International Journal of Antimicrobial Agents最新文献

{"title":"Molecular Investigation of an Epidemic Dissemination of Vancomycin-Resistant Enterococcus faecium Sequence Type 80 in Guangdong Province, China","authors":"Lianghui Peng ,&nbsp;Jingjie Song ,&nbsp;Hongli Sun ,&nbsp;Xiwei Zhang ,&nbsp;Yulan Huang ,&nbsp;Shihan Zeng ,&nbsp;Zhuoyang Zhou ,&nbsp;Xiaoyan Li ,&nbsp;Chao Zhuo","doi":"10.1016/j.ijantimicag.2024.107412","DOIUrl":"10.1016/j.ijantimicag.2024.107412","url":null,"abstract":"<div><div>Background: The detection rate of vancomycin-resistant <em>Enterococcus faecium</em> (VREfm) displayed a dramatic increase in Guangdong, China, from 2021 to 2023, for which the molecular epidemiology and genomic characteristics remain largely unexplored. In this study, we investigated the genetic features and epidemiology of VREfm isolates in Guangdong.</div><div>Methods: A total of 54 Guangdong VREfm isolates were collected from three tertiary hospitals in Guangdong. We preformed antimicrobial susceptibility tests, whole genome sequencing, risk factor analysis, and bioinformatics analysis to conduct this research.</div><div>Results: Our investigation indicated that VREfm isolates were highly clonal and multidrug-resistant ST80 <em>Enterococcus faecium</em> harboring <em>van</em>A-positive plasmid. Phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) demonstrated that VREfm isolates exhibited minimal genetic similarity to previously reported <em>E. faecium</em> in China, whereas they exhibited high genomic similarity to an India strain A10290 isolated in 2019 and Hiroshima isolates detected in 2020, indicative of a possible exogeneous import. The genetic environment of <em>cps</em> region showed a novel type of <em>wzy</em> gene cluster involved in capsule polysaccharide (CPS) biosynthesis flanked by ISEf1 and IS16 identified in VREfm isolates, which displayed a remarkably divergence from the downstream of putative <em>cps</em>ABCD region in other sequence types (STs) <em>E. faecium</em>. Heat map of plasmid-mediated virulence factors suggested that several predicted proteins including Cag pathogenetic island proteins existed in VREfm isolates at a high frequency.</div><div>Conclusions: This study highlighted the importance of ongoing surveillance to track the dynamic dissemination of multidrug-resistant ST80 VREfm isolates harboring multiple virulence genes in Guangdong Province, China.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107412"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872003","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":"Characterization of a Novel KPC-2 Variant, KPC-228, Conferring Resistance to Ceftazidime–Avibactam in an ST11-KL64 Hypervirulent Klebsiella pneumoniae","authors":"Peiyao Zhou ,&nbsp;Haojin Gao ,&nbsp;Meilan Li ,&nbsp;Chunyang Wu ,&nbsp;Weihua Han ,&nbsp;Cailing Wan ,&nbsp;Li Shen ,&nbsp;Xinru Yuan ,&nbsp;Junhong Shi ,&nbsp;Yu Huang ,&nbsp;Jianbo Lv ,&nbsp;Ying Zhou ,&nbsp;Fangyou Yu","doi":"10.1016/j.ijantimicag.2024.107411","DOIUrl":"10.1016/j.ijantimicag.2024.107411","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;With the widespread clinical use of ceftazidime–avibactam (CZA), reports of resistance have increased continuously, posing immense threats to public health worldwide. In this study, we explored the underlying mechanisms leading to the development of CZA resistance in an ST11-KL64 hypervirulent &lt;em&gt;Klebsiella pneumoniae&lt;/em&gt; CRE146 that harbored the &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-228&lt;/sub&gt; gene.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Twelve carbapenem-resistant &lt;em&gt;Klebsiella pneumoniae&lt;/em&gt; (CRKP) strains were isolated from the same patient, including &lt;em&gt;K. pneumoniae&lt;/em&gt; CRE146. Whole-genome sequencing (WGS), phylogenetic analysis, &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC&lt;/sub&gt; gene cloning and pACYC-KPC construction assays were conducted to further explore the molecular mechanisms of CZA resistance. Quantitative siderophore production assay, string test, capsule quantification and &lt;em&gt;Galleria mellonella in vivo&lt;/em&gt; infection model were applied to verify the level of pathogenicity of &lt;em&gt;K. pneumoniae&lt;/em&gt; CRE146.