This study used kill-kinetic methods to provide data on the bactericidal activity of subinhibitory (1/2x MIC), inhibitory (lx MIC), and suprainhibitory (4X, 6x, and 8x MIC) concentrations of deptomycin (LY146032) against strains of enterococci compared with those of ciprofloxacin, vancomycin, and ampicillin. Deptomycin was the most active agent tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations <2 ,ug/ml. The kill-kinetic studies demonstrated that deptomycin had greater activity at aDl concentrations tested than the other cell wall-active agents; regrowth was seen, however, at lower concentrations. At higher concentrations (6x and 8x MIC), all aagents tested demonstrated the same or less bactericidal activity than at 4x MIC, presumably due to the Eagle effect. Nevertheless, these results suggest that further evaluation of deptomycin as a therapeutic agent for serious enterococcal infections is warranted.Deptomycin (LY146032) is a cyclic polypeptide which by standard broth dilution techniques has been shown to be bactericidal against enterococci at concentrations near the MIC (4, 6). This suggests that deptomycin may be useful clinically as a single agent against serious enterococcal infections, including endocarditis. This study used killkinetic methods to provide data on the bactericidal activity of subinhibitory (1/2 x MIC), inhibitory (lx MIC), and suprainhibitory (4x, 6x, and 8x MIC) concentrations of deptomycin against strains of enterococci compared with those of ciprofloxacin, vancomycin, and ampicillin. MATERIALS AND METHODSMicroorganisms. Ten clinical isolates of enterococci and Streptococcus faecalis ATCC 29212 were studied. These isolates were selected from more than 200 blood culture isolates of enterococci for which the MICs of vancomycin, ampicillin, and gentamicin had been determined previously.Selection was done to provide a wide range of MICs of the three agents previously tested. Identification was performed by established methods (5), which included the ability to grow in medium containing 40% bile, to hydrolyze esculin, and to grow in broth containing 6.5% sodium chloride. All strains were identified as S. faecalis.Antimicrobial agents. Standard antimicrobial reference powders and their sources were as follows: deptomycin and vancomycin, Eli Lilly & Co., Indianapolis, Ind.; ciprofloxacin, Miles Pharmaceuticals, West Haven, Conn.; and ampicillin, Bristol Laboratories, Syracuse, N.Y. Antimicrobial agent stock solutions were prepared as specified by the manufacturers and stored at -70°C until use. Final concentrations were prepared on the day they were used.Media. Mueller-Hinton broth (BBL Microbiology Systems, Cockeysville, Md.) was used in both the broth microdilution method and the kill-kinetic method. The broth was supplemented with physiologic concentrations of calcium and magnesium to achieve a final concentration of 50 mg of (14). For this method, 10-fold dilutions were made in physiologic saline, and a calibrated micropipetter was us...

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Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (ix MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillinsusceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were compared with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin. LY146032 was among the most active of the antistaphylococcal agents tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations of '1 ,ug/ml. Time kill-kinetic studies demonstrated that at 4x MIC, LY146032 was rapidly bactericidal against all strains of staphylococci. Our data show that LY146032 has significant bactericidal activity against staphylococci in comparison with other antistaphylococcal agents. Further evaluation of LY146032 against serious staphylococcal infections is warranted.LY146032 is a cyclic polypeptide which has been shown by standard broth dilution techniques to be bactericidal against staphylococci at concentrations near the MIC (6-8, 14, 25). This suggests that LY146032 may be useful clinically as a single agent against serious staphylococcal infectons, including endocarditis. To provide additional data on the bactericidal activity of LY146032 in comparison with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin, kill-kinetic methods were used in this study to compare the subinhibitory (0.5x MIC), inhibitory (lx MIC), and suprainhibitory (4x MIC) concentrations of these agents. MATERIALS AND METHODSMicroorganisms. One hundred isolates of staphylococci obtained from blood were studied. Included in these isolates were 25 strains of methicillin-susceptible (MIC, .2 jig/ml) S. aureus, 25 strains of methicillin-resistant (MIC, -16 ptg/ml) S. aureus, 25 strains of methicillin-susceptible (MIC, .2 ,ug/ml) S. epidermidis, and 25 strains of methicillin-resistant (MIC, .16 ,ug/ml) S. epidermidis. Identification of S. aureus was performed by a previously established methodology (13) which included colony morphology, Gram stain characteristics, ability to coagulate rabbit serum, and the presence of heat-stable DNase activity. Identification of S. epidermidis was done by using criteria and methods established by Kloos and Jorgensen (13). Methicillin-susceptible and -resistant strains were determined by a reference broth microdilution method with Mueller-Hinton broth containing 2% NaCl (20,24 ciprofloxacin, Miles Pharmaceuticals, West Haven, Conn. Antimicrobial stock solutions were prepared according to the instructions of the manufacturers and stored at -70°C until use. Final concentrations were prepared on the day they were used.Media. Mueller-Hinton broth (BBL Microbiology Systems, Cockeysville, Md.) was used in both the broth microdilution method and the kill-kinetic method and was supplemented with 2% NaCl for the testing of beta-lactam agents (20,24) and with physiologic concentrations of calcium and mag...

Kill-kinetic studies often are used to determine the rate and degree of kiling of aerobic bacteria by antimicrobial agents. Few studies, however, make use of this method for determining antimicrobial activity against anaerobic bacteria. To evaluate kill-kinetic studies for anaerobes, kill-kinetic studies were performed for selected antimicrobial agents against members of the Bacteroides fragilis group and compared with MICs obtained by using a reference agar dilution method and a broth microdilution method. Results of the kill-kinetic studies showed that the degree of killing over a 24-h test period was related to the MIC for the test organism. In general, the higher the MIC of an antimicrobial agent for a test organism, the less the killing observed. In addition, these studies demonstrate subtle differences in bactericidal activity at various concentrations of the antimicrobial agents, which cannot be determined by agar or broth dilution methods. Kill-kinetic studies are a useful addition to dilution methods for the evaluation of antimicrobial agents against anaerobes.

Previous reports documenting the essentially identical spectra of activity of ceftizoxime, cefotaxime, and ceftriaxone prompted our hospital formulary committee to replace the latter two drugs with ceftizoxime on the basis of cost differences. However, we subsequently observed that every one of 60 isolates of Streptococcus pneumoniae tested was less susceptible to ceftizoxime than to either cefotaxime or ceftriaxone. The difference between minimal inhibitory concentrations (MICs) was greatest for strains moderately or fully resistant to penicillin, which at our institution represent approximately 32% of all isolates of S. pneumoniae. Ten isolates with cefotaxime and ceftriaxone MICs of 2.0-6.0 micrograms/mL had ceftizoxime MICs of > or = 256 micrograms/mL. Time-kill kinetic studies assessing bactericidal activity confirmed the diminished activity of ceftizoxime against penicillin-resistant isolates of S. pneumoniae. Ceftizoxime should not be used to treat proven or suspected pneumococcal infection in areas where resistance to penicillin is prevalent.