Nataliia P. Antonova , Daria V. Vasina , Igor V. Grigoriev , Aleksei I. Laishevtsev , Andrey V. Kapustin , Vasiliy A. Savinov , Aleksei M. Vorobev , Andrei V. Aleshkin , Anastasia A. Zackharova , Timofey A. Remizov , Valentine V. Makarov , Sergey M. Yudin , Vladimir A. Gushchin
{"title":"Pharmacokinetic and Preclinical Safety Studies of Endolysin-Based Therapeutic for Intravenous Administration","authors":"Nataliia P. Antonova , Daria V. Vasina , Igor V. Grigoriev , Aleksei I. Laishevtsev , Andrey V. Kapustin , Vasiliy A. Savinov , Aleksei M. Vorobev , Andrei V. Aleshkin , Anastasia A. Zackharova , Timofey A. Remizov , Valentine V. Makarov , Sergey M. Yudin , Vladimir A. Gushchin","doi":"10.1016/j.ijantimicag.2024.107328","DOIUrl":"10.1016/j.ijantimicag.2024.107328","url":null,"abstract":"<div><div>Pharmacokinetics and safety studies of innovative drugs is an essential part of drug development process. Previously we have developed a novel drug for intravenous administration (lyophilizate) containing modified endolysin LysECD7-SMAP that showed notable antibacterial effect in different animal models of systemic infections. Here we present data on pharmacokinetics of endolysin in mice after single and multiple injections. Time-concentration curves were obtained, and pharmacokinetic parameters for preparation (C<sub>0</sub>, k<sub>el</sub> t<sub>1/2</sub>, AUC<sub>0–∞</sub>, MRT, Cl<sub>T</sub>, V<sub>ss</sub>) were calculated. It was shown that although endolysin is rather short-lived in blood serum (t<sub>1/2</sub> = 12.5 min), the therapeutic concentrations of LysECD7-SMAP (in degraded and non-degraded form) were detected for 60 minutes after injection that is sufficient for antibacterial effect. Based on the obtained data, it was proposed that endolysin distributes presumably in murine blood, degrades in blood and liver, and is eliminated via glomerular filtration. Safety profile of the preparation relating to general toxicity, immunotoxicity and allergenicity was assessed in rodents. It was demonstrated that LysECD7-SMAP in potential therapeutic (12.5 mg/kg), 10-fold (125 mg/kg) and 40-fold (500 mg/kg) doses showed no signs of intoxication and significant abnormalities after single and repeated i.v. administrations, preparation was non-immunogenic and induced minor and reversible allergic reaction in animals.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145570","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 preventive effect of inhaled antibiotic against ventilator-associated pneumonia: A systematic review and meta-analysis","authors":"Wan-Hsuan Hsu , Jheng-Yan Wu , Bo-Wen Shiau , Po-Yu Huang , Min-Hsiang Chuang , Ya-Wen Tsai , Ting-Hui Liu , Hung-Jen Tang , Chih-Cheng Lai","doi":"10.1016/j.ijantimicag.2024.107324","DOIUrl":"10.1016/j.ijantimicag.2024.107324","url":null,"abstract":"<div><h3>Background</h3><div>Ventilator-associated pneumonia (VAP) constitutes a considerable challenge for patients in intensive care units (ICUs) and necessitates the development of effective preventive strategies. This study aimed to evaluate the clinical efficacy of inhaled antibiotics for preventing VAP.</div></div><div><h3>Methods</h3><div>PubMed, Embase, and ClinicalTrials.gov were searched until 21 January 2024. Randomized controlled trials investigating the clinical efficacy of inhaled antibiotics for VAP prevention were included.</div></div><div><h3>Results</h3><div>Seven randomized controlled trials, involving 1465 patients, of whom 734 were classified as the study group receiving inhaled antibiotics and 731 as the control group receiving placebo were included in this meta-analysis. Overall, the occurrence of VAP was significantly lower in the study group than in the control group (risk ratio, 0.69; 95% confidence interval [CI], 0.51–0.92). However, there were no significant differences in mortality (risk ratio, 0.90; 95% CI, 0.74–1.09), length of stay in ICU (mean difference [MD], 0.10 d; 95% CI, −0.91 to 1.1), and hospital (MD, 0.30 d; 95% CI, −1.82 to 2.43), and mechanical ventilation duration (MD, 0.45 d; 95% CI, −0.45 to 1.35) between groups.