International Journal of Antimicrobial Agents最新文献

{"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}

{"title":"Identification of blaKPC-90 in Klebsiella pneumoniae associated with ceftazidime-avibactam resistance and the translocation & truncation of resistant genes mediated by IS26","authors":"Weiwei Yang ,&nbsp;Heping Xu ,&nbsp;Yuanxun Zhao ,&nbsp;Wannan Chen ,&nbsp;Xiaobo Ma ,&nbsp;Fupin Hu","doi":"10.1016/j.ijantimicag.2024.107388","DOIUrl":"10.1016/j.ijantimicag.2024.107388","url":null,"abstract":"<div><h3>Objectives</h3><div>In this study, we discovered <em>bla</em>_KPC-90 in ceftazidime-avibactam resistant clinical isolates of <em>K. pneumoniae</em> from a patient with multiple comorbidities and investigated the resistance &amp; transfer mechanism of <em>bla</em>_KPC-90.</div></div><div><h3>Methods</h3><div><em>K. pneumoniae</em> strains carrying <em>bla</em>_KPC-2 and <em>bla</em>_KPC-90 were isolated from the patient. Antimicrobial susceptibility tests and whole genome sequencing were performed to investigate the phenotype &amp; genotype of strains. Conjugation assays, cloning experiment, kinetic parameters measuring, outer membrane protein SDS-PAGE and qRT-PCR were performed to explore the spread and antimicrobial resistance mechanisms.</div></div><div><h3>Results</h3><div>KPC-90 isolates had an insertion of two amino acids (Thr180_Ser181 ins Tyr Thr) compared to the wildtype KPC-2. Antimicrobial susceptibility testing of isolates with KPC-90 vs. KPC-2 showed ceftazidime-avibactam MICs of &gt;128 vs. 1–2 mg/L, meropenem-vaborbactam MICs of 4 vs. 1 mg/L, meropenem MICs of 4–8 vs. &gt;128 mg/L and imipenem MICs of 0.5–1 vs. 64 mg/L. Analysis of kinetic parameters of KPC-90 compared to KPC-2 showed decreased hydrolysis of carbapenems and increased IC50 of avibactam. Genetic characterization of the plasmid revealed that IS26 could mediate the intramolecular inversion, translocation and truncation of the resistance determinant region.</div></div><div><h3>Conclusion</h3><div>We have described the case of a patient infected with <em>bla</em>_KPC-90-carrying <em>K. pneumoniae</em> strains and investigated the mechanism of resistance to carbapenems and ceftazidime-avibactam associated with <em>bla</em>_KPC-2 and its variants. We have also focused on the functional diversity of IS26 in relation to antimicrobial resistance. In the future, it is crucial to pay more attention to the evolution and horizontal transmission of <em>bla</em>_KPC.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107388"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647974","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":"Rethinking dormancy: Antibiotic persisters are metabolically active, non-growing cells","authors":"K. M. Taufiqur Rahman ,&nbsp;Ruqayyah Amaratunga ,&nbsp;Xuan Yi Butzin ,&nbsp;Abhyudai Singh ,&nbsp;Tahmina Hossain ,&nbsp;Nicholas C. Butzin","doi":"10.1016/j.ijantimicag.2024.107386","DOIUrl":"10.1016/j.ijantimicag.2024.107386","url":null,"abstract":"<div><h3>Objectives</h3><div>Bacterial persisters are a subpopulation of multidrug-tolerant cells capable of surviving and resuming activity after exposure to bactericidal antibiotic concentrations, contributing to relapsing infections and the development of antibiotic resistance. In this study, we challenge the conventional view that persisters are metabolically dormant by providing compelling evidence that an isogenic population of <em>Escherichia coli</em> remains metabolically active in persistence.</div></div><div><h3>Methods</h3><div>Using transcriptomic analysis, we examined E. coli persisters at multiple time points following exposure to bactericidal concentrations of ampicillin (Amp). Some genes were consistently upregulated in Amp treated persisters compared to the untreated controls, a change that can only occur in metabolically active cells capable of increasing RNA levels.</div></div><div><h3>Results</h3><div>Some of the identified genes have been previously linked to persister cells, while others have not been associated with them before. If persister cells were metabolically dormant, gene expression changes over time would be minimal during Amp treatment. However, network analysis revealed major shifts in gene network activity at various time points of antibiotic exposure.</div></div><div><h3>Conclusions</h3><div>These findings reveal that persisters are metabolically active, non-dividing cells, thereby challenging the traditional view that they are dormant.