AUTHOR=Zhu Junying , Ding Baixing , Xu Xiaogang , Zhu Demei , Yang Fan , Zhang Hong , Hu Fupin 

TITLE=Klebsiella pneumoniae: Development of Carbapenem Resistance due to Acquisition of blaNDM-1 During Antimicrobial Therapy in Twin Infants with Pneumonia

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 6 - 2015

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.01399

DOI=10.3389/fmicb.2015.01399

ISSN=1664-302X

ABSTRACT=Objectives: To identify the mechanism of in vivo development of carbapenem resistance in Klebsiella pneumoniae.
Methods: Seven sequential isolates of K. pneumoniae were obtained from twin infants with pneumonia. Antimicrobial susceptibility testing was performed by agar dilution. Carbapenemases including KPC and ML were initially screened using phenotypic methods, and carbapenemase-encoding genes were identified by PCR and amplicon sequencing. Plasmids of all clinical isolates and the conjugants of resistant isolates were estimated by S1 pulsed-field gel electrophoresis (PFGE). Molecular typing were conducted by PFGE of XbaI-digested genomic DNA and multilocus sequence typing (MLST). 
Results: For old brother, the first and third isolates were susceptible to meropenem, whereas the second and fourth isolates were resistant (MICs 16 mg/L). The first and second isolates from the young brother were susceptible to meropenem whereas the third isolate was resistant. All the resistant isolates produced NDM-1 metallo--lactamase. PFGE of XbaI-digested DNA revealed identical patterns for all the 7 isolates. All the isolates had the same sequence type named sequence type 37 (ST37). 
Conclusions: To our knowledge, this is the first documented case of development of carbapenem resistance in vivo mediated by NDM-1 metallo-b-lactamase in K. pneumoniae during treatment of pneumonia with meropenem.