Anti-biofilm and resistance suppression activities of CXA-101 against chronic respiratory infection phenotypes of Pseudomonas aeruginosa strain PAO1

Objectives Biofilm growth, mucoid phenotype and proficient resistance development by hypermutable strains dramatically limit the efficacy of current therapies for Pseudomonas aeruginosa chronic respiratory infection (CRI) in cystic fibrosis (CF) patients. We evaluated the activity of the new cephalo...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2010-07, Vol.65 (7), p.1399-1404
Main Authors: Riera, Elena, Macià, María D., Mena, Ana, Mulet, Xavier, Pérez, José L., Ge, Yigong, Oliver, Antonio
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
antibiotic resistance
Antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
antipseudomonal agents
Bacteria
Biofilms
Biofilms - drug effects
Biological and medical sciences
cephalosporin
Cephalosporins - pharmacology
Clinical trials
Colony Count, Microbial
Cystic fibrosis
Drug resistance
Drug Resistance, Bacterial
Errors of metabolism
Genotype & phenotype
Humans
Medical sciences
Metabolic diseases
Microbial Sensitivity Tests
Microbial Viability - drug effects
Miscellaneous hereditary metabolic disorders
Mutation
mutator
Pharmacology. Drug treatments
Phenotype
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - physiology
Pseudomonas Infections - microbiology
Respiratory Tract Infections - microbiology
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Summary:Objectives Biofilm growth, mucoid phenotype and proficient resistance development by hypermutable strains dramatically limit the efficacy of current therapies for Pseudomonas aeruginosa chronic respiratory infection (CRI) in cystic fibrosis (CF) patients. We evaluated the activity of the new cephalosporin CXA-101, ceftazidime, meropenem and ciprofloxacin against biofilms of wild-type PAO1 and its mucoid (mucA), hypermutable (mutS) and mucoid-hypermutable derivatives, and analysed the capacity of these strains to develop resistance during planktonic and biofilm growth. Methods MICs and MBCs were determined by microdilution, and mutant frequencies were determined at 4× and 16× the MICs. Biofilms were formed using a modified Calgary device and were incubated for 24 h with 0×, 1×, 4× or 16× the MIC of each antibiotic. Biofilms were plated, and total cells and resistant mutants enumerated. Results CXA-101 showed concentration-independent biofilm bactericidal activity, being the most potent agent tested at 1× the MIC for wild-type, mucoid and hypermutable strains. The spontaneous mutant frequencies for CXA-101 were extremely low (
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkq143