Genome characterization of a Klebsiella pneumoniae co-producing OXA-181 and KPC-121 resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and cefiderocol isolated from a critically ill patient

Gaibani, Paolo; Amadesi, Stefano; Lazzarotto, Tiziana; Ambretti, Simone

doi:10.1016/j.jgar.2022.06.021

Cited by 14 publications

(10 citation statements)

References 7 publications

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“…Resistance to β-lactamases activity together with the “Trojan horse” entry strategy into bacterial cells represent the strengths of the recently approved siderophore-cephalosporin cefiderocol. Although surveillance studies have reported potent activity with low MIC90 and MIC50 values, even on MDR isolates, reports of cefiderocol resistance are steadily increasing [ 11 , 12 , 13 , 14 , 15 , 16 ]. The combination of several mechanisms, including mutations affecting function of siderophore receptors and expression of certain β-lactamases, seems to be the main cause of resistance to cefiderocol [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

et al. 2022

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The role of β-lactamases in reduced susceptibility or resistance to cefiderocol has been supported by recent reports. The purpose of this study was to investigate the in vitro impact of clinically available β-lactamase inhibitors on cefiderocol activity against characterized carbapenemase-producing Gram-negative isolates. A collection of 39 well-characterized Gram-negative isolates obtained from various clinical sources and countries were included. Cefiderocol antimicrobial susceptibility was evaluated via reference broth microdilution. The chequerboard microdilution method and time–kill assays were used to determine the synergy of tazobactam, avibactam, vaborbactam and relebactam in combination with cefiderocol. MICs of cefiderocol presented a 4- to 256-fold reduction against Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative isolates (predominantly K. pneumoniae) when avibactam, vaborbactam and relebactam were combined individually. Notably, the KPC-inhibitors led to a 4- to 32-fold reduction in cefiderocol MICs in the four cefiderocol-resistant KPC-producing K. pneumoniae isolates, showing restoration of cefiderocol susceptibility (MIC ≤ 2 mg/L) in ten out of twelve cases. Tazobactam led to a 4- to 64-fold decrease in cefiderocol MICs only in K. pneumoniae strains harbouring blaKPC-41, blaKPC-31, blaKPC-53 and blaKPC-66. The synergistic effect of all serine-β-lactamase inhibitors on cefiderocol activity was also shown in OXA-48-like-producing Enterobacterales strains. Conversely, a combination of β-lactamases inhibitors with cefiderocol was not synergistic with all OXA-23-like-producing strains and most metallo-β-lactamases producers. In conclusion, the addition of clinically available serine β-lactamase inhibitors to cefiderocol might represent an important development in the formulation to increase its spectrum and therapeutic efficacy, and to limit in vivo resistance emergence.

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Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

et al. 2022

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“…The pKPC_4_29_19 plasmid carried the toxin/antitoxin vapB / vapC systems and parB/parM partitioning genes encoding proteins involved in plasmid stability. Comparative analysis of the pKPC_4_29_19 plasmid was performed using the reference pKpQIL plasmid (GU595196), the bla KPC-3 -carrying plasmid harboured by the carbapenem-resistant K. pneumoniae clone ST258 isolated in Israel [ 14 ], and the p120Kb (CP095782) plasmid, showing the best match using BLASTN, isolated in Italy from a K. pneumoniae strain co-producing OXA-181 and KPC-121, a KPC variant conferring resistance to ceftazidime/avibactam ( Figure 1 ) [ 27 ]. The plasmid comparison revealed that the reference pKpQIL plasmid (GU595196) [ 14 ] showed 57% coverage, and 99.96% nucleotide identity, with pKPC_4_29_19.…”

Section: Resultsmentioning

confidence: 99%

“…The plasmid comparison revealed that the reference pKpQIL plasmid (GU595196) [ 14 ] showed 57% coverage, and 99.96% nucleotide identity, with pKPC_4_29_19. Similarly, the p120Kb (CP095782) plasmid [ 27 ] displays 58% coverage and 99.99% identity with the pKPC_4_29_19 plasmid. With respect to the reference pKpQIL plasmid (GU595196), the pKPC_4_29_19 plasmid showed a deletion of 49,520 bp, including the FIIK 2 replicon and the entire transfer locus regions.…”

Section: Resultsmentioning

confidence: 99%

Isolation and Characterisation of Human-Derived blaKPC-3-Producing Salmonella enterica Serovar Rissen in 2018

