Journal of global antimicrobial resistance最新文献

Objectives

The treatment options available for infections caused by multidrug-resistant Gram-negative pathogens are often limited. Cefiderocol (CFDC) is a novel siderophore cephalosporin that exhibits activity against these pathogens. Several studies have reported the in vitro activity of CFDC against isolates from Europe, the United States, and China, but the activity against carbapenem-resistant bacteria with IMP-type carbapenemase has not been extensively studied. We, therefore, studied the in vitro activities of CFDC against carbapenem-resistant bacteria with available genomic backgrounds based on whole-genome sequencing (WGS) in Japan, where the IMP-type is the predominant carbapenemase produced by Gram-negative rods.

Methods

We selected 603 isolates (528 Enterobacterales, 18 Pseudomonas aeruginosa, and 57 Acinetobacter spp.) from a collection of Gram-negative clinical isolates collected during a Japan Antimicrobial Resistance Bacterial Surveillance program and evaluated the antimicrobial activities of CFDC, ceftolozane/tazobactam (CTLZ/TAZ), imipenem-relebactam (IPM/REL), and ceftazidime/avibactam (CAZ/AVI) against carbapenemase-producing Enterobacterales, carbapenemase-non-producing meropenem-non-susceptible Enterobacterales, and carbapenemase-producing nonfermentative bacteria.

Results

Among these, 97.7% of carbapenemase-producing Enterobacterales (99.2% of IMP-type carbapenemase-producing Enterobacterales), 100% of carbapenemase-producing P. aeruginosa, and 91.2% of carbapenemase-producing Acinetobacter spp. were susceptible to CFDC, showing better antimicrobial activity than the other antimicrobial agents evaluated in this study. CFDC was highly effective against class A-, B-, and D β-lactamase-harbouring isolates when compared to the other antimicrobial agents. In addition, the relationship between CFDC resistance and three genetic factors involved in resistance was discussed.

Conclusions

This is the first large-scale study to systematically demonstrate the efficacy of CFDC against IMP-type carbapenemase-producing strains with known genomic backgrounds.

Introduction

Single-nucleotide variants (SNVs) in Mycobacterium tuberculosis (M. tuberculosis) genomes can predict multidrug resistance (MDR) but not all phenotype-genotype correlations can be explained. We investigated SNVs in efflux pumps (EPs) in the context of M. tuberculosis drug resistance.

Methods

We analysed 2221 M. tuberculosis genomes from 1432 susceptible and 200 MDR, 172 pre-extensively drug resistant (XDR) and 417 XDR isolates. Analysis of 47 EP genes was conducted using MTB-VCF, an in-house bioinformatics pipeline. SNVs were categorized according to their SIFT/Polyphen scores. Resistance genotypes were also called using the TB-Profiler tool.

Results

Genome comparisons between susceptible and drug resistant (DR) isolates identified 418 unique SNVs in EP of which; 53.5% were in MDR, 68.9% in pre-XDR and 61.3% in XDR isolates. Twenty EPs had unique SNVs with a high SIFT/PolyPhen score, comprising 38 unique SNVs. Sixteen SNVs across 12 EP genes were significantly associated with drug resistance and enriched in pre-XDR and XDR strains. These comprised 12 previously reported SNVs (in Rv0191, Rv0507, Rv0676, Rv1217, Rv1218, Rv1273, Rv1458, Rv1819, and Rv2688) and 4 novel SNVs (in Rv1877 and Rv2333). We investigated their presence in genomes of 52 MDR isolates with phenotype-genotype discrepancies to rifampicin (RIF), isoniazid (INH), or fluoroquinolones. SNVs associated with RIF and INH (Rv1217_1218, Rv1819, Rv0450, Rv1458, Rv3827, Rv0507, Rv0676, Rv1273, and Rv2333), and with fluoroquinolone (Rv2688) resistance were present in these discrepant strains.

Conclusions

Considering SNVs in EPs as part of M. tuberculosis genome-based resistance interpretation may add value, especially in evaluation of XDR resistance in strains with phenotype-genotype discrepancies.

Objectives

To investigate the genomic differences between two extensively drug resistant, ST16 strains of Klebsiella pneumoniae recovered from patients in the same ICU, one of which was colistin resistant.

Methods

Antimicrobial susceptibilities of the isolates were determined using VITEK-2. Hybrid assemblies for both strains were generated using Oxford Nanopore and Illumina technologies. The sequence type, capsule type, O-locus type, antimicrobial resistance determinants and plasmids carried by the isolates were inferred from the genome sequence. The phylogenetic placement, antimicrobial resistance, and virulence determinants of the isolates relative to a collection (n = 871) of ST16 isolates were assessed.

Results

Both BC16, a colistin-resistant blood stream isolate and U23, a colistin-sensitive urinary isolate displayed near-identical antimicrobial resistance profiles and genome sequences with varying plasmid profiles. The BC16 genome only had 21 SNPs relative to U23 and belonged to the same capsule, O-antigen locus and multi-locus sequence types. The mgrB locus in BC16 was disrupted by an IS5 element. Phylogenetically, U23 and BC16 were placed on a clade with 4 strains belonging to K-type K48 and O-type O2a as opposed to majority (n = 807) of the strains (K-type K51 and O-type O3b).

Conclusions

BC16 was a colistin resistant derivative of U23, which evolved colistin resistance by an IS5-mediated disruption of the mgrB locus, likely during treatment of the index patient with colistin in the ICU. The strains belong to a rare subtype of ST16 with unique capsular and O-antigen types underscoring the utility of genomic surveillance networks and open-access genomic surveillance data in tracking problem clones.

Background

Enterococcus faecium (E. faecium) stands as a prominent pathogen contributing to Gram-positive bacterial infections in individuals who have undergone liver transplantation.

Case presentation

A 66-year-old male with a three-year history of treated anxiety disorder was admitted to our hospital due to recurrent abdominal distension and oliguria. He was diagnosed with hepatic veno-occlusive disease (HVOD), hepatic failure, pneumonia, renal insufficiency and abdominal ascites. A liver transplantation procedure was performed, but the patient's infection index increased on the first day after surgery. Empirical antibiotic therapy with ceftriaxone and meropenem and preventive antifungal therapy were applied. Sputum culture, blood culture, ascites culture and bronchoalveolar lavage fluid (BALF) next-generation sequencing (NGS), revealed the presence of E. faecium. Given the application of various nephrotoxic immunosuppressive agents after liver transplantation, pre-existing renal insufficiency, severe bone marrow suppression, and a history of anxiety disorder treated with sertraline, contezolid was added for the treatment of the Gram-positive bacterial infection. Sixteen days after surgery, cultures from ascites and sputum yielded negative results for fungi and bacteria. Contezolid was subsequently discontinued without any reported adverse events during follow-up.

Conclusion

Treatment with contezolid as the first-line therapy for sepsis and pneumonia caused by E. faecium following liver transplantation has shown satisfactory efficacy and safety. Therefore, contezolid may hold great promise for managing this life-threatening condition.

As a widely spread Gram-negative bacteria, Klebsiella pneumoniae (KP) mainly causes acquired infections in hospitals, such as lung infections, urinary tract infections, and bloodstream infections. In recent years, the number of multidrug-resistant KP strains has increased dramatically, posing a great threat to human health. Carbapenem-resistant KP (CRKP) can be colonized in human body, especially in gastrointestinal tract, and some colonized patients can be infected during hospitalization, among which invasive operation, underlying disease, admission to intensive care unit, antibiotic use, severity of the primary disease, advanced age, operation, coma, and renal failure are common risk factors for secondary infection. Active screening and preventive measures can effectively prevent the occurrence of CRKP infection. Based on the epidemiological status, this study aims to discuss the correlation between colonization and secondary infection induced by CRKP and risk factors for their happening and provide some reference for nosocomial infection prevention and control.

Objectives

Acinetobacter pittii has emerged as an opportunistic nosocomial pathogen associated with hospital-acquired infections. The purpose of this study was to investigate the genetic structures of plasmids carrying carbapenemase genes bla_OXA-58 and bla_OXA-72 in A. pittii strains AR3676 and AR3651 isolated from patients.

