Journal of Antimicrobial Chemotherapy, Vol 40, 533-541, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
R Gheorghiu, M Yuan, LM Hall and DM Livermore
Nineteen isolates of Klebsiella oxytoca were examined, representing 18
distinct strains. All were from a 1994 survey of resistance amongst
klebsiellae in intensive care units in Europe, and all had reduced
susceptibility, or were resistant, to cefuroxime, ceftriaxone and
aztreonam, suggesting hyperproduction of the chromosomal K1 beta-
lactamase. We sought to confirm this mechanism and to identify why the
levels of resistance varied between isolates. Possible reasons for
variation were differences in the quantity or subtype of the K1 enzyme or
differences in this enzyme's interplay with permeability.
Spectrophotometric assays showed that all 19 isolates had K1-like beta-
lactamases and that these were present at > or = 15-fold higher levels
than in beta-lactam-sensitive K. oxytoca isolates. Fourteen of the 19
isolates had the OXY-2 form of K1 enzyme, while the remaining five had the
OXY-1 form, as determined by isoelectric focusing and PCR amplification.
Most isolates with the OXY-2 enzyme were more resistant than those with the
OXY-1 subtype, but this difference partly reflected enzyme quantity rather
than subtype. More generally, and irrespective of enzyme subtype, levels of
resistance were broadly related to beta- lactamase specific activity, and
the degree of hyperproduction was a major determinant of the level of
resistance. Nevertheless, other factors had a role too: several isolates
had reduced susceptibility or were resistant to cefoxitin, which is not a
substrate for K1 enzyme, and examination of outer membrane protein profiles
revealed considerable strain-to-strain diversity in the molecular weight
range typical of the major enterobacterial porins (40-48 kDa).
ORIGINAL ARTICLES
Bases of variation in resistance to beta-lactams in Klebsiella oxytoca isolates hyperproducing K1 beta-lactamase
Royal London School of Medicine and Dentistry, UK.
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