Emergence of a KPC-90 Variant that Confers Resistance to Ceftazidime-Avibactam in an ST463 Carbapenem-Resistant Pseudomonas aeruginosa Strain

Tu, Yuexing; Wang, Dairong; Zhu, Yiwei; Li, Jiayan; Jiang, Yan; Wu, Wenhao; Li, Xi; Zhou, Hua

doi:10.1128/spectrum.01869-21

Cited by 13 publications

(16 citation statements)

References 26 publications

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“…The 53 studies included in this review were conducted in American, European, and Asian countries. China (14 studies) [ 14 , 15 , 17 , 19 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], Brazil (10 studies) [ 21 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ], and Colombia (9 studies) [ 22 , 26 , 27 , 28 , 29 , 51 , 52 , 53 , 54 ] were the countries with the most reported studies, followed by Puerto Rico (4 studies) [ 55 , 56 , 57 , 58 ], Chile (2 studies) [ 59 , 60 ], Argentina (2 studies) [ 61 , 62 ], Vietnam (1 study) [ 63 ], Trinidad and Tobago (1 study) [ 64 ], Nepal (1 study) [ 65 ], India (1 study) [ 66 ], Germany (1 study) [ 18 ], Spain (1 study) [ 6 ], and the USA (1 study) […”

Section: Resultsmentioning

confidence: 99%

“…The current systematic review indicated that KPC-2 remains the most successful KPC variant worldwide, followed by KPC-5, which has only been reported in Puerto Rico. Recently, KPC-33 and KPC-90 variants have also been identified in Zhejiang, China, both belonging to ST463 [ 36 , 41 ]. Although all isolates have reported resistance against carbapenem antibiotics, some variants, such as KPC-90, have already shown to be resistant to more advanced combinations of antibiotics, such as ceftazidime–avibactam (CZA), a treatment that has demonstrated high efficacy against bla KPC-2 -harboring CRPA strains [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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Worldwide Dissemination of blaKPC Gene by Novel Mobilization Platforms in Pseudomonas aeruginosa: A Systematic Review

et al. 2023

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The dissemination of blaKPC-harboring Pseudomonas aeruginosa (KPC-Pa) is considered a serious public health problem. This study provides an overview of the epidemiology of these isolates to try to elucidate novel mobilization platforms that could contribute to their worldwide spread. A systematic review in PubMed and EMBASE was performed to find articles published up to June 2022. In addition, a search algorithm using NCBI databases was developed to identify sequences that contain possible mobilization platforms. After that, the sequences were filtered and pair-aligned to describe the blaKPC genetic environment. We found 691 KPC-Pa isolates belonging to 41 different sequence types and recovered from 14 countries. Although the blaKPC gene is still mobilized by the transposon Tn4401, the non-Tn4401 elements (NTEKPC) were the most frequent. Our analysis allowed us to identify 25 different NTEKPC, mainly belonging to the NTEKPC-I, and a new type (proposed as IVa) was also observed. This is the first systematic review that consolidates information about the behavior of the blaKPC acquisition in P. aeruginosa and the genetic platforms implied in its successful worldwide spread. Our results show high NTEKPC prevalence in P. aeruginosa and an accelerated dynamic of unrelated clones. All information collected in this review was used to build an interactive online map.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Worldwide Dissemination of blaKPC Gene by Novel Mobilization Platforms in Pseudomonas aeruginosa: A Systematic Review

et al. 2023

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“…Meanwhile, although we did not find any KPC variants that usually result in CZA resistance in Enterobacteriaceae [23], we should still pay close attention to the CZA-resistant KPC-producing P. aeruginosa , as bla KPC-2 is a potential factor leading to CZA resistance [24], while, Tu et al have already found a KPC-90 variant that confers resistance to CZA in a clinical ST463 CRPA strain [25]. In our study, several KPC-2-producing ST463 strains showed resistance to CZA, with a MIC value of 16 µg ml −1 (Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…However, with the use of CZA, CZA-resistant P. aeruginosa strains have been reported in succession, mainly due to the overexpression or amino acid substitutions/insertions/deletions of bla PDC , as well as the efflux and permeability of CZA [6]. Mutations in bla KPC have also been reported in P. aeruginosa sporadically [7].…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial susceptibility study and molecular epidemiology of ceftazidime/avibactam against Pseudomonas aeruginosa collected from clinical patients in PR China (2004–2021)

