Use of the Echinocandins (Caspofungin) in the Treatment of Disseminated Coccidioidomycosis in a Renal Transplant Recipient

We report a case of disseminated coccidioidomycosis in a renal transplant recipient treated successfully with caspofungin. A 51-year-old man who received a cadaveric renal transplant was admitted with a 3–4 week history of fever, chills, dry cough, and weight loss of 10–12 lbs. His immunosuppressive therapy included Prograf, CellCept, and prednisone. Vital signs included a temperature of 103.2°F, blood pressure of 102/78 mm Hg, pulse of 98 beats/min, respiratory rate of 28 breaths/min, and oxygen saturation of 80%. Clinical examination revealed a moderately ill-appearing man in mild respiratory distress with expiratory rales and crackles in both lung fields. The rest of the examination was unremarkable. Diagnostic studies included a chest x-ray, which showed evidence of multiple nodules without any mediastinal masses. A CT scan confirmed findings from the chest x-ray. Significant laboratory values included the following: serum glutamic oxaloacetic transaminase (SGOT), 88 IU/L; serum glutamic pyruvic transaminase (SGPT), 92 IU/L; alkaline phosphatase, 210 IU/L; bilirubin, 1.2 mg/dL; WBC, 12.0/mm3; hemoglobin, 9.6 g/dL; platelet count, 411 K/mm3; and serum creatinine, 1.9 mg/dL. Serum cocci titers were undetectable. The patient underwent a bronchoscopy and biopsy of a nodule, which revealed the presence of abundant Coccidioides immitis. Initially, the patient was treated with fluconazole. However, within 3 days the level of serum creatinine increased to 3.2 mg/dL, and the levels of SGOT and SGPT increased to 126 IU/L and 137 IU/L, respectively. Fluconazole was then switched to liposomal amphotericin at 3mg/kg/day. The patient remained febrile. Levels of SGOT and SGPT increased to 234 IU/L and 354 IU/L, respectively. The level of serum creatinine increased to 4.2 mg/dL. On day 7 of hospitalization, treatment with liposomal amphotericin B was switched to treatment with caspofungin. The patient was also treated with caspofungin (50 mg per day, iv) for a total of 4 weeks. Within the first 5 days after initiating therapy with caspofungin, the patient defervesced and started to feel better, with resolution of the respiratory distress, cough, and chills. His renal failure and abnormal liver function also began to improve over the next 2 weeks. Fever, shortness of breath, and cough had completely resolved when he was seen for followup 4 weeks later. He was subsequently treated with fluconazole 200 mg per day for the next 6 months. Followup during the next 6 months revealed normalization of renal insufficiency and liver function and showed reduction in the size and number of nodules visible on CT scan. His immunosuppressive therapy, although initially decreased at the time of acute infection, was increased to appropriate doses. A CT scan performed 6 months later showed minimal residual nodules and scar tissue. The serum cocci levels, however, remained undetectable during this illness. Followup 1 year later revealed no recurrence of the coccidiomycosis, although he is still being treated with suppressive fluconazole. This case has several interesting aspects. This appears to be the first case of a renal transplant recipient with coccidioidomycosis who has been treated successfully with caspofungin. The brief treatment with fluconazole and liposomal amphotericin was probably unlikely to have had sufficient activity against C. immitis to be effective as “real antifungals” in this case. There is some in vitro data on the activity of caspofungin in coccidioidomycosis [1,2–3]. The murine model of infection caused by C. immitis shows that caspofungin appears to be active, with the minimal effective concentration (MEC) being a better predicator of therapeutic outcome than the MIC. In this study [1], mice infected with 1 of 2 strains of C. immitis—each mouse having a MEC of 0.125 µg/mL, one having a MIC of 8 µg/mL, and the other having a MIC of 64 µg/L—responded equally well to treatment with caspofungin. The presence of multiple nodules in the lungs suggests this patient probably had severe coccidioidomycosis, which may be a reflection of infection prior to transplantation. The use of liposomal amphotericin in renal transplant patients with coccidioidomycosis could possibly result in progressive renal insufficiency and loss of the allograft; therefore, treatment with liposomal amphotericin may not always be useful. Alternative therapy with echinocandins may be an option in patients with coccidioidomycosis in whom azole therapy is contraindicated. Further studies evaluating this drug in nontransplant patients as well as transplant recipients is warranted. Conflict of interest. S.A.: No conflict.