International Journal of Antimicrobial Agents最新文献

{"title":"Whole genome sequencing revealed high occurrence of antimicrobial resistance genes in bacteria isolated from poultry manure","authors":"Animesh Tripathi ,&nbsp;Anjali Jaiswal ,&nbsp;Dinesh Kumar ,&nbsp;Ramesh Pandit ,&nbsp;Damer Blake ,&nbsp;Fiona Tomley ,&nbsp;Madhvi Joshi ,&nbsp;Chaitanya G. Joshi ,&nbsp;Suresh Kumar Dubey","doi":"10.1016/j.ijantimicag.2025.107452","DOIUrl":"10.1016/j.ijantimicag.2025.107452","url":null,"abstract":"<div><h3>Background</h3><div>Global demand for food has driven expansion and intensification of livestock production, particularly in developing nations where antibiotic use is often routine. Waste from poultry production, including manure, is commonly utilized as fertilizers in agroecosystems, risking environmental contamination with potentially zoonotic bacteria and antimicrobial resistance genes (ARGs).</div></div><div><h3>Methods</h3><div>Here, 33 bacterial isolates were recovered from broiler (<em>n</em> = 17) and layer (<em>n</em> = 16) chicken manure by aerobic culture using Luria Bertani agar. Antimicrobial susceptibility testing (AST) was performed using disc diffusion method. MALDI-ToF and 16S rRNA sequencing were used to identify and compare a subset of antibiotic-resistant isolates (<em>n</em> = 13). Comparison of whole genome sequence assemblies and phenotypic assays were used to assess capacity for biofilm formation, heavy metal tolerance and virulence.</div></div><div><h3>Results</h3><div>AST by disc diffusion revealed all isolates were resistant to a minimum of three antibiotics, with resistance to ampicillin, co-trimoxazole, fluoroquinolones, tetracyclines, streptomycin, rifampicin and/or chloramphenicol detected. <em>Stutzerimonas</em> sp. and <em>Acinetobacter</em> sp. were the common genera observed in this study. Genome sequencing of each selected isolate revealed carriage of multiple ARGs capable of conferring resistance to many antimicrobials commonly employed in poultry production and human medicine, including tetracyclines, quinolones, macrolides, sulfonamide and cephalosporins.</div></div><div><h3>Conclusions</h3><div>The high occurrence of ARGs in studied bacterial isolates confirms that poultry manure could act as a source of genetic material that could be transferred to commensal microbiota and opportunistic pathogens of humans. Understanding the complex resistome interplay between humans, animals, and the environment requires a One Health approach, with implications for agricultural settings and public health.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107452"},"PeriodicalIF":4.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065201","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":"Safety of ceftobiprole in patients with impaired renal, hepatic or immune function: A multinational retrospective hospital chart review (RETRACE study)","authors":"Francisco Javier Membrillo de Novales ,&nbsp;Marco Falcone ,&nbsp;Alex Soriano ,&nbsp;Nuria Fernández-Hidalgo ,&nbsp;Daniela Francisci ,&nbsp;Ivan Gentile ,&nbsp;Eve Cedar ,&nbsp;Noëlle Jemmely ,&nbsp;Juan Quevedo ,&nbsp;Miriam Estébanez ,&nbsp;Emanuele Durante-Mangoni ,&nbsp;RETRACE Study Group","doi":"10.1016/j.ijantimicag.2025.107450","DOIUrl":"10.1016/j.ijantimicag.2025.107450","url":null,"abstract":"<div><h3>Background and Aim</h3><div>Ceftobiprole, an advanced-generation cephalosporin with broad bactericidal activity, is approved for community-acquired and hospital-acquired pneumonia (excluding ventilator-associated pneumonia). We aimed to evaluate, in a real-world setting, the safety profile of ceftobiprole in patients with risk conditions (severe renal impairment, hepatic impairment, and immunocompromised status), groups excluded from clinical trials.