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Antimicrobial Agents and Chemotherapy, April 1998, p. 857-861, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activities and Time-Kill Studies of Selected Penicillins, beta -Lactamase Inhibitor Combinations, and Glycopeptides against Enterococcus faecalis

Dianne B. Hoellman,1 Melissa A. Visalli,1 Michael R. Jacobs,2 and Peter C. Appelbaum1,*

Departments of Pathology (Clinical Microbiology), Hershey Medical Center, Hershey, Pennsylvania 17033,1 and Case Western Reserve University, Cleveland, Ohio 441062

Received 14 August 1997/Returned for modification 12 December 1997/Accepted 22 January 1998

The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were tested against 212 Enterococcus faecalis strains (9 beta -lactamase producers) by standard agar dilution MIC testing (104 CFU/spot). The MICs at which 50 and 90% of the isolates were inhibited (MIC50s and MIC90s, respectively) were as follows (µg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and 1. Agar dilution MIC testing of the nine beta -lactamase-positive strains with an inoculum of 106 CFU/spot revealed higher beta -lactam MICs (piperacillin, 64 to >256 µg/ml; ticarcillin, 128 to >256 µg/ml; and ampicillin, 16 to 128 µg/ml); however, MICs with the addition of inhibitors were similar to those obtained with the lower inoculum. Time-kill studies of 15 strains showed that piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24 h at four times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Ampicillin gave 99.9% killing of 14 beta -lactamase-negative strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate was slower than that observed for piperacillin-tazobactam, relative to the MIC. For the one beta -lactamase-producing strain tested by time-kill analysis with a higher inoculum, addition of the three inhibitors (including sulbactam) to each of the beta -lactams resulted in bactericidal activity at 24 h at two times the MIC. For an enzyme-negative strain, addition of inhibitors did not influence kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than those of the beta -lactams, with bactericidal activity against 6 strains after 24 h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at four times the MIC. Slower-kill kinetics by both glycopeptides were observed at earlier periods.


* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail: pappelba{at}psuhmc.hmc.psu.edu.


Antimicrobial Agents and Chemotherapy, April 1998, p. 857-861, Vol. 42, No. 4
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.






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