A1.13 Comparative study of In Vitro activity of carbapenems and other β-lactams against Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and enterobacteriaceae isolated from blood

2005 ◽  
Vol 26 ◽  
pp. S69-S70
2009 ◽  
Vol 53 (11) ◽  
pp. 4915-4920 ◽  
Author(s):  
Heather J. Adam ◽  
Nancy M. Laing ◽  
C. Richard King ◽  
Ben Lulashnyk ◽  
Daryl J. Hoban ◽  
...  

ABSTRACT The in vitro activity of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, was tested against 2,440 clinical isolates. Nemonoxacin was at least fourfold more active than levofloxacin and moxifloxacin against most gram-positive cocci tested (shown by the following MIC90/range [μg/ml] values; community-associated methicillin [meticillin]-resistant Staphylococcus aureus, 0.5/0.015 to 2; Staphylococcus epidermidis, 0.5/0.015 to 4 for methicillin-susceptible staphylococci and 2/0.12 to 2 for methicillin-resistant staphylococci; Streptococcus pneumoniae, 0.015/≤0.008 to 0.25; Enterococcus faecalis, 1/0.03 to 128). Nemonoxacin activity against gram-negative bacilli was similar to levofloxacin and moxifloxacin (MIC90/range [μg/ml]; Escherichia coli, 32/≤0.015 to ≥512; Klebsiella pneumoniae, 2/≤0.015 to 128; K. oxytoca, 0.5/0.06 to 1; Proteus mirabilis, 16/0.25 to ≥512; Pseudomonas aeruginosa, 32/≤0.015 to ≥512; Acinetobacter baumannii, 1/0.12 to 16).


Author(s):  
María Díez-Aguilar ◽  
Marta Hernández-García ◽  
María-Isabel Morosini ◽  
Ad Fluit ◽  
Michael M Tunney ◽  
...  

Abstract Background Murepavadin, a novel peptidomimetic antibiotic, is being developed as an inhalation therapy for treatment of Pseudomonas aeruginosa respiratory infection in people with cystic fibrosis (CF). It blocks the activity of the LptD protein in P. aeruginosa causing outer membrane alterations. Objectives To determine the in vitro activity of murepavadin against CF P. aeruginosa isolates and to investigate potential mechanisms of resistance. Methods MIC values were determined by both broth microdilution and agar dilution and results compared. The effect of artificial sputum and lung surfactant on in vitro activity was also measured. Spontaneous mutation frequency was estimated. Bactericidal activity was investigated using time–kill assays. Resistant mutants were studied by WGS. Results The murepavadin MIC50 was 0.125 versus 4 mg/L and the MIC90 was 2 versus 32 mg/L by broth microdilution and agar dilution, respectively. Essential agreement was >90% when determining in vitro activity with artificial sputum or lung surfactant. It was bactericidal at a concentration of 32 mg/L against 95.4% of the strains within 1–5 h. Murepavadin MICs were 2–9 two-fold dilutions higher for the mutant derivatives (0.5 to >16 mg/L) than for the parental strains. Second-step mutants were obtained for the PAO mutS reference strain with an 8×MIC increase. WGS showed mutations in genes involved in LPS biosynthesis (lpxL1, lpxL2, bamA2, lptD, lpxT and msbA). Conclusions Murepavadin characteristics, such as its specific activity against P. aeruginosa, its unique mechanism of action and its strong antimicrobial activity, encourage the further clinical evaluation of this drug.


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