Daniel M. Keller, PhD

October 26, 2011

October 26, 2011 (Boston, Massachusetts) — On May 22, a very ill wind blew through Joplin, Missouri, causing death, destruction, and severe illness. The EF5 tornado (wind speeds over 200 miles/hour) destroyed more than 2000 structures, damaged 25% to 30% of the city, killed more than 150 people, and injured more than 1000.

Two of the injured were teenagers who were thrown from a car and whose wounds eventually became infected with an unusual pathogen, Gina Weddle, RN, MSN, CPNP, a pediatric nurse practitioner in infectious diseases at the Children's Mercy Hospital in Kansas City, Missouri, reported during a poster session here at the Infectious Diseases Society of America (IDSA) 49th Annual Meeting.

Both patients, a 16-year-old boy and a 13-year-old girl, sustained traumatic injuries. The boy had a large open chest wound and multiple rib fractures with flail chest, an open humeral fracture, and multiple other injuries. The girl had multiple facial fractures and complex lacerations of her scalp and right thigh. All victims of the tornado went to the only remaining hospital in Joplin, where all wounds were sutured closed; in retrospect, this was the wrong approach in these 2 cases.

The 2 teenagers were considered to be immunocompetent, but on hospital day 10, they both showed evidence of infected wounds. The boy had fever, leukocytosis, and necrosis of the chest wound. The girl developed redness, tenderness, and swelling of her thigh, with wound dehiscence and serous fluid drainage. In both cases, pathologic examination showed fungal elements and environmental debris.

"The 2 cases had significant large wounds that turned very necrotizing, were difficult to control, and were difficult to get clean margins on. We later found out that it was a mold that hadn't been really described in the literature, called Apophysomyces trapeziformis," Ms. Weddle told Medscape Medical News. It took a call to a surgeon at Walter Reed National Military Medical Center, in Bethesda, Maryland, who had seen similar wounds in Afghanistan, to lead clinicians in the direction of A trapeziformis.

When the mold was diagnosed, liposomal amphotericin (pushed to 7.5 mg/kg per day) was initiated, and the 2 patients eventually transitioned to oral posaconazole. The clinicians also used amphotericin-soaked dressings on the chest wound "until we lost his subcutaneous tissue. Once we were in the chest cavity, we no longer used the amphotericin soak," Ms. Weddle said. The organisms was resistant to common antifungal agents.

The patients underwent multiple wound debridements (12 for the boy and 10 for the girl). Ms. Weddle explained that the margins were difficult to define.

"The lesson here is that if you don't have trauma experience and you have a large wound, be very cautious about closing it. The other thing I think we learned is to have more than 1 antifungal on board until you know what it is, and aggressive debridement," she advised. "The debridement scared a lot of our surgeons, and we have some pretty aggressive surgeons. This fungus is very necrotizing very quickly, so you have to aggressively debride these kids."

Ms Weddle said the surgeon at Walter Reed advised that during debridement, one always needs to plan for reconstruction.

"Both children ended up surviving. The girl had a leg wound, and she ended up getting skin grafted.... The young man actually did get off mechanical ventilation. He lost all of his ribs and skin overlying [on one side of his chest]. He has skin grafting over that and will have to have chest reconstruction in the future. He ended up coming off mechanical ventilation, which we were very surprised about, and walked out of the hospital after 3 months," she said. The girl was discharged from the hospital after 6 weeks.

Ms. Weddle said a lesson learned here is that "in natural disasters, you have to think about unusual organisms and resistant organisms, which is what we saw in both these kids, and you have to start broadening your coverage and how you treat them."

Barbara Alexander, MD, director of the transplant infectious diseases service, head of the clinical mycology laboratory, and associate professor of medicine and pathology at Duke University, Durham, North Carolina, and head of the IDSA Annual Meeting Program Committee, who was not involved in the study, told Medscape Medical News that A trapeziformis is not an organism that is commonly seen. It is a primitive fungus in the subphylum Mucoromycotina (phylum: Zygomycota), a group of fungi causing mucormycosis.

"We most often see these organisms causing infection in really immunosuppressed patients.... The thing that first catches our attention is that this is an infection that's occurring in nonimmunosuppressed patients," she said.

These molds are ubiquitous in the environment, and are often associated with water and dirt. Generally, people inhale the spores and the infection originates in the lung and then disseminates in the body. However, in this case, cutaneous or traumatic inoculation of the skin probably occurred when the teens were thrown from the car and their wounds became contaminated with dirt or water. "If you're more immunocompetent, then...it's going to take a really...big dose of the spores to cause the infection; that's probably what's happened.... You don't necessarily think of a mold infection in an immunocompetent patient," Dr. Alexander explained.

These organisms have a very characteristic appearance on tissue histopathology. "This is clue number 1," she said. The clinician needs to know the specific organism and its resistance pattern to be able to choose appropriate antimicrobials. Amphotericin is effective but is limited by renal toxicity. She advised that once the infection is under control, step-down therapy to oral posaconazole is in order.

Dr. Alexander noted the aggressive tissue invasion and necrosis seen in these cases. "The thing that's characteristic of these types of fungi is that they don't usually spread through the bloodstream, [but instead] by direct contiguous spread through the tissues," she said. "They have no respect for tissue planes, so it gets into the skin...directly along the chest wall, and then goes directly into the chest and the pericardial cavity," as in the case of the teenage boy.

"These infections are frightening because once they develop, they tend to go very rapidly. The extension into the contiguous tissue is very quick, so almost as much as getting the right antifungal on board, it's about the surgeons and the trauma physicians recognizing that the organism is there and being very aggressive, very aggressive with the surgical debridement...and recognizing that the tissue that's infected may actually appear healthy," Dr. Alexander warned. "One of the things that's gaining more attention in cases of zygomycetous infections is having a pathologist doing [potassium hydroxide tests] in real time in the operating room for the surgeons, so that they can cut out tissue that might not look infected [to the naked eye]."

Because of rapid progression and necrosis, these infections have reported mortality rates of up to 80%. In her poster discussion, Ms. Weddle said that the Centers for Disease Control and Prevention investigated 13 cases of Apophysomyces infections from injuries sustained during the tornado. Wounds should be excised of all debris and any nonviable tissue, and serial debridements might be required. She said that aggressive high-pressure wound irrigation should be avoided, and primary wound closure should be delayed. It is best to have a surgeon with trauma training. Broad antibacterial coverage with meropenem or piperacillin–tazobactam should be instituted promptly, and all debrided tissue should be cultured and tested for antimicrobial sensitivity, she advised.

There was no commercial funding for the study. Ms. Weddle and Dr. Alexander have disclosed no relevant financial relationships.

Infectious Diseases Society of America (IDSA) 49th Annual Meeting: Abstract LB-7. Presented October 22, 2011.


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