</div></div><div><h3>Methods</h3><div>In this retrospective study (NCT04170309), 396 consecutive charts of patients treated with ceftobiprole during 2016–2022 in 15 centres in France, Italy, and Spain were analysed: 62 had severe renal impairment, 51 had a hepatic impairment, 120 were immunocompromised, and 203 had no predefined risk condition (controls).</div></div><div><h3>Results</h3><div>Ceftobiprole was used for off-label indications in 110/396 (27.8%) patients; 46/396 (11.6%) patients received a higher-than-recommended dose. Treatment-emergent adverse events (TEAEs) considered as ceftobiprole-related occurred in 44 patients, more frequently in the risk groups compared to controls (severe renal impairment: 8/62 [12.9%]; hepatic impairment: 7/51 [13.7%]; immunocompromised: 19/120 [15.8%]; controls: 15/203, [7.4%]); in 7/44 patients, these events were serious. Compared to controls, liver-related AEs occurred more frequently in the impaired hepatic function (17/51 [33.3%] vs. 22/203 [10.8%], odds ratio [OR:]: 4.11; 95% confidence interval [CI]: 1.98–8.55) and immunocompromised (30/120 [25.0%] vs. 22/203 [10.8%], OR: 2.74; 95% CI: 1.50–5.02) groups. Hyponatremia was also more frequent in immunocompromised patients than controls (14/120 [11.7%] vs. 9/203 [4.4%], OR: 2.85; 95% CI: 1.19–6.80). Underlying disease, concomitant medications and the poor health status of the patients likely affected these imbalances.</div></div><div><h3>Conclusion</h3><div>Overall, no new safety concerns related to ceftobiprole use in real-world patients with severe renal impairment, hepatic impairment or immunocompromised status were identified.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 4","pages":"Article 107450"},"PeriodicalIF":4.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046657","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":"Novel Hsp90α inhibitor inhibits HSV-1 infection by suppressing the Akt/β-catenin pathway","authors":"Zexu Wang ,&nbsp;Weixiangmin Zou ,&nbsp;Qiongzhen Zeng ,&nbsp;Xiaowei Song ,&nbsp;Menghe Li ,&nbsp;Jiaping Pang ,&nbsp;Hai Zhu ,&nbsp;Caiwenjie La ,&nbsp;Xiao Wang ,&nbsp;Yifei Wang ,&nbsp;Kai Zheng","doi":"10.1016/j.ijantimicag.2025.107448","DOIUrl":"10.1016/j.ijantimicag.2025.107448","url":null,"abstract":"<div><h3>Objective</h3><div>The prevalence of herpes simplex virus type 1 (HSV-1) infection and the emergence of drug-resistant HSV-1 strains posts a significant global health challenge, necessitating the urgent development of effective anti-HSV-1 drugs. As one of the most prevalent molecular chaperones, heat shock protein 90 α (Hsp90α) has been extensively demonstrated to regulate a range of viral infections, thus representing a promising antiviral target. In this study, we identified JD-13 as a novel Hsp90α inhibitor and explored its capability in inhibiting HSV-1 infection.</div></div><div><h3>Methods</h3><div>The inhibitory effect of JD-13 on Hsp90α activity was confirmed by molecular docking, molecular dynamic stimulations, fluorescence quench titration and cellular thermal shift assay. The antiviral activity of JD-13 was examined by viral plaque assay, RT-qPCR, Western blot, flow cytometry, fluorescence microscopy and time-of-addition assay. The in vivo antiviral efficacy of JD-13 was evaluated in the HSV-1 skin infection guinea pig model by analyzing skin lesions and herpes formation.</div></div><div><h3>Results</h3><div>JD-13 significantly inhibited the infection of both normal and acyclovir-resistant HSV-1 strains. In addition, JD-13 alleviated skin damage in guinea pigs caused by cutaneous HSV-1 infection. Further studies revealed that JD-13 impaired HSV-1 early infection and suppressed the Akt/β-catenin signalling pathway by promoting Akt degradation. Consequently, the inhibition of the Akt/β-catenin signalling pathway restricted HSV-1 infection.