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.
J. R. Mediavilla,
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