Tags

Type your tag names separated by a space and hit enter

Anti-biofilm and resistance suppression activities of CXA-101 against chronic respiratory infection phenotypes of Pseudomonas aeruginosa strain PAO1.
J Antimicrob Chemother. 2010 Jul; 65(7):1399-404.JA

Abstract

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 4x and 16x the MICs. Biofilms were formed using a modified Calgary device and were incubated for 24 h with 0x, 1x, 4x or 16x 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 1x the MIC for wild-type, mucoid and hypermutable strains. The spontaneous mutant frequencies for CXA-101 were extremely low (<5 x 10(-11)), even for the hypermutable strain at low concentrations (4x the MIC), in sharp contrast to the other antipseudomonal agents. Accordingly, mutants resistant to 4x the MIC of CXA-101 did not emerge in biofilms for any of the strains/concentrations tested.

CONCLUSION

These data strongly suggest that resistance to CXA-101 (at least 4x the MIC) cannot be driven by single-step mutations, either in planktonic or in biofilm growth. CXA-101 shows encouraging properties for the treatment of CRI by P. aeruginosa, which need to be further evaluated in animal models and pertinent clinical trials.

Authors+Show Affiliations

Servicio de Microbiología and Unidad de Investigación, Hospital Son Dureta, Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Palma de Mallorca, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20435779

Citation

Riera, Elena, et al. "Anti-biofilm and Resistance Suppression Activities of CXA-101 Against Chronic Respiratory Infection Phenotypes of Pseudomonas Aeruginosa Strain PAO1." The Journal of Antimicrobial Chemotherapy, vol. 65, no. 7, 2010, pp. 1399-404.
Riera E, Macià MD, Mena A, et al. Anti-biofilm and resistance suppression activities of CXA-101 against chronic respiratory infection phenotypes of Pseudomonas aeruginosa strain PAO1. J Antimicrob Chemother. 2010;65(7):1399-404.
Riera, E., Macià, M. D., Mena, A., Mulet, X., Pérez, J. L., Ge, Y., & Oliver, A. (2010). Anti-biofilm and resistance suppression activities of CXA-101 against chronic respiratory infection phenotypes of Pseudomonas aeruginosa strain PAO1. The Journal of Antimicrobial Chemotherapy, 65(7), 1399-404. https://doi.org/10.1093/jac/dkq143
Riera E, et al. Anti-biofilm and Resistance Suppression Activities of CXA-101 Against Chronic Respiratory Infection Phenotypes of Pseudomonas Aeruginosa Strain PAO1. J Antimicrob Chemother. 2010;65(7):1399-404. PubMed PMID: 20435779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-biofilm and resistance suppression activities of CXA-101 against chronic respiratory infection phenotypes of Pseudomonas aeruginosa strain PAO1. AU - Riera,Elena, AU - Macià,María D, AU - Mena,Ana, AU - Mulet,Xavier, AU - Pérez,José L, AU - Ge,Yigong, AU - Oliver,Antonio, Y1 - 2010/04/30/ PY - 2010/5/4/entrez PY - 2010/5/4/pubmed PY - 2010/9/18/medline SP - 1399 EP - 404 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 65 IS - 7 N2 - 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 4x and 16x the MICs. Biofilms were formed using a modified Calgary device and were incubated for 24 h with 0x, 1x, 4x or 16x 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 1x the MIC for wild-type, mucoid and hypermutable strains. The spontaneous mutant frequencies for CXA-101 were extremely low (<5 x 10(-11)), even for the hypermutable strain at low concentrations (4x the MIC), in sharp contrast to the other antipseudomonal agents. Accordingly, mutants resistant to 4x the MIC of CXA-101 did not emerge in biofilms for any of the strains/concentrations tested. CONCLUSION: These data strongly suggest that resistance to CXA-101 (at least 4x the MIC) cannot be driven by single-step mutations, either in planktonic or in biofilm growth. CXA-101 shows encouraging properties for the treatment of CRI by P. aeruginosa, which need to be further evaluated in animal models and pertinent clinical trials. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/20435779/Anti_biofilm_and_resistance_suppression_activities_of_CXA_101_against_chronic_respiratory_infection_phenotypes_of_Pseudomonas_aeruginosa_strain_PAO1_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkq143 DB - PRIME DP - Unbound Medicine ER -