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 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.
Research Service, VA Medical Center, Cleveland, OH 44106, USA.
L B
LB
Rice
L L
LL
Carias
R A
RA
Bonomo
D M
DM
Shlaes
D018784:Abdominal Abscess / Q000188:drug therapy; D000595:Amino Acid Sequence; D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002442:Ceftazidime / Q000494:pharmacology*; D018550:Cephalosporin Resistance / Q000235:genetics*; D002511:Cephalosporins / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000032:analysis; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007710:Klebsiella Infections / Q000188:drug therapy; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008967:Molecular Biology; D008969:Molecular Sequence Data; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010403:Penicillin Resistance / Q000235:genetics*; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D011815:R Factors / Q000737:chemistry; D051381:Rats; D013407:Sulbactam / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
D002511:Cephalosporins; D004269:DNA, Bacterial; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; C035444:sultamicillin; D000667:Ampicillin; D010397:Penicillanic Acid; D002442:Ceftazidime; C054882:beta-lactamase PIT-2; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D013407:Sulbactam; D010878:Piperacillin