1181. Molecular Characterization of Piperacillin-Tazobactam (TZP) Resistant Escherichia coli Susceptible to Cephalosporins, Monobactams, and Carbapenems
Session: Poster Abstract Session: Resistance Mechanisms
Friday, October 9, 2015
Room: Poster Hall
Background: Piperacillin-tazobactam (TZP) is among the most widely used parenteral antimicrobials in the U.S., and the prevalence of non-susceptible organisms has risen sharply in recent years. While TZP resistance is generally mirrored by other β-lactams, we have identified Escherichia coli strains that are pan-susceptible to all cephalosporins (CS), monobactams (MB) and carbapenems (CP), but highly resistant to TZP (TZP-R). Here we characterized a representative collection of TZP-R isolates to investigate the resistance mechanisms responsible for this novel phenotype.

Methods: 40 non-duplicate, CS/MB/CP-susceptible TZP-R E. coli isolates were obtained from hospitals in 20 U.S. states between 2013-2015. MICs were determined using reference broth microdilution methods. Confirmation of highly-resistant TZP-R profiles was further assessed by Vitek, TREK and Etest. Isolates were genetically characterized by PCR/sequencing for MLST, porin mutations, and carbapenemase, ESBL and AmpC genes. 

Results: All 40 E. coli isolates were highly resistant to TZP, but susceptible to aztreonam, cefepime, ceftolozane/tazobactam, ceftriaxone, ceftazidime, ertapenem, and meropenem. Of these, 38 harbored TEM-1, but no TEM or SHV ESBLs were identified. All isolates were negative for KPC, NDM, IMP, VIM, OXA-48, CTX-M and AmpC. Interestingly, ompF and ompC porin gene sequencing revealed highly heterogeneous mutant profiles. Both frameshifts (n=4) and IS-associated insertions (n=1) were observed, with additional SNPs (n=1) or deletions (n=3) identified in promoter regions. A wide range of non-synonymous mutations and in-frame insertions/deletions were also found, with the same mutations observed in different backgrounds. The isolates clustered into more than ten different MLST groups, including the epidemic ST131 clone (n=3). 

Conclusion: We report the non-clonal dissemination of a novel TZP-R E. coli phenotype, associated with deleted or dysfunctional porins which likely contribute to the observed resistance. The potential for these strains to acquire ESBL- or carbapenemase-bearing plasmids, thereby spreading high-level resistance into the community, raises significant clinical and public health concerns.

Jose R. Mediavilla, MPH, MBS1, Zachary Schneider, BA1, Chinedum Nwaigwe, HS1, Kalyan D. Chavda, MS1, Liang Chen, PhD1, Michael Satlin, MD, MS2, Stephen Jenkins, PhD3, David P. Nicolau, PharmD, FCCP, FIDSA4 and Barry N. Kreiswirth, PhD1, (1)Public Health Research Institute - Rutgers University, Newark, NJ, (2)New York-Presbyteria, New York, NY, (3)Weill Cornell Medical College, New York, NY, (4)Ctr. for Anti-Infect. Res. & Dev., Hartford Hospital, Hartford, CT


J. R. Mediavilla, None

Z. Schneider, None

C. Nwaigwe, None

K. D. Chavda, None

L. Chen, None

M. Satlin, None

S. Jenkins, None

D. P. Nicolau, Cubist Pharmaceuticals: Consultant , Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Grant recipient , Research grant , Research support and Speaker honorarium

B. N. Kreiswirth, None

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