|Hepatic safety of caspofungin during treatment of invasive fungal diseases in elderly patients
WANG Li-li, ZHUGE Xin, XIAO Guang-hui , ZHANG Yun
|WANG Li-li Department of Geriatrics, General Hospital of Tianjin Medical University, Tianjin 300052, China; ZHUGE Xin Department of Geriatrics, General Hospital of Tianjin Medical University, Tianjin 300052, China; XIAO Guang-hui Department of Geriatrics, General Hospital of Tianjin Medical University, Tianjin 300052, China; ZHANG Yun Department of Geriatrics, General Hospital of Tianjin Medical University, Tianjin 300052, ChinaCorrespondence to: XIAO Guang-hui Department of Geriatrics, General Hospital of Tianjin Medical University, Tianjin 300052, China (Tel:86-22-60361151 Email:firstname.lastname@example.org )|
|No abstract available
To the Editor: Caspofungin is a new class of antifungal agents (echinocandins) for the treatment of fungal infections. By noncompetitive inhibition β-(1,3)-D-glucan synthase, it can destroy the glucan synthesis of the fungal cell wall and produce bactericidal activity. β-(1,3)-D-glucan does not exist in mammalian cells; thus the toxicity of this drug could be avoided.1 In a recent meta analysis on tolerance and liver toxicity of antifungal agents, Wang et al2 showed that caspofungin had less side effects and better hepatic safety than the other antifungal agents. The pooled risks of treatment discontinuation due to adverse reactions were above 13.4% for amphotericin B, whereas they were 3.8% for caspofungin. Furthermore, 14.1% of amphotericin B users had elevated serum liver enzyme levels, whereas 7.0% of caspofungin. However, there was no data related the hepatic safety of caspofungin in elderly patients.
Recently we performed a retrospective analysis to investigate hepatic safety of caspofungin during treatment of invasive fungal diseases (IFD) in elderly patients. Fifty patients above 80 years old with IFD who were treated with caspofungin in our department from May 2007 to May 2010 were included in this analysis. Of these 50 cases, 16 were proven in diagnosis, 18 were probable and 16 were possible. In the 34 proven and probable cases, Candida albicans infection was 41.2% (14/34 cases), with the effective rate of 64.3% (9/14 cases) by caspofungin; non-Candida albicans infection was 58.8% (20/34 cases), with the effective rate of 70% (14/20 cases) by caspofungin.
We evaluated liver damage degree according to the classification of medicamentous liver lesion issued by WHO3 before and after the treatment by caspofungin. The classification was as follows. (1) Mild liver damage: Patients with normal liver function before treatment had alanine aminotransferase (ALT) ranging from 1.25 to 2.5 times the upper limit of normal value, or total bilirubin (TBil) from 1.0–1.5 times the upper limit of normal value during the treatment. Patients with abnormal liver function before treatment had the increase of ALT or TBil between 0.1–1.0 times the upper limit of normal value during the treatment. (2) Moderate liver damage: Liver function indexes were between the mild and the severe range. (3) Severe liver damage: Patients with normal liver function before treatment had ALT more than 5.0 times the upper limit of normal value, or TBil more than 2.5 times the upper limit of normal value during the treatment. Patients with abnormal liver function before treatment had the increase of ALT or TBil value more than 2. 0 times the upper limit of normal value during the course of treatment. Further liver damage referred to the condition that the treatment aggravates the liver damage.
Before the treatment, 21/50 cases (42%) had abnormal liver function, 18 had increased ALT, averaging (76.83±33.69) U/L. Twelve cases had increased TBil, averaging (43.02±31.95) μmol/L. During the treatment, among the 21 cases which had already showed abnormal liver function before, 3/21 (14.3%) had further liver damage including 1 case of mild liver damage and 2 of severe liver damage. In the 29 patients with normal liver function before, 2/29 (6.9%) had liver damage during treatment, both of them were mild. In the 5 patients with abnormal liver function or further damage during the treatment, one had mild liver damage on 26th day and died on 34th day, the abnormal liver function might be related to caspofungin. The remaining 4 cases had deterioration of liver function, whereas might be irrelevant to caspofungin. There was no case showing that the abnormal liver function or further damage was definitely related to or likely related to caspofungin. In a multi-center, double-blind clinical trial carried out on adult patients infected by invasive candidiasis and treated by caspofungin with a high dose (150 mg/d) and standard dose (first day of 75 mg/d, followed by 50 mg/d), the increases of ALT were 2.0% in both group following administration.4 In another study,5 caspofungin was used to treat fungal infection after liver transplantation. Therefore, we consider that caspofungin has good hepatic safety in elderly patients. But we still need to monitor the liver function in the course of treatment, and use hepatoprotective agents if necessary.
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2.Wang JL, Chang CH, Young-Xu Y, Chan KA. Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. Antimicrob Agents Chemother 2010; 54: 2409-2419.
3.WHO ART adverse drug reaction terminology. Geneva: WHO Collaborating Center for Drug International Monitoring; 1979.
4.Betts RF, Nucci M, Talwar D, Gareca M, Queiroz-Telles F, Bedimo RJ, et al. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 2009; 48: 1676-1684.
5.Shi XJ, Lü SC, He L, Lu F, Liang YR, Luo Y, et al. Diagnosis and treatment of fungal infection after liver transplantation. Chin Med J 2011; 124: 1015-1017.