CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop

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 hospi talized 5-month-old girl. These isolates had a clavulanic acid-inhibited su bstrate 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 ceftazidi me. Genetic and biochemical analyses revealed that E. coli ILT-1 and K. pne umoniae ILT-2 produced the CTX-M-18 beta -lactamase, while K. pneumoniae IL T-3 produced the CTX-M-19 beta -lactamase. The amino acid sequence of the C TX-M-18 beta -lactamase differed from that of the CTX-M-9 beta -lactamase b y an Ala-to-Val change at position 231, while CTX-M-19 possessed an additio nal Pro-to-Ser change at position 167 in the omega loop of Ambler class A e nzymes. The latter amino acid substitution may explain the CTX-M-19-mediate d hydrolysis of ceftazidime, which has not been reported for other CTX-M-ty pe enzymes. The bla(CTX-M-18) and bla(CTX-M-19) genes were located on trans ferable plasmids that varied in size (ca. 60 and 50 kb, respectively) but t hat showed similar restriction patterns.