Activity of LBM415 Compared to Those of 11 Other Agents against Haemophilus Species
Open Access
- 1 July 2006
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 50 (7), 2323-2329
- https://doi.org/10.1128/aac.00106-06
Abstract
When tested against 254 Haemophilus influenzae strains, LBM415, a peptide deformylase inhibitor, gave MIC 50 and MIC 90 values of 2.0 μg/ml and 8.0 μg/ml, respectively. The MICs were independent of β-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 β-lactamase-negative, ampicillin-resistant strains, all strains were susceptible to the β-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 2× the MIC against 8 of 10 strains after 24 h. For comparison, the macrolides and β-lactams were bactericidal against 8 to 10 strains each at 2× the MIC after 24 h. Quinolones were bactericidal against all 10 strains tested at 2× 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.Keywords
This publication has 30 references indexed in Scilit:
- Role of the AcrAB-TolC Efflux Pump in Determining Susceptibility of Haemophilus influenzae to the Novel Peptide Deformylase Inhibitor LBM415Antimicrobial Agents and Chemotherapy, 2005
- Activities of Two Novel Macrolides, GW 773546 and GW 708408, Compared with Those of Telithromycin, Erythromycin, Azithromycin, and Clarithromycin against Haemophilus influenzaeAntimicrobial Agents and Chemotherapy, 2004
- Antipneumococcal Activity of LBM415, a New Peptide Diformylase Inhibitor, Compared with Those of Other AgentsAntimicrobial Agents and Chemotherapy, 2004
- Antistaphylococcal Activity of LBM415, a New Peptide Deformylase Inhibitor, Compared with Those of Other AgentsAntimicrobial Agents and Chemotherapy, 2004
- Commercial broth microdilution panel validation and reproducibility trials for NVP PDF-713 (LBM 415), a novel inhibitor of bacterial peptide deformylaseClinical Microbiology & Infection, 2004
- Antimicrobial spectrum and activity of NVP PDF-713, a novel peptide deformylase inhibitor, tested against 1,837 recent gram-positive clinical isolatesDiagnostic Microbiology and Infectious Disease, 2004
- Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodologyAntimicrobial Agents and Chemotherapy, 1994
- Bacteriostatic and bactericidal activity of azithromycin against Haemophilus influenzaeJournal of Antimicrobial Chemotherapy, 1990
- Comparative in-vitro activity of azithromycin and erymromycin against Gram-positive cocci, Haemophilus influenzae and anaerobesJournal of Antimicrobial Chemotherapy, 1990
- Haemophilus influenzae: antibiotic susceptibilityClinical Microbiology Reviews, 1988