Invasive Fungal Infections Complicate Treatment, Increase Mortality of IED-Wounded Servicemembers

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By Brenda L. Mooney

U.S. Marine Cpl. Sean Grady, a dog handler and pointman with Echo Company, 1st Light Armored Reconnaissance Battalion, and Ace, an improvised explosive device detection dog, pause for a break while sweeping a chokepoint during a patrol in southern Helmand province earlier this year. Photo by Cpl. Alfred V. Lopez.

BETHESDA, MD -Invasive fungal wound infections are on the increase in military personnel wounded by improvised explosive devices, leading to significant morbidity and even death in some cases where the victims initially survived.

David R. Tribble, MD, of the Uniformed Services University of the Health Sciences, and colleagues report in the journal Clinical Infectious Diseases that IEDs can cause gross contamination of wounds. According to the published correspondence, researchers looked at 2,413 patients wounded in Afghanistan and moved via Landstuhl Regional Medical Center in Germany to one of four U.S. military hospitals between 2009 and 2010. 1

Of 37 cases identified, 20 had proven fungal wound infections, four were probable and 13 were possible. The rates reached 3.5% of trauma admissions in late 2010.

All of the cases were related to blast injury, with 92% of them occurring during foot patrols, especially in southern Afghanistan (94%). Some 80% involved lower extremity amputation, and nearly all required large volume blood transfusions. Mold isolates were recovered in 83% of cases.

Clinical outcomes included three deaths, 11 cases where frequent debridements were required and amputation revisions in 58% of cases, according to the report. Antifungal therapy was employed in nearly 90% of the patients, including lipid formulations of amphotericin Bs, voriconazole, and posaconazole.

“Major advances in combat casualty care have led to increased survival of patients with complex extremity trauma,” the authors write. “Invasive fungal wound infections (IFIs) are an uncommon, but increasingly recognized, complication following trauma that require greater understanding of risk factors and clinical findings to reduce morbidity.”

The authors note that their findings are in line with a previous report on wounded British troops, published last year in the journal Philosophical Transactions B of the Royal Society.2

The British report suggested that wounds with heavy environmental contamination were associated with soft-tissue infection by invasive fungi, including zygomycetes such as Rhizopus spp., Apophysomyces spp., Mucor spp., Saksenaea spp., and Absidia spp., the environmental fungi such as Chaetomium spp., and finally the parasitic oomycete (once considered a fungus), Pythium spp.

Common factors found in the injured British troops were:

  • Sustaining injuries in the “Green Zone,” Helmand Province, Afghanistan, in an area where there is extensive exposure to decaying vegetation;
  • Receiving a blast or other severe injury, usually on foot patrol;
  • Suffering extensive wounds/amputations, which were heavily contaminated with environmental debris; and
  • Requiring massive blood transfusion, i.e. more than eight units of blood within the first 24 hours after the injury.

“Fungal infection was not seen in wounded soldiers from Iraq, and probably reflects differences in combat, mode of injury and survival, rather than a unique feature of Afghanistan environmental flora, since these fungi are distributed worldwide,” the British authors noted. “Invasive fungal infection may present several days to several weeks after return to the UK usually with non-specific features of infection, such as fever and raised inflammatory markers. In such cases, wounds are urgently inspected for signs of necrosis and non-viable fat and muscle, which might suggest invasive fungal infection. There have been rare cases of invasive fungal infection where a patient’s mode of injury and initial assessment did not indicate that such an infection was likely. Therefore, all patients who have had major injuries have this diagnosis considered if clinical symptoms and signs are suggestive.”

The USUHS authors pointed out that awareness of the likely factors leading to invasive fungal wound infections can help field clinicians better identify them.

“IFIs are an emerging trauma-related infection leading to significant morbidity,” they write. “Early identification, using common characteristics of patient injury profile and tissue-based diagnosis, should be accompanied by aggressive surgical and antifungal therapy (liposomal amphotericin B and a broad-spectrum triazole pending mycology results) among patients with suspicious wounds.”

That training also can have some benefits in civilian medicine. While deep skin wound fungal infection is rare in non-military trauma, it can occur.

Last year, the Missouri Department of Health and Senior Services (MDHSS) reported suspected deep skin fungal infection in patients injured by a tornado in Joplin, MO. It warned healthcare professionals to be alert to cases in which a patient who has a major clinical condition such as severe head injury, pneumothoraces, kidney injury, severe lacerations, bacterial sepsis, bacterial wound infections, and pneumonia with acute respiratory failure presents with a potential fungal infection. The Missouri health department also noted that patients with diabetes and/or compromised immune system are also at increased risk of illness associated with such a fungal infection.

1. Warkentien T, Rodriguez C, Lloyd B, Wells J, Weintrob A, Dunne JR, Ganesan A,
Li P, Bradley W, Gaskins LJ, Seillier-Moiseiwitsch F, Murray CK, Millar EV,
Keenan B, Paolino K, Fleming M, Hospenthal DR, Wortmann GW, Landrum ML,
Kortepeter MG, Tribble DR; for the Infectious Disease Clinical Research Program
Trauma Infectious Disease Outcomes Study Group. Invasive Mold Infections
Following Combat-related Injuries. Clin Infect Dis. 2012 Oct 5. [Epub ahead of
print] PubMed PMID: 23042971.

