Amphotericin B/ciclosporin/foscarnet
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Crystal precipitation and granulomatous inflammation in multiple organs: case report A man in his early 40s developed crystal precipitation with granulomatous and fibrinous inflammation in multiple organs while receiving foscarnet [Foscavir] for cytomegalovirus (CMV) reactivation; he was also receiving ciclosporin and amphotericin B [durations of treatment to reaction onset not stated]. He later died. The man underwent bilateral lung transplantation in July 2007 at the age of 42. Due to an increase in CMV load, IV foscarnet [dosage not stated] was administered for 4 weeks. He was hospitalised in August 2008 (day 0) due to increased dyspnoea and CMV viral load. He had experienced a progressive decrease in lung function over the past 2 months. Bronchiolitis obliterans syndrome stage 2 was apparent. His medications included ciclosporin 60mg twice daily [route not stated] for immunosuppression and amphotericin B 10mg in 5mL, inhaled twice daily, for antifungal prophylaxis. Ganciclovir was started, but a ganciclovir-resistance mutation was detected after 9 days. Intravenous foscarnet 3600mg twice daily (90 mg/kg/day), infused over 2 hours, was started. His serum creatinine level was normal until day 45, and a 4-day break of foscarnet was applied. His condition was further complicated by a large haematoma, which occurred during treatment with heparin. The man’s serum creatinine level decreased during the foscarnet break and treatment was restarted at 3600mg twice daily. An attempt to reduce the dosage to 3600mg once daily was abandoned to control viral load. On day 148, foscarnet was reduced to 3600mg daily and then eventually withdrawn. He died 5.5 months after the initial deterioration in lung function and CMV reactivation. Autopsy disclosed crystal structures surrounded by granulomatous inflammation in both lungs and the epi- and pericardium, as well as crystal nephropathy, acute tubular necrosis, and acute fibrinous endocarditis. Author comment: "An important question is the causality of the observed crystallizations and foscarnet therapy. Upon applying the Naranjo scale questionnaire, a score of 5 (probable adverse drug reaction) is obtained. . . Furthermore, synergistic toxic effects of the drugs foscarnet/cyclosporine and foscarnet/amphotericin B . . . may have contributed to the organ dysfunction observed." Tischler V, et al. Crystal precipitation and granulomatous inflammation in multiple organs after foscarnet therapy in a lung transplant recipient. Journal of Heart and Lung Transplantation 31: 1037-1040, No. 9, Sep 2012. Available from: URL: 803078549 http://dx.doi.org/10.1016/j.healun.2012.05.008 - Switzerland
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Reactions 20 Oct 2012 No. 1424
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