Emergence of resistance to beta-lactam antibiotics in Pseudomonas aeruginosa during treatment with new beta-lactams.
In 12 patients treated with cefsulodin for Pseudomonas aeruginosa infections, resistance to cefsulodin developed in the infecting strains of two patients who failed to improve clinically. In both cases, cross-resistance also appeared for a broad spectrum of new antipseudomonal beta-lactams, except imipenem. The resistant isolate from one patient had a new constitutive beta-lactamase for cephalothin which also had modest activity for cefsulodin, ceftazidime, and carbenicillin. Furthermore, all of the non-hydrolyzed beta-lactams appeared to be bound by a beta-lactamase in this isolate. The origin and role in beta-lactam resistance of the observed beta-lactamase activity are obscure. The resistant isolate from the other patient had no demonstrable beta-lactamase activity that could account for the beta-lactam resistance. In five patients treated with imipenem for P. aeruginosa infections, resistance to imipenem developed in the strains of two patients who failed to improve clinically. The strain from one patient was already resistant to all other antipseudomonal beta-lactams before imipenem therapy. The initial strain from the other patient was broadly susceptible, and it developed resistance only to imipenem. Prior to imipenem therapy, another patient, who had P. aeruginosa endocarditis, had isolates from blood with three different susceptibility patterns: susceptible to all antipseudomonal beta-lactams, resistant to all but imipenem, and resistant to imipenem alone. There was no demonstrable beta-lactamase activity to account for imipenem resistance in any of the isolates in these patients. None of the resistant P. aeruginosa isolates had a change in penicillin-binding proteins from those of their susceptible counterparts that might explain the development of resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000032:analysis; D002675:Child, Preschool; D004352:Drug Resistance, Microbial; D005260:Female; D006602:Hexosyltransferases; D006801:Humans; D008297:Male; D008875:Middle Aged; D002267:Muramoylpentapeptide Carboxypeptidase / Q000032:analysis; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000032:analysis / Q000187:drug effects; D001618:beta-Lactamases / Q000032:analysis; D047090:beta-Lactams
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases