International Journal of Antimicrobial Agents最新文献

{"title":"Genomic characterisation of a multidrug-resistant Klebsiella pneumoniae co-harbouring blaNDM-1, blaKPC-2, and tet(A) isolated from the bloodstream infections of patients","authors":"","doi":"10.1016/j.ijantimicag.2024.107290","DOIUrl":"10.1016/j.ijantimicag.2024.107290","url":null,"abstract":"<div><h3>Objectives</h3><p>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP), a superbug that can be difficult or impossible to treat, has become a worldwide problem. This study presents the first report of a CRKP strain carrying a plasmid co-harbouring <em>bla</em>_NDM-1, <em>bla</em>_KPC-2, and <em>tet(A)</em> and the subsequent analysis of its genomic features.</p></div><div><h3>Methods</h3><p>Isolation and identification of bacteria, antimicrobial susceptibility test, whole genome sequencing, and conjugation experiments assay were conducted in clinical epidemiological investigations and plasmid genetic characterisation analysis.</p></div><div><h3>Results</h3><p>A total of 116 strains of bacteria were isolated from patients with bloodstream infections (BSI) between 2018 and 2023. A total of 89.66% of the isolates were carbapenem-resistant Enterobacteriaceae (CRE), with the majority (75/116) being CRKP. Among these, a novel plasmid co-harbouring <em>bla</em>_NDM-1, <em>bla</em>_KPC-2, and <em>tet(A)</em> simultaneously was found in CRKP46, and the three genes mediated conjugation by IS<em>26</em>, IS<em>Aba125</em>, and IS<em>26</em>, respectively. This plasmid conferred carbapenem resistance to <em>E. coli</em> J53 after conjugative transfer, which was 2 times greater than that of CRKP46.</p></div><div><h3>Conclusion</h3><p>The present study identified the occurrence of a rare plasmid co-harbouring <em>bla</em>_NDM-1, <em>bla</em>_KPC-2, and <em>tet(A)</em>, and the spread of these genes was mediated by the corresponding mobile elements. The increased carbapenem resistance created by this novel plasmid challenges public health security and poses a potential threat to human health; therefore, it deserves attention.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Colonization With Antibiotic-Resistant Escherichia coli Pathobionts Leads to Disease Severity in Ulcerative Colitis","authors":"","doi":"10.1016/j.ijantimicag.2024.107289","DOIUrl":"10.1016/j.ijantimicag.2024.107289","url":null,"abstract":"<div><h3>Background</h3><p><em>Escherichia coli</em> is a Gram-negative commensal of human gut. Surprisingly, the role of <em>E. coli</em> in the pathogenesis of ulcerative colitis (UC) has not been explored until now.</p></div><div><h3>Methods</h3><p>Human gut microbiota composition and meta-gut resistome were evaluated using metagenomics. Antibiotic susceptibility of <em>E. coli</em> isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of <em>E. coli</em> isolates was performed to gain insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology.</p></div><div><h3>Results</h3><p>In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy controls (HC) [518]. The metagenome study revealed a higher prevalence of AMR genes in the rural population (378 in HC; 607 in UC) compared to the urban (340 in HC; 578 in UC). Approximately, 40% of all <em>E. coli</em> isolates were multi-drug resistant (MDR), with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and inflammatory mediator (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut.</p></div><div><h3>Conclusions</h3><p>In addition to the conventional culturomics method, a multi-omics strategy provides deeper insights into the disease etiology, emergence of MDR pathobionts, and their roles in the disruption of the healthy gut environment in UC patients.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The novel drug candidate VOMG kills Mycobacterium abscessus and other pathogens by inhibiting cell division","authors":"","doi":"10.1016/j.ijantimicag.2024.107278","DOIUrl":"10.1016/j.ijantimicag.2024.107278","url":null,"abstract":"<div><h3>Aims</h3><p>The incidence of lung infections is increasing worldwide in individuals suffering from cystic fibrosis and chronic obstructive pulmonary disease. <em>Mycobacterium abscessus</em> is associated with chronic lung deterioration in these populations. The intrinsic resistance of <em>M. abscessus</em> to most conventional antibiotics jeopardizes treatment success rates. To date, no single drug has been developed targeting <em>M. abscessus</em> specifically<em>.