Journal of global antimicrobial resistance最新文献

Objectives: We studied two Klebsiella pneumoniae carbapenemase (KPC)-14 variants from clinical Pseudomonas aeruginosa isolates (C137 and C159) to better understand the genomic diversity, mechanisms, and genes that confer antibiotic resistance and pathogenicity.

Methods: Genomic DNA from C137/159 was subjected to Illumina and Oxford Nanopore sequencing. Horizontal transmission of the plasmid was evaluated using cloning experiments. The expression of efflux pumps, the outer membrane protein OprD, and the enzyme AmpC was quantified using qRT-PCR. The detectability of KPC-14 was evaluated using different methods, and biofilm formation assays and growth curves were assessed.

Results: C137 and C159, sequence type 463 ExoU-positive multidrug-resistant strains, were concurrently resistant to carbapenems and ceftazidime-avibactam (CZA). Both strains possessed five intrinsic antimicrobial resistance genes (fosA, catB7, crpP, bla_PAO, and a bla_OXA-486 variant) as well as bla_KPC-14. In strain C137, bla_KPC-14 was located on a plasmid (pC137). Both strains expressed the bla_KPC-14 gene, concurrent inactivation of OprD, overexpression of the MexX efflux pump, and a pronounced capacity for biofilm formation. The genomic environment of KPC-14 consisted of IS26/IS26/TnpR_Tn3/ISKpn27/ISKpn6/IS26, which classified it as pseudo-compound transposon (PCT). IS26-mediated PCTs may store a variety of resistance genes, including bla_KPC-2 and KPC variants, which are currently disseminating in this region.

Conclusion: The KPC-14 variant presents significant challenges for clinical treatment. The bla_KPC-14 gene carried by PCTs was integrated into the chromosome and exhibited stability throughout bacterial inheritance. Our research highlights the need for improved clinical surveillance of KPC-producing P. aeruginosa.

Objectives: Infections due to carbapenemase-producing Enterobacterales harboring more than one carbapenemase-encoding gene spreads mainly by plasmid and transposon mobilization.

Objectives: Analyze the mobile genetic elements carrying bla_KPC and bla_NDM of K. pneumoniae carbapenemase co-producers (KpKN).

Methods: K. pneumoniae isolates with reduced susceptibility to carbapenems were obtained from 2016 to 2023. To evaluate the genetic environment of KpKN, 22 isolates were selected for antimicrobial susceptibility testing and whole-genome sequencing (WGS).

Results: The bla_KPC-2 gene was carried mainly by IncN/IncFIB, a novel co-integrated plasmid in the Tn4401b transposon. The bla_NDM-1 was disseminated in the only two KpKN isolates recovered before 2020 by IncHI1B/IncFIB plasmid type, in the Tn3000 transposon. Noteworthy, isolates obtained since 2020 showed the bla_NDM-1 gene carried by IncA/C in an IS26-flanked pseudo-composite transposon containing ISCR1, which also had genes that confer resistance to sulfonamides, aminoglycosides, macrolides, quinolones, amphenicols, tetracyclines, rifampicin, sulfonamide, and trimethoprim. The isolates belong mainly to ST11 and ST16.

Conclusions: The plasmid and transposon changes during the different periods could be related to higher dissemination of the bla_NDM-1 and the large number of resistance genes present in the IS26-flanked transposon may have increased the co-selection of this plasmid through the wide use of antimicrobials during the pandemic.

Background: Ceftazidime-avibactam was approved in patients with hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), based on the multinational Phase 3 REPROVE study. This study assessed efficacy and safety of ceftazidime-avibactam in Chinese adults with HAP/VAP.

Methods: This was a Phase 4, prospective, multi-centre, open-label study, conducted at 42 sites in China. Patients with HAP/VAP received ceftazidime-avibactam 2.5 g by 2-hour IV infusion every 8 hours for 7-14 days. Primary efficacy endpoint was clinical response at the test-of-cure (TOC) visit in the clinical modified intent-to-treat (cMITT) analysis set. Secondary endpoints included microbiological response at TOC (microbiological modified intent-to-treat; [mMITT] analysis set) and all-cause mortality at TOC and Day 28. Results were summarized descriptively.