Fortini,

García-Fernández,

Lucarelli

et al. 2023

Antibiotics

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In this study, we describe a Salmonella enterica serovar (S.) Rissen strain with a reduced susceptibility to meropenem, isolated from a urinary infection in an 89-year-old woman in 2018 during activity surveillance in Italy (Enter-Net Italia). The genomic characteristics, pathogenicity, and antimicrobial resistance mechanisms were investigated via a genomic approach. Antimicrobial susceptibility testing revealed a “susceptible, increased exposure” phenotype to meropenem in the S. Rissen strain (4_29_19). Whole-genome sequencing (WGS) was performed using both the NovaSeq 6000 S4 PE150 XP platform (Illumina, San Diego, CA, USA) and MinION (Oxford Nanopore). The S. Rissen 4_29_19 strain harboured two plasmids: a pKpQIL-like plasmid carrying the blaKPC-3 resistance gene in a Tn4401a transposon (pKPC_4_29_19), and a ColE-like plasmid (p4_4_29_19) without resistance genes, highly prevalent among Enterobacterales. Comparative analysis revealed that the pKPC_4_29_19 plasmid was highly related to the pKpQIL reference plasmid (GU595196), with 57% coverage and 99.96% identity, but lacking a region of about 30 kb, involving the FIIK2 replicon region and the entire transfer locus, causing the loss of its ability to conjugate. To our knowledge, this is the first time that a pKpQIL-like plasmid, carrying blaKPC-3, highly diffused in Klebsiella pneumoniae strains, has been identified in a Salmonella strain in our country. The acquisition of blaKPC genes by Salmonella spp. is extremely rare, and is reported only sporadically. In zoonotic bacteria isolated from humans, the presence of a carbapenem resistance gene carried by mobile genetic elements, usually described in healthcare-associated infection bacteria, represents an important concern for public health.

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“…Previous studies have reported the co-producing of OXA-181 and other carbapenemases, such as co-harboring bla OXA-181 and bla NDM-5 in Nepal, bla OXA-181 and bla NDM-1 in French, and bla OXA-181 and bla KPC-121 in Italy (Sherchan et al, 2020;Gaibani et al, 2022). Remarkably, the spread of mcr gene into CRE resulting the accumulation of multidrug resistance genes.…”

Section: Discussionmentioning

confidence: 97%

First report of Klebsiella pneumoniae co-producing OXA-181, CTX-M-55, and MCR-8 isolated from the patient with bacteremia

Qiao²,

Xu³

et al. 2022

Front. Microbiol.

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The worldwide spread of carbapenem-resistant Enterobacteriaceae (CRE) has led to a major challenge to human health. In this case, colistin is often used to treat the infection caused by CRE. However, the coexistence of genes conferring resistance to carbapenem and colistin is of great concern. In this work, we reported the coexistence of blaOXA-181, blaCTX-M-55, and mcr-8 in an ST273 Klebsiella pneumoniae isolate for the first time. The species identification was performed using MALDI-TOF MS, and the presence of various antimicrobial resistance genes (ARGs) and virulence genes were detected by PCR and whole-genome sequencing. Antimicrobial susceptibility testing showed that K. pneumoniae 5589 was resistant to aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, gentamicin, piperacillin-tazobactam, cefepime, and polymyxin B, but sensitive to amikacin. S1-pulsed-field gel electrophoresis (PFGE) and Southern blotting revealed the mcr-8 gene was carried on a ~ 138 kb plasmid with a conserved structure (IS903B-ymoA-inhA-mcr-8-copR-baeS-dgkA-ampC). In addition, blaOXA-181 was found on another ~51 kb plasmid with a composite transposon flanked by insertion sequence IS26. The in vitro conjugation experiments and plasmid sequence probe indicated that the plasmid p5589-OXA-181 and the p5589-mcr-8 were conjugative, which may contribute to the propagation of ARGs. Relevant detection and investigation measures should be taken to control the prevalence of pathogens coharboring blaOXA-181, blaCTX-M-55 and mcr-8.

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Genome characterization of a Klebsiella pneumoniae co-producing OXA-181 and KPC-121 resistant to ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam and cefiderocol isolated from a critically ill patient

Cited by 14 publications

References 7 publications

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

Synergistic Effect of Clinically Available Beta-Lactamase Inhibitors Combined with Cefiderocol against Carbapenemase-Producing Gram-Negative Organisms

Isolation and Characterisation of Human-Derived blaKPC-3-Producing Salmonella enterica Serovar Rissen in 2018

First report of Klebsiella pneumoniae co-producing OXA-181, CTX-M-55, and MCR-8 isolated from the patient with bacteremia

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