</em> The objective of this study was to characterize VOMG, a pyrithione-core drug-like small molecule, as a new compound active against <em>M. abscessus</em> and other pathogens.</p></div><div><h3>Methods</h3><p>A multi-disciplinary approach including microbiological, chemical, biochemical and transcriptomics procedures was used to validate VOMG as a promising anti-<em>M. abscessus</em> drug candidate.</p></div><div><h3>Results</h3><p>To the authors’ knowledge, this is the first study to report the <em>in-vitro</em> and <em>in-vivo</em> bactericidal activity of VOMG against <em>M. abscessus</em> and other pathogens. Besides being active against <em>M. abscessus</em> biofilm, the compound showed a favourable pharmacological (ADME-Tox) profile. Frequency of resistance studies were unable to isolate resistant mutants. VOMG inhibits cell division, particularly the FtsZ enzyme.</p></div><div><h3>Conclusions</h3><p>VOMG is a new drug-like molecule active against <em>M. abscessus</em>, inhibiting cell division with broad-spectrum activity against other microbial pathogens.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924001961/pdfft?md5=da4fde3ee6a0ba4b2485793d4fec22a0&pid=1-s2.0-S0924857924001961-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary adaptation of KPC-2-producing Pseudomonas aeruginosa high-risk sequence type 463 in a lung transplant patient","authors":"","doi":"10.1016/j.ijantimicag.2024.107279","DOIUrl":"10.1016/j.ijantimicag.2024.107279","url":null,"abstract":"<div><h3>Objectives</h3><p>KPC-2-producing <em>Pseudomonas aeruginosa</em> high-risk sequence type (ST) 463 is increasingly prevalent in China and poses severe threats to public health. In this study, we aimed to investigate within-host adaptive evolution of this clone during therapy.</p></div><div><h3>Methods</h3><p>Using nine serial respiratory isolates from a post-lung transplantation patient undergoing multiple antibiotic treatments, we conducted genomic, transcriptomic and phenotypic analyses to uncover the adaptive mechanisms of a KPC-2-producing ST463 <em>P. aeruginosa</em> strain.</p></div><div><h3>Results</h3><p>The early-course isolates exhibited low-level resistance to ceftazidime/avibactam (CZA), facilitated by the <em>bla</em>_KPC-2 gene's presence on both chromosome and plasmid, and its overexpression. Comparative genomic analysis revealed that chromosomal integration of <em>bla</em>_KPC-2 resulted from intracellular replicative transposition of the plasmid-derived IS<em>26-bla</em>_KPC-2-IS<em>26</em> composite transposon. As the infection progressed, selective pressures, predominantly from antibiotic interventions and host immune response, led to significant genomic and phenotypic changes. The late-course isolates developed a Δ242-GT-243 deletion in plasmid-encoded <em>bla</em>_KPC-2 (<em>bla</em>_KPC-14) after sustained CZA exposure, conferring high-level CZA resistance. Increased expression of pili and extracellular polysaccharides boosted biofilm formation. A D143N mutation in the global regulator <em>vfr</em> rendered the strain aflagellate by abrogating the ability of <em>fleQ</em> to positively regulate flagellar gene expression. The enhancement of antibiotic resistance and immune evasion collaboratively facilitated the prolonged survival of ST463 <em>P. aeruginosa</em> within the host.</p></div><div><h3>Conclusions</h3><p>Our findings highlight the remarkable capacity of ST463 <em>P. aeruginosa</em> in adapting to the dynamic host pressures, supporting its persistence and dissemination in healthcare.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924001973/pdfft?md5=7ab1b50b41cfbc7590a3ab028fd4903e&pid=1-s2.0-S0924857924001973-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxoplasma gondii infection or acute retinal necrosis in early stage: A case report","authors":"","doi":"10.1016/j.ijantimicag.2024.107280","DOIUrl":"10.1016/j.ijantimicag.2024.107280","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zanamivir and baloxavir combination to cure persistent influenza and coronavirus infections after hematopoietic stem cell transplant","authors":"","doi":"10.1016/j.ijantimicag.2024.107281","DOIUrl":"10.1016/j.ijantimicag.2024.107281","url":null,"abstract":"<div><h3>Objectives</h3><p>Immunocompromised patients may experience prolonged shedding of influenza virus potentially leading to severe infections. Alternatives to monotherapy with neuraminidase inhibitors should be evaluated to entirely suppress viral replication and prevent drug-resistant mutations.