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.
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.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Ghady
G
Haidar
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Ammar
A
Alkroud
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Shaoji
S
Cheng
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Travis M
TM
Churilla
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bryce M
BM
Churilla
University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Ryan K
RK
Shields
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Yohei
Y
Doi
University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA.
Cornelius J
CJ
Clancy
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 mhn5@pitt.edu.
M Hong
MH
Nguyen
D000583:Amikacin / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001711:Biotransformation; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004754:Enterobacter / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology; D015870:Gene Expression; D005839:Gentamicins / Q000378:metabolism / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000737:chemistry / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D012853:Sisomicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014031:Tobramycin / Q000378:metabolism / Q000494:pharmacology; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005839:Gentamicins; D000583:Amikacin; D001618:beta-Lactamases; C550938:plazomicin; D014031:Tobramycin; D012853:Sisomicin