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;This strain carried key virulence factors, &lt;em&gt;iutA-iucABCD&lt;/em&gt; operon and &lt;em&gt;rmpA&lt;/em&gt; gene. Compared to the wild-type KPC-2 carbapenemase, the novel KPC-228 enzyme exhibited a deletion of four amino acids in the Ω-loop (del_167-170_ELNS). In addition, the emergence of CZA resistance appeared to be associated with drug exposure, and we observed the &lt;em&gt;in vivo&lt;/em&gt; evolution of wild-type KPC-2 to KPC-228 and then the reversion to its original wild-type KPC-2. The &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-228&lt;/sub&gt; gene was located within the double IS&lt;em&gt;26&lt;/em&gt; flanking the IS&lt;em&gt;Kpn6&lt;/em&gt;-&lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-228&lt;/sub&gt;-IS&lt;em&gt;Kpn27&lt;/em&gt; core structure and carried on an IncFII/IncR-type plasmid. Notably, CRE146 exhibited high-level resistance to CZA (64/4 mg/L) but increased susceptibility to meropenem (1 mg/L) and imipenem (0.5 mg/L) respectively. PACYC-KPC plasmids were constructed and expressed in &lt;em&gt;K. pneumoniae&lt;/em&gt; ATCC13883. Compared to &lt;em&gt;K. pneumoniae&lt;/em&gt; ATCC13883 harboring &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-2&lt;/sub&gt;, &lt;em&gt;K. pneumoniae&lt;/em&gt; ATCC13883 harboring &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-228&lt;/sub&gt; exhibited a high-level resistance to CZA (32/4 mg/L) and increased susceptibility to meropenem (1 mg/L) and imipenem (0.5 mg/L). Interestingly, &lt;em&gt;K. pneumoniae&lt;/em&gt; ATCC13883 harboring &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-228&lt;/sub&gt; showed a significant decrease in their resistance to all β-lactamases tested except CZA and ceftazidime.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;In conclusion, we reported a novel KPC variant, KPC-228, in a clinical ST11-KL64 hypervirulent &lt;em&gt;K. pneumoniae&lt;/em&gt; strain, which conferred CZA resistance, possibly through enhancing ceftazidime affinity and reducing avibactam binding. The &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-228&lt;/sub&gt; can mutate back to &lt;em&gt;bla&lt;/em&gt;&lt;sub&gt;KPC-2&lt;/sub&gt; under carbapenem pressure, which was very detrimental to clinical treatment. This strain carried both resistance and virulence genes, posing a major challeng","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107411"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871997","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 outcomes of a twice-daily metronidazole dosing strategy for Bacteroides spp. bloodstream infections","authors":"Sunish Shah ,&nbsp;Kathleen Adams ,&nbsp;Lloyd Clarke ,&nbsp;Justin Ludwig ,&nbsp;Dayna McManus ,&nbsp;Minh-Hong Nguyen ,&nbsp;Jeffrey E. Topal ,&nbsp;Ryan K. Shields","doi":"10.1016/j.ijantimicag.2024.107403","DOIUrl":"10.1016/j.ijantimicag.2024.107403","url":null,"abstract":"<div><h3>Objective</h3><div>The optimal dose of metronidazole for the treatment of <em>Bacteroides</em> spp. bacteraemia has not been well defined.</div></div><div><h3>Methods</h3><div>This study was a multi-centre, retrospective chart review of adult patients with bacteraemia secondary to <em>Bacteroides</em> spp. between October 2010 and March 2024. Clinical outcomes of patients who received metronidazole 500 mg twice daily were compared with those who received metronidazole 500 mg thrice daily. Clinical failure was defined as a composite of 30-day recurrent infection due to <em>Bacteroides</em> spp. or all-cause mortality.</div></div><div><h3>Results</h3><div>Of the 242 patients who met the inclusion criteria, 76 received metronidazole twice daily and 166 received metronidazole thrice daily. Patients who received metronidazole twice daily did not have significantly different rates of clinical failure (15% vs 18%; <em>P</em>=0.561) or 30-day mortality (15% vs 17%; <em>P</em>=0.638) compared with those who received metronidazole thrice daily. After applying full-cohort matching, patients who received metronidazole twice daily were not at increased risk of clinical failure [odds ratio (OR)=0.859, 95% confidence interval (CI) 0.283–2.606; <em>P</em>=0.801] or 30-day mortality (OR=0.897, 95% CI 0.292–2.752; <em>P</em>=0.8573) compared with those who received metronidazole thrice daily.</div></div><div><h3>Conclusions</h3><div>In the largest study to date of patients with <em>Bacteroides</em> spp. bacteraemia treated with metronidazole, twice-daily dosing strategies were not associated with worse outcomes compared with thrice-daily dosing strategies.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107403"},"PeriodicalIF":4.