Caspofungin acetate

During the study period, immunosuppressive and anti-microbial agents were administered by clinicians according to patient health status (Table 1). Standard perioperative antibiototic prophylaxis was piperacillin-tazobactam, cefepime dihydochoride, imipenem-cilastatin sodium, cefoperazone sodium and sulbactam sodium, micafungin sodium, or caspofungin acetate. Vancomycin and teicoplanin were used to treat infections caused by Gram-positive organisms such as Enterococcus feacium (OLT2), Acinetobacter baumannii (OLT4), and periodic episodes of fever (OLT9 and OLT10). Flucytosine and amphotericin B were used to treat cryptococcus-associated infections (OLT3). Most patients received tacrolimus as a primary immunosuppressive therapy. Plasma concentrations of tacrolimus were 10-15 ng/ml. All medicines were taken as advised.

Single-dose kinetics of caspofungin acetate were studied over 24 h. Immediately before use, caspofungin acetate was dissolved in sterile 0.9% sodium chloride to a concentration of 0.5 mg/ml. Twenty-four hours after induction of uveitis, 16 rabbits were given 1 mg/kg caspofungin over 6 min by steady bolus injection via a central venous catheter. The drug dosage used corresponds to the standard dose recommended for the treatment of human fungal infections and is well tolerated by rabbits. Four animals per time point were sacrificed by cervical dislocation and subsequent exsanguination at 4, 8, 16, and 24 h after drug administration. Blood samples were collected during bleeding, and serum was separated by centrifugation. Aqueous humor was drawn from the freshly enucleated eyes with a tuberculin syringe using a 30-gauge needle. The cornea was excised at the limbus. After sectioning the eyes just behind the lens, vitreous humor was obtained by dissecting it carefully from the retina.

It has been well established, first for S. cerevisiae (Inoue et al. 1996; Cabib et al. 1998) and subsequently for several fungi (Odds et al. 2003; Ruge et al. 2005) that one of the roles of Rho1p is to be a regulatory protein of the b-1,3-glucan synthase complex, involved in the synthesis of b-1,3-glucans, a major component of cell walls from most fungi. It has been described that Rho1 proteins are involved in polar growth, branching and cell wall synthesis (Guest et al. 2004). However, glucans have not been detected in zygomycetes, such as M. rouxii, at least as major components (Bartnicki-Garcı ´a and Reyes 1968; Dow and Rubery 1977). In order to evaluate whether there is also a b-1,3-glucan synthase complex in M. rouxii, and thus infer that Rho1 might be participating in this complex, we assayed the effect of an echinochandin, caspofungin acetate, in cell growth and morphology. Echinocandins are antifungal agents which inhibit the 1,3-b-D-glucan synthase complex. Caspofungin acetate (registered name, Cancidas, from Merck) is a member of this family of lipopeptides consisting of cyclic hexapeptides N-linked to a fatty acyl side chain (Letscher-Bru and Herbrecht 2003).