</div></div><div><h3>Conclusions</h3><div>These results suggest JD-13 as a novel HSP90α inhibitor with the potential to be developed as an antiviral agent for the treatment of HSV-1-related diseases.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107448"},"PeriodicalIF":4.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038309","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 hidden threat: Klebsiella pneumoniae may develop co-resistance to colistin and cefiderocol under pressure of colistin","authors":"Xin Chen ,&nbsp;Zhewei Sun ,&nbsp;Jinhong Chen ,&nbsp;Xiaogang Xu ,&nbsp;Minggui Wang ,&nbsp;Jiachun Su","doi":"10.1016/j.ijantimicag.2025.107445","DOIUrl":"10.1016/j.ijantimicag.2025.107445","url":null,"abstract":"<div><h3>Objectives</h3><div>Carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) has become a global concern owing to its difficult treatment. This study aimed to determine the impact of colistin resistance on susceptibility to cefiderocol.</div></div><div><h3>Methods</h3><div>The colistin-susceptible clinical strain CRKP12-130 (colistin minimum inhibitory concentration [MIC] 0.5 mg/L) was cultured in medium containing 4× and 8× the MIC of colistin. Eight colistin-resistant derivatives were randomly selected for susceptibility testing of cefiderocol and zeta potential changes. To compare the impact of colistin resistance on bacterial uptake of iron, growth curve experiments were conducted in cation-adjusted Mueller-Hinton broth (CAMHB) and iron-depleted CAMHB (ID-CAMHB). Resistant strains and the original strain CRKP12-130 were subjected to next-generation sequencing.</div></div><div><h3>Results</h3><div>Colistin MICs ranged from 16 to 128 mg/L for the eight colistin-resistant derivatives. The key genetic variants identified in colistin-resistant strains involved insertions and deletions in <em>mgrB,</em> and missense mutations in <em>pmrB</em> and <em>phoQ</em>. The colistin-resistant derivatives also exhibited reduced susceptibility to cefiderocol, with MICs increasing from 1 mg/L to 2–8 mg/L. Additionally, colistin-resistant strains demonstrated higher zeta potentials, ranging from -45.2 mV to levels between -32.8 mV and -14.2 mV. Resistant strains showed a more significant decrease in growth rate when cultivated in ID-CAMHB medium.</div></div><div><h3>Conclusion</h3><div>This study investigated the phenomenon of co-resistance to colistin and cefiderocol in CRKP under pressure of colistin. The simultaneous decrease in susceptibility poses a potential threat to the efficacy of clinical treatment of CRKP infections.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107445"},"PeriodicalIF":4.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004987","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":"Comparison of piperacillin-tazobactam and vancomycin (TZP-VAN) with piperacillin-tazobactam and teicoplanin (TZP-TEI) for the risk of acute kidney injury (CONCOMITANT): A prospective observational, multinational, multi-centre cohort study","authors":"Abdullah Tarık Aslan ,&nbsp;Emre Kara ,&nbsp;Gamze Köksal ,&nbsp;Yeliz Bilir ,&nbsp;Kemal Tolga Saraçoğlu ,&nbsp;Fatma Eser ,&nbsp;Rahmet Güner ,&nbsp;Sevil Alkan ,&nbsp;Alessandro D'Avino ,&nbsp;Rosa Escudero-Sanchez ,&nbsp;Kürşat Kutluca ,&nbsp;Sibel Yıldız Kaya ,&nbsp;Neşe Saltoğlu ,&nbsp;Laura Loiacono ,&nbsp;Simona Coladonato ,&nbsp;Paola Del Giacomo ,&nbsp;Antonio Cascio ,&nbsp;Carlo Pallotto ,&nbsp;Daniela Francisci ,&nbsp;Barçın Öztürk ,&nbsp;Murat Akova","doi":"10.1016/j.ijantimicag.2025.107446","DOIUrl":"10.1016/j.ijantimicag.2025.107446","url":null,"abstract":"<div><h3>Objective</h3><div>Both vancomycin (VAN) and teicoplanin (TEI) augment the risk of acute kidney injury (AKI) when combined with piperacillin-tazobactam (TZP). We aimed to compare the risk of AKI among patients receiving TZP-VAN vs. TZP-TEI.