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817552","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":"Title Page & Editorial Board","authors":"","doi":"10.1016/S0924-8579(24)00316-9","DOIUrl":"10.1016/S0924-8579(24)00316-9","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107400"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143557","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":"Developing a human monoclonal antibody combination CRM25 to prevent rabies after exposure","authors":"Caifeng Long ,&nbsp;Wenbo Wang ,&nbsp;Jialiang Du ,&nbsp;Gangling Xu ,&nbsp;Chuanfei Yu ,&nbsp;Lan Wang","doi":"10.1016/j.ijantimicag.2024.107383","DOIUrl":"10.1016/j.ijantimicag.2024.107383","url":null,"abstract":"<div><h3>Objective</h3><div>Immunization against rabies post-exposure prophylaxis requires passive immunization with either monoclonal antibody (mAb) or blood-derived rabies immunoglobin (RIG). Currently, replacing traditional RIG with emerging mAb or mAb combinations is highly recommended due to the limited supply and potential safety risks of RIG.</div></div><div><h3>Methods</h3><div>We developed a mAb combination named CRM25 by combining two human mAbs, RM02 and RM05, at a 1:1 mass ratio.</div></div><div><h3>Results</h3><div>RM02 and RM05 were non-competing and non-overlapping mAbs targeting epitopes I and III, respectively. K226 and G229 were found to be the critical amino acid sites for RM02 neutralization, but the mutant I338T displayed decreased susceptibility to RM05 neutralization. Notably, CRM25 was capable of cross-neutralizing rabies virus (RABV) strains containing K226M or I338T mutations. CRM25 additionally showed an inhibitory effect on the infection of all tested common RABVs and non-RABV phylogroup I lyssaviruses. CRM25 not only exhibited neutralizing activity but also exhibited antiviral effects via Fc-mediated effector functions. Importantly, CRM25 was comparable to human RIG in terms of its capacity to protect Syrian golden hamsters from lethal RABV challenges.</div></div><div><h3>Conclusions</h3><div>These findings promote more thorough research on CRM25’s antiviral properties in cells and in vivo to enhance its clinical applicability and suggest that it may be a viable candidate medication for rabies post-exposure prophylaxis.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107383"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619961","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":"Acquired blaCfxA-3 carried by a conjugative transposon or duplicated intrinsic blaCME-3 mediates cefiderocol resistance in Elizabethkingia anophelis clinical isolates","authors":"Ya-Sung Yang ,&nbsp;Yu-Lin Lee ,&nbsp;Yuag-Meng Liu ,&nbsp;Chen-Feng Kuo ,&nbsp;Mei-Chen Tan ,&nbsp;Wei-Cheng Huang ,&nbsp;Shu-Yuan Hsu ,&nbsp;Yea-Yuan Chang ,&nbsp;Hung-Sheng Shang ,&nbsp;Shu-Chen Kuo","doi":"10.1016/j.ijantimicag.2024.107378","DOIUrl":"10.1016/j.ijantimicag.2024.107378","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Elizabethkingia</em> spp. are resistant to multiple antibiotics. This study aimed to determine <em>in vitro</em> and <em>in vivo</em> activities of cefiderocol against <em>Elizabethkingia</em> spp. and to investigate resistance mechanisms.</div></div><div><h3>Methods</h3><div>Bloodstream isolates were collected from four hospitals. <em>In vitro</em> and <em>in vivo</em> activities were determined using broth microdilution and the wax moth model, respectively. Genome comparison and gene editing were used to confirm the contribution of target genes. Conjugation experiments and serial passage were used to determine transferability and stability, respectively. A MIC of ≤4 mg/L was designated as the susceptibility breakpoint.</div></div><div><h3>Results</h3><div>Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤4 mg/L with MIC_50/90 of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both patients had multiple comorbidities, were ventilator-dependent and had not received cefiderocol previously. Resistance was attributable to acquisition of <em>bla</em>_CfxA-3, carried by a conjugative transposon from <em>Prevotella jejuni</em>, and duplication of intrinsic <em>bla</em>_CME-3, which led to its overexpression. <em>tetQ</em> coexisted with <em>bla</em>_CfxA-3 in this conjugative transposon and minocycline facilitated its transfer among <em>E. anophelis</em>. Antibiotics prescribed for source patients did not induce <em>bla</em>_CME-3 duplication. The stabilities of <em>bla</em>_CfxA-3 and double <em>bla</em>_CME-3 were 100% and &gt; 90%, respectively, after 10-day serial passage. Cefiderocol failed to rescue moth larvae infected with resistant strains, but removal of resistance mechanisms restored <em>in vivo</em> efficacy.