Invasive fungal infections are a major cause of morbidity and mortality in pediatric oncology patients. A case of fomite-transmitted, disseminated coccidioidomycosis in a neutropenic 3-year-old boy is presented, highlighting several potential pitfalls in the management of neutropenic fever patients.
A 3-year-old Caucasian boy, undergoing treatment of bilateral Wilms' tumor, presented with a 1-day history of fever, diarrhea, and emesis in the setting of neutropenia. A regimen of empiric broad-spectrum antibiotics was administered and 5 days later expanded to include liposomal amphotericin B (Ambisome), as the physical examination did not suggest an etiology for his symptoms. Laboratory tests included a white blood cell count of <400/mm3 with an absolute neutrophil count of zero and 100% lymphocytes. Hemoglobin was 8.6 g/dL. The platelet count was 34,000/mm3. Liver associated enzymes were trending downward from a prior chemotherapy-associated hepatitis with alanine aminotransferase of 125 U/L and aspartate aminotransferase of 127 U/L. Multiple aerobic and anaerobic blood cultures, viral hepatitis studies and stool studies for C. difficile and bacterial culture were all negative.
The appearance of unique dermatologic findings, the finding on noncontrast chest computed tomography of bilateral pneumonia with left pleural effusion and a new pulmonary nodule, and sonographic diagnosis of typhlitis complicated his 14 day ICU course. Skin findings included an erythematous indurated plaque on his left, proximal posteriolateral thigh, and sharply demarcated erythema and edema of the distal fingers. Skin biopsy and bronchoscopy were considered, but not performed. Gradually, the dermatologic, gastrointestinal and pulmonary findings remitted. With clinical improvement and no other identifiable source of infection, the patient's antimicrobial therapy was discontinued after receiving 3 weeks of antibacterial and antifungal coverage.
The day following discontinuation of antimicrobial therapy, 1 of the patient's fungal blood cultures grew Coccidioides immitis, which was confirmed by rRNA probe. As the patient became more active, he had difficulty bearing weight and complained of left leg pain. Magnetic resonance imaging demonstrated a solid, enhancing lesion in the left vastus lateralis muscle. The primary service opted to manage conservatively without biopsy and continue empiric treatment with antifungal therapy, given patient improvement and consistency of the vastus lateralis lesion with Coccidioides immitis infection.
Detailed review of the patient's social history revealed that the patient lived in the Washington DC metropolitan area, and had never traveled to regions endemic for Coccidioides immitis. The patient's grandparents had visited from Arizona one week before the patient received chemotherapy, and 17 days before onset of symptoms. The parents reported specific contact with 2 of the Grandfather's items. The child helped carry an old, “dirty and dusty” suitcase, and played with a pair of everyday-use shoes that had been worn in an outdoor construction site at the grandparent's home. Upon learning of the diagnosis, the grandfather disposed of the shoes and suitcase, so microbiological testing could not be performed. We postulate that these items served as the mode of transmission of this geophilic fungi.
Having received 20 days of liposomal amphotericin B, the patient was continued on oral fluconazole (Diflucan) therapy. High dose fluconazole (12 mg/kg/d) was chosen because of the extent of this patient's illness, the need for ongoing chemotherapy, and its increased efficacy in severe disseminated and meningeal coccidioidomycosis.1 Acute and convalescent serum Coccidioides complement fixation titers were negative (<1:2). Six months after infection, the patient has undergone multiple rounds of chemotherapy without recurrence. The patient's therapy is planned for at least one year, although ongoing immunosuppression may require lengthening treatment.
Disseminated coccidioidomycosis in an immunocompromised host outside of endemic areas is rarely described in the published literature, and is typically caused by reactivation of past infection.2,3 Three such pediatric cases presenting in Germany, New York, and Illinois were discussed by MacDonald et al.2 The latter 2 patients died with underlying diagnoses of ALL and Hodgkin lymphoma, respectively, and with unknown exposures to C. immitis. The patient from Germany had lived his first two and a half years in Arizona, and was the first reported immunocompromised, pediatric patient to survive disseminated coccidioidomycosis caused by a reactivated, latent infection.
This patient represents an unusual, nonendemic case of fomite-transmitted, disseminated coccidioidomycosis. Transmission of Coccidioides immitis by fomites has been previously reported in only a limited number of publications.4–8 Dry C. immitis spores can remain viable for 6 months if stored at temperatures less than 37°C, and then transfer from inanimate objects to humans through inhalation.6 Albert and Sellers discuss a case of coccidoidomycosis in a Georgian man who probably acquired the disease from bales of cotton originating from the San Joaquin Valley. The authors also review other reports of transmission of C. immitis by fomites, including fruit, sisal, grain, oat hay and animal products.6 Rothman et al further emphasize the reality and danger of fomite transmission with a review of cases of coccidioidomycosis associated with exposure to Native American relics, cotton balls, dusty clothing, and powdered cloth waste termed “flock.”7 Desai et al present a more recent case series of patients with coccidioidomycosis. The etiology of one patient's infection is explained by an occupational history of exposure to fomites, including graphite, from the endemic region of Mexico.8
The case presented herein emphasizes the need of an extended and thorough history of potential exposures to opportunistic pathogens in pediatric oncology patients. This should include detailed travel, social and environmental history. Moreover, physicians should be cautious in narrowing the breadth of diagnostic and therapeutic interventions despite a negative history, if the clinical course is consistent with the disease. In the absence of a positive blood culture, invasive diagnostic procedures may be necessary because serologic tests, the most common way of diagnosing Coccidioides immitis, may be less accurate in immunocompromised patients.9 Clinicians should understand that coccidioidomycosis can present outside of its endemic areas and poses a serious risk of mortality in the pediatric oncology population. Timely diagnosis and treatment of disseminated coccidioidomycosis is critical for clinical improvement.
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