Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and blaKPC–2 Coharboring Plasmids in Shandong, China

Abstract

Treatment strategies of infection by carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight <i>K. pneumoniae</i> infections. However, reports on fosfomycin-resistant <i>K. pneumoniae</i> are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole-genome sequencing and bioinformatics analysis were conducted to reveal molecular characteristics of fosfomycin-resistant <i>K. pneumoniae</i>. Twenty-three isolates coharbored <i>fosA</i> <i>^kp</i> and <i>fosA3</i>, with <i>K. pneumoniae</i> carbapenemase (KPC)-producing ST11-KL64-wzi64-O2 (<i>n</i> = 13) and ST11-KL47-wzi209-OL101 (<i>n</i> = 8), the predominating clonal groups, while <i>fosA3</i> was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive for <i>rmpA2</i>, of which 12 carried <i>fosA3</i>. Four of the 23 <i>fosA3</i>-positive isolates could successfully transfer their fosfomycin-resistant determinants to <i>Escherichia coli</i> J53Azi <i>^R</i> . All four strains belonged to ST11-KL47 with the same pulsed-field gel electrophoresis profile, and their transconjugants acquired fosfomycin, carbapenem, and aminoglycoside resistance. A 127-kb conjugative pCT-KPC-like hybrid plasmid (pJNKPN52_KPC_fosA) coharboring <i>fosA3</i>, <i>bla</i> _<i>KPC</i>-2, <i>bla</i> _{<i>CTX-M</i>-65}, <i>bla</i> _{<i>SHV</i>-12}, <i>rmtB</i>, and <i>bla</i> _<i>TEM</i>-1 was identified. ST11-KL64 and ST11-KL47 <i>K. pneumoniae</i>, with higher resistance and virulence, should be critically monitored to prevent the future dissemination of resistance.