scholarly journals CTX-M Expression and Selection of Ertapenem Resistance in Klebsiella pneumoniae and Escherichia coli

2008 ◽  
Vol 53 (2) ◽  
pp. 832-834 ◽  
Author(s):  
Delphine Girlich ◽  
Laurent Poirel ◽  
Patrice Nordmann

ABSTRACT In vitro selection of mutants with decreased susceptibility to ertapenem was performed using Escherichia coli and Klebsiella pneumoniae clinical strains producing either the bla CTX-M-2, bla CTX-M-3, bla CTX-M-9, or bla CTX-M-15 gene. Frequencies of mutants with decreased susceptibilities to ertapenem were similar for all β-lactamases expressed.

2008 ◽  
Vol 52 (4) ◽  
pp. 1297-1301 ◽  
Author(s):  
Marina N. Stepanova ◽  
Maxim Pimkin ◽  
Anatoly A. Nikulin ◽  
Varvara K. Kozyreva ◽  
Elena D. Agapova ◽  
...  

ABSTRACT We report on a novel CTX-M extended-spectrum β-lactamase (ESBL), designated CTX-M-42, with enhanced activity toward ceftazidime. CTX-M-42 was identified in a hypermutable Escherichia coli nosocomial isolate (isolate Irk2320) and is a Pro167Thr amino acid substitution variant of CTX-M-3. By molecular typing of ESBL-producing E. coli strains previously isolated in the same hospital ward, we were able to identify a putative progenitor (strain Irk1224) of Irk2320, which had a mutator phenotype and harbored the CTX-M-3 β-lactamase. To reproduce the natural evolution of CTX-M-3, we selected for ceftazidime resistance mutations in bla CTX-M-3 gene in vitro both in clinical isolate Irk1224 and in laboratory-derived hypermutable (mutD5) strain GM2995. These experiments yielded CTX-M-3Pro167Ser and CTX-M-3Asn136Lys mutants which conferred higher levels of resistance to ceftazidime than to cefotaxime. CTX-M-3Asn136Lys had a level of low activity toward ampicillin, which may explain its absence from clinical isolates. We conclude that the selection of CTX-M-42 could have occurred in vivo following treatment with ceftazidime and was likely facilitated by the hypermutable background.


2014 ◽  
Vol 174 (3-4) ◽  
pp. 514-522 ◽  
Author(s):  
Xiaoqiang Liu ◽  
Caterina Lazzaroni ◽  
Sherine A. Aly ◽  
Kamoltip Thungrat ◽  
Dawn M. Boothe

1994 ◽  
Vol 242 (3) ◽  
pp. 186-192 ◽  
Author(s):  
Ellen Tinkle Peterson ◽  
Tao Pan ◽  
Julia Coleman ◽  
Olke C. Uhlenbeck

2012 ◽  
Vol 417 (1) ◽  
pp. 414-420 ◽  
Author(s):  
Young Ju Lee ◽  
Seung Ryul Han ◽  
Jin-Soo Maeng ◽  
Yong-Jin Cho ◽  
Seong-Wook Lee

2019 ◽  
Vol 75 (3) ◽  
pp. 559-565 ◽  
Author(s):  
Siqiang Niu ◽  
Jie Wei ◽  
Chunhong Zou ◽  
Kalyan D Chavda ◽  
Jingnan Lv ◽  
...  

Abstract Objectives To examine the in vitro selection of aztreonam/avibactam resistance among MBL-producing Klebsiella pneumoniae and to understand the mechanism of increased resistance. Methods The MICs of aztreonam were determined with and without avibactam (4 mg/L) using a broth microdilution method. Single-step and multi-step mutant selection was conducted on five MBL-producing K. pneumoniae strains, including two dual carbapenemase producers. Genomic sequencing and gene cloning were performed to investigate the mechanism of increased resistance. Results We examined the MICs for 68 MBL-producing K. pneumoniae isolates, including 13 dual carbapenemase producers. Compared with aztreonam alone, the addition of avibactam (4 mg/L) reduced the MICs for all isolates by >128-fold, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively. One NDM-1-, OXA-48-, CTX-M-15- and CMY-16-positive ST101 K. pneumoniae strain was selected to be resistant to aztreonam/avibactam, with a >16-fold increase in MIC (>128 mg/L). WGS revealed that the resistant mutants lost the blaNDM-1 gene, but acquired amino acid substitutions in CMY-16 (Tyr150Ser and Asn346His). Construction of blaCMY-16 mutants confirmed that the substitutions (Tyr150Ser and Asn346His) were primarily responsible for the decreased susceptibility to aztreonam/avibactam. In addition, transfer of blaCMY-16 mutant (Tyr150Ser and Asn346His) plasmid constructs into certain clinical carbapenemase-producing isolates demonstrated >64-fold increased MICs of aztreonam/avibactam and aztreonam/avibactam/ceftazidime. Conclusions Aztreonam in combination with avibactam showed potent in vitro activity against MBL-producing K. pneumoniae. However, our study suggested the likelihood of aztreonam/avibactam resistance among MBL- and AmpC-co-producing strains and clinical practice should beware of the possibility of the emerging resistance.


2007 ◽  
Vol 17 (5) ◽  
pp. 1216-1220 ◽  
Author(s):  
Shinsuke Sando ◽  
Atsushi Ogawa ◽  
Teruyuki Nishi ◽  
Masayoshi Hayami ◽  
Yasuhiro Aoyama

2005 ◽  
Vol 49 (1) ◽  
pp. 269-270 ◽  
Author(s):  
Atsushi Ogawa ◽  
Teruyuki Nishi ◽  
Shinsuke Sando ◽  
Yasuhiro Aoyama

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