Apophysomyces Elegans Infection Associated With Cactus Spine Injury in an Immunocompetent Pediatric Patient

Zygomycosis refers to an infection resulting from molds belonging to the orders Mucorales and Entophthorales, including Absidia, Rhizomucor, Rhizopus and Saksenaea.1 These organisms are ubiquitous in the environment and can be readily isolated from soil. They can cause rhinocerebral, pulmonary, gastrointestinal, cutaneous or disseminated infection. Zygomycosis is often life-threatening and hosts are usually compromised by diabetes mellitus, malignancy or immunosuppressive therapy. Zygomycosis has also been reported in neonates, burn patients, drug abusers and patients with hepatic or renal insufficiency. Only rarely has zygomycosis been reported to occur in healthy patients. We describe a previously healthy pediatric patient who, after cactus spine injury, underwent extensive tissue debridement, nephrectomy and amphotericin B treatment because of Apophysomyces elegans infection. Case report. A healthy 6-year-old boy fell onto a cholla cactus and retained several dozen spines in his left arm and flank. The child's father removed the spines. During the next several days severe ecchymoses developed at the sites of injury. The ecchymotic areas were not thought to be of fungal origin and were not biopsied. One week after the initial injury the patient developed severe abdominal pain, resulting in surgical evaluation and appendectomy. The appendix was normal according to the pathology report. A computerized tomography scan revealed that the left kidney was enlarged, nonperfused and nonviable. Surgical exploration showed the left kidney to be ischemic, with no appreciable flow through the renal blood vessels. Left nephrectomy was performed and ligation of the renal vessels revealed thrombosis. The patient was discharged home 3 days later in stable condition. Histopathology of kidney sections showed the presence of broad, nonseptate (coenocytic) hyphae characteristic of the zygomycetes. One week later he presented with persistent abdominal pain and discharge at the surgical site. The microbiology report revealed that a mold resembling a zygomycete was growing from the culture of the left kidney. Isolates recovered from culture of renal tissue and exudate from a wound site were confirmed as A. elegans after inducement of sporulation via the agar flotation method.1 Infectious disease and immunology consultations were obtained. A treatment of long term intravenous amphotericin B, vigorous surgical debridement and irrigation of the wound with amphotericin B was initiated. During each of the first seven debridements, there was gross evidence of infection in the peritoneal space, including necrotic tissue and gray exudate. The infection involved the spleen, left diaphragm, colon and periaortic tissue. On the 23rd hospital day therapy was changed to liposomal amphotericin B (Abelcet®) to achieve higher tissue concentrations with less potential toxicity.2-4 His remaining kidney functioned normally throughout hospitalization, with normal blood urea nitrogen, creatinine and glomerular filtration rate. There was no evidence of a preexisting immunocompromised state, and extensive immunologic tests were normal. HIV testing was negative and quantitative immunoglobulin and T cell lymphocyte typing studies were normal, as were complement studies and skin testing. No neoplasm, diabetes mellitus or other risk factors were found. His hospital course was complicated by a bacterial central venous catheter infection, which resolved with antibiotic therapy and removal of the catheter. By the 20th hospital day repeated wound fungal cultures revealed no growth, and evidence of infection was no longer grossly visible intraoperatively. The patient underwent 10 debridements. He was discharged home on the 39th hospital day and returned 3 times per week for liposomal amphotericin B infusions for an additional 5 weeks. He received a cumulative dose of 8 mg/kg amphotericin B and 100 mg/kg liposomal amphotericin (Abelcet®), for a total equivalent amphotericin B dose of 28 mg/kg. This does not include the amphotericin used to irrigate the wound during his surgeries. The efficacy of applying amphotericin B-soaked dressings within the wound is unknown, but the practice appeared to result in no complications. The patient's wound healed by delayed closure of 2 granulating surfaces, and he returned to his baseline state of health. Amphotericin B was the only antifungal medication required. Discussion.A. elegans was originally isolated from soil samples collected in a mango orchard in India.5 The organism grows well at temperatures up to 42°C, and reported cases of infection tend to occur in areas with warm climates.6 Colonies in vitro are initially white, then become creamy white to buff with age and consist of broad, coenocytic hyphae. The organism does not sporulate well on routine fungal media but can be induced to sporulate by the water flotation method.1, 7, 8 A. elegans produces sporangiophores arising from rhizoids as well as swollen, funnel-shaped apophyses and pear-shaped (pyriform) sporangia filled with spores.1 It is further distinguished by a thick walled, darkly pigmented zone below the apophysis, as well as a foot cell at the union of the sporangiophore and mycelium. The importance of A. elegans as a pathogen in immunocompetent adults is becoming increasingly recognized.6, 9-13 As suggested by Weinberg et. al.13 this may be the result of the thermophilic nature of the organism, which allows it to grow in the deep tissues of febrile patients. The fungi gain entry primarily through traumatized skin, including cases in postoperative patients and in burn patients. The trauma can be minor, as in the cases caused by intramuscular injection9 or insect bites.13 This is the first reported case involving A. elegans infection after trauma from a cactus spine, although a case of zygomycosis secondary to Saksenaea vasiformis was thought to be secondary to thorn injury.14 Cactus spine injuries are more classically associated with a chronic granulomatous reaction. This reaction may be secondary to an allergic response to the fungal organism Alternaria, which is found on up to two-thirds of cactus specimens.15-17 Zygomycosis is classically described in terms of rhinocerebral, pulmonary, gastrointestinal, cutaneous or disseminated involvement. The case described here most closely resembles cutaneous transmission with local spread. The initial inoculation was through cutaneous tissue, although the patient's disease progressed to the point of extensive retroperitoneal involvement, including renal and vascular structures. Renal involvement of zygomycosis has only previously been seen in disseminated forms,7, 18 or in a few cases of isolated renal involvement.19-21 Thomson et al.22 describe isolated, yet severe clinical zygomycosis of the gastrointestinal tract and suggest that there is a clinical and histologic spectrum of severity of zygomycosis. They suggest that an infiltrative, histologic category exists that represents severe clinical disease. This case is analogous in that it represents cutaneous inoculation with local spread of the infection. Zygomycosis in the pediatric population is almost exclusively seen in patients with associated immunocompromising conditions. In 18 cases treated at Texas Children's Hospital between 1954 and 1984, only one patient had no underlying condition.23 The patient described here is unusual in that he is immunocompetent, and he is the youngest reported patient with zygomycosis secondary to A. elegans. Infection caused by the zygomycetes and by Apophysomyces or Saksenaea is to be considered in any patient who has a progressive, necrotic lesion, especially after a thorn injury or other penetrating trauma. A rapid presumptive diagnosis may be made by microscopic observation of coenocytic, broad hyphae in tissue or exudate, although a definitive identification may be delayed because of the frequent failure of the organism to sporulate on standard fungal media. Therefore a high index of suspicion is needed, and rapid surgical debridement in combination with amphotericin B therapy may be life-saving in these cases. Sonja R. Burrell, M.D. Daniel J. Ostlie, M.D. Michael Saubolle, Ph.D. Michael Dimler, M.D. Stephen D. Barbour, M.D., Ph.D.