In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases

被引:85
作者
Shields, Ryan K. [1 ,2 ]
Nguyen, M. Hong [1 ,2 ]
Press, Ellen G. [1 ]
Chen, Liang [3 ]
Kreiswirth, Barry N. [3 ]
Clancy, Cornelius J. [1 ,2 ,4 ]
机构
[1] Univ Pittsburgh, Dept Med, 930 Scaife Hall, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Med Ctr, XDR Pathogen Lab, Pittsburgh, PA 15260 USA
[3] Rutgers State Univ, Publ Hlth Res Inst, New Jersey Med Sch, TB Ctr, Newark, NJ USA
[4] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA
基金
美国国家卫生研究院;
关键词
carbapenem-resistant Enterobacteriaceae; Klebsiella pneumoniae carbapenemase; ceftazidime-avibactam resistance; sequence type 258 Klebsiella pneumoniae; KPC mutations; SEQUENCE TYPE 258; BETA-LACTAMASES; DORIPENEM; COLISTIN; STRAINS; ENTEROBACTERIACEAE; MUTATIONS; RESPONSES; GENOTYPES;
D O I
10.1128/AAC.00079-17
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Ceftazidime-avibactam resistance is mediated by bla(KPC-3) mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different bla(KPC-3) mutations (n=5) or wild-type bla(KPC-3) (n=2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, bla(KPC-3) mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. pneumoniae infections may select for carbapenem resistance.
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