</div></div><div><h3>Conclusions</h3><div>Inhaled antibiotics hold promise for mitigating the risk of VAP among critically ill patients. However, their impact on mortality, length of stay in ICU and hospital, and mechanical ventilation duration was not statistically significant.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145572","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}
Jin Seok Kim, Hyo-Won Jeong, Young Hee Jin, JinWoo Kim, Jin-ah Kim, Sook Hyun Park, Jae In Lee, Jib-Ho Lee
{"title":"Identification of a multi-replicon plasmid co-harboring mcr-1 and tmexCD3-toprJ1 in Escherichia coli ST101 isolated from wastewater in South Korea","authors":"Jin Seok Kim, Hyo-Won Jeong, Young Hee Jin, JinWoo Kim, Jin-ah Kim, Sook Hyun Park, Jae In Lee, Jib-Ho Lee","doi":"10.1016/j.ijantimicag.2024.107322","DOIUrl":"10.1016/j.ijantimicag.2024.107322","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145569","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}
Bárbara Rodríguez-Urretavizcaya , Lluïsa Vilaplana , M. -Pilar Marco
{"title":"Strategies for Quorum Sensing inhibition as a tool for controlling Pseudomonas aeruginosa infections","authors":"Bárbara Rodríguez-Urretavizcaya , Lluïsa Vilaplana , M. -Pilar Marco","doi":"10.1016/j.ijantimicag.2024.107323","DOIUrl":"10.1016/j.ijantimicag.2024.107323","url":null,"abstract":"<div><div>Antibiotic resistance is one of the most important concerns in global health today. A growing number of infections are becoming harder to treat with conventional drugs and fewer new antibiotics are being developed. In this context, strategies based on blocking or attenuating virulence pathways that do not focus on eradication of bacteria are potential therapeutic approaches that should reduce the selective pressure exerted on the pathogen. This virulence depletion can be achieved by inhibiting the conserved quorum sensing (QS) system, a mechanism that enables bacteria to communicate with one another in a density-dependent manner. QS regulates gene expression, leading to the activation of important processes such as virulence and biofilm formation. This review highlights the approaches reported so far for disrupting different steps of the QS system of the multiresistant pathogen <em>Pseudomonas aeruginosa.</em> The authors describe different types of molecules (including enzymes, natural and synthetic small molecules, and antibodies) already identified as <em>P. aeruginosa</em> quorum quenchers (QQs) or QS inhibitors (QSIs), grouped according to the QS circuit that they block (Las, Rhl, Pqs and some examples from the controversial pathway Iqs). The discovery of new QQs and QSIs is expected to help reduce antibiotic doses, or at least to provide options that act as adjuvants to enhance the effect of antibiotic treatment. Moreover, this article outlines the advantages and possible drawbacks of each strategy and provides perspectives on the potential developments in this field in the future.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145571","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}
Sofía De la Villa , Celia Sánchez-Martínez , Emilia Cercenado , Belén Padilla , Teresa Vicente , Julia Serrano , Luciana Urbina , Patricia Muñoz