</p></div><div><h3>Methods</h3><p>We investigated the clinical and virological evolution in a case of persistent influenza A and human coronavirus OC43 (HCoV-OC43) coinfection in a hematopoietic stem cell transplant recipient after different therapeutic strategies.</p></div><div><h3>Results</h3><p>Successive oseltamivir and zanamivir monotherapies failed to control both infections, with positive results persisting for over 110 days each. This led to the emergence of highly resistant oseltamivir strains due to neuraminidase mutations (E119V and R292K) followed by a deletion (del245-248), while maintaining sensitivity to zanamivir. The intra-host viral diversity data showed that the treatments impacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient's underlying condition and the impact of prolonged viral shedding on pulmonary function, eradicating the influenza virus was necessary. A 10-day regimen combining zanamivir and baloxavir-marboxil effectively controlled influenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in comprehensive respiratory recovery.</p></div><div><h3>Conclusion</h3><p>These observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924001997/pdfft?md5=96d24e0f8c736d6ad10a8bfcd23f8e6a&pid=1-s2.0-S0924857924001997-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Q48K mutation in the type IB nitroreductase NrmA is responsible for nitrofurantoin resistance in Enterococcus faecium","authors":"","doi":"10.1016/j.ijantimicag.2024.107277","DOIUrl":"10.1016/j.ijantimicag.2024.107277","url":null,"abstract":"<div><h3>Objectives</h3><p>Nitrofurantoin is recommended as first-line therapy for the optimal treatment of uncomplicated urinary tract infections (UTIs) caused by enterococci and <em>Escherichia coli</em>. However, the mechanisms of nitrofurantoin resistance in enterococci have not been elucidated. This study aimed to investigate the mechanisms of nitrofurantoin resistance in <em>E. faecium</em>, focusing on the role of the nitroreductase NrmA.</p></div><div><h3>Methods</h3><p>Enterococcus strains isolated from the urinary tract samples were collected and were tested for nitrofurantoin susceptibility. Potential genes associated with nitrofurantoin resistance were screened in the NCBI nucleotide database and by polymerase chain reaction (PCR). Complementation assays and enzyme kinetic tests were performed to assess the impact of the Q48K mutation in NrmA on nitrofurantoin resistance.</p></div><div><h3>Results</h3><p>Of the 128 <em>E. faecium</em> isolates tested, 59 (46.1%) were resistant to nitrofurantoin. Analysis revealed the presence of a type IB nitroreductase, designated NrmA, in all <em>E. faecium</em> strains studied, shared 18.7% sequence identity with nitroreductase NfsB in <em>E. coli</em>. Different from NrmA in nitrofurantoin-susceptible <em>E. faecium</em>, nitrofurantoin-resistant strains had a single amino acid substitution, i.e., a lysine instead of a glutamine at position 48 (Q48K mutation). Complementation assays of nitrofurantoin-resistant <em>E. faecium</em> HS17-112 showed that the nitrofurantoin minimal inhibitory concentration of the complemented strain HS17-112: pIB166-<em>nrmA</em> (wild type [WT]) decreased from 128 mg/L to 4 mg/L. Compared with NrmA (WT), NrmA (Q48K) showed significantly reduced catalytic efficiency, with a <em>kcat/Km</em> value decreasing from 0.122 µM⁻¹ s⁻¹ to 0.000042 µM⁻¹ s⁻¹.</p></div><div><h3>Conclusion</h3><p>The Q48K mutation in nitroreductase NrmA is responsible for nitrofurantoin resistance in <em>E. faecium</em>.