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Treatment strategies of infection by carbapenem-resistant  Klebsiella pneumoniae  (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight  K. pneumoniae  infections. However, reports on fosfomycin-resistant  K. pneumoniae  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  K. pneumoniae . Twenty-three isolates coharbored  fosA   kp   and  fosA3 , with  K. pneumoniae  carbapenemase (KPC)-producing ST11-KL64-wzi64-O2 ( n  = 13) and ST11-KL47-wzi209-OL101 ( n  = 8), the predominating clonal groups, while  fosA3  was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive for  rmpA2 , of which 12 carried  fosA3 . Four of the 23  fosA3 -positive isolates could successfully transfer their fosfomycin-resistant determinants to  Escherichia coli  J53Azi  R  . 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  fosA3 ,  bla   KPC –2 ,  bla   CTX–M –65 ,  bla   SHV –12 ,  rmtB , and  bla   TEM –1  was identified. ST11-KL64 and ST11-KL47  K. pneumoniae , with higher resistance and virulence, should be critically monitored to prevent the future dissemination of resistance.

frontiers in microbiology

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