Immunosuppressants/antibacterials interactions

Abstract

administration of tacrolimus with flucloxacillin and prednisolone. The man, who had left ventricular assist device X S Immunosuppressants/antibacterials (LVAD), received oral flucloxacillin 2g every 4h for MSSA interactions bacteraemia from a presumed LVAD drive line infection. He underwent orthotopic heart transplantation with LVAD Subtherapeutic drug concentrations: 4 case reports removal. He received oral tacrolimus 3mg three times a day, A case series described four men aged 32–63 years, who prednisolone 1 mg/kg/day, tapered by 5 mg/day to 20 mg/day exhibited subtherapeutic concentration of everolimus or and mycophenolate mofetil as immunosuppressive therapy. tacrolimus during concomitant administration of flucloxacillin Target trough concentration of tacrolimus was 10–15 μg/L. At with everolimus or tacrolimus. Additionally, in two of the four the time of transplantation, oral flucloxacillin was changed to men, the concentration of tacrolimus decreased secondary to IV flucloxacillin 2g every 4h, which was planned to be stopped concomitant administration of tacrolimus with prednisolone after total 14 days of therapy. However, on day 3 after the or methylprednisolone [not all routes stated; duration of transplantation, the trough concentration of tacrolimus was treatments to reaction onsets not stated]. 3.2 μg/L. Despite an increase in the dose of tacrolimus, the Case 1: A 63-year-old man exhibited subtherapeutic concentration remained subtherapeutic. On day 6 after the concentration of everolimus and tacrolimus during transplantation, biopsy showed grade 2R rejection. He concomitant administration of flucloxacillin with everolimus received pulse corticosteroid therapy with and tacrolimus: The man underwent orthotopic heart methylprednisolone, and flucloxacillin was discontinued. transplantation and received tacrolimus 1.5 mg two times a Following flucloxacillin discontinuation, the biopsy showed day, everolimus 2mg two times a day, prednisolone and grade 1R rejection. After 14 days of flucloxacillin cessation, the mycophenolate mofetil as immunosuppressive therapy. Target target concentration for tacrolimus was achieved. A probable trough concentration of tacrolimus was 5–10 μg/L and drug interaction between flucloxacillin and tacrolimus was everolimus was 3–8 μg/L. After 25 days of transplantation, he considered. Additionally, prednisolone reduced tacrolimus developed methicillin-sensitive Staphylococcus aureus serum concentration. The Naranjo scale showed a probable infectious (MSSA) empyema and sternal wound infection. (score 6) causal relationship between flucloxacillin and the Hence, he started receiving IV flucloxacillin 2g every 6h. Prior reduction in tacrolimus trough concentrations. to flucloxacillin initiation, biopsies showed no signs of Case 4: A 55-year-old man exhibited subtherapeutic rejection. On initiation of flucloxacillin, the trough concentration of tacrolimus during concomitant concentration of tacrolimus was 8.3 μg/L and of everolimus administration of tacrolimus with flucloxacillin and was 6.9 μg/L. However, after 12 days of flucloxacillin therapy, methylprednisolone: The man orthotopic heart transplantation the trough concentration of tacrolimus and everolimus and received tacrolimus 4mg two times a day, prednisolone reduced. On day 36 following the transplantation, biopsy and mycophenolate mofetil as immunosuppressive therapy. showed grade 2R rejection. Despite pulse corticosteroid Target trough concentration of tacrolimus was 10–15 μg/L. therapy with methylprednisolone and increase in everolimus After 19 days of the transplantation, he developed MSSA and tacrolimus doses, his plasma trough concentrations of bacteraemia secondary to a sternal wound infection. Hence, tacrolimus and everolimus remained subtherapeutic. On he started receiving IV flucloxacillin 2g every 4h. On initiation day 53 after transplantation, biopsy showed persistent of flucloxacillin, the trough concentration of tacrolimus was grade 2R rejection. Treatment with flucloxacillin was 15.9 μg/L. and biopsy showed no evidence of rejection. discontinued. After 8 days of flucloxacillin discontinuation, the However, on day 4 of the flucloxacillin initiation, trough trough concentrations of tacrolimus and everolimus increased concentration of tacrolimus decreased. Despite increasing the to therapeutic range. A probable drug interaction between dose of tacrolimus to 8mg twice a day, the trough flucloxacillin and everolimus and tacrolimus was considered. concentrations remained subtherapeutic. On day 33, the The Naranjo scale showed a probable (score 6) causal biopsy showed grade 2R rejection. He received pulse relationship between flucloxacillin and the reduction in corticosteroid therapy with methylprednisolone 1g on day , tacrolimus and everolimus trough concentrations. followed by 500mg on day 2 and day 3. However, the Case 2: A 54-year-old man exhibited subtherapeutic following day after initiation of IV methylprednisolone, his concentration of tacrolimus during concomitant tacrolimus trough concentration decreased further. On day 39, administration of flucloxacillin with tacrolimus: The man biopsy showed grade 1R rejection with persistent underwent orthotopic heart transplantation and received subtherapeutic tacrolimus trough concentrations. On day 51, tacrolimus 2mg two times a day, prednisolone and the tacrolimus trough concentration was achieved. Following mycophenolate mofetil as immunosuppressive therapy. Target discontinuation of flucloxacillin, the concentration of trough concentration of tacrolimus was 10–15 μg/L. Fourteen tacrolimus became supratherapeutic. The dose of tacrolimus days after the transplantation, he developed Staphylococcus was reduced and after 7 days of flucloxacillin cessation, the aureus bacteraemia. Hence, he started receiving IV therapeutic tacrolimus trough concentration was achieved. A flucloxacillin 2g every 6h. Prior to the flucloxacillin initiation, probable drug interaction between flucloxacillin and biopsies showed no signs of rejection. On initiation of tacrolimus was considered. Additionally, methylprednisolone flucloxacillin, the trough concentration of tacrolimus was reduced the tacrolimus serum concentration. The Naranjo 8 μg/L. Thereafter, a decrease in concentration of trough scale showed a probable (score 6) causal relationship between concentration of tacrolimus was noted. Despite an increase in flucloxacillin and the reduction in tacrolimus trough the dose of tacrolimus, his trough concentration of tacrolimus concentrations. continued to be low. Seven days after initiation of Author comment: Herein we report four cases of flucloxacillin, biopsy showed grade 2R rejection. Treatment probable drug interactions between tacrolimus and with diltiazem was initiated to increase the concentration of everolimus with flucloxacillin in orthotopic heart transplant tacrolimus, and flucloxacillin was discontinued. Additionally, recipients. Prednisolone is thought to reduce tacrolimus he received pulse corticosteroid therapy with serum concentrations. . .This did not occur in Cases 1, 2 and methylprednisolone. Five days after flucloxacillin 4. In Case 3, the concurrent tapering of steroids and the discontinuation, the trough concentration of tacrolimus commencement of IV flucloxacillin on Day 0 of transplant increased to 20.1 μg/L. On day 29, the biopsy showed make this more difficult to interpret . grade 0R rejection. A probable drug interaction between flucloxacillin and tacrolimus was considered. The Naranjo Gellatly RM, et al. Case series of immunosuppressant drug interactions with