Journal of global antimicrobial resistance最新文献

Background: The darkling beetle Zophobas morio can be implemented as an alternative in vivo model to study different intestinal colonization aspects. Recently, we showed that its larvae can be colonized by multidrug-resistant Escherichia coli strains administered via contaminated food (for 7 days) for a total experimental duration of 28 days.

Method: In the present work, we aimed to shorten the model to 14 days (T14) by administering the previously used CTX-M-15 ESBL-producing ST131 Escherichia coli strain Ec-4901.28 via a single oral administration (5 µL dose of 10⁸ CFU/mL) , using a blunt 26s-gauge needle connected to a 250 μL gastight syringe. Force-feeding was performed either without or with (larvae placed on ice for 10 minutes before injection) anesthesia. In addition, phage-treated larvae were orally injected with 10 µL of INTESTI bacteriophage cocktail (∼10^5-6 PFU/mL) on days 4 (T4) and 7 (T7) .

Results: Growth curve analyses showed that, while larvae rapidly became colonized with Ec-4901.28 (T1, ∼10^6-7 CFU/mL) , only those anesthetized maintained a high bacterial load (∼10^2-3vs. ∼10^5-6 CFU/mL) and survival rate (76% vs. 99%; P<0.001) by T14. Moreover, bacteriophage administration to anesthetized larvae significantly reduced the bacterial count of INTESTI-susceptible Ec-4901.28 at T14 (5.17 × 10⁵vs. 2.26 × 10^4, for non-treated and phage-treated larvae, respectively; P=0.04) .

Conclusion: The methodological refinements applied to establish the intestinal colonization model simplify the use of Z. morio larvae, facilitate prompt evaluation of novel decolonization approaches and reduce experiments involving vertebrate animals in accordance with the Replacement, Reduction and Refinement principles.

Enterobacter cloacae complex belong to a group for which colistin resistance is not well documented, due to their frequent heteroresistance. Previous studies have examined the role of the two-component systems PhoP-PhoQ and its negative regulator mgrB or the arnBCADTEF operon. We investigated the molecular basis of colistin heteroresistance using genome analysis and random mutagenesis in a strain of Enterobacter cloacae and identified the arnA gene as responsible for colistin resistance.

Objectives: The unregulated use of antibiotics has led to the rise of antibiotic-resistant bacterial strains. This study explores bacteriophage therapy as an alternative treatment, highlighting its history, significance, and advancements in Europe, the USA, and the Middle East.

Methods: A comprehensive literature review on bacteriophage therapy was conducted, focusing on its development, clinical trials, and patient treatment applications. The study also examined challenges, limitations, criteria for ideal phage selection, and manipulation techniques.

Results: The USA and several European countries have advanced in phage therapy, progressing from clinical trials to patient treatment, while Middle Eastern countries are still in the early stages. Bacteriophages offer specificity, abundance, and minimal side effects, but challenges like safety concerns and potential resistance limit their widespread use.

Conclusion: Bacteriophage therapy shows promise as an antibiotic alternative but faces safety and resistance challenges. Continued research and better regulatory frameworks, especially in the Middle East, are needed to realize its potential.

Objectives: Carbapenem resistance is increasing worldwide. Earlier detection of this resistance, combined with appropriate treatment, could improve the prognosis of bloodstream infection. This study aims to evaluate the detection of carbapenemase producing gram-negative bacteria directly from positive blood cultures to quickly adapt antibiotic therapy before the results of antibiotic susceptibility testing are available.

Method: A prospective single-center study was conducted over a five-month period at Lille University Hospital. Carbapenemase detection by immunochromatographic testing was performed directly from positive blood cultures with gram-negative rods of thirty-five patients previously colonized with carbapenemase-producing bacteria.

Results: Among these thirty-five positive blood cultures, 15 carbapenemase-producing strains were directly detected, mainly OXA-48 and NDM. This rapid procedure provided results in less than one hour, compared to several hours for conventional methods. Of the patients with infections caused by carbapenemase-producing isolates, 67% (10 patients) received inappropriate empiric treatment, highlighting the potential of the rapid test to adjust antibiotic therapy sooner.

