Molecular Genetics of Resistance to Both Ceftazidime and β-Lactam-β-Lactamase Inhibitor Combinations in Klebsiella pneumoniae and In Vivo Response to β-Lactam Therapy
The molecular basis of ceftazidime resistance in 2 isolates of Klebsiella 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-tazobactam. The 2 strains harbored similar large plasmids that hybridized to TEM- and SHY-related β-lactamase genes. An Escherichia coli strain harboring the plasmid conferring resistance to both compounds (pLRM7) produced β-lactamases of pI 5.9 (TEM-6) and pi 7.6 (SHY-1). E. coli harboring the other plasmid (pLRM8) expressed only the TEM enzyme because of insertion of IS15 within blaSHV-1. In vivo studies suggested that resistance to β-lactam-β-lactamase inhibitor combinations conferred by pLRM7 will be clinically important. Clinical resistance to both extended-spectrum cephalosporins and β-lactam-β-lactamase inhibitor combinations is achievable via the production of two enzymes, with only one possessing an extended spectrum of activity.