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

J Infect Dis. 1996 Jan;173(1):151-8. doi: 10.1093/infdis/173.1.151.

Abstract

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 SHV-related beta-lactamase genes. An Escherichia coli strain harboring the plasmid conferring resistance to both compounds (pLRM7) 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 blaSHV-1. In vivo studies suggested that resistance to beta-lactam-beta-lactamase inhibitor combinations conferred by pLRM7 will be clinically important. Clinical resistance to both extended-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations is achievable via the production of two enzymes, with only one possessing an extended spectrum of activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abdominal Abscess / drug therapy
  • Amino Acid Sequence
  • Ampicillin / pharmacology
  • Animals
  • Base Sequence
  • Ceftazidime / pharmacology*
  • Cephalosporin Resistance / genetics*
  • Cephalosporins / pharmacology*
  • DNA, Bacterial / analysis
  • Drug Therapy, Combination / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Klebsiella Infections / drug therapy
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Klebsiella pneumoniae / metabolism
  • Molecular Biology
  • Molecular Sequence Data
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology
  • Penicillin Resistance / genetics*
  • Piperacillin / pharmacology
  • Piperacillin, Tazobactam Drug Combination
  • R Factors / chemistry
  • Rats
  • Sulbactam / pharmacology
  • beta-Lactamase Inhibitors*
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics

Substances

  • Cephalosporins
  • DNA, Bacterial
  • beta-Lactamase Inhibitors
  • Piperacillin, Tazobactam Drug Combination
  • sultamicillin
  • Ampicillin
  • Penicillanic Acid
  • Ceftazidime
  • beta-lactamase PIT-2
  • beta-Lactamases
  • beta-lactamase TEM-1
  • Sulbactam
  • Piperacillin