Conclusions: Carbapenemase detection by immunochromatographic testing directly on blood culture pellets is reliable and can lead to early adaptation of antibiotic therapy in these severe infections.

Objective: To characterise four bla_NDM-5-harbouring plasmids recovered in Enterobacterales isolated in Argentina.

Methods: DNA was sequenced by Illumina and Oxford Nanopore technologies, assembled using Unicycler, analysed using PlasmidFinder, MOB-Typer, IslandViewer4 and Resfinder, and visualised by Proksee and Clinker. bla_NDM-5-harbouring plasmids were compared with deposited similar ones using PLSDB.

Results: two plasmids belonged to incompatibility group IncFII where bla_NDM-5 was located in a previously described genetic context, immersed in an antimicrobial resistance island (ARI). Local IncFII plasmids displayed high similarity (≥ 90% shared hashes (sh)) with four deposited in PLSDB. The other two local plasmids belonged to the multi-replicon group IncFIB-HI1B, harbouring bla_NDM-5 in a novel variant of the genetic context. Both multi-replicon plasmids, presented two ARI, one containing bla_NDM-5 in addition to other ARM; and the second ARI carrying bla_CTX-M-15 and a class 1 integron. Plasmids deposited in PLSDB showed low similarity to local multi-replicon plasmids. The most similar plasmids (n:5) displayed less than 60% sh showing the same Inc groups but lacking ARM.

Conclusion: This study broadens the limited understanding of bla_NDM-5-harbouring plasmids in Latin America. Furthermore, it represents the first description of bla_NDM-5 in a novel variant of the common genetic platform and its location in multi-replicon IncFIB-IncHI1B plasmids, which were not previously associated with any antimicrobial resistance marker (ARM).

Objectives: This systematic review aims to [1] determine the risk of AMR development associated with AMU and other exposure factors in broiler, and [2] identify the best management practices to mitigate preharvest AMR development in enteric bacteria along the broiler production.

Methods: Study selection criteria was PECO/PICO framework and included broiler (population), AMU or other management practices (exposure or intervention), organic or antibiotic-free production (comparator), and presence of AMR-enteric bacteria/genes (outcome). Peer-reviewed primary research studies were searched in PubMed on December 19, 2022, and AGRICOLA, Embase, Scopus, and Web of Science on February 10, 2023. The risk of bias in studies was assessed using modified ROBIS-E risk of bias assessment tool. Results were synthesized and presented narratively according to PRISMA-2020 guidelines.

Results: 205/2699 studies were subjected to full-text review, and fifteen included in the final synthesis. Enteric bacteria Escherichia coli, Salmonella and Campylobacter exhibited AMR and multidrug resistance (MDR) against several critically important antimicrobials (aminoglycoside, cephalosporin, chloramphenicol, macrolide, penicillin, quinolone, tetracycline, and sulfonamide) for human health. The risk of AMR development in bacteria is potentially higher with AMU in broiler production. Substandard farm management practices, poor biosecurity measures, and conventional production system are also associated with dissemination of AMR in bacteria.

Conclusion: Findings indicate, AMU exposure is associated with considerably higher risks of AMR development in enteric bacteria. Antimicrobial stewardship, organic/antibiotic-free broiler production, good farm management practices, and high-level biosecurity measures can substantially mitigate preharvest AMR development in enteric bacteria. However, most of the studies are cross-sectional and therefore, causal inference cannot be established.

Objectives: This study aimed to determine the genetic environment and characterize plasmid carrying a novel VIM-type β-lactamase (VIM-84) in a multidrug-resistant Pseudomonas monteilii isolate obtained from the human gut through whole-genome sequencing.

Methods: DNA extraction of P. monteilii L2757hy was performed using the Genomic DNA Isolation Kit (QIAGEN, Hilden, Germany). Whole-genome sequencing was performed by Illumina NovaSeq 6000 and Oxford Nanopore platforms. The transferability of resistance genes was screened single clonal on MHA plates containing rifampicin and meropenem. Verification was performed using MALDI/TOF-MS and PCR with Pseudomonas aeruginosa PAO1Ri as the recipient strain.

