TY - JOUR
T1 - Carbapenem-resistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes, which exert differing effects on plazomicin and other agents
AU - Almaghrabi, Reem
AU - Clancy, Cornelius J.
AU - Doi, Yohei
AU - Hao, Binghua
AU - Chen, Liang
AU - Shields, Ryan K.
AU - Press, Ellen G.
AU - Iovine, Nicole M.
AU - Townsend, Bethany M.
AU - Wagener, Marilyn M.
AU - Kreiswirth, Barry
AU - Nguyen, M. Hong
PY - 2014/8
Y1 - 2014/8
N2 - We measured in vitro activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenemresistant Klebsiella pneumoniae strains from two centers and correlated the results with the presence of various aminoglycosidemodifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% and 10% of strains produced Klebsiella pneumoniae carbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6=)-Ib (98%), APH(3=)-Ia (56%), AAC(3)-IV (38%), and ANT(2")-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r=0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1 × MIC) and 94% (4 × MIC) of strains. All strains with AAC(6=)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6=)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6=)-Ib alone (P=0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P=0.0006, P<0.0001, and P=0.01, respectively). The combination of AAC(6=)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3=)-Ia were each associated with gentamicin resistance (P=0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant K. pneumoniae strains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant K. pneumoniae strains should be a research priority.
AB - We measured in vitro activity of plazomicin, a next-generation aminoglycoside, and other aminoglycosides against 50 carbapenemresistant Klebsiella pneumoniae strains from two centers and correlated the results with the presence of various aminoglycosidemodifying enzymes (AMEs). Ninety-four percent of strains were sequence type 258 (ST258) clones, which exhibited 5 ompK36 genotypes; 80% and 10% of strains produced Klebsiella pneumoniae carbapenemase 2 (KPC-2) and KPC-3, respectively. Ninety-eight percent of strains possessed AMEs, including AAC(6=)-Ib (98%), APH(3=)-Ia (56%), AAC(3)-IV (38%), and ANT(2")-Ia (2%). Gentamicin, tobramycin, and amikacin nonsusceptibility rates were 40, 98, and 16%, respectively. Plazomicin MICs ranged from 0.25 to 1 μg/ml. Tobramycin and plazomicin MICs correlated with gentamicin MICs (r=0.75 and 0.57, respectively). Plazomicin exerted bactericidal activity against 17% (1 × MIC) and 94% (4 × MIC) of strains. All strains with AAC(6=)-Ib were tobramycin-resistant; 16% were nonsusceptible to amikacin. AAC(6=)-Ib combined with another AME was associated with higher gentamicin, tobramycin, and plazomicin MICs than AAC(6=)-Ib alone (P=0.01, 0.0008, and 0.046, respectively). The presence of AAC(3)-IV in a strain was also associated with higher gentamicin, tobramycin, and plazomicin MICs (P=0.0006, P<0.0001, and P=0.01, respectively). The combination of AAC(6=)-Ib and another AME, the presence of AAC(3)-IV, and the presence of APH(3=)-Ia were each associated with gentamicin resistance (P=0.0002, 0.003, and 0.01, respectively). In conclusion, carbapenem-resistant K. pneumoniae strains (including ST258 clones) exhibit highly diverse antimicrobial resistance genotypes and phenotypes. Plazomicin may offer a treatment option against strains resistant to other aminoglycosides. The development of molecular assays that predict antimicrobial responses among carbapenem-resistant K. pneumoniae strains should be a research priority.
UR - https://www.scopus.com/pages/publications/84905393404
UR - https://www.scopus.com/pages/publications/84905393404#tab=citedBy
U2 - 10.1128/AAC.00099-14
DO - 10.1128/AAC.00099-14
M3 - Article
C2 - 24867988
AN - SCOPUS:84905393404
SN - 0066-4804
VL - 58
SP - 4443
EP - 4451
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 8
ER -
