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Antimicrob Agents Chemother. 2016 Aug 22;60(9):5208-14. doi: 10.1128/AAC.00869-16. Print 2016 Sep.

Association between the Presence of Aminoglycoside-Modifying Enzymes and In Vitro Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter Species.

Antimicrobial agents and chemotherapy

Ghady Haidar, Ammar Alkroud, Shaoji Cheng, Travis M Churilla, Bryce M Churilla, Ryan K Shields, Yohei Doi, Cornelius J Clancy, M Hong Nguyen

Affiliations

  1. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  2. University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  3. University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  4. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  5. University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA.
  6. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA [email protected].

PMID: 27297487 PMCID: PMC4997819 DOI: 10.1128/AAC.00869-16

Abstract

We compared the in vitro activities of gentamicin (GEN), tobramycin (TOB), amikacin (AMK), and plazomicin (PLZ) against 13 Enterobacter isolates possessing both Klebsiella pneumoniae carbapenemase and extended-spectrum β-lactamase (KPC+/ESBL+) with activity against 8 KPC+/ESBL-, 6 KPC-/ESBL+, and 38 KPC-/ESBL- isolates. The rates of resistance to GEN and TOB were higher for KPC+/ESBL+ (100% for both) than for KPC+/ESBL- (25% and 38%, respectively), KPC-/ESBL+ (50% and 17%, respectively), and KPC-/ESBL- (0% and 3%, respectively) isolates. KPC+/ESBL+ isolates were more likely than others to possess an aminoglycoside-modifying enzyme (AME) (100% versus 38%, 67%, and 5%; P = 0.007, 0.06, and <0.0001, respectively) or multiple AMEs (100% versus 13%, 33%, and 0%, respectively; P < 0.01 for all). KPC+/ESBL+ isolates also had a greater number of AMEs (mean of 4.6 versus 1.5, 0.9, and 0.05, respectively; P < 0.01 for all). GEN and TOB MICs were higher against isolates with >1 AME than with ≤1 AME. The presence of at least 2/3 of KPC, SHV, and TEM predicted the presence of AMEs. PLZ MICs against all isolates were ≤4 μg/ml, regardless of KPC/ESBL pattern or the presence of AMEs. In conclusion, GEN and TOB are limited as treatment options against KPC+ and ESBL+ Enterobacter PLZ may represent a valuable addition to the antimicrobial armamentarium. A full understanding of AMEs and other aminoglycoside resistance mechanisms will allow clinicians to incorporate PLZ rationally into treatment regimens. The development of molecular assays that accurately and rapidly predict antimicrobial responses among KPC- and ESBL-producing Enterobacter spp. should be a top research priority.

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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