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Daptomycin Is Highly Efficacious against Penicillin-Resistant and Penicillin- and Quinolone-Resistant Pneumococci in Experimental Meningitis. Philippe Cottagnoud, 2004.The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%) . Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of –1.20 ± 0.32  log10 CFU/ml · h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of –0.97 ± 0.32
log10 CFU/ml · h against a penicillin- and quinolone-resistant strain found in cerebrospinal fluid (CSF) . For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h . In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC .
The Growth Advantage in Stationary-Phase Phenotype Conferred by rpoS Mutations Is Dependent on the pH and Nutrient Environment. Michael J. Farrell, 2003.Escherichia coli cells that are aged in batch culture display an increased fitness referred to as the growth advantage in stationary phase, or GASP, phenotype . A common early adaptation to this culture environment is a mutant rpoS allele, such as rpoS819, that results in attenuated RpoS activity . However, it is important to note that during long-term batch culture, environmental conditions are in flux . To date, most studies of the GASP phenotype have focused on identifying alleles that render an advantage in a specific environment, Luria-Bertani broth (LB) batch culture . To determine what role environmental conditions play in rendering relative fitness advantages to E . coli cells carrying either the wild-type or rpoS819 alleles, we performed competitions under a variety of culture conditions in which either the available nutrients, the pH, or both were manipulated . In LB medium, we found that while the rpoS819 allele confers a strong competitive fitness advantage at basic pH, it confers a reduced advantage under neutral conditions, and it is disadvantageous under acidic conditions . Similar results were found using other media . rpoS819 conferred its greatest advantage in basic minimal medium in which either glucose or Casamino Acids were the sole source of carbon and energy . In acidic medium supplemented with either Casamino Acids or glucose, the wild-type allele conferred a slight advantage . In addition, populations were dynamic under all pH conditions tested, with neither the wild-type nor mutant rpoS alleles sweeping a culture . We also found that the strength of the fitness advantage gained during a 10-day incubation is pH dependent .
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