MOLECULAR-GENETICS OF RESISTANCE TO BOTH CEFTAZIDIME AND BETA-LACTAM-BETA-LACTAMASE INHIBITOR COMBINATIONS IN KLEBSIELLA-PNEUMONIAE AND IN-VIVO RESPONSE TO BETA-LACTAM THERAPY

The molecular basis of ceftazidime resistance in 2 isolates of Klebsie lla pneumoniae was studied. The first (21300) expressed resistance to ceftazidime and piperacillin-tazobactam. The second (26139) expressed resistance to ceftazidime but remained susceptible to piperacillin-taz obactam. The 2 strains harbored similar large plasmids that hybridized to TEM- and SHV-related beta-lactamase genes. An Escherichia coli str ain harboring the plasmid conferring resistance to both compounds (pLR M7) produced beta-lactamases of pI 5.9 (TEM-6) and pI 7.6 (SHV-1). E. coli harboring the other plasmid (pLRM8) expressed only the TEM enzyme because of insertion of IS15 within bla(SHV-1). In vivo studies sugge sted that resistance to beta-lactam-beta-lactamase inhibitor combinati ons conferred by pLRM7 will be clinically important. Clinical resistan ce to both extended-spectrum cephalosporins and beta-lactam-beta-lacta mase inhibitor combinations is achievable via the production of two en zymes, with only one possessing an extended spectrum of activity.