Selection of variants of pseudomonas aeruginosa resistant to beta-lactam antibiotics

Publisher Website
Google Scholar
Abstract
Summary In broth cultures ofPseudomonas aeruginosa, containing carbenicillin or azlocillin, regrowth occurred after a period of bactericidal action, to reach visible proportions overnight. Regrowth in the presence of relatively high concentrations of carbenicillin or azlocillin could not be accounted for on the basis of growth of resistant variants nor as a result of drug inactivation. On the other hand, resistant variants could be selected from the regrowth which occurred at concentrations of carbenicillin or azlocillin only slightly in excess of the minimum inhibitory concentration (MIC). Antibiotic resistant variants could also be isolated from individual colonies growing on agar plates containing carbenicillin, ticarcillin, azlocillin or piperacillin at concentrations above the MIC for the majority of the population. Two types of resistant variant were isolated. The first showed a 2–5 fold increase in resistance to carbenicillin, ticarcillin, azlocillin and piperacillin while β-lactamase production in these variants appeared to be unchanged. The second type of resistant variant showed unchanged sensitivity to carbenicillin and ticarcillin, or only a slight increase in resistance, whereas resistance to azlocillin and piperacillin was increased as much as 40-fold or more. These variants showed increased constitutive β-lactamase production and may be derepressed mutants of the parent culture. Variants of this type were readily selected by culture in the presence of azlocillin or piperacillin but only infrequently as a result of culture in the presence of carbenicillin or ticarcillin. The existence in cultures ofP. aeruginosa of variants showing elevated β-lactamase production may account at least in part for the effect of inoculum size on the activity of azlocillin and piperacillin againstP. aeruginosa and the marked discrepancy between MIC and minimum bactericidal concentration (MBC) which is characteristic of the ureido penicillins.