Amphotericin B methyl ester (AME) has been reported to possess in vitro antifungal activity similar to that of amphotericin B and to have less intrinsic toxicity in mice and dogs. For these reasons AME has been porposed as an alternative to amphotericin B in the therapy of deep mycoses. For comparison of the therapeutic efficacy of the two polyenes in laboratory animals before initiation of studies in humans, groups of mice were infected with Candida albicans, Cryptococcus neoformans, and Blastomyces dermatitidis. Treatment consisted of two or more doses of each drug given by the intravenous route. Concurrently, studies of subacute toxicity were conducted in the same species to permit calculation of therapeutic indices. These studies have shown that AME, as the ascorbate salt, is substantially less efficacious than amphotericin B (in colloidal dispersion with sodium deoxycholate) for treatment of the fungal infections and that amphotericin B had a higher therapeutic ratio for all infections studied than did AME.
A series of 7/'-ureidoacetyl, 7a-H and 7a-OCH, cephalosporin antibiotics have shown broad-spectrum antibacterial activity in vitro. In the 7a-H but not in the 7x-OCH3 series, contrary to experience in the antibiotic field, the L-isomers were substantially more active than the n-isomers both in vitro and in vivo particularly, but not exclusively, against Enterohacteriaceae that produce potent chromosomal cephalosporinases. Enhanced resistance to and inhibition of /3-lactamase (s) appeared to be responsible for this effect. Studies in vitro specifically with 7/3-thienylureidoacetyl derivatives showed that n-isomers interacted with L-isomers in the 7a-OCH3 series in a synergistic manner against "cephalosporinase-type" enzyme producers while isomers in the 7a-H series did not. Examples were presented in which this favorable event resulted in improved efficacy of the racemic mixture over the pure D-or Lisomer alone in appropriate experimental infections.
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