Tags

Type your tag names separated by a space and hit enter

Resistance development of cystic fibrosis respiratory pathogens when exposed to fosfomycin and tobramycin alone and in combination under aerobic and anaerobic conditions.
PLoS One. 2013; 8(7):e69763.Plos

Abstract

Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4:1 (w/w) combination of fosfomycin and tobramycin (F:T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F:T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F:T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F:T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F:T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F:T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F:T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F:T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F:T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa.

Authors+Show Affiliations

CF and Airways Microbiology Research Group, Queen's University Belfast, Belfast, United Kingdom.No 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

23936095

Citation

McCaughey, Gerard, et al. "Resistance Development of Cystic Fibrosis Respiratory Pathogens when Exposed to Fosfomycin and Tobramycin Alone and in Combination Under Aerobic and Anaerobic Conditions." PloS One, vol. 8, no. 7, 2013, pp. e69763.
McCaughey G, Diamond P, Elborn JS, et al. Resistance development of cystic fibrosis respiratory pathogens when exposed to fosfomycin and tobramycin alone and in combination under aerobic and anaerobic conditions. PLoS One. 2013;8(7):e69763.
McCaughey, G., Diamond, P., Elborn, J. S., McKevitt, M., & Tunney, M. M. (2013). Resistance development of cystic fibrosis respiratory pathogens when exposed to fosfomycin and tobramycin alone and in combination under aerobic and anaerobic conditions. PloS One, 8(7), e69763. https://doi.org/10.1371/journal.pone.0069763
McCaughey G, et al. Resistance Development of Cystic Fibrosis Respiratory Pathogens when Exposed to Fosfomycin and Tobramycin Alone and in Combination Under Aerobic and Anaerobic Conditions. PLoS One. 2013;8(7):e69763. PubMed PMID: 23936095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resistance development of cystic fibrosis respiratory pathogens when exposed to fosfomycin and tobramycin alone and in combination under aerobic and anaerobic conditions. AU - McCaughey,Gerard, AU - Diamond,Paul, AU - Elborn,J Stuart, AU - McKevitt,Matt, AU - Tunney,Michael M, Y1 - 2013/07/25/ PY - 2013/04/12/received PY - 2013/06/14/accepted PY - 2013/8/13/entrez PY - 2013/8/13/pubmed PY - 2014/3/7/medline SP - e69763 EP - e69763 JF - PloS one JO - PLoS One VL - 8 IS - 7 N2 - Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4:1 (w/w) combination of fosfomycin and tobramycin (F:T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F:T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F:T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F:T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F:T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F:T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F:T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F:T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F:T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23936095/Resistance_development_of_cystic_fibrosis_respiratory_pathogens_when_exposed_to_fosfomycin_and_tobramycin_alone_and_in_combination_under_aerobic_and_anaerobic_conditions_ L2 - https://dx.plos.org/10.1371/journal.pone.0069763 DB - PRIME DP - Unbound Medicine ER -