A 38-year-old patient, diagnosed with FAD in 1990, was put on hemodialysis since 1999 due to end-stage renal insufficiency and received a kidney transplant in 2007. Renal function did not recover immediately after renal transplantation, and sequential renal biopsies documented early rejection. For this reason, the patient was put on high dose oral Cyclosporine (150 mg twice daily) and was treated with high dose steroids without benefit. Everolimus (2.5 mg/daily) was therefore added and steroids tapered. Renal function improved 4 months after transplantation; hemodialysis was continued until that time. Due to relapsing decreases in renal function after each attempt to interrupt Everolimus, the association of these drugs could not be stopped ever since, although Cyclosporine could be reduced to 100 mg twice daily after 1 year. Levels of both drugs were frequently monitored, falling in the therapeutic range throughout follow-up without further adjustments. Additional drugs prescribed after transplantation were: Cardioaspirin, 100 mg/daily; Allopurinol 100 mg/daily; Carvedilol 25 mg/daily, Furosemide 25 mg/daily, Replagal® (Agalsidase α) 3 times/weekly until hospitalization. During hemodialysis, he suffered several traumatic and ischemic bone lesions; a Dual-energy X-ray absorptiometry (DEXA) scan, performed in 2006, revealed diffuse osteopenia, in spite of intact parathyroid glands and normal parallel parathormone levels.
In March, 2008, the patient was assisted in our ward due to a large pulmonary infiltrate and treated with i.v. Amoxicillin/Clavulanate and Fluconazole. The next month he was hospitalized in the orthopedic ward of Ortona Hospital (Chieti, Italy) because of an ulcerative lesion at his right heel with redness, swelling and the presence of necrotic tissue (Figure ). He was apyretic, with normal white and red cell counts and near-normal renal function tests, the estimated glomerular filtration rate ranging between 56 and 83 mL/min/1.73 m2 during hospitalization, as calculated using the CKD-EPI formula. Standard Rx scans of his right foot documented a detachment of a wide fragment of his cortical spongiosa in the lateral malleolus (Figure ). Cultural examination of wound essudates did not yield any isolate. The patient underwent extensive debridement of necrotic tissues and was put on hyperbaric oxygen therapy and Teicoplanin 200 mg i.v. for 4 weeks, without benefit. The dose of Teicoplanin was decided by the assisting orthopedists at that time, the fear of renal overload causing patent underdosing. In July, 2008, the patient was again evaluated in the Infectious Disease Unit of Pescara General Hospital for persistent fever and localized pain. Inflammation indexes were remarkably altered. A second debridement procedure was requested; cultures of debris grew several Streptococcus agalactiae isolates. To avoid renal overload, treatment with i.v. Tigecycline, 50 mg daily twice daily, together with Metronidazole, 500 mg three times daily, was prescribed. The patient was still assisted at the orthopedic ward of Ortona Hospital after consultation; a double daily access was arranged for him as outpatient, and the prescription of Metronidazole reduced to 500 mg twice daily. A slight local improvement was noted, but relapsing fever ensued after 30 days of treatment. ESR rose to 112 mm, CRP to 85 mg/L. A focused CT scan of his right heel confirmed the presence of a fracture of his right calcaneus with fragmentation and irregular thickening of fracture edges, tarsal bone loss, gaseous components in neighboring soft tissues, abnormal spacing between calcaneus and cuboid. A few days later, the patient underwent a third debridement procedure. Culture specimens grew MRSA isolates, sensitive to Vancomycin (MIC = 0.5 mg/L) and Daptomycin. Based on these findings, i.v. Daptomycin (4 mg/kg daily) was started, and administered for 4 weeks. CRP levels had dropped to 56 mg/L at this time. CPK levels during treatment were frequently monitored and found unmodified. At the end of treatment, deep palpation of the lesion did not cause pain; accompanying skin lesions had resolved; liver and renal function tests were normal, ESR was 50 mm and CRP 6,5 mg/L. Standard Rx scans and focused control tomography of the heel documented a reduction of bone resorption at affected segments, indicating effective control of osteomyelitis (Figure ). The patient was discharged, and antibiotic therapy was continued at home with oral Trimetoprim/Sulfamethoxazole (1 double strength tablet twice daily) and Doxycycline (100 mg twice daily) for 4 additional weeks, with frequent monitoring of hematological parameters, immunosuppressant drugs and renal function tests. No signs of toxicity were noted; the estimated value of GFR ranged between 63 and 85 mL using the CKD-EPI formula. At the end of treatment, the patient could walk with the support of crutches. In February, 2009, a complete normalization of inflammation indices was documented.
3,5