</div></div><div><h3>Methods</h3><div>This was a prospective, multinational, multicentre cohort study conducted in 12 centres from Turkiye, Italy, and Spain between 1 June 2022, and 31 December 2023. The primary outcome was the occurrence of AKI between the first day of antibiotic treatment and the third day after completing therapy, according to the Kidney Disease Improving Global Outcomes criteria. Multivariable logistic regression and propensity-score match analyses were employed to adjust for confounding variables. Stratified Kaplan-Meier analysis was used to assess the time-to-AKI between the comparison groups.</div></div><div><h3>Results</h3><div>Of 187 patients (TZP-TEI, <em>n</em> = 102; TZP-VAN, <em>n</em> = 85), the AKI occurred in 21 patients (24.7%) who received TZP-VAN and in 15 patients (14.7%) with TZP-TEI (unadjusted odds ratio [OR], 1.90; 95% CI: 0.91–3.97; <em>P</em> = 0.087). After adjusting for confounding variables with multivariable analysis, TZP-VAN was not associated with increased odds of AKI compared with TZP-TEI; with an adjusted OR of 2.24 (95% CI: 0.78–6.42; <em>P</em> = 0.133). In propensity-score matched analysis (<em>n</em> = 49 pairs), the AKI risk was similar between the two groups (OR, 2.10; 95% CI: 0.67–6.50; <em>P</em> = 0.199). The stratified Kaplan-Meier analysis indicated no difference between the treatment groups in terms of time-to-AKI (log-rank test, <em>P</em> = 0.107).</div></div><div><h3>Conclusions</h3><div>The risk of AKI in TZP-VAN was similar to that in TZP-TEI. These results should be confirmed in randomized controlled trials.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107446"},"PeriodicalIF":4.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004975","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":"Population pharmacokinetics and pharmacodynamics of HFB30132A, a monoclonal antibody against SARS-CoV-2, in healthy Chinese and US subjects","authors":"Yuancheng Chen ,&nbsp;Size Li ,&nbsp;William Hedrich ,&nbsp;Xiaojie Wu ,&nbsp;Shanshan Li ,&nbsp;Chao Qiu ,&nbsp;Ke Lin ,&nbsp;Xingchen Bian ,&nbsp;Jinjie He ,&nbsp;He Zhou ,&nbsp;Francisco Adrian ,&nbsp;Liang Schweizer ,&nbsp;Jing Zhang","doi":"10.1016/j.ijantimicag.2024.107439","DOIUrl":"10.1016/j.ijantimicag.2024.107439","url":null,"abstract":"<div><div>Development of neutralizing monoclonal antibodies (nAbs) is a strategy for treatment of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of HFB30132A, a fully human nAb targeting the SARS-CoV-2 spike protein receptor binding domain in healthy subjects. A randomized, double-blind, placebo-controlled phase I trial was performed in healthy Chinese and US subjects. The subjects (<em>n</em>=44) received a single ascending dose (400, 1000, 2000 mg) or placebo. Safety and PK data were analysed. PD were evaluated with a pseudovirus neutralization test <em>in vitro</em> using serum samples of Chinese subjects. A population PK/PD model was developed using non-linear mixed effects modelling. The effects of covariates were evaluated via covariate screening, Monte Carlo simulation and randomization tests. The PK profile was consistent with a three-compartment model. Clearance and V1 were 0.38 mL/h and 2.9 L, respectively. Ethnicity and body weight were factors affecting PK. Compared with subjects who were not Hispanic or Latino, area under the curve increased by 64% in subjects of Han nationality. PD were consistent with the effect-compartment model when 50% of neutralization dilution titre was used as the PD index. Maximal effect (E_max) reduced with time, consistent with the exponential model. The concentration of HFB30132A exerting 50% of E_max was 4590 mg/L. The half-life for reduction of E_max was 133 days. Albumin, lymphocytes, neutrophils and monocytes affected PD. Ethnic differences in PK and tolerance of PD were found for HFB30132A. The population PK/PD model characterized the dose–exposure–response relationship of HFB30132A in healthy subjects. These findings are useful for drug development in the future.