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Journal of Antimicrobial Chemotherapy (1987) 20, 323-334
© 1987 The British Society for Antimicrobial Chemotherapy


research-article

Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel ß-lactamase

D. Sirot*,a, J. Sirota, R. Labiab, A. Morandb, P. Courvalinc, A. Darfeuille-Michauda, R. Perrouxa and R. Cluzela

aService de Bactériologie, Faculté de Médecine 28 place Henri Dunant, 63001 Clermont-Ferrand bMusèum National d'Histoire Naturelle CNRS UA 401,63, rue Buffon, 75231 Paris Cedex 05 cUnité des Agents Antibactériens CNRS UA 271, Institut Pasteur, 75724 Paris Cedex 15, France

Received 9 March 1987;


*Corresponding author

Approximately 10% (89 isolates) of Klebsiella pneumoniae isolated in 1985 from patients in intensive care units in Clermont-Ferrand exhibited a complex resistance phenotype towards antibiotics. They were resistant to amino-, carboxy- and ureidopenicillins, aminoglycosides (except gentamicin), chloramphenicol, sulphonamides, tetracyclines and, most importantly, to cephalosporins (except cefoxitin and latamoxef) and to aztreonam. The metabolic profile of fifty isolates was identical and seven were selected for further study. All the resistance characters in these isolates were transferable to Escherichia coli by conjugation and were lost en bloc after treatment with ethidium bromide. Agarose gel electrophoresis of crude lysates of the wild types and their transconjugants indicated that the multiple resistances were mediated by a 95kb plasmid, pCF04. The seven isolates selected for study and their corresponding transconjugants, constitutively produced a plasmid-mediated ß-lactamase with a pI of 6.3 that was much more active against third-generation cephalosporins than against cephalothin. The substrate profile and the isoelectric-focusing behaviour of this enzyme differed from those of other known plasmid-mediated ß-lactamases, and the enzyme was designated CTX-1. A chromosomally-encoded SHV-1 (PIT-2) penicillinase (pI 7.7) was also present in the seven K. pneumoniae isolates but did not transfer. Resistance to aminoglycosides in the K. pneumoniae isolates was due to synthesis of a 6'-aminoglycoside acetyltransferase type IV. Our data indicate an epidemic of antibiotic multiply-resistant strains of K. pneumoniae producing a new ß-lactamase.


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