Antibacterials/immunosuppressants/voriconazole

A 26-year-old male lung-transplant recipient developed Aspergillus fumigatus osteomyelitis during post-transplant immunosuppression and antibacterial therapy; he also developed reversible posterior leukoencephalopathy attributed to tacrolimus, and liver dysfunction during treatment with voriconazole [routes not stated; not all treatment durations and times to onset stated].

The man had a history of cystic fibrosis and was CMV seropositive prior to transplantation; perioperative complications included heart arrest secondary to methylprednisolone hypersensitivity. His post-transplant immunosuppression comprised ciclosporin at target trough serum concentrations of 300-350 �g/L, twice daily mycophenolate 1.5g [salt not stated], daily dexamethasone 1.5mg, and basiliximab [Simulect; dosage not stated] as ciclosporin replacement on days 1 and 5. On post-transplant day 15, ciclosporin was switched to tacrolimus at target serum concentrations of 10-15 �g/L; he also received prophylactic valganciclovir, amphotericin B, and twice weekly cotrimoxazole [trimethoprim/sulfamethoxazole; dosage not stated] for Pneumocystis jiroveci (P. carinii) prophylaxis. Candida tropicalis was isolated from pleural fluid after transplantation, and fluconazole was added on day 14. He subsequently developed Pseudomonas aeruginosa and Candida albicans organising pneumonia, which was treated with meropenem, ciprofloxacin and fluconazole [dosages not stated]. He presented in status epilepticus 3 months post-transplant, and required intubation. He had poorly-controlled diabetes mellitus, and a blood sugar level of 1.2 mmol/L. Tacrolimus-induced reversible posterior leukoencephalopathy was diagnosed. His hypoglycaemia was corrected, tacrolimus was switched back to ciclosporin [dosage not stated], and he was admitted to an ICU. His condition improved and he was extubated. He then reported experiencing pain, heat and swelling in his right shoulder for 1 week. Fluid aspiration yielded A. fumigatus.

The man started receiving voriconazole [dosage not stated] and caspofungin. Increased vascularity and radiotracer uptake were evident on bone scan. A cranial MRI confirmed tacrolimus-induced reversible posterior leukoencephalopathy. Ten days after the initial presentation, CT findings were suggestive of septic arthritis and osteomyelitis. His CRP level had decreased, but deterioration of his liver function prompted a switch from voriconazole to posaconazole after 13 days of therapy. He reported increased pain in his right shoulder and associated movement restrictions 20 days after presentation, and developed fever and CRP elevations. Radiology findings had worsened. His ciclosporin dosage was then decreased, targeting a 2-hour post-dose concentration of 300-400 [units not stated], and amphotericin was added to his therapy. His right shoulder was washed out, and he underwent synovectomy of the biceps sheath. Daily hyperbaric oxygen was initiated on day 23. MRI findings had improved on day 35. Amphotericin, caspofungin and meropenem were discontinued on hospital day 46, and he was discharged; hyperbaric oxygen and posaconazole were continued. He presented with osteomyelitis recurrence in his right shoulder 6 months after the initial presentation, and underwent open debridement of the humeral head and amphotericin cement bead insertion. Posaconazole was again replaced with voriconazole, without significant worsening of his liver function. At 15 months after fungal osteomyelitis onset, he had fully recovered.Author Comment"Risk factors for invasive aspergillosis after tnrasplantation include; dose and legth of immunosupperssive therapy, presence of vasculr complications, neutropenia, defective phagocytes, allograft rejection, diabetes, renal failure, malignancy, bacterial and CMV infections, use of antibiotics, parenteral nutrition, and dialysis."

[Reference]

1. Allsopp T, Chandratilleke MG, Kermeen F, Chambers DC, Hopkins P.Successful management of aspergillus fumigatus osteomyelitis in a lung transplant recipient. Internet Journal of Pulmonary Medicine 12: No. 1, 2010 - Australia.