In vitro synergy of tigecycline against Burkholderia cepacia complex and other multi-resistant, nonfermentative, Gram negative bacteria from cystic fibrosis patients
Student thesis: Doctoral Thesis
Options for treating Burkholderia cepacia complex (Bcc) and other multi-resistant Gram negative bacilli isolated from people with cystic fibrosis (CF) are limited. We assessed the in-vitro activity of tigecycline and eleven other antimicrobial agents against a collection of these organisms. The collection comprised 128 isolates of CF-associated Gram negative bacilli (31 Burkholderia multivorans, 16 Burkholderia cenocepacia, 4 other members of the Burkholderia species, 47 Stenotrophomonas maltophilia, 20 Achromobacter xylosoxidans, and 10 other miscellaneous CF-associated Gram negative bacilli. Minimum inhibitory concentrations (MIC) of tigecycline and eleven other antimicrobials for each isolate were determined using E-test. Synergy between tigecycline and each of eight other antimicrobials was determined using an E-test overlay method. The epidemiological spread of organisms indicated that the Leeds Teaching Hospitals NHS Trust (LTHT) infection control policies have had a measure of success and our work followed the pattern of many other CF units. Tigecycline showed poor in-vitro activity versus all members of the Bcc, with only 13% and 3% of B. cenocepacia and B. multivorans susceptible, respectively. Conversely minocycline showed good activity against these species, with 94% and 91% of isolates being susceptible. Tigecycline showed good activity against A. xyloxidans and S. maltophilia with 85% and 77% of isolates being susceptible, respectively. Tigecycline in combination with other agents mostly resulted in indifference. Although the in-vitro activity of tigecycline is variable, we reviewed the potential and future clinical impact of this study and the likely issues for further study. Whilst the relationship between synergy/MIC testing and clinical success remains unclear, there are a number of promising developments and ideas that may clarify this situation – further studies are warranted.
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