Journal List > J Korean Soc Transplant > v.24(1) > 1034326

Park: A Case of Successful Treatment of Cutaneous Aspergillosis with Voriconazole at the Low Cyclosporine Trough Level in a Renal Transplant

Abstract

Aspergillosis is a serious infectious complication with high mortality in transplant recipients. Voriconazole is a broad spectrum triazole antifungal agent, but it has a drug-drug interaction with immunosuppressants. Herein we report a case of the use of a small dose of cyclosporine (CsA) with coadministration of voriconazole. A 23 year old woman received a kidney transplant from a deceased donor. The initial immunosuppressant was tacrolimus, mycophenolate mofetil, steroids, and basiliximab. Thirty-two days after kidney transplantation, because of hemolytic uremic syndrome, she received Rabbit anti-human thymocyte immunoglobulin and plasmapheresis. Cyclosporine was used instead of tacrolimus. Three months after transplantation, she was admitted to the hospital because of an erythematous nodule on her trunk and a dry cough. Skin biopsy revealed an Aspergillus species and tissue culture showed that it was A. fumigatus. We treated her with itraconazole and subsequently with amphotericin B. Afterwards, her condition got worse. So we changed amphotericin B to voriconazole and a minimum dose of CsA (25 mg bid) at the peril of graft failure. Eventually, she recovered and maintained good graft function. The trough level of CsA ranged from 3.2 to 27.9 ng/mL.

References

1). Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2005; 18:44–69.
2). Hoffer FA, Gow K, Flynn PM, Davidoff A. Accuracy of percutaneous lung biopsy for invasive pulmonary aspergillosis. Pediatr Radiol. 2001; 31:144–52.
crossref
3). Husain S, Kwak EJ, Obman A, Wagener MM, Kusne S, Stout JE, et al. Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Am J Transplant. 2004; 4:796–802.
4). Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001; 32:358–66.
crossref
5). Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med. 2006; 173:707–17.
crossref
6). Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis. 2002; 34:563–71.
crossref
7). Cantarovich M, Besner JG, Barkun JS, Elstein E, Loertscher R. Two-hour cyclosporine level determination is the appropriate tool to monitor Neoral therapy. Clin Transplant. 1998; 12:243–9.
8). Knight SR, Morris PJ. The clinical benefits of cyclosporine C2-level monitoring: a systematic review. Transplantation. 2007; 83:1525–35.
crossref
9). Coto E, Tavira B. Pharmacogenetics of calcineurin inhibitors in renal transplantation. Transplantation. 2009; 88(3S):62–7.
crossref
10). Ford J, Hoggard PG, Owen A, Khoo SH, Back DJ. A simplified approach to determining P-glycoprotein expression in peripheral blood mononuclear cell subsets. J Immunol Methods. 2003; 274:129–37.
crossref
11). Goto M, Masuda S, Kiuchi T, Ogura Y, Oike F, Tanaka K, et al. Relation between mRNA expression level of multidrug resistance 1/ABCB1 in blood cells and required level of tacrolimus in pediatric living-donor liver transplantation. J Pharmacol Exp Ther. 2008; 325:610–6.
crossref
12). Crettol S, Venetz JP, Fontana M, Aubert JD, Ansermot N, Fathi M, et al. Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients. Pharmacogenet Genomics. 2008; 18:307–15.
crossref
13). Cattaneo D, Ruggenenti P, Baldelli S, Motterlini N, Gotti E, Sandrini S, et al. ABCB1 genotypes predict cyclosporine-related adverse events and kidney allograft outcome. J Am Soc Nephrol. 2009; 20:1404–15.
14). Barbari AG, Masri MA, Stephan AG, El Ghoul B, Rizk S, Mourad N, et al. Cyclosporine lymphocyte maximum level monitoring in de novo kidney transplant patients: a prospective study. Exp Clin Transplant. 2006; 4:400–5.
15). Falck P, Asberg A, Guldseth H, Bremer S, Akhlaghi F, Reubsaet JL, et al. Declining intracellular T-lymphocyte concentration of cyclosporine a precedes acute rejection in kidney transplant recipients. Transplantation. 2008; 85.
crossref
16). de Jonge H, Naesens M, Kuypers DR. New insights into the pharmacokinetics and pharmacodynamics of the calcineurin inhibitors and mycophenolic acid: possible consequences for therapeutic drug monitoring in solid organ transplantation. Ther Drug Monit. 2009; 31:416–35.
17). Saad AH, DePestel DD, Carver PL. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants. Pharmacotherapy. 2006; 26:1730–44.
crossref
18). Levêque D, Nivoix Y, Jehl F, Herbrecht R. Clinical pharmacokinetics of voriconazole. Int J Antimicrob Agents. 2006; 27:274–84.
19). Romero AJ, Le Pogamp P, Nilsson LG, Wood N. Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients. Clin Pharmacol Ther. 2002; 71:226–34.
crossref
20). Anglicheau D, Pallet N, Rabant M, Marquet P, Cassinat B, Méria P, et al. Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction. Kidney Int. 2006; 70:1019–25.
crossref

Fig. 1.
Erythematous subcutaneous nodules located on the trunk.
jkstn-24-35f1.tif
Fig. 2.
Thoracic computed tomography showing nodular lesions in the right lung parenchyma which was suggestive of fungal infection.
jkstn-24-35f2.tif
Fig. 3.
Skin biopsy demonstrating fungal hyphae with acute angle branching consistent with Aspergillus (hematoxylin-eosin staining; ×400).
jkstn-24-35f3.tif
Fig. 4.
The clinical course of patient demonstrates the good allograft function with low blood concentration of CsA. Abbreviations: CsA, cyclosporine A; b.i.d, bis in die; PDS, pre-dnisolone AmB, amphotericin B; s-Cr, serum-creatinin BT, body temperature.
jkstn-24-35f4.tif
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