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Time-kill activity of the streptogramin NXL 103 against Gram-positive and -negative bacteria.

ABSTRACT: Against 33 Gram-positive and -negative bacteria, NXL 103 MICs were 0.03 to 1 ?g/ml. NXL 103 was bactericidal by 12 h at 2 × MIC against all 5 pneumococci and at 2 × MIC after 24 h against all 5 group A and B ?-hemolytic streptococci. NXL 103 was bactericidal against all 8 Haemophilus influenzae strains at 2 × MIC and all 5 Moraxella catarrhalis strains at 4 × MIC after 24 h but was mainly bacteriostatic against 5 methicillin-resistant Staphylococcus aureus strains. After the exposure of one strain of each species to NXL 103 for 10 daily subcultures, the MICs remained within ± 1 dilution.

SUBMITTER: Pankuch GA

PROVIDER: S-EPMC3067140 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Time-kill activity of the streptogramin NXL 103 against Gram-positive and -negative bacteria.

Pankuch Glenn A GA Lin Gengrong G Clark Catherine C Appelbaum Peter C PC

Antimicrobial agents and chemotherapy 20110118 4

Against 33 Gram-positive and -negative bacteria, NXL 103 MICs were 0.03 to 1 μg/ml. NXL 103 was bactericidal by 12 h at 2 × MIC against all 5 pneumococci and at 2 × MIC after 24 h against all 5 group A and B β-hemolytic streptococci. NXL 103 was bactericidal against all 8 Haemophilus influenzae strains at 2 × MIC and all 5 Moraxella catarrhalis strains at 4 × MIC after 24 h but was mainly bacteriostatic against 5 methicillin-resistant Staphylococcus aureus strains. After the exposure of one stra ...[more]

PMID: 21245439

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Project description:Gepotidacin is a first-in-class, novel triazaacenaphthylene antibiotic that inhibits bacterial DNA replication and has in vitro activity against susceptible and drug-resistant pathogens. Reference in vitro methods were used to investigate the MICs and minimum bactericidal concentrations (MBCs) of gepotidacin and comparator agents for Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli Gepotidacin in vitro activity was also evaluated by using time-kill kinetics and broth microdilution checkerboard methods for synergy testing and for postantibiotic and subinhibitory effects. The MIC90 of gepotidacin for 50 S. aureus (including methicillin-resistant S. aureus [MRSA]) and 50 S. pneumoniae (including penicillin-nonsusceptible) isolates was 0.5 μg/ml, and for E. coli (n = 25 isolates), it was 4 μg/ml. Gepotidacin was bactericidal against S. aureus, S. pneumoniae, and E. coli, with MBC/MIC ratios of ≤4 against 98, 98, and 88% of the isolates tested, respectively. Time-kill curves indicated that the bactericidal activity of gepotidacin was observed at 4× or 10× MIC at 24 h for all of the isolates. S. aureus regrowth was observed in the presence of gepotidacin, and the resulting gepotidacin MICs were 2- to 128-fold higher than the baseline gepotidacin MICs. Checkerboard analysis of gepotidacin combined with other antimicrobials demonstrated no occurrences of antagonism with agents from multiple antimicrobial classes. The most common interaction when testing gepotidacin was indifference (fractional inhibitory concentration index of >0.5 to ≤4; 82.7% for Gram-positive isolates and 82.6% for Gram-negative isolates). The postantibiotic effect (PAE) of gepotidacin was short when it was tested against S. aureus (≤0.6 h against MRSA and MSSA), and the PAE-sub-MIC effect (SME) was extended (>8 h; three isolates at 0.5× MIC). The PAE of levofloxacin was modest (0.0 to 2.4 h), and the PAE-SME observed varied from 1.2 to >9 h at 0.5× MIC. These in vitro data indicate that gepotidacin is a bactericidal agent that exhibits a modest PAE and an extended PAE-SME against Gram-positive and -negative bacteria and merits further study for potential use in treating infections caused by these pathogens.

Dataset Information

Time-kill activity of the streptogramin NXL 103 against Gram-positive and -negative bacteria.

Publications

Time-kill activity of the streptogramin NXL 103 against Gram-positive and -negative bacteria.

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