</div></div><div><h3>Conclusions</h3><div>Cefiderocol was <em>in vitro</em> and <em>in vivo</em> active against <em>Elizabethkingia</em> spp. but resistance may emerge due to the availability, transferability, and/or stability of resistance mechanisms.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107378"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603809","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":"PK/PD modelling and simulation of longitudinal meropenem in vivo effects against Escherichia coli and Klebsiella pneumoniae strains with high MICs","authors":"Raphaël Saporta ,&nbsp;Elisabet I. Nielsen ,&nbsp;Jon U. Hansen ,&nbsp;Edgars Liepinsh ,&nbsp;Iris K. Minichmayr ,&nbsp;Lena E. Friberg","doi":"10.1016/j.ijantimicag.2024.107389","DOIUrl":"10.1016/j.ijantimicag.2024.107389","url":null,"abstract":"<div><h3>Background</h3><div>Carbapenem-resistant bacteria pose a threat to public health. Characterising the pharmacokinetics-pharmacodynamics (PKPD) of meropenem longitudinally <em>in vivo</em> against resistant bacteria could provide valuable information for development and translation of carbapenem-based therapies.</div></div><div><h3>Objectives</h3><div>To assess the time course of meropenem effects <em>in vivo</em> against strains with high MIC to predict PK/PD indices and expected efficacy in patients using a modelling approach.</div></div><div><h3>Methods</h3><div>A PKPD model was built on longitudinal bacterial count data to describe meropenem effects against six <em>Escherichia coli</em> and <em>Klebsiella pneumoniae</em> strains (MIC values 32–128 mg/L) in a 24 h mouse thigh infection model. The model was used to derive PK/PD indices from simulated studies in mice and to predict the efficacy of different infusion durations with high-dose meropenem (2 g q8 h/q12 h for normal/reduced kidney function) in patients.</div></div><div><h3>Results</h3><div>Data from 592 mice were available for model development. The estimated meropenem concentration-dependent killing rate was not associated with differences in MIC. The fraction of time that unbound concentrations exceeded EC₅₀ (<em>f</em>T_&gt;EC50, EC₅₀ = 1.01 mg/L) showed higher correlations than <em>f</em>T_&gt;MIC. For all investigated strains, bacteriostasis at 24 h was predicted for prolonged infusions of high-dose meropenem monotherapy in &gt;90% of patients.</div></div><div><h3>Conclusions</h3><div>The developed PKPD model successfully described bacterial growth and meropenem killing over time in the thigh infection model<em>.</em> For the investigated strains, the MIC, determined <em>in vitro</em>, or MIC-based PK/PD indices, did not predict <em>in vivo</em> response. Simulations suggested prolonged infusions of high-dose meropenem to be efficacious in patients infected by the studied strains.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107389"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647987","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":"Access to phage therapy at Hospices Civils de Lyon in 2022: Implementation of the PHAGEinLYON Clinic programme","authors":"Tristan Ferry ,&nbsp;Myrtille Le Bouar ,&nbsp;Thomas Briot ,&nbsp;Tiphaine Roussel-Gaillard ,&nbsp;Thomas Perpoint ,&nbsp;Sandrine Roux ,&nbsp;Florence Ader ,&nbsp;Florent Valour ,&nbsp;Behrouz Kassai ,&nbsp;Inesse Boussaha ,&nbsp;Marietou Ndiaye ,&nbsp;Fabien Craighero ,&nbsp;Clément Javaux ,&nbsp;Sébastien Lustig ,&nbsp;Cécile Batailler","doi":"10.1016/j.ijantimicag.2024.107372","DOIUrl":"10.1016/j.ijantimicag.2024.107372","url":null,"abstract":"<div><h3>Objectives</h3><div>To describe the PHAGE<em>in</em>LYON <em>Clinic</em> programme, set up in 2022 to improve access to phage therapy in France using pharmaceutical-grade phages.</div></div><div><h3>Methods</h3><div>All phage therapy requests received during 2022 were collected prospectively, and reviewed retrospectively to analyse the decision and the patient care pathway (NCT05883995).