In vivo acquisition of blaKPC-2 with low biological cost in blaAFM-1-harboring ST463 hypervirulent Pseudomonas aeruginosa from a patient with hematologic malignancy

Zhang, Piaopiao; Wang, Jie; Shi, Weixiao; Wang, Nanfei; Jiang, Yan; Chen, Hongchao; Yang, Qing; Qu, Tingting

doi:10.1016/j.jgar.2022.09.004

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…For example, O4 is associated with ST175’s MDR/XDR profile [ 37 ]. However, we found that O4 mainly belonged to ST1800 XDR-hvPA and a bla KPC-2 -carried ST463 isolate, which were also found in other regions in China [ 8 , 9 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 78%

“…The bla KPC first detected in Klebsiella pneumoniae has been worldwide dissemination in this strain [ 28 , 29 ]. In recent years, it has come to be increasingly found in P. aeruginosa , and some reports have shown that the KPC gene is also found in hvPA, which was mainly in the southeastern coastal areas of China and predominantly in a potentially high-risk clone of P. aeruginosa ST463 [ 8 , 9 , 30 , 31 ]. De Paula-Petroli et al also reported a KPC-2-producing hvPA ST235 in Brazil [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Zhang et al reported the emergence and recurrence of KPC-producing hvPA ST697 and ST463 between 2010 and 2021 in China [ 8 ]. In vivo acquisition of bla KPC-2 in bla AFM-1 -expressing hvPA ST463 was also reported in a patient with hematologic malignancy [ 9 ]. Early detection of a KPC-2-producing hvPA ST235 was reported by de Paula-Petroli et al in Brazil [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Li,

Tang,

Liu

et al. 2024

Ann Clin Microbiol Antimicrob

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Background Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination. Methods Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing. Results A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES−1 (10/47), blaVIM−2 (6/47), blaGES−14 (4/47), blaIMP−45 (2/47), blaKPC−2 (1/47), and blaNDM−14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4–O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018–2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L). Conclusions The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Li,

Tang,

Liu

et al. 2024

Ann Clin Microbiol Antimicrob

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“…AYV97588.1 Sputum Unreported 2 Zhang X, et al 2021 17 HS18-89 ST463 blaIMP-45 blaAFM-1 Shanghai,China No.AYV97588.1 Unreported Unreported 3 Zhang X, et al 2021 13 RJ19-28 ST708 blaIMP-45 blaOXA-1 blaAFM-1 Shanghai,China N Wound fluid Unreported 4 Zhang P, et al 2022 16 U1121 ST463 blaPDC-374 blaOXA-486 blaCARB-2 blaKPC-2 blaAFM-1 Zhejiang,China No. MZ050803 Urinary Acute lymphoblastic leukemia 5 Zhang P, et al 2022 16 B1122 ST463 blaPDC-374 blaOXA-486 blaCARB-2, blaAFM-1, Zhejiang,China No.CP064394 Blood Acute lymphoblastic leukemia 6 Fang Y, et al 2023 14 PA30 ST463 blaIMP-45 blaAFM-1, blaKPC-2 Zhejiang,China No.LT799039.1 Catheter No 7 Chen M, et al 2022 14 AR19640,AR19726,AR19727,AR23664 ST671 blaAFM-2 …”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

Shen,

Cao,

et al. 2024

IDR

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Background Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam . The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment. Herein, we reported a case of perianal infection with hypervirulent ST463 Pseudomonas aeruginosa . Case Presentation The case is a 32-year-old acute myeloid leukemia (AML) patient with fever and septic shock during hematopoietic stem cell transplantation (HSCT), and the pathogen was finally identified as a highly virulent sequence type 463 (ST463) P. aeruginosa harboring carbapenem-resistant genes bla AFM-1 and bla KPC-2 , which was detected in the bloodstream and originated from a perianal infection. The strain was resistant to ceftazidime/avibactam but successfully treated with polymyxin B , surgical debridement, and granulocyte engraftment after HSCT. The AML was cured during the 19-month follow-up. Conclusion This case emphasizes the importance of metagenomic next-generation sequencing (mNGS) and whole-genome sequencing (WGS) in identifying microbes with rare resistant genes, and managing CRPA, especially in immunocompromised patients. Polymyxin B may be the least resistant option.

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“…However, the spread and evolution of bacterial resistance are always more complex than are imagined. The in vivo evolution driving the acquisition of bla KPC-2 under carbapenem exposure in a bla AFM-1 -harboring ST463 P. aeruginosa strain has been reported ( 17 ). The ST463 P. aeruginosa strain in our study contains two MBLs genes, namely, bla IMP-45 and bla AFM-1 , and these are harbored by the IncP-2 megaplasmid.…”

Section: Discussionmentioning

confidence: 99%

An XDR Pseudomonas aeruginosa ST463 Strain with an IncP-2 Plasmid Containing a Novel Transposon Tn 6485f Encoding bla _IMP-45 and bla _AFM-1 and a Second Plasmid with Two Copies of bla _KPC-2

Fang

Wang

et al. 2023

Microbiol Spectr

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The ST463 clone is an emerging high-risk sequence type that is spreading with bla KPC-2 -containing plasmids. The core bla KPC-2 genetic platform is IS Kpn27 -b la KPC-2 -IS Kpn6 in almost all samples, and the adjacent region beyond the core platform varies by IS 26 -mediated inversion or duplication events, amplifying the bla KPC-2 gene copies.

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In vivo acquisition of blaKPC-2 with low biological cost in blaAFM-1-harboring ST463 hypervirulent Pseudomonas aeruginosa from a patient with hematologic malignancy

Cited by 7 publications

References 33 publications

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

An XDR Pseudomonas aeruginosa ST463 Strain with an IncP-2 Plasmid Containing a Novel Transposon Tn 6485f Encoding bla _IMP-45 and bla _AFM-1 and a Second Plasmid with Two Copies of bla _KPC-2

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In vivo acquisition of blaKPC-2 with low biological cost in blaAFM-1-harboring ST463 hypervirulent Pseudomonas aeruginosa from a patient with hematologic malignancy

Cited by 7 publications

References 33 publications

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China

Successful Treatment of an AML Patient Infected with Hypervirulent ST463 Pseudomonas Aeruginosa Harboring Rare Carbapenem-Resistant Genes blaAFM-1 and blaKPC-2 Following Allogeneic Hematopoietic Stem Cell Transplantation

An XDR Pseudomonas aeruginosa ST463 Strain with an IncP-2 Plasmid Containing a Novel Transposon Tn 6485f Encoding bla IMP-45 and bla AFM-1 and a Second Plasmid with Two Copies of bla KPC-2

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An XDR Pseudomonas aeruginosa ST463 Strain with an IncP-2 Plasmid Containing a Novel Transposon Tn 6485f Encoding bla _IMP-45 and bla _AFM-1 and a Second Plasmid with Two Copies of bla _KPC-2