Results: L2757hy was identified as P. monteilii through sequencing and ANI analysis. The genome was assigned as ST147 and comprised a 6,130,057 bp chromosome with a GC content of 61.8% and a 49,704 bp plasmid. Several resistance genes, including bla_IMP-1, aac(6')-IIa and tmexCD-toprJ, as well as virulence genes such as iroN, and wzaJ, were identified on the chromosome. A novel VIM-type bla_VIM-84 was found on the plasmid, which was previously identified in Pseudomonas aeruginosa. Plasmid harboring bla_VIM-84 was untypable, and it could be transferred to P. aeruginosa PAO1Ri and was associated with a class I integron with the genetic environment intI1-bla_VIM-84-tniR-tniQ-tniB-tniA, likely derived from Tn402.

Conclusions: Our study revealed that the novel bla_VIM-84 gene was harbored by P. monteilii rather than P. aeruginosa. We suggested that P. monteilii may serve as a reservoir for resistance genes.

Objectives: In this study, we report the complete genome sequence of a ST65 hypervirulent Klebsiella pneumoniae isolate carrying mcr-8 from China. The aim was to investigate its molecular characteristics and resistant mechanism.

Methods: A colistin-resistant hvKP was isolated from an inpatient in China. The whole genome was sequenced on Illumina NovaSeq 6000 and long-read ONT platforms. de novo assembly was conducted using SPAdes and Unicycler. S1 nuclease pulsed-field gel electrophoresis, Southern-blot, and antimicrobial susceptibility testing were performed. Sequence type, antimicrobial resistance and virulence-related genes were predicted from the sequence. The circular maps of multiple plasmids comparisons were drawn by the BLAST Ring Image.

Results: The complete genome sequence of K. pneumoniae ACESH00926 consists of one chromosome and two plasmids. ACESH00926 belongs to K2 ST65 according to the MLST scheme. ACESH00926 showed high resistance to colistin (MIC > 8 µg/mL). Several ARGs were identified, including mobile colistin-resistant gene mcr-8 which was located in an IncFIl(K)/IncFIA(HI1) type plasmid. The bigger plasmid was a pK244-like virulence plasmid. It carrying a series of virulence genes, such as the regulator of the mucoid phenotype (rmpA and rmpA2), salmochelin siderophore biosynthesis (iroB), ABC transporter (iroC), ferric aerobactin receptor (iutA), aerobactin siderophore biosynthesis protein (iucC), and aerobactin synthetase (iucA) encoded genes. And another plasmid carrying mcr-8 with a conserved genetic context (dgkA-sasA-copR-mcr-8-ccdA-ccdB-xerD-repE-parM-umuC-lexA-klcA).

Conclusions: It is necessary to emphasize the necessity of monitoring a combination of colistin-resistant and hypervirulent Klebsiella pneumoniae strains in the future.

Objective: We investigated a rapid detection method for carbapenemase-producing gram-negative bacilli (CP-GNR) using meropenem (MEPM) to assess the efficiency of the antimicrobial susceptibility testing.

Methods: We used the function that can monitor the growth curve with the resistant bacteria monitoring function (RAISUS S4). Rapid detection of CP-GNR was performed using RAISUS S4 in two types of antimicrobial susceptibility testing, the RAISUS 18-hour method (18-h method) and RAISUS rapid method (rapid method) for Enterobacterales (F-GNR) and non-fermenting Gram-negative bacilli (NF-GNR).

Results: When F-GNR were based on MEPM MIC ≥ 0.25 μg/mL, CP-GNR were detected with a sensitivity of 100% (58/58) for the 18-h method and 98.3% (57/58) for the rapid method; the shortest detection times were 5.3 and 4.0 h, respectively. When NF-GNR were based on MEPM MIC > 8 μg/mL, it was possible to detect CP-GNR with 100% sensitivity (58/58) in both methods. Furthermore, in the analysis using the 18-h method for monitoring resistant bacteria, when ≥ 2 µg/mL was used as the screening concentration for F-GNR, approximately 50% of the resistant genotypes, NDM, GES, and KPC, were detected in approximately 7 h. However, detecting the IMP and VIM took 11-12 h.

Conclusions: The 18-h and rapid methods with RAISUS S4 were highly correlated with the results of the microdilution method of CLSI, and CP-GNR detection was rapid using a function that can monitor the growth curve with RAISUS S4.