Background: Piperacillin / tazobactam (P/T) plays an important role in the empirical therapy of many infections. While Enterobacteraciae resistance to P/T remains relatively low in our institution we have identified an increasing number of E.coli and Klebsiella sp. isolates with intermediate susceptibility or resistance to P/T (P/T-R). We report the increasing prevalence of P/T-R among E.coli and Klebsiella sp., antimicrobial usage, and attempts to document the mechanism of resistance in these isolates.
Methods: Antimicrobial susceptibility results using Kirby Bauer disk diffusion method for E.coli and Klebsiella sp. from all clinical sites (hospitalized patients) were reviewed from January 2006 through December 2016. Duplicates were excluded. Antimicrobial use was expressed as the number of hospital days on antimicrobials per 1000 hospital days. Whole genome sequencing was performed on a subset of isolates identified as P/T-R in order to identify a mechanism of resistance.
Results: From 2006 through 2016 we identified 126,422 E.coli and Klebsiella sp. isolates; 978 were P/T-R (0.78%). Of these 336 were extended spectrum beta lactamase (ESBL) producers. Of the 642 non ESBL- P/T-R, 179 (27.8%) retained susceptibility to all cephalosporins tested. Figure 1 shows the distribution of P/T-R isolates and total antibiotic and P/T use in hospitalized patients. Whole genome sequencing of 4 isolates (K. pneumoniae from blood; n=3 and E. coli from urine; n=1) showed the presence of Class A beta-lactamase genes; SHV (n=3) and TEM (n=1). All isolates showed the presence genes for outer membrane porins and protein efflux pumps, however, there were no detectable mutations that could explain the phenotypic susceptibility profile seen in these isolates.
Conclusion: We describe a novel phenotypic resistance pattern to P/T in E. coli and Klebsiella sp.which doubled in incidence from 2013 - 2016. This is concurrent with increasing P/T and overall antimicrobial use during the same time period. While a porin mutation has been described in similar strains, we have not been able to demonstrate this mechanism of resistance to date. Clinicians should be aware of this emerging resistance pattern when prescribing empiric antimicrobials.
J. Semel, None
R. Thomson Jr., None