</div><div><em>Clinical trial registration:</em> ClinicalTrial.gov NCT04590430, NCT05275660.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107439"},"PeriodicalIF":4.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964527","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":"An integrative and translational PKPD modelling approach to explore the combined effect of polymyxin B and minocycline against Klebsiella pneumoniae","authors":"Chenyan Zhao ,&nbsp;Sanne van den Berg ,&nbsp;Zhigang Wang ,&nbsp;Anna Olsson ,&nbsp;Vincent Aranzana-Climent ,&nbsp;Christer Malmberg ,&nbsp;Pernilla Lagerbäck ,&nbsp;Thomas Tängdén ,&nbsp;Anouk E. Muller ,&nbsp;Elisabet I. Nielsen ,&nbsp;Lena E. Friberg","doi":"10.1016/j.ijantimicag.2025.107443","DOIUrl":"10.1016/j.ijantimicag.2025.107443","url":null,"abstract":"<div><h3>Objectives</h3><div>To expand a translational pharmacokinetic–pharmacodynamic (PKPD) modelling approach for assessing the combined effect of polymyxin B and minocycline against <em>Klebsiella pneumoniae</em>.</div></div><div><h3>Methods</h3><div>A PKPD model developed based on <em>in vitro</em> static time-kill experiments of one strain (ARU613) was first translated to characterize that of a more susceptible strain (ARU705), and thereafter to dynamic time-kill experiments (both strains) and to a murine thigh infection model (ARU705 only). The PKPD model was updated stepwise using accumulated data. Predictions of bacterial killing in humans were performed.</div></div><div><h3>Results</h3><div>The same model structure could be used in each translational step, with parameters being re-estimated. Dynamic data were well predicted by static-data-based models. The <em>in vitro</em>/<em>in vivo</em> differences were primarily quantified as a change in polymyxin B effect: a lower killing rate constant <em>in vivo</em> compared with <em>in vitro</em> (concentration of 3 mg/L corresponds to 0.05/h and 57/h, respectively), and a slower adaptive resistance rate (the constant <em>in vivo</em> was 2.5% of that <em>in vitro</em>). There was no significant difference in polymyxin B–minocycline interaction functions. Predictions based on both <em>in vitro</em> and <em>in vivo</em> parameters indicated that the combination has a greater-than-monotherapy antibacterial effect in humans, forecasting a reduction of approximately 5 and 2 log₁₀ colony-forming units/mL at 24 h, respectively, under combined therapy, while the maximum bacterial load was reached in monotherapy.</div></div><div><h3>Conclusions</h3><div>This study demonstrated the utility of the PKPD modelling approach to understand translation of antibiotic effects across experimental systems, and showed a promising antibacterial effect of polymyxin B and minocycline in combination against <em>K. pneumoniae</em>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107443"},"PeriodicalIF":4.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964526","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":"Metagenomic next-generation sequencing on treatment strategies and prognosis of patients with lower respiratory tract infections: A systematic review and meta-analysis","authors":"Mengwei Yan ,&nbsp;Lianhan Shang ,&nbsp;Yeming Wang ,&nbsp;Chenhui Wang ,&nbsp;Bin Cao","doi":"10.1016/j.ijantimicag.2024.107440","DOIUrl":"10.1016/j.ijantimicag.2024.107440","url":null,"abstract":"<div><h3>Objectives</h3><div>Controversy exists regarding the benefits of metagenomic next-generation sequencing (mNGS) in lower respiratory tract infections (LRTIs). We assessed the impact of mNGS on the treatment and prognosis of LRTI patients through a systematic review and meta-analysis.