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Antimicrobial Agents and Chemotherapy, July 1998, p. 1671-1676, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Ceftazidime-Resistant Klebsiella
pneumoniae and Escherichia coli Isolates Producing
TEM-10 and TEM-43
-Lactamases from St. Louis, Missouri
Youjun
Yang,1,*
Niraja
Bhachech,1
Patricia A.
Bradford,1
Bradley D.
Jett,2
Daniel F.
Sahm,2,
and
Karen
Bush1,
Wyeth-Ayerst Research, Pearl River, New
York,1 and
Barnes-Jewish Hospital,
Washington University School of Medicine, St. Louis,
Missouri2
Received 3 November 1997/Returned for modification 24 February
1998/Accepted 9 April 1998
Ceftazidime-resistant Escherichia coli and
Klebsiella pneumoniae (49 and 102 isolates, respectively)
were collected from Barnes-Jewish Hospital, St. Louis, Mo., from 1992 to 1996. They were uniformly resistant to ceftazidime, generally
resistant to aztreonam, and variably susceptible to cefotaxime. Four
representative E. coli strains and 15 Klebsiella strains were examined. From one to four
-lactamases were produced per strain, with three possible enzymes related to ceftazidime resistance: enzymes with pI values of 5.6, 6.1, or 7.6. By pulsed-field gel electrophoresis there were at least 13 different Klebsiella strain types and 3 different E. coli strain types, indicating that the outbreak was not clonal. After cloning and sequencing of the
-lactamase-encoding genes, the
enzyme with a pI of 5.6 was identified as TEM-10. The enzyme with a pI
of 6.1 was a novel TEM variant (TEM-43) with Lys at 104, His at 164, and Thr at 182. TEM-43 showed broad-spectrum hydrolytic activity
against all penicillins, with the highest hydrolysis rate for
ceftazidime compared to those for the other expanded-spectrum
cephalosporins. Aztreonam was also a good substrate for TEM-43, with
hydrolytic activity similar to that of ceftazidime and affinity higher
than that of ceftazidime. The TEM-43
-lactamase was well inhibited
by clavulanic acid and tazobactam at concentrations of <10 nM.
Sulbactam was less effective than the other inhibitors. The Thr182
mutation previously reported in an inhibitor-resistant
-lactamase
did not cause the TEM-43 enzyme to become resistant to any of the
inhibitors.
*
Corresponding author. Mailing address: 205/227,
Infectious Disease Research, Wyeth-Ayerst, 401, North Middletown Rd.,
Pearl River, NY 10965. Phone: (914) 732-4466. Fax: (914) 732-2480. E-mail: Yangy{at}war.wyeth.com.

Present address: MRL Pharmaceutical Services Inc., Reston, Va.

Present address: R. W. Johnson Pharmaceutical Research
Institute, Raritan, N.J.
Antimicrobial Agents and Chemotherapy, July 1998, p. 1671-1676, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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