ABSTRACT The rise of carbapenem-resistant Enterobacteriaceae coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1- Citrobacter freundii is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1- C. freundii isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) ≥ 8 µg/mL] and imipenem (MICs > 8 µg/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1- C. freundii belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of blaKPC-2 and blaNDM-1 on an IncR plasmid named pC275-2 with 46,050 bp. The blaNDM-1 was integrated within the blaNDM-1 related region, which includes ΔIS Aba125 , blaNDM-1 , ble-MBL , trpF , dsbD , and IS CR1 , while the blaKPC-2 gene was located on a novel non-Tn 4401 genetic element. The blaKPC-2 genetic architectures containing blaKPC-2 differed from classical structures, underscoring the ongoing evolution of these genetic elements. IMPORTANCE Our study described the largest cohort to date of eight ST523 KPC-2-NDM-1- C. freundii isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine β -lactamases, and NDM-1, a metallo-β-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant C . freundii . The conserved insertion structure mediated the blaNDM-1 , and the propagation of blaKPC-2 gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1- C. freundii were disseminated in a children’s hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1- C. freundii s.

2024-12-01·Journal of Infection and Public Health

Emergence of multidrug-resistant E. coli ST8346 isolates carrying three distinct plasmids with NDM-5, KPC-2, and OXA-181

Article

作者: Chen, Po-Yu ; Chiang, Che-Ming ; Ho, Chung-Han ; Chen, Ping-Yuan ; Tsai, Chia-Hung ; Tang, Hung-Jen ; Chang, Tu-Hsuan ; Chow, Julie Chi ; Chen, Yu-Chin ; Lai, Chih-Cheng ; Chen, Chi-Chung

BACKGROUNDE. coli ST8346 is a unique strain associated with the potential carriage of multiple carbapenemases. Three unique E. coli ST8346 isolates were identified, each concurrently harboring multiple carbapenemases, including bla_NDM-5, bla_KPC-2, and/or bla_OXA-181. This study aimed to characterize the genetic and plasmid structures of these isolates to understand their transmission and resistance mechanisms.METHODSAntibiotic resistance profiles, genetic relatedness, and plasmid structures were determined using antibiotic susceptibility testing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), S1 nuclease PFGE, and long-read sequencing.RESULTSAll the strains were carbapenem resistant. PFGE revealed close genetic relationships among the isolates, despite the lack of geographical or epidemiological connections. bla_NDM-5, bla_KPC-2, and bla_OXA-181 were located on separate plasmids. Plasmids harboring bla_NDM-5 showed genetic similarities to bla_NDM-5-bearing IncF plasmids in the United Kingdom. The IncA/C plasmids harboring bla_KPC-2 had identical sequences resembling a plasmid from a K. pneumoniae strain in Taiwan, except for the bla_KPC-2 region, which matched a strain from China, indicating a hybrid plasmid.CONCLUSIONThis study is the first to identify and characterize the coexistence of bla_NDM-5, bla_KPC-2, and bla_OXA-181 in E. coli ST8346 isolates. The spread appears to be due to independent acquisition events. We identified the putative origins of these plasmids and detected a possible recombination event in a novel IncA/C plasmid. These findings emphasize the importance of ongoing surveillance and further investigations.

2024-10-03·Microbiology Spectrum

Reversion of KPC-114 to KPC-2 in ceftazidime-avibactam- resistant/meropenem-susceptible Klebsiella pneumoniae ST11 is related to low mutation rates

Article

作者: Pariona, Jesus G. M. ; Esposito, Fernanda ; Madueño, Fabio T. ; Galhardo, Rodrigo S. ; Pariona, Eva M. M. ; Lincopan, Nilton ; Mello Sampaio, Jorge L. ; V. de Lima, Aline ; Vásquez-Ponce, Felipe ; Martins-Gonçalves, Thais ; Becerra, Johana

ABSTRACTKlebsiella pneumoniae strains that produce Klebsiella pneumoniae Carbapenemase (KPC) variants displaying resistance to ceftazidime-avibactam (CZA) often remain susceptible to meropenem (MEM), suggesting a potential therapeutic use of this carbapenem antibiotic. However, in vitro studies indicate that these sorts of strains can mutate becoming MEM-resistant, raising concerns about the effectiveness of carbapenems as treatment option. We have studied mutation rates occurring from the reversion of MEM-susceptible KPC-114 to MEM-resistant KPC-2, in CZA-resistant K. pneumoniae belonging to ST11. Two-step fluctuation assays (FAs) were conducted. In brief, initial cultures of KPC-114-producing K. pneumoniae showing 1 µg/mL MEM MIC were spread on Mueller–Hinton agar plates containing 2–8 µg/mL MEM. A second step of FA, at 4–16 µg/mL MEM was performed from a mutant colony obtained at 2 µg/mL MEM. Mutation rates were calculated using maximum likelihood estimation. Parental and mutant strains were sequenced by Illumina NextSeq, and mutations were predicted by variant-calling analysis. At 8 µg/mL MEM, mutants derived from parental CZA-resistant (MIC ≥ 64 µg/mL)/MEM-susceptible (MIC = 1 µg/mL) KPC-114-positive K. pneumoniae exhibited an accumulative mutation rate of 3.05 × 10 −19 mutations/cell/generation, whereas at 16 µg/mL MEM an accumulative mutation rate of 1.33 × 10 −19 mutations/cell/generation resulted in the reversion of KPC-114 (S181_P182 deletion) to KPC-2. These findings highlight that the reversion of MEM-susceptible KPC-114 to MEM-resistant KPC-2, in CZA-resistant K. pneumoniae ST11 is related to low mutation rates suggesting a low risk of therapeutic failure. In vivo investigations are necessary to confirm the clinical potential of MEM against CZA-resistant KPC variants. IMPORTANCE The emergence of ceftazidime-avibactam (CZA) resistance among carbapenem-resistant Klebsiella pneumoniae is a major concern due to the limited therapeutic options. Strikingly, KPC mutations mediating CZA resistance are generally associated with meropenem susceptibility, suggesting a potential therapeutic use of this carbapenem antibiotic. However, the reversion of meropenem-susceptible to meropenem-resistant could be expected. Therefore, knowing the mutation rate related to this genetic event is essential to estimate the potential use of meropenem against CZA-resistant KPC-producing K. pneumoniae . In this study, we demonstrate, in vitro , that under high concentrations of meropenem, reversion of KPC-114 to KPC-2 in CZA-resistant/meropenem-susceptible K. pneumoniae belonging to the global high-risk ST11 is related to low mutation rates.

100 项与 KPC-2 相关的药物交易

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