The emergence of various new Klebsiella pneumoniae carbapenemase (KPC) variants leading to ceftazidime-avibactam treatment failure is a new challenge in current clinical anti-infection treatment. Here, we report a ceftazidime-avibactam-resistant K. pneumoniae 1072-2 clinical strain carrying a novel KPC variant, KPC-134, which differs from KPC-2 by both single mutation (D178A) and 8-amino acid insertions (asp-asp-asn-arg-ala-pro-asn-lys). The results of antimicrobial susceptibility testing showed that the isolate was resistant to meropenem (MIC = 4 mg/L), ceftazidime (MIC ≥ 32 mg/L), cefepime (MIC ≥128 mg/L), aztreonam (MIC ≥128 mg/L), and ceftazidime-avibactam (MIC ≥128 mg/L) but sensitive to imipenem (MIC = 0.5 mg/L), imepenem-relebactam (MIC = 0.5 mg/L), meropenem-vaborbactam (MIC = 2 mg/L), and aztreonam-avibactam (MIC = 4 mg/L). The plasmid containing bla_KPC-134 was isolated from K. pneumoniae, and the bla_KPC-134 gene was cloned into plasmid pHSG398 and transformed into an Escherichia coli DH5α to observe changes in antimicrobial resistance. The results indicated that the transformant was positive for bla_KPC-134 and increased MICs of ceftazidime-avibactam, ceftazidime, cefepime, and aztreonam by 512-fold, 256-fold, 16-fold, and 4-fold, respectively, compared with the recipient. The results of third-generation sequencing showed that the bla_KPC-134 gene was carried by a 133,789 bp IncFII-IncR plasmid, and many common resistance genes (including bla_CTX-M-65, bla_TEM-1B, bla_SHV-12, rmtB, and catB4) along with the IS26, tnpR, ISkpn8, ISkpn6-like, and Tn1721 elements were identified. IMPORTANCE The emergence of various new KPC variants leading to ceftazidime-avibactam treatment failure is a new challenge for clinical anti-infection treatment. Here, we describe the characterization of a ceftazidime-avibactam-resistant blaKPC-134-positive Klebsiella pneumoniae clinical strain for the first time. K. pneumoniae bearing with KPC variant often mislead clinical anti-infection treatment because of their unique antimicrobial susceptibility profile and the tendency of conventional carbapenemase assays to give false negative results. Therefore, timely identification of KPC variants and effective anti-infective therapy are key to saving infected patients.

#	Concept	H-Index	Publications	Citations
1	Medicine	2	2	445
2	Allergy	1	1	431
3	Gastroenterology	1	1	14
4	Immunology	1	1	431
5	Microbiology	1	1	14

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