Methods

Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing and bioinformatics analysis were performed to characterize the genome of A. pittii AR3676 and AR3651. Conjugation experiments were conducted to evaluate plasmid transferability. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant A. pittii isolates worldwide.

Results

The AR3676 strain showed resistance to imipenem. The 19 700-bp plasmid pAR3676-OXA-58 harboured bla_OXA-58 with genetic contexts consisting of a truncated ISAba3-like-bla_OXA58-ISAba3. Additionally, the AR3651 strain showed resistance to imipenem and meropenem. The AR3651 genome comprised one 9,837-bp RepA_AB plasmid pAR3651-OXA-72 harbouring bla_OXA-72. This bla_OXA-72 was flanked by XerC/XerD recombination sites. The conjugation of plasmids pAR3676-OXA-58 and pAR3651-OXA-72 from A. pittii to Acinetobacter baumannii ATCC 17978RIF^R failed three independent times. Phylogenetic analysis of A. pittii strains AR3676, AR3651, and a further 504 A. pittii strains collected between 1966 and 2022 from various geographic localities revealed genetic diversity with a heterogeneous distribution of carbapenemase genes.

Conclusions

A. pittii strains with a plasmid carrying bla_OXA-58 or bla_OXA-72 may serve as an important reservoir of carbapenemase genes. Carbapenemase genes on a single plasmid may facilitate their dissemination and persistence. Additionally, pdif sites and mobile elements play an important role in the mobilization of resistance genes and plasmid evolution.

Objectives

Klebsiella aerogenes is a largely understudied opportunistic pathogen that can cause sepsis and lead to high mortality rates. In this study, we reported the occurrence of carbapenem-resistant bla_OXA-181-carrying Klebsiella aerogenes from swine in China and elucidate their genomic characteristics.

Methods

A total of 126 samples, including 109 swine fecal swabs, 14 environmental samples, and three feed samples were collected from a pig farm in China. The samples were enriched with LB broth culture and then inoculated into MacConkey agar plates for bacterial isolation. After PCR detection of carbapenemases genes, the bla_OXA-181-carrying isolates were subjected to antimicrobial susceptibility testing, and whole-genome sequence analysis.

Results

Four Klebsiella aerogenes isolates carrying the bla_OXA-181 gene were obtained from swine faecal samples. All the 4 strains were belonged to ST438. The bla_OXA-181 genes were located in IncX3-ColKP3 hybrid plasmids with the core genetic structure of IS26-ΔIS3000-ΔISEcp1-bla_OXA-181-ΔlysR-ΔereA-ΔrepA-ISKpn19-tinR-qnrS1-ΔIS2-IS26, which suggests the potential for horizontal transfer and further dissemination of this resistance gene among Enterobacteriaceae and other sources.

Conclusions

This study represents the first instance of OXA-181-producing K. aerogenes being identified from swine faeces in China. It is crucial to maintain continuous monitoring and ongoing attention to the detection of K. aerogenes carrying bla_OXA-181 and other resistance genes in pigs.

Objectives

The aim of this study was to characterise the first complete genome of Porphyromonas pogonae strain PP01-1 of human origin in China.

Methods

The Illumina NovaSeq 6000 (200X coverage) and Nanopore MinION platforms (100× coverage) were used for genome sequencing. A de novo hybrid assembly of short Illumina reads and long MinION reads was performed using Unicycler (v.0.5.0). Genome annotation of PP01-1 was performed using the prokaryotic gene-prediction tool Prokka1.14.6. The genome was further analysed using several bioinformatics tools, including ResFinder, VFDB, VirulenceFinder, Type Strain Genome Server, AntiSMASH, PathogenFinder, MobileElementfinder, CRISPRFinder, and IslandViewer.

