Comparative in vitro activity of ABT-773, a novel antibacterial ketolide.

The in vitro activities of ABT-773, erythromycin, clarithromycin, and azithromycin were compared. ABT-773 was the most active compound against macrolide-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Enterococcus spp. and multidrug-resistant Streptococcus pneumoniae. It also had good activity against gram-negative and atypical respiratory tract pathogens and Helicobacter pylori.

Structure-activity relationships in the series of eremomycin carboxamides.

A series of new carboxamides of the glycopeptide antibiotic eremomycin was synthesized and investigated in vitro. The goal of the study was the comparison of the influence of the substituents introduced onto the eremomycin skeleton on the activity of these compounds against vancomycin susceptible and resistant bacterial strains. Eremomycin amides derived from amines with small substituents (C0 approximately C4) demonstrated antibacterial activity against vancomycin susceptible strains similar to that of the parent antibiotic and were inactive against vancomycin resistant strains. The derivatives of alkylamines with linear lipophilic substituents (like C10H21) were active against VanA and VanB enterococci strains with the scope of activity similar to that of N'-decyl or 7d-CH2NH-decyl eremomycins described earlier. Eremomycin amides of 5-methoxy- and 5-benzyloxytryptamine were active both against vancomycin susceptible and resistant strains. The introduction of a spacer (lysine or piperazine) between the decyl and antibiotic moieties did not seriously influence antibacterial properties of the compounds in comparison with the corresponding derivatives without a spacer. The most active carboxamides are of interest for secondary modifications of the antibiotic.

In vitro activity of A-192411.29, a novel antifungal lipopeptide.

A-192411.29 is a novel antifungal agent derived from the structural template of the natural product echinocandin. The in vitro activity of A-192411.29 against common pathogenic yeasts was assessed by National Committee for Clinical Laboratory Standards method M27-A. It demonstrated broad-spectrum, fungicidal activity and was active against the most clinically relevant yeasts, such as Candida albicans, Candida tropicalis, and Candida glabrata, as well as less commonly encountered Candida species; in general, its potency on a weight basis was comparable to that of amphotericin B. It maintained potent in vitro activity against Candida strains with reduced susceptibilities to fluconazole and amphotericin B. The in vitro activity of A-192411.29 against Cryptococcus neoformans was comparable to its activity against Candida spp. However, A-192411.29 did not demonstrate complete growth inhibition of Aspergillus fumigatus by the broth microdilution method used. A-192411.29 possesses an antifungal profile comparable to or better than those of fluconazole and amphotericin B against pathogenic yeasts, including strains resistant to fluconazole or amphotericin B, suggesting that it may be a therapeutically useful new antifungal drug.