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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 beta -Lactamases from St. Louis, Missouri

Youjun Yang,1,* Niraja Bhachech,1 Patricia A. Bradford,1 Bradley D. Jett,2 Daniel F. Sahm,2,dagger and Karen Bush1,Dagger

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 beta -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 beta -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 beta -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 beta -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.

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

Dagger 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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