</div></div><div><h3>Methods</h3><div>A literature search was conducted in PubMed, Embase, and CENTRAL databases up to 19 February 2024. Studies investigating the clinical value of mNGS in patients with LRTIs were included. The Risk-of-Bias Tool for randomized controlled trials and the Newcastle–Ottawa scale for observational studies were used to assess risk of bias. Antibiotic change rates and prognostic outcomes were evaluated using random-effects analyses with 95% confidence intervals (CIs). This study is registered with PROSPERO, CRD42024509738.</div></div><div><h3>Results</h3><div>Twelve studies were included in the meta-analysis. The use of mNGS was associated with a higher rate of antibiotic change (odds ratio, 2.47; 95% CI, 1.42–4.28; <em>P</em> &lt; 0.01). Consistent findings were observed in adults, patients with severe LRTIs, and in those who underwent mNGS testing exclusively on bronchoalveolar lavage fluid. We also observed a reduction in in-hospital mortality (odds ratio, 0.49; 95% CI, 0.36–0.67; <em>P</em> &lt; 0.01), though no significant impact on length of hospital stay was observed (mean difference, −1.79; 95% CI, −5.20 −1.63; <em>P</em> = 0.31).</div></div><div><h3>Conclusions</h3><div>This meta-analysis indicates that the application of mNGS may lead to changes in antibiotic prescriptions for patients with LRTIs, and might reduce the risk of mortality. However, large-scale randomized controlled clinical trials are urgently needed to validate the findings of this study.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 3","pages":"Article 107440"},"PeriodicalIF":4.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038320","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":"Response regulator protein CiaR regulates the transcription of ccn-microRNAs and β-lactam antibiotic resistance conversion of Streptococcus pneumoniae","authors":"Mei-Juan Yang ,&nbsp;Meng-Jie Li ,&nbsp;Li-Dan Huang ,&nbsp;Xin-Wei Zhang ,&nbsp;Yan-Ying Huang ,&nbsp;Xiao-Yu Gou ,&nbsp;Sui-Ning Chen ,&nbsp;Jie Yan ,&nbsp;Peng Du ,&nbsp;Ai-Hua Sun","doi":"10.1016/j.ijantimicag.2024.107387","DOIUrl":"10.1016/j.ijantimicag.2024.107387","url":null,"abstract":"<div><h3>Background</h3><div><em>Streptococcus pneumoniae</em> does not produce β-lactamases, and its reduced susceptibility to β-lactam antibiotics is predominantly caused by mutations of penicillin-binding proteins (PBPs). However, mechanisms of non–PBP mutation–related β-lactam antibiotic resistance in pneumococcal strains remain poorly characterized.</div></div><div><h3>Methods</h3><div>Susceptibility of <em>S. pneumoniae</em> ATCC49619 and its <em>ciaR</em> gene knockout, complemented, or overexpression mutant (Δ<em>ciaR</em>, CΔ<em>ciaR</em>, or <em>ciaR^OE</em>) to penicillin, cefotaxime, and imipenem was detected using an E-test. Levels of pneumococcal <em>ciaR</em>-mRNA, 5 ccn-microRNAs, and 6 <em>pbps</em>-mRNAs were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Recombinant CiaR (rCiaR) binding to the promoters of ccn-microRNA genes was confirmed using electrophoresis mobility shift and chromatin immunoprecipitation assays. Sequence matching between the ccn-microRNAs and <em>pbps</em>-mRNAs was analyzed using IntaRNA software.