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Cancidas

Caspofungin is an antifungal drug, the first of a new class termed the echinocandins. It shows activity against infections with Aspergillus and Candida, and works by inhibiting cell wall synthesis. It is administered intravenously. more...

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Indications

Currently caspofungin acetate has been approved by the FDA for the treatment of invasive aspergillosis in patients whose disease is refractory to, or who are intolerant of, other first-line antifungal agents (i.e. conventional or liposomal amphotericin B preparations and flucytosine or itraconazole). Caspofungin acetate itself has so far not been studied as first-line therapy for aspergillosis or other mycotic diseases.

Off-Label Use

Caspofungin can be tried as empirical therapy against invasive forms of Candidosis in adult patients.

Clinical Efficacy

Thirty six (36) percent of patients refractory to other therapies responded well to caspofungin therapy, while even 70% of patients intolerant to other therapies were classified as responders. Direct comparative studies to other drugs in the treatment of invasive aspergillosis have so far not been undertaken.

Contraindications

Known hypersensitivity to caspofungin acetate or any other ingredient contained in the formulation

Warnings

Hepatic Effects

The concomitant use of caspofungin and cyclosporine in healthy volunteers led to a more frequent increase of liver enzymes (ALT=SGPT and AST=SGOT) than noted with cyclosporine alone. Combination treatment is only indicated, if the potential benefit for the patient outweighs the potential risk.

Dosage reduction in patients with moderately impaired liver function is recommended. No clinical data exists regarding the use of caspofungin in patients with severely impaired liver function.

Sensitivity Reactions

Reactions due to histamine release (rash, facial swelling, pruritus, sensation of warmth and one case of anaphylaxis) have been seen. Those reactions should be carefully watched for.

Drug Resistance

In clinical studies development of resistance in Aspergillus spp., the causative fungus of aspergillosis, has so far not been seen. Likewise, experiments on the emergence of resistance with fungi-cultures and studies in animals were negative. However, the emergence of resistance cannot be excluded.

Pregnancy and Lactation

Caspofungin has been assigned to class C.

Capsofungin is found in the milk of lactating rats; it is not known, whether this effect can be seen in women, too. Lactating women should be treated cautiously.

Geriatric Patients

Ordinarily, no dose adjustments are necessary.

Pediatric Patients

There is no sufficient clinical experience to judge the safety and efficacy in patients younger than 18 years of age.

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GENES EXPRESSED IN THE PATHOGENIC PHASE OF PARACOCCIDIOIDES BRASILIENSIS AND THEIR POTENTIAL INVOLVEMENT IN VIRULENCE AND MORPHOLOGY
From Revista do Instituto de Medicina Tropical de Sao Paulo, 10/1/05 by Nino-Vega, G

Nino-Vega, G.; Barreto, L.; Sorais, F.; Moreno, B.; San-Bias, G.

Intituto Venezolano de Investigaciones Cientificas (IVIC), Laboraiorio de Micologia, Apartado 21827. Caracas, 1020A, Venezuela. E-maii: gnino@ivic.ve

Paracoccidioides brasilienxix, a thernlodimorphic fungus, is the causative agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis in Latin America. Like in other pathogenic dimorphic fungi, its pathogenicity appears to be related to the dimorphic transition from the hyphal to the yeast form, which is triggered by a shift from environmental temperature to the temperature of the mammalian host. So far, information on genes necessary for the establishment and morphology of the pathogenic phase in R brasiliensis is not certain, although valuable and increasing information on genes preferentially expressed on this phase is been given by the groups working on the construction of expressed sequence tags (ESTs) libraries on this fungus (Yeast 20:263-271, 2003; Eukariotic Cell 2:34-48, 2003; MoI. Gen. Genomics 271:667-677, 2005; J. Biol. Chem. 280:24706-24714, 2005)

In this work, we present three genes expressed only in the pathogenic phase of P. brasiliensis, on which our group has been working in the last few years. Two of them (PbrAGSl, for alpha- 1,3-glucan synthase and PbrCHS3 for a class III chitin synthase) are related to the synthesis of cell wall components and are potentially involved in morphology and virulence of the fungus. Preliminary experimental data prompt us to speculate on a possible post-transcriptional regulation for PbrAGSl. The deduced product of the third gene, PbrCHPl, presents identity with a HiMopia.siua capsitlaium calcium binding protein (MoI. Microbiol. 27:531-539, 1998), involved in virulence in the yeast phase of this dimorphic fungus (Science 290:1368-1372, 2000). Also, our group has been working on the testing of several antifungal and potential anttfungal drugs, one of them caspofungin (Cancidas, Merck). To our surprise, caspofungin, a beta-1,3-glucan synthase inhibitor, affected not only the mycelial phase as expected, but also the yeast phase of P. brasilien.sis, despite the low amount of this glucan in the yeast cell wall. Micrographs show damage to the cell wall of the yeast phase. When we explored by northern the expression of one of two reported beta-1,3-glucan synthase genes, FAT1V/ (Yeast 16:451-462, 2000), we found to our surprise, that f-'KSI has a higher expression in the yeast phase than in the mycelial phase, which together with the results mentioned above from the caspofungin microbiological experiments, made us wonder if beta-1,3-glucan, even when represents a small percentage of the yeast cell wall components, would be essential for its maintenance.

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