Interaction between piperacillin and pefloxacin or amikacin on the selection of resistant mutants of Pseudomonas aeruginosa.

Pseudomonas aeruginosa mutants were selected with piperacillin, pefloxacin, amikacin and the combinations pefloxacin-piperacillin and amikacin-piperacillin. With amikacin and the piperacillin-amikacin combination no mutants were selected. With piperacillin (1-32 x MIC) mutants resistant to carboxypenicillins, ureidopenicillins, monobactam and cephalosporins were selected. With pefloxacin, three different types of mutant were observed which showed different patterns of cross-resistance to pefloxacin, sulphonamides, imipenem, piperacillin and other beta-lactam antibiotics. With the pefloxacin-piperacillin association, mutants similar to one of the types selected by pefloxacin alone and resistant to both of the selective antibiotic were predominantly obtained. No mutants were selected with this combination if one of the antibiotics was used at a concentration equal to its MIC for the wild type strain and the other at concentrations above 4 x MIC. Since the association of piperacillin and pefloxacin was only moderately bactericidal against the predominantly cross-resistant mutant selected, the concentration of these antibiotics may have to be carefully controlled to prevent the emergence of such mutants.