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107386"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647972","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":"LL-37, the master antimicrobial peptide, its multifaceted role from combating infections to cancer immunity","authors":"Anand K. Keshri ,&nbsp;Suraj S. Rawat ,&nbsp;Anubha Chaudhary ,&nbsp;Swati Sharma ,&nbsp;Ananya Kapoor ,&nbsp;Parul Mehra ,&nbsp;Rimanpreet Kaur ,&nbsp;Amit Mishra ,&nbsp;Amit Prasad","doi":"10.1016/j.ijantimicag.2024.107398","DOIUrl":"10.1016/j.ijantimicag.2024.107398","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) represent a unique group of naturally occurring molecules having diverse biological activities, including potent antimicrobial properties. Among them, LL-37 has emerged as a significant player, demonstrating its multifaceted roles during bacterial, fungal, and viral infections, as well as exhibiting intriguing implications in cancer. This review delves into the versatile functions of LL-37, elucidating its mechanisms of action against microbial pathogens and its potential to modulate immune responses. We explored the efficacy of LL-37 in disrupting bacterial membranes, inhibiting fungal growth, and interfering with viral replication, highlighting its potential as a therapeutic agent against a wide array of infectious diseases. Furthermore, we discussed the emerging role of LL-37 in cancer immunity, where its immunomodulatory effects and direct cytotoxicity towards cancer cells offer novel avenues for cancer therapy in the near future. We provided a comprehensive overview of the activities of LL-37 across various diseases and underscored the importance of further research into harnessing the therapeutic potential of this potential antimicrobial peptide along with other suitable candidates.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107398"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791640","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":"Corrigendum to “Clostridioides difficile infections were predominantly driven by fluoroquinolone-resistant Clostridioides difficile ribotypes 176 and 001 in Slovakia in 2018-2019” [International Journal of Antimicrobial Agents, 62 (2023) 1-9/106824]","authors":"Adriana Plankaova ,&nbsp;Marie Brajerova ,&nbsp;Vaclav Capek ,&nbsp;Gabriela Balikova Novotna ,&nbsp;Pete Kinross ,&nbsp;Jana Skalova ,&nbsp;Anna Soltesova ,&nbsp;Pavel Drevinek ,&nbsp;Marcela Krutova","doi":"10.1016/j.ijantimicag.2024.107408","DOIUrl":"10.1016/j.ijantimicag.2024.107408","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107408"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894250","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":"Anakinra efficacy in COVID-19 pneumonia guided by soluble urokinase plasminogen activator receptor: Association with the inflammatory burden of the host","authors":"Evdoxia Kyriazopoulou ,&nbsp;Karolina Akinosoglou ,&nbsp;Eleni Florou ,&nbsp;Elli Kouriannidi ,&nbsp;Artemis Bogosian ,&nbsp;Olga Tsachouridou ,&nbsp;Konstantinos N. Syrigos ,&nbsp;Nikolaos Gatselis ,&nbsp;Haralampos Milionis ,&nbsp;Ilias C. Papanikolaou ,&nbsp;Styliani Sympardi ,&nbsp;Maria Dafni ,&nbsp;Antonia Alevizou ,&nbsp;Alexia-Vasiliki Amvrazi ,&nbsp;Errika Alexandrou ,&nbsp;Kyprianos Archontoulis ,&nbsp;Katerina Argyraki ,&nbsp;Zoi Alexiou ,&nbsp;Yakinthi Georgiou ,&nbsp;Dimitra Gkogka ,&nbsp;Evangelos J. Giamarellos-Bourboulis","doi":"10.1016/j.ijantimicag.2024.107405","DOIUrl":"10.1016/j.ijantimicag.2024.107405","url":null,"abstract":"<div><h3>Background</h3><div>Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization by the United States Food and Drug Administration for patients with COVID-19 pneumonia at risk for severe respiratory failure (SRF) with blood levels of soluble urokinase plasminogen activator receptor (suPAR) ≥ 6 ng/mL. We report the final results of the phase II open-label single-arm SAVE trial in a large population.</div></div><div><h3>Methods</h3><div>Patients with COVID-19 pneumonia and suPAR levels ≥ 6 ng/mL received subcutaneous anakinra 100 mg once daily for 10 days. The primary outcome was the incidence of SRF by day 14. Secondary outcomes were 30-day mortality, incidence of SRF according to time delay for start of treatment, safety, and associations with the inflammatory burden of the host.</div></div><div><h3>Results</h3><div>From March 2020 to March 2022, a total of 992 patients were enrolled. The incidence of SRF was 18.8%, similar to the results of the phase III pivotal SAVE-MOREtrial. The overall 30-day mortality was 9.5%. Participants were divided into 4 subgroups according to time delay between symptoms onset and start of anakinra. The incidence of SRF was similar for all subgroups. Serious adverse events were reported in 15.4%; only 3 were possibly related to anakinra. The most common adverse event was increased liver function tests. A post hoc comparison with the pivotal phase III trial showed similar anakinra outcomes among patient subgroups by levels of inflammatory mediators and D-dimers.</div></div><div><h3>Conclusions</h3><div>Results support the efficacy of anakinra as being similar to that of the pivotal registrational trial for COVID-19 pneumonia. The lack of a comparator group is a limitation.</div></div><div><h3>Trial Registration</h3><div>ClinicalTrials.gov, NCT04357366</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107405"},"PeriodicalIF":4.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794597","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}