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Antimicrobial Agents and Chemotherapy, December 2001, p. 3355-3361, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3355-3361.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

CTX-M-Type Extended-Spectrum beta -Lactamase That Hydrolyzes Ceftazidime through a Single Amino Acid Substitution in the Omega Loop

Laurent Poirel,1 Thierry Naas,1 Isabelle Le Thomas,2 Amal Karim,1 Edouard Bingen,2 and Patrice Nordmann1,*

Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre Cedex,1 and Service de Microbiologie, Hôpital Robert Debré, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Xavier-Bichat, 75018 Paris,2 France

Received 18 December 2000/Returned for modification 11 April 2001/Accepted 21 August 2001

Escherichia coli ILT-1, Klebsiella pneumoniae ILT-2, and K. pneumoniae ILT-3 were isolated in May 1999 in Paris, France, from a rectal swab of a hospitalized 5-month-old girl. These isolates had a clavulanic acid-inhibited substrate profile that included expanded-spectrum cephalosporins. The MICs of cefotaxime were higher for E. coli ILT-1 and K. pneumoniae ILT-2 than for K. pneumoniae ILT-3, while the opposite was found for the MICs of ceftazidime. Genetic and biochemical analyses revealed that E. coli ILT-1 and K. pneumoniae ILT-2 produced the CTX-M-18 beta -lactamase, while K. pneumoniae ILT-3 produced the CTX-M-19 beta -lactamase. The amino acid sequence of the CTX-M-18 beta -lactamase differed from that of the CTX-M-9 beta -lactamase by an Ala-to-Val change at position 231, while CTX-M-19 possessed an additional Pro-to-Ser change at position 167 in the omega loop of Ambler class A enzymes. The latter amino acid substitution may explain the CTX-M-19-mediated hydrolysis of ceftazidime, which has not been reported for other CTX-M-type enzymes. The blaCTX-M-18 and blaCTX-M-19 genes were located on transferable plasmids that varied in size (ca. 60 and 50 kb, respectively) but that showed similar restriction patterns.

* Corresponding author. Mailing address: Service de Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France. Phone: 33-1-45-21-36-32. Fax: 33-1-45-21-63-40. E-mail: nordmann.patrice{at}bct.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3355-3361, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3355-3361.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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