Chen

Ling

et al. 2023

Journal of Medical Microbiology

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Introduction. The increasing prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa worldwide is a significant global public health concern. Ceftazidime/avibactam (CZA) has been considered a novel promising β-lactam/β-lactamase inhibitor combination antibiotic against difficult-to-treat P. aeruginosa isolates. Big data studies on CZA susceptibility against P. aeruginosa have been limited. Gap statement. Production of metallo-β-lactamases was the most prevalent resistance mechanism for P. aeruginosa against CZA. Aim. To assess the in vitro activity of CZA against P. aeruginosa strains and the relevant resistance mechanisms. Methodology. One thousand three hundred and sixty-three P. aeruginosa isolates were collected from 2004 to 2021. Antimicrobial susceptibility testing was carried out for commonly used antipseudomonal drugs via the broth microdilution method. Polymerase chain reaction (PCR) or whole-genome sequencing were performed to analyse the most common carbapenemase genes. Molecular epidemiology was analysed by uploading the sequencing data to the Center for Genomic Epidemiology website. Results. Antimicrobial susceptibility testing showed that CZA and lipopeptides are the most active antibiotics against P. aeruginosa isolates. PCR and genome sequencing revealed that the most prevalent resistance mechanism for P. aeruginosa against CZA was the production of metallo-β-lactamases. None of the bla PDC mutations were found to be associated with avibactam resistance. Conclusion. Our findings revealed that CZA and lipopeptides are the most active antibiotics against P. aeruginosa isolates. The most prevalent resistance mechanism for P. aeruginosa against CZA was the production of metallo-β-lactamases, and none of the bla PDC mutations were found to be associated with avibactam resistance.

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“…Notably, KPC variants showing ceftazidime-avibactam resistance have been reported in different regions of the world, commonly with high MICs, which lead to limited therapeutic options and should be fully evaluated ( 20 – 23 ). The two ceftazidime-avibactam disk diffusion tests showed excellent consistency with BMD for bla MBL -positive isolates (including those with bla NDM , bla IMP , bla KPC+NDM , and bla KPC+NDM+IMP ) and bla KPC-variant -positive isolates, which were all resistant to ceftazidime-avibactam by BMD.…”

Section: Discussionmentioning

confidence: 99%

Performance of Ceftazidime-Avibactam 30/20-μg and 10/4-μg Disks for Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa

et al. 2023

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Multidrug-resistant Enterobacterales and P. aeruginosa strains have become a global public threat, with the emergence and prevalence of plasmid-mediated extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases disseminated worldwide. Ceftazidime-avibactam, which is commercially available, has shown excellent in vitro activity against multidrug-resistant and carbapenem-resistant Enterobacterales and P. aeruginosa isolates.

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Emergence of a KPC-90 Variant that Confers Resistance to Ceftazidime-Avibactam in an ST463 Carbapenem-Resistant Pseudomonas aeruginosa Strain

Abstract: For the first time, we reported a KPC variant, KPC-90, in a clinical ST463 CRPA strain with CZA resistance. CZA resistance was mediated by a 2 amino acid insertion outside the KPC omega-loop region in CRPA.

Cited by 13 publications

References 26 publications

Worldwide Dissemination of blaKPC Gene by Novel Mobilization Platforms in Pseudomonas aeruginosa: A Systematic Review

Worldwide Dissemination of blaKPC Gene by Novel Mobilization Platforms in Pseudomonas aeruginosa: A Systematic Review

Antimicrobial susceptibility study and molecular epidemiology of ceftazidime/avibactam against Pseudomonas aeruginosa collected from clinical patients in PR China (2004–2021)

Performance of Ceftazidime-Avibactam 30/20-μg and 10/4-μg Disks for Susceptibility Testing of Enterobacterales and Pseudomonas aeruginosa

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