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and laboratory insights into the threat of hypervirulent Klebsiella pneumoniae","authors":"","doi":"10.1016/j.ijantimicag.2024.107275","DOIUrl":"10.1016/j.ijantimicag.2024.107275","url":null,"abstract":"<div><p>Hypervirulent <em>Klebsiella pneumoniae</em> (hvKP) typically causes severe invasive infections affecting multiple sites in healthy individuals. In the past, hvKP was characterized by a hypermucoviscosity phenotype, susceptibility to antimicrobial agents, and its tendency to cause invasive infections in healthy individuals within the community. However, there has been an alarming increase in reports of multidrug-resistant hvKP, particularly carbapenem-resistant strains, causing nosocomial infections in critically ill or immunocompromised patients. This presents a significant challenge for clinical treatment. Early identification of hvKP is crucial for timely infection control. Notably, identifying hvKP has become confusing due to its prevalence in nosocomial settings and the limited predictive specificity of the hypermucoviscosity phenotype. Novel virulence predictors for hvKP have been discovered through animal models or machine learning algorithms, while standardization of identification criteria is still necessary. Timely source control and antibiotic therapy have been widely employed for the treatment of hvKP infections. Additionally, phage therapy is a promising alternative approach due to escalating antibiotic resistance. In summary, this narrative review highlights the latest research progress in the development, virulence factors, identification, epidemiology of hvKP, and treatment options available for hvKP infection.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteriophages as potential antibiotic potentiators in cystic fibrosis: A new model to study the combination of antibiotics with a bacteriophage cocktail targeting dual species biofilms of Staphylococcus aureus and Pseudomonas aeruginosa","authors":"","doi":"10.1016/j.ijantimicag.2024.107276","DOIUrl":"10.1016/j.ijantimicag.2024.107276","url":null,"abstract":"<div><h3>Objectives</h3><p><em>Staphylococcus aureus</em> and <em>Pseudomonas aeruginosa</em> co-infections in patients with cystic fibrosis (CF) are associated with disease severity. Their treatment is complicated by biofilm formation in the sticky mucus obstructing the airways. We investigated the activity of phages-antibiotics combinations using a dual species biofilm (<em>P. aeruginosa/S. aureus</em>) formed in artificial sputum medium.</p></div><div><h3>Methods</h3><p>Biofilmswere incubated with broad-spectrum antibiotics (meropenem, ceftazidime, ciprofloxacin, tobramycin) combined with a cocktail of two (bacterio)phages (PSP3 and ISP) proven active via spot tests and double agar on <em>P. aeruginosa</em> PAO1 and <em>S. aureus</em> ATCC 25923.</p></div><div><h3>Results</h3><p>At the highest tested concentrations (100 x MIC), antibiotics alone caused a 20–50% reduction in biomass and reduced <em>S. aureus</em> and <em>P. aeruginosa</em> CFU of 2.3 to 2.8 and 2.1 to 3.6 log₁₀, respectively. Phages alone reduced biofilm biomass by 23% and reduced <em>P. aeruginosa</em> CFU of 2.1 log₁₀, but did not affect <em>S. aureus</em> viability. Phages enhanced antibiotic effects on biomass and exhibited additive effects with antibiotics against <em>P. aeruginosa</em>, but not against <em>S. aureus.</em> Following inhibition of bacterial respiration by phages in planktonic cultures rationalised these observations by demonstrating that PSP3 was effective at multiplicities of infection (MOI) as low as 10⁻⁴ plaque forming units (PFU)/CFU on <em>P. aeruginosa</em>, but ISP, at higher MOI (&gt; 0.1) against <em>S. aureus</em>.</p></div><div><h3>Conclusion</h3><p>Pre-screening inhibition of bacterial respiration by phages may assist in selecting those showing activity at sufficiently low titers to showcase anti-biofilm activity in this complex but clinically-relevant in vitro model of biofilm.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Society of Antimicrobial Chemotherapy (ISAC) News and Information Page","authors":"","doi":"10.1016/j.ijantimicag.2024.107270","DOIUrl":"https://doi.org/10.1016/j.ijantimicag.2024.107270","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924001882/pdfft?md5=6846b4f064efa5df90b39bc4542ed6ce&pid=1-s2.0-S0924857924001882-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141595053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}