OXA-16, a further extended-spectrum variant of OXA-10 beta-lactamase, from two Pseudomonas aeruginosa isolates


DANEL F., HALL L., Gur D. , LIVERMORE D.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol.42, no.12, pp.3117-3122, 1998 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 42 Issue: 12
  • Publication Date: 1998
  • Doi Number: 10.1128/aac.42.12.3117
  • Title of Journal : ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
  • Page Numbers: pp.3117-3122

Abstract

Two extended-spectrum mutants of the class D beta-lactamase OXA-10 (PSE-2) from Pseudomonas aeruginosa isolates obtained in Ankara, Turkey, were described previously and were designated OXA-11 and -14. P. aeruginosa 906 and 961, isolated at the same hospital, were highly resistant to ceftazidime (MIC greater than or equal to 128 mu g/ml) and produced a p-lactamase with a pi of 6.2. The MICs of ceftriaxone, cefoperazone, cefsulodin, and cefepime were 4- to 16-fold above the typical values for P. aeruginosa, whereas the MICs of penicillins and cefotaxime were raised only marginally. Ceftazidime MICs were not significantly reduced by clavulanate or tazobactam at 4 mu g/ml. Ceftazidime resistance did not transfer conjugatively but was mobilized to P. aeruginosa PU21 by plasmid pUZ8. Both isolates gave similar DNA restriction patterns, suggesting that they were replicates; moreover, they yielded identically sized BamHI fragments that hybridized with a bla(OXA-10) probe. DNA sequencing revealed that both isolates had the same new beta-lactamase, designated OXA-16, which differed from OXA-10 in having threonine instead of alanine at position 124 and aspartate instead of glycine at position 157. The latter change is also present in OXA-11 and -14 and seems critical to ceftazidime resistance. Kinetic parameters showed that OXA-16 enzyme was very active against penicillins, cephaloridine, cefotaxime, and ceftriaxone, but hydrolysis of ceftazidime was not detected despite the ability of the enzyme to confer resistance.