</div></div><div><h3>Results</h3><div>Of 143 requests for phage therapy, the indication was confirmed at a multidisciplinary team meeting for 57 (40%) patients. Forty-four patients were infected with bacteria that could be targeted easily by phages in France. Finally, 33 patients were treated, including 26 at the study institution, through a compassionate access programme or in a clinical trial. The main indication were complex bone and joint infections, endovascular infection and lung infection. In order to manage these patients, 172 pharmaceutical phage cocktails targeting <em>Staphylococcus aureus</em> and/or <em>Pseudomonas aeruginosa</em> were prepared: 57 for local injection and 99 for intravenous injection. During follow-up, 18 (69%) patients showed a favourable clinical evolution, and six (23%) patients required subsequent phage therapy, either with the same phage with greater exposure, or with a different phage from elsewhere.</div></div><div><h3>Conclusions</h3><div>Implementation of the PHAGE<em>in</em>LYON <em>Clinic</em> programme in 2022 was associated with groundbreaking access to phage therapy in France.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107372"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567496","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":"Monitoring of the cerebrospinal fluid voriconazole level in a patient with recurrent Candida meningitis after pituitary surgery","authors":"Mete Ucdal ,&nbsp;Emre Kara ,&nbsp;Mustafa Berker ,&nbsp;Aslı Pinar ,&nbsp;Dolunay Gulmez ,&nbsp;Sevtap Arikan-Akdagli ,&nbsp;Ahmet Cağkan Inkaya ,&nbsp;Gokhan Metan","doi":"10.1016/j.ijantimicag.2024.107379","DOIUrl":"10.1016/j.ijantimicag.2024.107379","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107379"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619971","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":"Genomic and growth fitness study of extended-spectrum β-lactamase-producing Escherichia coli from bloodstream infections after introduction of a national 4C antimicrobial stewardship policy in Scotland","authors":"Istifanus Nkene ,&nbsp;Susanth Alapati ,&nbsp;Antonio Ribeiro ,&nbsp;Ijeoma Okoliegbe ,&nbsp;Sreedevi Unnikrishnan ,&nbsp;Corinne Ironside ,&nbsp;Becky Wilson ,&nbsp;Karolin Hijazi","doi":"10.1016/j.ijantimicag.2024.107380","DOIUrl":"10.1016/j.ijantimicag.2024.107380","url":null,"abstract":"<div><h3>Background</h3><div>Extended-spectrum β-lactamase-producing <em>Escherichia coli</em> remains a major cause of hospital-acquired bloodstream infections in countries with high antimicrobial stewardship compliance.</div></div><div><h3>Methods</h3><div>Isolates from bloodstream infections that occurred between 2010 and 2020 in a tertiary-level hospital in North-East Scotland soon after introduction of the ‘4C’ antimicrobial stewardship policy were analysed for phylogenetic structure, antimicrobial resistance, plasmid, and virulence gene carriage. Growth fitness was measured in kinetic assays. Non-metric-multidimensional-scaling was used to evaluate clonal relationships, antimicrobial resistance, and virulence profiles in early and later years after the 4C policy introduction. Clonal and fitness trends over the study period were determined by generalised additive modelling. The relationship between clonal type, antimicrobial resistance, and fitness was evaluated by linear regression.</div></div><div><h3>Results</h3><div>Three hierarchical phylogenetic clusters were identified, with the most dominant cluster (O25:H4/<em>fimH30</em>) including all, and nearly exclusively, Clade C ST131 isolates as well as minor non-ST131 sequence types. The prevalence of ST131 was largely stable over the study period. Resistance to aminoglycosides and aztreonam in ST131 was lower (<em>P =</em> 0.019 and <em>P =</em> 0.004, respectively) during later years (2016–2020) by 28% on average compared to early years soon after 4C policy implementation (2010–2014). Carriage of virulence factors involved in bacterial adaptation was higher in ST131 compared to non-ST131 but mostly stable in early vs. later years. Growth fitness of ST131 was lower than non-ST131 and declined steadily in later years (<em>P &lt;</em> 0.0001).</div></div><div><h3>Conclusions</h3><div>Despite stable virulence factor carriage, population structure, and resistance to cephalosporins, we show increased susceptibility of ST131 to aminoglycosides and aztreonam and concurrent fitness decline years after the introduction of the 4C policy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"64 6","pages":"Article 107380"},"PeriodicalIF":4.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619966","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}