2. Evriviades D, Jeffery S, Cubison T, Lawton G, Gill M, Mortiboy D. 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
Jan 27;366(1562):219-30. PubMed PMID: 21149357; PubMed Central PMCID: PMC3013433.

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Invasive Fungal Infections Complicate Treatment, Increase Mortality of IED-Wounded Servicemembers

Bookmark and Share

By Brenda L. Mooney

BETHESDA, MD – Invasive fungal wound infections are on the increase in military personnel wounded by improvised explosive devices, leading to significant morbidity and even death in some cases where the victims initially survived.

David R. Tribble, MD, of the Uniformed Services University of the Health Sciences, and colleagues report in the journal Clinical Infectious Diseases that IEDs can cause gross contamination of wounds. According to the published correspondence, researchers looked at 2,413 patients wounded in Afghanistan and moved via Landstuhl Regional Medical Center in Germany to one of four U.S. military hospitals between 2009 and 2010.1

Of 37 cases identified, 20 had proven fungal wound infections, four were probable and 13 were possible. The rates reached 3.5% of trauma admissions in late 2010.

All of the cases were related to blast injury, with 92% of them occurring during foot patrols, especially in southern Afghanistan (94%). Some 80% involved lower extremity amputation, and nearly all required large volume blood transfusions. Mold isolates were recovered in 83% of cases.

Clinical outcomes included three deaths, 11 cases where frequent debridements were required and amputation revisions in 58% of cases, according to the report. Antifungal therapy was employed in nearly 90% of the patients, including lipid formulations of amphotericin Bs, voriconazole, and posaconazole.

“Major advances in combat casualty care have led to increased survival of patients with complex extremity trauma,” the authors write. “Invasive fungal wound infections (IFIs) are an uncommon, but increasingly recognized, complication following trauma that require greater understanding of risk factors and clinical findings to reduce morbidity.”

The authors note that their findings are in line with a previous report on wounded British troops, published last year in the journal Philosophical Transactions B of the Royal Society.2

The British report suggested that wounds with heavy environmental contamination were associated with soft-tissue infection by invasive fungi, including zygomycetes such as Rhizopus spp., Apophysomyces spp., Mucor spp., Saksenaea spp., and Absidia spp., the environmental fungi such as Chaetomium spp., and finally the parasitic oomycete (once considered a fungus), Pythium spp.

Common factors found in the injured British troops were:

  • Sustaining injuries in the “Green Zone,” Helmand Province, Afghanistan, in an area where there is extensive exposure to decaying vegetation;
  • Receiving a blast or other severe injury, usually on foot patrol;
  • Suffering extensive wounds/amputations, which were heavily contaminated with environmental debris; and
  • Requiring massive blood transfusion, i.e. more than eight units of blood within the first 24 hours after the injury.

    “Fungal infection was not seen in wounded soldiers from Iraq, and probably reflects differences in combat, mode of injury and survival, rather than a unique feature of Afghanistan environmental flora, since these fungi are distributed worldwide,” the British authors noted. “Invasive fungal infection may present several days to several weeks after return to the UK usually with non-specific features of infection, such as fever and raised inflammatory markers. In such cases, wounds are urgently inspected for signs of necrosis and non-viable fat and muscle, which might suggest invasive fungal infection. There have been rare cases of invasive fungal infection where a patient’s mode of injury and initial assessment did not indicate that such an infection was likely. Therefore, all patients who have had major injuries have this diagnosis considered if clinical symptoms and signs are suggestive.”

    The USUHS authors pointed out that awareness of the likely factors leading to invasive fungal wound infections can help field clinicians better identify them.

    “IFIs are an emerging trauma-related infection leading to significant morbidity,” they write. “Early identification, using common characteristics of patient injury profile and tissue-based diagnosis, should be accompanied by aggressive surgical and antifungal therapy (liposomal amphotericin B and a broad-spectrum triazole pending mycology results) among patients with suspicious wounds.”

    That training also can have some benefits in civilian medicine. While deep skin wound fungal infection is rare in non-military trauma, it can occur.

    Last year, the Missouri Department of Health and Senior Services (MDHSS) reported suspected deep skin fungal infection in patients injured by a tornado in Joplin, MO. It warned healthcare professionals to be alert to cases in which a patient who has a major clinical condition such as severe head injury, pneumothoraces, kidney injury, severe lacerations, bacterial sepsis, bacterial wound infections, and pneumonia with acute respiratory failure presents with a potential fungal infection. The Missouri health department also noted that patients with diabetes and/or compromised immune system are also at increased risk of illness associated with such a fungal infection.

    1. Warkentien T, Rodriguez C, Lloyd B, Wells J, Weintrob A, Dunne JR, Ganesan A,
    Li P, Bradley W, Gaskins LJ, Seillier-Moiseiwitsch F, Murray CK, Millar EV,
    Keenan B, Paolino K, Fleming M, Hospenthal DR, Wortmann GW, Landrum ML,
    Kortepeter MG, Tribble DR; for the Infectious Disease Clinical Research Program
    Trauma Infectious Disease Outcomes Study Group. Invasive Mold Infections
    Following Combat-related Injuries. Clin Infect Dis. 2012 Oct 5. [Epub ahead of
    print] PubMed PMID: 23042971.

    2.Evriviades D, Jeffery S, Cubison T, Lawton G, Gill M, Mortiboy D. 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
    Jan 27;366(1562):219-30. PubMed PMID: 21149357; PubMed Central PMCID: PMC3013433.

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