a The University of Illinois at Chicago, College of Pharmacy, Department of Pharmacy Practice, Microbiology Research Laboratory, 833 South Wood Street, Chicago, IL 60612; b The University of Houston College of Pharmacy, Department of Clinical Sciences and Administration, Houston, TX, USA
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Abstract |
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Introduction |
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The ketolides, semisynthetic 14-membered ring macrolides, represent a new subclass of agents among the macrolidelincosamidestreptogramin group. One of the newest agents, ABT-773, has demonstrated excellent in vitro activity against both erythromycin-susceptible and -resistant strains of S. pyogenes.3 While the MIC data look very promising, additional information is needed on the timekill kinetics of these new agents. The purpose of this study was to compare the bactericidal activity of ABT-773 and amoxicillin against S. pyogenes in vitro.
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Materials and methods |
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ABT-773 (Abbott Laboratories, Abbott Park, IL, USA), amoxicillin and erythromycin (United States Pharmacopeia, Rockville, MD, USA) powders were prepared according to NCCLS guidelines or manufacturer's recommendations.4 Cation-supplemented MuellerHinton broth with 3% lysed horse blood (Remel, Lenexa, KS, USA) was the medium used for the MIC and timekill assays. MICs were performed in duplicate following NCCLS guidelines using the broth microdilution method.4
The bactericidal activity of the antimicrobial agents was determined in duplicate using the timekill method following NCCLS guidelines.5 Antimicrobial concentrations tested were 2 x and 8 x MIC. Sampling for colony counts was performed at 0, 2, 6 and 24 h. Antibiotic carryover was prevented by saline dilutions. Viable counts were determined after 24 h of incubation at 35°C with 5% CO2. The rate and extent of killing were determined by plotting colony counts (log10 cfu/mL) against time (h). Bactericidal activity was defined as a 3 log10 decrease in cfu/mL, while bacteriostatic activity was defined as a <3 log10 decrease in cfu/mL. The lower limit of detection was 1.3 log10 cfu/mL.
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Results and discussion |
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The results of the timekill experiments are given in Figures 1 and 2. At 24 h, ABT-773 8 x MIC demonstrated bactericidal activity against six strains (four erythromycin susceptible and two containing the mefA gene). Bactericidal activity was observed at 24 h against three strains at an ABT-773 concentration of 2 x MIC (one erythromycin susceptible and two containing the mefA gene). In comparison, amoxicillin at concentrations of 2 x and 8 x MIC was bactericidal against all 10 isolates at 24 h. Both the rate and extent of killing were less for ABT-773 than amoxicillin against the 10 isolates.
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In conclusion, ABT-773 demonstrated in vitro activity against both erythromycin-susceptible and -resistant strains of S. pyogenes. Further in vitro and in vivo studies are needed to define further the role of ABT-773 in infections due to S. pyogenes.
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Acknowledgements |
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Notes |
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References |
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2 . Betriu, C., Casado, M. C., Gómez, M., Sanchez, A., Palau, M. L. & Picazo, J. J. (1999). Incidence of erythromycin resistance in Streptococcus pyogenes: a 10-year study. Diagnostic Microbiology and Infectious Disease 33, 2556.[ISI][Medline]
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Nilius, A. M., Bui, M. H., Almer, L., Hensey-Rudloff, D., Beyer, J., Ma, Z. et al. (2001). Comparative in vitro activity of ABT-773, a novel antibacterial ketolide. Antimicrobial Agents and Chemotherapy 45, 21638.
4 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA.
5 . National Committee for Clinical Laboratory Standards. (1999). Methods for Determining Bactericidal Activity of Antimicrobial Agents: Approved Guideline M26-A. NCCLS, Wayne, PA.
6 . Stone, G., Nilius, A., Hensey, D., Almer, L., Beyer, J. & Flamm, R. (2000). Development of tentative interpretive criteria for ABT-773, a novel ketolide antibacterial agent. In Programs and Abstracts of the Fortieth Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, 2000. Abstract 2164, p. 181. American Society for Microbiology, Washington, DC.
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Odenholt, I., Lowdin, E. & Cars, O. (2001). Pharmacodynamics of telithromycin in vitro against respiratory tract pathogens. Antimicrobial Agents and Chemotherapy 45, 239.
8 . Boswell, F. J., Andrews, J. M. & Wise, R. (1998). Pharmacodynamic properties of HMR 3647, a novel ketolide, on respiratory pathogens, enterococci, and Bacteroides fragilis demonstrated by studies of timekill kinetics and postantibiotic effect. Journal of Antimicrobial Chemotherapy 41, 14953.[Abstract]
Received 3 August 2001; returned 19 November 2001; revised 4 January 2002; accepted 14 January 2002