Beschreibung:
<jats:title>ABSTRACT</jats:title>
<jats:p>
When tested against 254
<jats:italic>Haemophilus influenzae</jats:italic>
strains, LBM415, a peptide deformylase inhibitor, gave MIC
<jats:sub>50</jats:sub>
and MIC
<jats:sub>90</jats:sub>
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
<jats:italic>H. parainfluenzae</jats:italic>
strains were similar to those against
<jats:italic>H. influenzae</jats:italic>
. 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
<jats:italic>H. parainfluenzae</jats:italic>
strains were similar to those against
<jats:italic>H. influenzae</jats:italic>
. Time-kill studies with 10
<jats:italic>Haemophilus</jats:italic>
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
<jats:italic>H. influenzae</jats:italic>
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 (
<jats:italic>def</jats:italic>
) and formyltransferase (
<jats:italic>fmt</jats:italic>
) genes were detected in any of the LBM415-resistant mutants.
</jats:p>