Results

The assembled circular genome of P. pogonae strain PP01-1 was 2 916 423 bp in length, with a GC content of 41.0%, and no plasmid sequence was detected. A total of 2399 coding sequences were predicted by Prokka. PP01-1 harbours antimicrobial resistance genes bla_OXA-347 (β-lactamase resistance), tet(Q) (tetracycline resistance), and floR (chloramphenicol and florfenicol resistance).

Conclusions

Here, we are the first to report the complete genome of P. pogonae strain PP01-1 of human origin. In this strain, we first identified bla_OXA-347 and tet(Q) in P. pogonae, which will pave the way for further analysis that could identify the potential mechanism of antibiotic resistance and virulence factors in P. pogonae.

Objectives

To investigate the clinical and molecular epidemiological characteristics of bla_IMP-4-carrying Klebsiella pneumoniae in a tertiary hospital in China.

Methods

Ten carbapenem-resistant K. pneumoniae (CRKP) isolates carrying the bla_IMP-4 gene were collected. Molecular characteristics were analysed using whole-genome sequencing. Plasmid conjugation experiments were used to analyse conjugation of the plasmids. We compared and analysed K. pneumoniae-carrying bla_IMP-4 genomic datasets obtained from the National Center for Biotechnology Information (NCBI) with the strains in this study.

Results

All 10 CRKP isolates carrying bla_IMP-4 were collected from 10 adult patients in the respiratory intensive care unit. These strains were only sensitive to polymyxins and tigecycline due to them simultaneously carrying multiple resistance genes, namely bla_OKP-A-5, fosA, oqxA, and oqxB. Notably, R29 harboured two carbapenemase genes (bla_NDM-1 and bla_IMP-4). These strains had similar drug-resistant phenotypes and genes, all belonging to sequence type (ST)196. Additionally, the patients had experienced spatiotemporal intersection during hospitalization, suggesting that these strains underwent clonal transmission, but they belonged to different clonal clusters from the bla_IMP-4-positive K. pneumoniae currently published in the NCBI. Among the 10 strains, bla_IMP-4 was located on the IncN plasmid, and six strains had successfully transferred the plasmid to the recipient strain EC600 through plasmid conjugation.

Conclusions

The bla_IMP-4-positive ST196 CRKP isolate showed clonal distribution in the respiratory intensive care unit, which was mediated by the IncN plasmid. Consequently, there should be increased monitoring of carbapenem-resistant strains in clinical settings to prevent and control its transmission.

Objectives

The emergence and outbreak of carbapenem-resistant Pseudomonas aeruginosa are a major global public threat. In this study we aimed to characterize the genome of drug-resistant and virulent genes in an extremely drug-resistant (XDR) P. aeruginosa strain to understand its antimicrobial resistance trends and pathogenicity.

Methods

An XDR P. aeruginosa strain was isolated in China from a patient with severe pneumonia. Antimicrobial susceptibility testing, genome sequencing, and phylogenetic analysis were performed. Predictions were fulfilled using curated bioinformatics tools.

Results

Assembly of the strain (CRPA190) comprised 76 contigs with a total length of 7 009 318 bp. CRPA190 belongs to sequence type 1971 (ST1971) and the O11 serogroup. Nine prophage regions, three CRISPR arrays, and two Cas clusters were identified. However, no plasmids were predicted. Antibiotic susceptibility tests showed that CRPA190 was resistant to all the tested antibiotics, including carbapenem, polymyxin B, and ceftazidime-avibactam. Forty antimicrobial resistance genes were predicted in CRPA190, including several carbapenemase genes such as bla_PDC-142, bla_PME-1, bla_NDM-1, and bla_OXA-902. The isolate was predicted to be pathogenic and possess strong biofilm-forming ability. It harbours virulence genes that are associated with an arsenal of virulence determinants involved in adherence, motility, exotoxins, exoenzymes, immune modulation, biofilms, nutritional/metabolic factors, and effector delivery systems.

Conclusions

These findings enhance our understanding of the resistance and pathogenicity of the ST1971 P. aeruginosa strain that is unique in China and provide a broader perspective on the global epidemiological landscape, suggesting the emergence of P. aeruginosa ST1971, which requires control measures to limit its dissemination.