The effects of combination therapy on resistance evolution in P.aeruginosa Combination therapy with more than one conventional antibiotic or with inhibitors of specific fac-tors 16 involved in antibiotic resistance such as b-lactamases and efflux pumps has recently gotten renewed attention as an alternative way to reduce the incidence of resistance evolution. In theory combinations of different antibiotics or other inhibitors should lower the frequency of re-sistance evolution because the probability of mutations causing resistance to both agents is lower than the probability of resistance mutations to a single agent. However, there is a risk that combination therapy could change the nature of the resistance me-chanisms by selecting for general resistance mechanisms, such as multi-drug efflux pumps, ma-king the microbes resistant to multiple antibiotic classes instead of a single antibiotic class. The aim of this project is to study the effect of combination therapy on resistance evolution in P.aeruginosa. The project may include the following: 1) Susceptibility testing to single antibiotics and combination using standard clinical microbiology techniques 2) Studies to reveal synergistic and antagonistic interactions between drugs of different classes. 3) Determination of resistance mutation frequencies of single agents and in combination. 4) Identification of resistance mechanisms to specific drugs and to drugs in combination. 5) Determination of the frequency and mechanisms of resistance in clinical isolates from patients chronically infected with P. aeruginosa. Standard microbiological and genetic techniques will be used in combination with a number of state of the art molecular and systems biological methods to reach the project aim. Contact lector Anders Folkesson, afol@vet.dtu.dk, DTU Vet, Bülowsvej 27, 1870 Frederiksberg C
Projects 14
To see the actual publication please follow the link above