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This prospective randomized study was undertaken to determine the efficacy of antimicrobial therapy compared with no therapy for bacteriuria in elderly ambulatory nonhospitalized women. Sixty-one women (mean age, 85.8 years) with bacteriuria were in the no therapy control group and 63 women (mean age, 85.8 years) with bacteriuria were in the therapy group; none had symptoms of urinary tract infection. One short course of antimicrobial therapy achieved a cure rate of 68.3% (43 of 63 women cured) two weeks after treatment. During the six-month follow-up period, ten (16.4%) of 61 women in the no therapy group and five (7.9%) of 63 women in the therapy group developed symptomatic urinary tract infection. At the time of six-month follow-up, 19 (34.5%) of 55 women in the no therapy group and 35 (63.6%) of 55 women in the therapy group did not have bacteriuria. We conclude that for asymptomatic bacteriuria in elderly ambulatory nonhospitalized women, short-course antimicrobial therapy is effective at two-week follow-up and that antimicrobial therapy can eliminate bacteriuria in most of these women for at least a six-month period.

This study compared daptomycin (LY146032) with penicillin G procaine and vancomycin without and with gentamicin for treatment of experimental enterococcal endocarditis. The strain of Streptococcus (Enterococcus) faecalis used in this study was killed by daptomycin in vitro in broth but not in serum. In rabbits treated for 3 days, daptomycin signfficantly reduced bacterial counts of vegetations compared with no therapy but was significantly less effective than penicillin G procaine or vancomycin. Daptomycin-gentamicin significantly reduced bacterial counts of vegetations compared with daptomycin alone but was significantly less effective than vancomycin plus gentamicin. The efficacy of daptomycin-gentamicin did not differ significantly from that of penicillin G procaine-gentamicin. The lack of enterococcal killing by daptomycin alone in serum and in experimental endocarditis is probably related to the high protein binding of the agent.Enterococci are the third most common cause of infective endocarditis and are responsible for about 10% of infective endocarditis cases (8). Unlike most other streptococcal species, enterococci demonstrate resistance to a wide range of antimicrobial agents, and rarely is a single agent bactericidal against the organisms in vitro (15). To achieve in vitro bactericidal activity against enterococci, an aminoglycoside must be added to penicillin G, ampicillin, or vancomycin (16, 21). Although controlled trials are lacking, the recommended treatment of serious enterococcal infections, e.g., endocarditis, involves a combination of penicillin G or vancomycin plus an aminoglycoside (9, 11).The emergence of clinical enterococcal isolates which demonstrate high-level streptomycin resistance (16) and, more recently, strains with high-level gentamicin resistance (12, 23) threatens our ability to provide bactericidal antimicrobial therapy in cases of enterococcal endocarditis. In vitro experiments (12) and animal studies (2) have shown a loss of bactericidal activity with penicillin G plus an aminoglycoside against enterococcal isolates which demonstrate high-level aminoglycoside resistance. These developments, together with the recent demonstration of ,B-lactamase production by isolates of Streptococcus (Enterococcus)faecalis (17), illustrate the need for alternative antimicrobial therapy for serious enterococcal infections.Daptomycin (LY146032) is a cyclic lipopeptide compound that belongs to a class of antibiotics produced by Streptomyces roseosporus (4). It has a spectrum of activity against aerobic, facultative, and anaerobic gram-positive bacteria. Although its spectrum of activity is similar to those of the glycopeptide antibiotics vancomycin and teicoplanin, daptomycin differs from these antibiotics in structure and mechanism of action. Another characteristic of daptomycin which distinguishes it from the glycopeptide antibiotics is the in vitro demonstration of bactericidal activity against enterococci at concentrations near the MIC (4, 19). These features suggest that daptomycin may be...

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.