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Published on: April 18, 2019
In vitro evaluation of antibiotic synergy for NDM-1-producing Enterobacteriaceae
Béatrice Berçot1, Laurent Poirel, Laurent Dortet
1Service de Bactériologie-Virologie, INSERM U914 'Emerging Resistance to Antibiotics', Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine et Université Paris-Sud, K.-Bicêtre, Paris, France. beatrice.bercot@lrb.aphp.fr
Objectives:
To analyse the in vitro activity of colistin, fosfomycin and tigecycline alone or in combination against enterobacterial NDM-1 producers.
Methods:
MIC values of colistin, fosfomycin and tigecycline were determined for 28 NDM-1-producing enterobacterial isolates. In vitro synergy combination testing was performed for eight clinical isolates and one Escherichia coli transconjugant (six being susceptible to the three antibiotics) using microdilution and chequerboard techniques.
Results:
MICs of colistin, fosfomycin and tigecycline were determined, showing that one-third of NDM-1-producing isolates were resistant or intermediate to at least one of the three drugs. Nevertheless, in vitro synergistic activity was observed for colistin plus fosfomycin and colistin plus tigecycline in very rare cases.
Conclusions:
Synergistic activity was observed for colistin and fosfomycin, and colistin and tigecycline in rare cases, most of the interactions being indifferent.
Insights
Colistin, fosfomycin, and tigecycline showed limited in vitro synergy against New Delhi metallo-beta-lactamase 1 (NDM-1) producing enterobacteria. Most drug combinations demonstrated indifferent interactions, highlighting challenges in treating these resistant infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- The rise of carbapenem-resistant Enterobacteriaceae (CRE) producing New Delhi metallo-beta-lactamase 1 (NDM-1) poses a significant global health threat.
- Effective therapeutic options against NDM-1 producers are limited, necessitating the evaluation of existing antibiotics and combinations.
Purpose of the Study:
- To evaluate the in vitro activity of colistin, fosfomycin, and tigecycline, individually and in combination, against NDM-1 producing enterobacteria.
Main Methods:
- Minimum Inhibitory Concentrations (MICs) were determined for 28 NDM-1 producing enterobacterial isolates.
- In vitro synergy testing using microdilution and chequerboard assays was performed on selected isolates.
Main Results:
- One-third of NDM-1 producing isolates exhibited resistance or intermediate susceptibility to colistin, fosfomycin, or tigecycline.
- Synergistic activity between colistin and fosfomycin, or colistin and tigecycline, was observed in rare instances.
Conclusions:
- While some synergistic effects were noted, most drug interactions were indifferent, suggesting limited utility of these combinations.
- Further research is needed to identify effective treatment strategies for NDM-1 producing enterobacterial infections.
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