In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria - PubMed (original) (raw)

Comparative Study

In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria

K Malathum et al. Antimicrob Agents Chemother. 1999 Apr.

Abstract

The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (EMs), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 microgram/ml; range, 0.03 to 0.06 microgram/ml; MIC50 [erythromycin], 0.25 microgram/ml; range, 0.25 to 0.5 microgram/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of > 64 micrograms/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC < or = 0.5 microgram/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 micrograms/ml were 0.015 microgram/ml. E. faecalis strains that had erythromycin MICs of 128 to > 512 micrograms/ml showed HMR 3647 MICs in the range of 0.03 to 16 micrograms/ml and HMR 3004 MICs in the range of 0.03 to 64 micrograms/ml. In the group of E. faecium strains for which MICs of erythromycin were > or = 512 micrograms/ml, MICs of both ketolides were in the range of 1 to 64 micrograms/ml, with almost all isolates showing ketolide MICs of < or = 16 micrograms/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.

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Figures

FIG. 1

Time-kill curves of HMR 3647 against S. aureus isolates. Concentrations of HMR 3647 for the time-kill of MSSA JT9, MSSA JT22, and MSSA JT10 (4× MICs) were 0.25, 0.12, and 0.25 μg/ml, respectively.

FIG. 2

MICs of HMR 3647 for E. faecalis in relation to erythromycin (Em) susceptibility. The MICs for erythromycin-susceptible isolates were ≤0.5 μg/ml, those for erythromycin-intermediate isolates were 1 to 4 μg/ml, and those for erythromycin-resistant isolates were 128 to >512 μg/ml. For no isolates were erythromycin MICs 8 to 64 μg/ml.

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In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria - PubMed (original) (raw)