NDT Advance Access originally published online on January 8, 2007
Nephrology Dialysis Transplantation 2007 22(5):1487-1488; doi:10.1093/ndt/gfl749
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Caspofungin in kidney transplant recipients with refractory invasive candidiasis
Email: veroux{at}unict.itSir,
Fungal infections have been reported frequently in renal transplant recipients [1,2], and they were associated with greatly decreased patient survival [1,3,4].
The treatment of mucosal candidiasis and candidaemia has evolved in previous years: because of its infusion-related toxicity and nephrotoxicity, amphotericin B has been gradually replaced by fluconazole, which has less toxicity and a broader spectrum of activity [5]. However, invasive candidiasis such as oropharyngeal, oesophageal and urogenital candidiasis, are relatively less susceptible to fluconazole [5].
Caspofungin is the first of three new echinocandin antifungal agents to become available for the treatment of invasive mycoses and systemic candidiasis in patients refractory to or intolerant to other antifungal therapy [5,6], and it is more effective than amphotericin B in the treatment of refractory oropharyngeal and oesophageal candidiasis [7].
This study investigates the incidence of invasive candidiasis in a population of 245 kidney transplant recipients, performed in a 3-year period, and evaluates the use of caspofungin for the treatment of azole-refractory oesophageal and urinary candidiasis.
Twenty-two patients (8.9%) presented with an oesophageal candidiasis, while seven (2.8%) presented with a urogenital candidiasis (two with pyelonephritis, five with bladder infection) (Table 1).
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All patients with clinical signs of oesophageal candidiasis underwent an esophagogastroduodenoscopy with biopsy of the lesion. Only histologically proven oesophageal candidiasis were considered in this study. All patients with genital candidiasis underwent a topical treatment with econazole 150 mg for 3 days. None of the patients with urogenital candidiasis had urinary catheter at time of infection.
Fungal infections were more common in tacrolimus-treated patients and in those who experienced an acute rejection or a CMV infection, and the majority of fungal infection developed within 3 months post-transplantation. This could be easily related to the higher level of immunosuppression that could be expected in these patients. Moreover, patients with diabetes as cause of end-stage renal disease and recipients with post-transplant diabetes mellitus are at high risk of fungal infections (Table 2).
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Fluconazole was used as a first-line therapy in all patients with a proven fungal infection at a dose of 100–200 mg/day i.v. based on renal functionality; caspofungin was administered i.v. once daily with a loading dose of 70 mg, followed by 50 mg/day.
A refractory fungal infection was defined as an infection which did not improve with a 7–10 day fluconazole therapy with a total received dose of 1–2 g.
Thirteen patients with oro-pharyngeal and oesophageal candidiasis (59%) and four patients (57%) with a urogenital candidiasis did not improve after a treatment with azole. A treatment with caspofungin was started in all patients. A complete relief of symptoms was observed in all patients, after a median time of 12 days (range 3–19 days) of treatment.
The interaction of caspofungin with the immunosuppressive regimen was low, and only three patients in the tacrolimus group required an increase in immunosuppression dosage.
All patients tolerated well the administration of caspofungin; one patients showed a mild cephalea, while two patients, with a pre-existent hepatitis B and C, showed a mild increase in bilirubin and aminotransferase levels.
One patient with an oesophageal candidiasis recurred and was switched to amphotericin B therapy, and lost his graft because of discontinuation of immunosuppression.
There were no other recurrence of candidiasis in the group of patients treated with caspofungin at a median follow-up of 14 months (range 3–32 months).
The incidence of oesophageal candidiasis in renal transplant recipients is not well documented. Gupta et al. [3] reported a 10.5% incidence among 265 kidney transplant recipients, with 25% of unsuccessful treatment and 10.7% of mortality due to disseminated candidiasis; Abbott et al. [2] in their large series of hospitalizations of kidney transplant recipients for fungal infection, found 21.5% of patients with oesophageal candidiasis and 10.1% of patients with a urogenital candidiasis. Factors significantly associated with hospitalizations for fungal infection were recipient and donor age, cadaveric donation, older recipient age, diabetes as cause of end-stage renal disease, donor CMV seropositivity, pre-transplant dialysis, rejection, maintenance tacrolimus and antibody induction therapy [2].
Despite an improvement of antifungal prophylaxis, renal transplant patients remain at high risk for invasive fungal infections, and the correct treatment is often challenging. Our study showed that resistance to azole is now becoming common, and newer antifungals, which have a broader spectrum of activity that includes fluconazole-resistant Candida spp. should be considered for the treatment of refractory oropharyngeal candidiasis.
Although the number of patients was limited, the results of this study indicate that caspofungin is an effective, well-tolerated alternative for difficult-to-treat and azole-refractory candida infections in kidney transplant recipients. The high costs of the drug limit the use of caspofungin as first-line antifungal therapy, reserving its use to those recipients who underwent an unsuccessful therapy with azole.
Conflict of interest statement. None declared.
Department of Surgery
Transplantation and Advanced Technologies
Organ Transplant Unit
University Hospital of Catania
References
- Schmidt A and Oberbauer R. (1999) Bacterial and fungal infections after kidney transplantation. Curr Opin Urol 9:45–49.[CrossRef][Medline]
- Abbott KC, Hypolite I, Poropatich RK, et al. (2001) Hospitalizations for fungal infections after renal transplantation in the United States. Transpl Infect Dis 3:203–211.[CrossRef][Medline]
- Gupta KL, Ghosh AK, Kochhar R, Jha V, Chakrabarti A, Sakhuija V. (1994) Esophageal candidiasis after renal transplantation: comparative study in patients under different immunosuppressive protocols. Am J Gastroenterol 89:1062–1065.[Web of Science][Medline]
- Chigh KS, Sakhuia V, Jain S, et al. (1993) High mortality in systemic fungal infections following renal transplantation in third-world countries. Nephrol Dial Transplant 8:168–172.
[Abstract/Free Full Text] - Villanueva A, Gotuzzo E, Arathoon E, et al. (2002) A randomized double-blind study of caspofungin versus fluconazole for the treatment of oesophageal candidiasis. Am J Med 113:294–299.[CrossRef][Web of Science][Medline]
- Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. (2006) In vitro susceptibilities of Candida spp. To Caspofungin: four years of global surveillance. J Clin Microbiol 44:760–763.
[Abstract/Free Full Text] - Arathoon EG, Gotuzzo E, Noriega LM, Berman RS, DiNubile MJ, Sable A. (2002) Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother 46:451–457.
[Abstract/Free Full Text]
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