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Antimicrobial Agents and Chemotherapy, July 2006, p. 2323-2329, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.00106-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Activity of LBM415 Compared to Those of 11 Other Agents against Haemophilus Species

Tatiana Bogdanovich, Kathy A. Smith, Catherine Clark, Glenn A. Pankuch, Gengrong Lin, Pamela McGhee, Bonifacio Dewasse, and Peter C. Appelbaum^*

Hershey Medical Center, Hershey, Pennsylvania 17033

Received 25 January 2006/ Returned for modification 26 March 2006/ Accepted 10 April 2006

When tested against 254 Haemophilus influenzae strains, LBM415, a peptide deformylase inhibitor, gave MIC₅₀ and MIC₉₀ values of 2.0 µg/ml and 8.0 µg/ml, respectively. The MICs were independent of ß-lactam or quinolone susceptibility and the presence or absence of macrolide efflux or ribosomal protein mutations. The MICs of LBM415 against 23 H. parainfluenzae strains were similar to those against H. influenzae. In contrast, erythromycin, azithromycin, and clarithromycin gave unimodal MIC distributions, and apart from ß-lactamase-negative, ampicillin-resistant strains, all strains were susceptible to the ß-lactams tested. Apart from selected quinolone-resistant strains, all strains were susceptible to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin. Resistance to trimethoprim-sulfamethoxazole was common. The potencies of all drugs against 23 H. parainfluenzae strains were similar to those against H. influenzae. Time-kill studies with 10 Haemophilus strains showed LBM415 to be bactericidal at 2x the MIC against 8 of 10 strains after 24 h. For comparison, the macrolides and ß-lactams were bactericidal against 8 to 10 strains each at 2x the MIC after 24 h. Quinolones were bactericidal against all 10 strains tested at 2x the MIC after 24 h. Against six H. influenzae strains, postantibiotic effects for LBM415 lasted between 0.8 and 2.2 h. In multistep resistance selection studies, LBM415 produced resistant clones in 7 of the 10 strains tested, with MICs ranging from 4 to 64 µg/ml. No mutations in deformylase (def) and formyltransferase (fmt) genes were detected in any of the LBM415-resistant mutants.

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* Corresponding author. Mailing address: Department of Pathology, Hershey Medical Center, 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, July 2006, p. 2323-2329, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.00106-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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