Ceftazidime-avibactam based combinations against carbapenemase producing Klebsiella pneumoniae harboring hypervirulence plasmids

Bulman, Zackery P.; Tan, Xing; Chu, Tingyu; Huang, Yanqin; Rana, Amisha P; Singh, Nidhi; Flowers, Stephanie A.; Kyono, Yasuhiro; Kreiswirth, Barry N; Chen, Liang

doi:10.1016/j.csbj.2022.07.017

Cited by 2 publications

(3 citation statements)

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“…In addition, pNCRE-61-vir and pKP-2185-vir only contain a single replicon of IncFIB (repB_KLEB_VIR), while the second IncHIB (pNDM-MAR) found in p2683-Vir was missing. Overall, the three bla OXA-48 harboring plasmids, pKP-2683-OXA, pNCRE-61-OXA, and pKP2185-OXA, are highly similar to the bla OXA-48 prototype plasmid pOXA48a [ 22 , 24 ], with 94–96% query coverages and ~99.8% nucleotide identity ( Figure 1 ). The main difference is that the bla OXA-48 in pOXA48a is harbored by a Tn1999.1 element, while it was carried by a Tn1999.2 transposon in three plasmids sequenced in the current study.…”

Section: Resultsmentioning

confidence: 99%

“…Most CR-hvKP strains reported to date involve KPC or NDM-producing strains [ 5 , 6 ]. OXA-48-producing hvKP strains have been reported in Europe, but the in vivo virulence of these strains has not been evaluated [ 12 , 22 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Sequence types (ST), capsular types, and virulence genes were characterized using Kleborate v2.3.0 [ 20 ] and Kaptive v2.0.4 [ 21 ]. Plasmid replicon analysis was conducted using plasmidFinder [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

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RETRACTED: Drug Resistance and Molecular Characteristics of Carbapenem-Resistant OXA-48-Producing Klebsiella pneumoniae Strains in Hainan, China

Ye,

Liu,

Liu

et al. 2023

Microorganisms

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Background: The emergence and global spread of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) are of great concern to health services worldwide. These β-lactamases hydrolyze almost all β-lactams, are plasmid-encoded, and are easily transferable among bacterial species. They are mostly of the KPC types in CR-hvKp. OXA-48-producing hvKP strains have been rarely reported in the literature. Methods: OXA-48-producing hvKP strains were collected from clinical specimens at the First Affiliated Hospital of Hainan Medical University from January 2022 to March 2023. Hypervirulent strains were tested for virulence in a mouse lethality study and underwent whole genome sequencing to identify genomic features. Results: A total of 42 unique OXA-48-bearing K. pneumoniae strains were identified, including three CR-hvKP strains (KP2683-1, NCRE61, and KP2185), which were isolated from bacteremia, pulmonary abscess, and liver abscess separately. The three CR-hvKP strains belonged to two different clones of ST11 KL64 (KP2185 and NCRE61) and ST23 K1 (KP2683-1). The KP2683-1 strain had the highest virulence. Whole genome sequencing analysis indicated that NCRE61 and KP2185 acquired IncFIB-type plasmids with a set of virulence genes (iroBCDN, iucABCD, iutA, rmpA, and rmpA2), while KP2683-1 acquired an IncL-type blaOXA-48-harboring plasmid. Consecutive cultures showed that the blaOXA-48-harboring plasmids were highly stable in the three hvKP strains and could be transmitted to Escherichia coli J53 by conjugation. The drug susceptibility testing results show that Ceftazidime/avibactam is sensitive for OXA-48-producing hvKP. Conclusions: Our study highlighted the two evolutionary pathways of OXA-48-producing hvKP strains and confirmed their virulence through in vivo testing. Ceftazidime/avibactam may be a viable option for treating OXA-48-producing hvKP strains.

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Section: Resultsmentioning

confidence: 99%