Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients. J Infect Dis. 1992;165:891–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Calvano TP, Blatz PJ, Vento TJ, et al. Pythium aphanidermatum infection following combat trauma. J Clin Microbiol. 2011;49:3710–3.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Hospenthal DR, Chung KK, Lairet K, et al. Saksenaea erythrospora infection following combat trauma. J Clin Microbiol. 2011;49:3707–9.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Barsoumian A, Sanchez CJ, Mende K, et al. In vitro toxicity and activity of Dakin’s solution, mafenide acetate, and amphotericin B on filamentous fungi and human cells. J Orthop Trauma. 2013;27:428–36.PubMedCrossRefGoogle Scholar
  77. 77.
    Fares Y, El-Zaatari M, Fares J, Bedrosian N, Yared N. Trauma-related infections due to cluster munitions. J Infect Public Health. 2013;6:482–6.PubMedCrossRefGoogle Scholar
  78. 78.
    Lundy JB, Driscoll IR. Experience with proctectomy to manage combat casualties sustaining catastrophic perineal blast injury complicated by invasive mucor soft-tissue infections. Mil Med. 2014;179:e347–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Mitchell TA, Hardin MO, Murray CK, et al. Mucormycosis attributed mortality: a seven-year review of surgical and medical management. Burns. 2014. doi:10.1016/j.burns.2014.03.013.PubMedGoogle Scholar
  80. 80.
    Rodriguez CJ, Weintrob AC, Dunne JR, et al. Clinical relevance of mold culture positivity with and without recurrent wound necrosis following combat-related injuries. J Trauma Acute Care Surg. 2014. (in press).Google Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  1. 1.Infectious Disease Clinical Research Program, Preventive Medicine and Biometrics DepartmentUniformed Services University of the Health SciencesBethesdaUSA
  2. 2.Walter Reed National Military Medical CenterBethesdaUSA

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