The suppression of bacterial growth that persists after brief exposure to antimicrobial agents has been termed the postantibiotic effect (PAE). This pharmacodynamic interaction varies for each microorganismantimicrobial agent combination. Daptomycin (LY146032) is a new lipopeptide antibiotic with activity against gram-positive organisms. We studied the in vitro bactericidal activities and PAEs of the following drugs: daptomycin compared with penicillin G and vancomycin, without and with gentamicin against Enterococcus faecalis strains; daptomycin compared with nafcillin and vancomycin against methicillin-susceptible Staphylococcus aureus strains; and daptomycin compared with vancomycin against methicillin-resistant S. aureus strains. Daptomycin, alone and when used in combination with gentamicin, exhibited greater bactericidal activity and in general produced a longer PAE than standard effective regimens against the organism strains studied.
Enterococcus faecium accounts for a notable proportion of clinical enterococcal isolates. Many strains from patients at our institution, as well as from patients at other institutions throughout the country, are highly resistant to penicillin. Because high-level penicillin resistance has important therapeutic implications, periodic surveillance and MIC testing of significant enterococcal isolates, especially E. faecium, are suggested.
Animal models of infectious diseases may not predict clinical efficacy when species-related factors come into play. Recently, unexpected bactericidal activity of vancomycin alone against enterococci was observed in a rat model of endocarditis. A factor or factors in rat serum, but not rabbit or human serum, enhanced in vitro killing by vancomycin in four of five clinical isolates of enterococci. Bactericidal activity was maintained on dilution of rat serum to 5.0% and after exposure of serum to 56 degrees C for 30 min. Activity was lost by heating at 60 degrees C for 2 h, ultrafiltration, or absorption with bentonite or heat-killed bacteria. Rat serum appears to contain a factor or factors that contribute bactericidal activity to vancomycin, a drug normally bacteriostatic for these enterococci. The mechanism by which this factor enhances killing of enterococci by vancomycin is unknown.
The in vitro activity of trospectomycin against 97 clinical isolates of oral pigmented Bacteroides species was compared with the activities of five other antimicrobial agents. At 4 ,ug/mI, more than 90% of isolates were inhibited by trospectomycin. Overall, strains that produced I8-lactamase (n = 41) were more resistant to trospectomycin, penicillin G, cefoxitin, piperacillin, and tetracycline but not to clindamycin. In this study, trospectomycin had excellent in vitro activity against oral pigmented Bacteroides species.Trospectomycin (61 propylspectinomycin sulfate pentahydrate) is a new aminocylitol antibiotic that is derived from spectinomycin. In comparison to the parent molecule, trospectomycin has an expanded antimicrobial spectrum and enhanced potency (11). It has excellent in vitro activity against most gram-positive cocci, as well as against Haemophilus influenzae, Haemophilus ducreyi, Neisseria gonorrhoeae (both P-lactamase-positive and -negative strains), Mycoplasma species, and Chlamydia trachomatis (8, 9;
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