Results: Of 257 screened individuals, 235 were treated with ceftazidime-avibactam (safety analysis set); 71% were male; median age was 67 years. Klebsiella pneumoniae (n = 49 [61.3%]) and Pseudomonas aeruginosa (n = 16 [20.0%]) were the most frequently isolated baseline pathogens. Clinical cure at TOC was achieved in 62.7% patients (131/209, 95% CI: [56.0, 69.0]) in the cMITT analysis set. Favourable microbiological responses at TOC occurred in 51.3% (41/80, 95% CI: [40.4, 62.0]) patients (mMITT analysis set). All-cause mortality was 5.7% (12/209; 95% CI: 3.2, 9.6) at TOC and Day 28 (cMITT analysis set). No new safety signals were identified.

Conclusions: Ceftazidime-avibactam was effective in Chinese patients with HAP/VAP, and results were consistent with the Phase 3 REPROVE study. These findings support the use of ceftazidime-avibactam as a potential treatment option in Chinese adults with HAP/VAP.

Objectives: The present study aimed to green synthesize and characterize the zinc nanoparticles (ZNP) and evaluate its potency to control Toxoplasma gondii infection in mice by stimulating the immune system, antioxidant activity, and anti-inflammatory effects.

Methods: By in vivo, T. gondii infected mice were orally treated by ZNP (5-20 mg/kg) for 14 days. The number and size of tissue cysts, oxidant-antioxidant enzymes, the expression of inflammatory cytokines, apoptotic, and pathogenicity-related factors were evaluated by real-time polymerase chain reaction (PCR).

Results: ZNP ranged in size from 10-70 nm with an average size of 45.7±19.4 nm. ZNP treatment resulted in a significant reduction in the number and size of tissue cysts (p<0.05). The oral administration of infected mice with ZNP caused a considerable decrease in malondialdehyde levels and a marked increase (p<0.001) in the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. ZNP administration triggered a significant reduction in the expression levels of the genes of interleukin-1β, tumor necrosis factor-α, nuclear factor kappa B, bradyzoite antigen-1, and B-cell lymphoma-2. Conversely, there was an increase in the expression levels of the genes of IL-10, Serpin A3k, caspase-3, and Bcl-2-associated X protein (P < 0.001).

Conclusion: In summary, the recent investigation illustrated that ZNP demonstrates promising in vivo effects against T. gondii infection in mice. These effects are ascribed to its antioxidant properties, anti-inflammatory characteristics through the inhibition the specific inflammatory cytokines, and its ability to inhibit pathogenicity in mice without any observable signs of toxicity.

Objective: The spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) that produces Klebsiella pneumoniae carbapenemase-2 (KPC-2) has garnered significant attention due to their increasing prevalence. In China, the dissemination of KPC-2-producing CRKP is predominantly linked to sequence type 11 (ST11), with the capsular serotypes KL47 and KL64 being the primary capsular identified.

Methods: Sixty-four CRKP-ST11 strains were collected from 2020 to 2023. We performed whole-genome sequencing on all isolated ST11-CRKP strains. Antibiotic susceptibilities were tested with VITEK 2 systems. Growth curve test and in vitro competition experiments were used to assess growth adaptability of different capsular type isolates. Moreover, the biofilm assessment and phagocytosis assay were performed to evaluate the virulence of the CRKP isolates.

Results: During the observed period, a no subclonal shift was perceived within the prevailing ST11-CRKP clone, wherein the previously dominant KL64 and KL47 serotypes have been largely supplanted by the KL25 serotype since 2022. The ST11-KL25-CRKP strain significantly outgrew both ST11-KL64-CRKP and ST11-KL47-CRKP. Additionally, ST11-KL25-CRKP displayed a greater enhanced capacity to form biofilms than ST11-KL64-CRKP and ST11-KL47-CRKP. Furthermore, the ST11-KL25-CRKP strain demonstrated enhanced resistance to phagocytosis than both of its counterparts.

Conclusion: ST11-KL25-CRKP possesses a remarkable level of adaptability and has the potential to regionally replace ST11-KL64-CRKP as the predominant strain in the region. And the novel and high-risk ST11-KL25-CRKP strain may indicate stronger virulence.