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Antimicrobial Agents and Chemotherapy, June 2009, p. 2239-2247, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01531-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Antipneumococcal Activities of Sulopenem and Other Drugs{triangledown}

Klaudia Kosowska-Shick, Lois M. Ednie, Pamela McGhee, and Peter C. Appelbaum*

Hershey Medical Center, Hershey, Pennsylvania 17033

Received 17 November 2008/ Returned for modification 9 March 2009/ Accepted 13 March 2009

For 297 penicillin-susceptible, -intermediate, and -resistant pneumococcal strains, the sulopenem MIC50s were 0.008, 0.06, and 0.25, respectively, and the sulopenem MIC90s were 0.016, 0.25, and 0.5 µg/ml, respectively. The MIC50s of amoxicillin for the corresponding strains were 0.03, 0.25, and 2.0 µg/ml, respectively, and the MIC90s were 0.03, 1.0, and 8.0 µg/ml, respectively. The combination of amoxicillin and clavulanate gave MICs similar to those obtained with amoxicillin alone. The sulopenem MICs were similar to those of imipenem and meropenem. The MICs of ß-lactams increased with those of penicillin G, and among the quinolones tested, moxifloxacin had the lowest MICs. Additionally, 45 strains of drug-resistant type 19A pneumococci were tested by agar dilution and gave sulopenem MIC50s and MIC90s of 1.0 and 2.0 µg/ml, respectively. Both sulopenem and amoxicillin (with and without clavulanate) were bactericidal against all 12 strains tested at 2x MIC after 24 h. Thirty-one strains from 10 countries with various penicillin, amoxicillin, and carbapenems MICs, including those with the highest sulopenem MICs, were selected for sequencing analysis of the pbp1a, pbp2x, and pbp2b regions encoding the transpeptidase active site and MurM. We did not find any correlations between specific penicillin-binding protein-MurM patterns and changes in the MICs.

* 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: pappelbaum{at}psu.edu

{triangledown} Published ahead of print on 23 March 2009.

Antimicrobial Agents and Chemotherapy, June 2009, p. 2239-2247, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.01531-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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