Matthew Mayer 1127837

Pseudomonas aeruginosa infections are difficult to treat as this organism displays a high level of intrinsic antibiotic resistance. Treatment with fluoroquinolone antibiotics leads to dramatic increases in the Minimum Inhibitory Concentration (MIC), which may be associated with treatment failure. Achieving Mutant Prevention Concentration (MPC) for fluoroquinolones may kill single step resistant mutants, potentiating successful therapy. The fluoroquinolone MPC can theoretically be reduced if combined with a second antibiotic with good activity against P. aeruginosa. The MPC’s for three clinical isolates of P .aeruginosa were established for levofloxacin alone, or in the presence of tobramycin, ceftazidime, piperacillin/tazobactam or azithromycin. The levofloxacin MPC for the strains ranged from 4-8 times their MIC. The levofloxacin MPC was successfully reduced for all three strains in the presence of tobramycin, ceftazidime, and piperacillin/tazobactam, with 2-8 fold decreases. As expected, azithromycin caused no reduction in the MPC, as it is not active against P. aeruginosa. These results indicate a decrease in the emergence of P. aeruginosa resistance to levofloxacin in the presence of a second antibiotic with activity against the organism, compared to the fluoroquinolone alone, and suggest that dual-drug therapies can limit the emergence of fluoroquinolone resistance in P. aeruginosa.