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Antimicrobial Agents and Chemotherapy, January 2001, p. 67-72, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.67-72.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 Compared to Their Susceptibilities to 11 Other Agents

Kim L. Credito,¹ Gengrong Lin,¹ Glenn A. Pankuch,¹ Saralee Bajaksouzian,² Michael R. Jacobs,² and Peter C. Appelbaum^1,*

Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania 17033,¹ and Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106²

Received 21 July 2000/Returned for modification 13 September 2000/Accepted 3 October 2000

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% -lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 µg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 µg/ml). Of the -lactams, ceftriaxone had the lowest MICs (0.004 to 0.016 µg/ml), followed by cefixime and cefpodoxime (0.008 to 0.125 and 0.125 to 0.25 µg/ml, respectively), amoxicillin-clavulanate (0.125 to 4.0 µg/ml), and cefuroxime (0.25 to 8.0 µg/ml). Amoxicillin was only active against -lactamase-negative strains, and cefprozil had the highest MICs of all oral cephalosporins tested (0.5 to >32.0 µg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. -Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with -lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. -Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.

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^* 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.

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Antimicrobial Agents and Chemotherapy, January 2001, p. 67-72, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.67-72.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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