</div></div><div><h3>Results</h3><div><em>S. pneumoniae</em> ATCC49619 was sensitive to the 3 β-lactam antibiotics, but overexpression of CiaR, a response regulator protein in 2-component system, caused the increase of MICs against these antibiotics. The <em>ciaR^OE</em> mutant exhibited the significantly increased transcription of ccn-microRNAs but notably decreased transcription of <em>pbps</em>-mRNAs; conversely, the Δ<em>ciaR</em> mutant displayed decreased levels of ccn-microRNAs and increasesed transcription of <em>pbps</em>-mRNAs. rCiaR was able to bind to the promoters of all ccn-microRNA genes <em>in vitro</em> and within cells. The 3 antibiotics at 1/8 minimal inhibitory concentrations caused a significant increase in the <em>ciaR</em>-mRNA and ccn-microRNAs. The mRNA-binding seed sequences in the 5 ccn-microRNAs matched all the promoter-containing sequences of <em>pbps</em>-mRNAs.</div></div><div><h3>Conclusions</h3><div>β-Lactam antibiotics at low concentrations induce non–PBP mutation–related antibiotic resistance conversion of <em>S. pneumoniae</em> by decrease of PBPs through the pathway of CiaR-mediated transcriptional increase of ccn-microRNAs and ccn-microRNA-dependent degradation of <em>pbp-</em>mRNAs.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107387"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681685","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":"HIV-1 viral decay in blood and semen in antiretroviral-naïve adults initiating dolutegravir/lamivudine vs. bictegravir/emtricitabine/tenofovir alafenamide","authors":"Yongjian Liu ,&nbsp;Ran Wang ,&nbsp;Lijun Sun ,&nbsp;Aixin Li ,&nbsp;Zhengyang Li ,&nbsp;Qian Kang ,&nbsp;Yuxin Feng ,&nbsp;Shiyun Lv ,&nbsp;Yuanyi Zhai ,&nbsp;Rui Li ,&nbsp;Wei Hua ,&nbsp;Xi Wang ,&nbsp;Yue Gao ,&nbsp;Zhangli Wang ,&nbsp;Yuguang Feng ,&nbsp;Jingwan Han ,&nbsp;Lei Jia ,&nbsp;Xiaolin Wang ,&nbsp;Bohan Zhang ,&nbsp;Hanping Li ,&nbsp;Lili Dai","doi":"10.1016/j.ijantimicag.2024.107396","DOIUrl":"10.1016/j.ijantimicag.2024.107396","url":null,"abstract":"<div><h3>Background</h3><div>Co-formulated dolutegravir and lamivudine (DTG/3TC) is recommended as the first-line antiretroviral therapy (ART); however, the data on the viral decay in seminal plasma (SP) and blood plasma (BP), as well as changes in inflammatory biomarkers in BP, remain limited among antiretroviral-naïve people with HIV (PWH) receiving DTG/3TC. A prospective observational cohort study was conducted to compare the impact of DTG/3TC vs. bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) on viral decay kinetics and changes in inflammatory biomarkers in antiretroviral-naïve PWH.</div></div><div><h3>Methods</h3><div>Newly diagnosed PWH who initiated BIC/FTC/TAF (n=57) or DTG/3TC (n=43) were enrolled. BP and SP were collected at 0, 4, 12, 24, and 48 weeks after ART initiation. The primary endpoint was viral suppression of HIV-1 in BP and SP at week 48. Secondary endpoints included changes in HIV-1 DNA levels and inflammatory biomarkers over the 48-week follow-up.</div></div><div><h3>Results</h3><div>Overall, 96 (96.0%) PWH completed the 48-week follow-up (DTG/3TC, n=40; BIC/FTC/TAF, n=56). Viral suppression rates in BP and SP were comparable in the BIC/FTC/TAF and DTG/3TC groups in the per-protocol analyses at week 48 (BP, 96.4% vs. 100%, <em>P</em>=0.519; SP, 100% vs. 100%, <em>P</em>&gt;0.999). Both regimens demonstrated similar effectiveness in reducing HIV-1 RNA levels in BP (3.0 vs. 3.1 log₁₀ copies/mL) and SP (0.9 vs. 1.2 log₁₀ copies/mL). There were no statistically significant differences in the reductions in HIV-1 DNA levels and changes in inflammatory biomarkers over the 48-week follow-up.</div></div><div><h3>Conclusion</h3><div>These findings indicated comparable effectiveness of DTG/3TC vs. BIC/FTC/TAF in achieving viral suppression in BP and SP, and similar changes in inflammatory biomarkers in BP.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107396"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755101","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}