{"title":"Effectiveness of short treatment duration for carbapenemase-producing Enterobacterales in bloodstream-infections: A retrospective cohort study","authors":"Sofía De la Villa , Celia Sánchez-Martínez , Emilia Cercenado , Belén Padilla , Teresa Vicente , Julia Serrano , Luciana Urbina , Patricia Muñoz","doi":"10.1016/j.ijantimicag.2024.107318","DOIUrl":"10.1016/j.ijantimicag.2024.107318","url":null,"abstract":"<div><h3>Objective</h3><div>We analyse the effectiveness of short courses of adequate treatment in patients with episodes of carbapenemase-producing Enterobacterales bloodstream-infections (CPE-BSI).</div></div><div><h3>Methods</h3><div>Patients with first monomicrobial CPE-BSI episodes who received ≥72 h of appropriate treatment from 2014–2022 were selected. Detection of CPE was established on the basis of phenotypic antibiogram and confirmation by PCR and/or immunochromatographic methods. Patients were classified in short treatment group (STG) those who received 3–10 days of appropriate treatment, and long treatment (LTG) those receiving >10 days. Unfavourable outcome consisted in a composite of global 30-day mortality and/or persistent bacteremia and/or recurrent bacteremia. Inverse probability of treatment weighting (IPTW) analysis was performed to compare the outcome between the two study groups.</div></div><div><h3>Results</h3><div>We included 105 CPE-BSI episodes: 99 were caused by OXA-48-like, 4 VIM and 2 KPC carbapenemases. Thirty-nine patients (37.1%) were included in the STG and 66 (62.9%) in LTG. The STG group presented frequent treatment with ceftazidime-avibactam (43.6% vs. 24.2%, <em>P</em> = 0.03) and lower in-hospital stay (21 days vs. 32 days, <em>P</em> = 0.02). Overall, 28 patients (26.7%) presented unfavourable outcome: IPTW analysis showed no differences in the outcome between STG to LTG groups (24.2% vs. 30.8%, weighted-risk difference 6.6%, <em>P</em> = 0.44). Patients with unfavourable outcome presented more frequently source other than urinary-biliary (46.4% vs. 23.4%, <em>P</em> = 0.02), received less frequently ceftazidime-avibactam (14.3% vs. 37.7%, <em>P</em> = 0.02) and presented frequently with absence of source control when indicated (28.6% vs. 13.0%, <em>P</em> = 0.06).</div></div><div><h3>Conclusions</h3><div>Short treatment durations for CPE-BSI episodes may be effective, as long as they are appropriate and source control is performed.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132647","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}
Tsai-Wen Wan , Yu-Tsung Huang , Jian-Hong Lai , Qiao-Ting Chao , Hui-Hui Yeo , Tai-Fen Lee , Yung-Chi Chang , Hao-Chieh Chiu
{"title":"The emergence of transposon-driven multidrug resistance in invasive nontypeable Haemophilus influenzae over the last decade","authors":"Tsai-Wen Wan , Yu-Tsung Huang , Jian-Hong Lai , Qiao-Ting Chao , Hui-Hui Yeo , Tai-Fen Lee , Yung-Chi Chang , Hao-Chieh Chiu","doi":"10.1016/j.ijantimicag.2024.107319","DOIUrl":"10.1016/j.ijantimicag.2024.107319","url":null,"abstract":"<div><div>Nontypeable <em>Haemophilus influenzae</em> (NTHi), once considered a harmless commensal, has emerged as a significant concern due to the increased prevalence of multidrug-resistant (MDR) strains and their association with invasive infections. This study aimed to explore the epidemiology and molecular resistance mechanisms of 51 NTHi isolates collected from patients with invasive infections in northern Taiwan between 2011 and 2020. This investigation revealed substantial genetic diversity, encompassing 29 distinct sequence types and 18 clonal complexes. Notably, 68.6% of the isolates exhibited ampicillin resistance, with 28 categorised as MDR and four isolates were even resistant to up to six antibiotic classes. Among the MDR isolates, 18 pulsotypes were identified, indicating diverse genetic lineages. Elucidation of their resistance mechanisms revealed 18 β-lactamase-producing amoxicillin–clavulanate-resistant (BLPACR) isolates, 12 β-lactamase-producing ampicillin-resistant (BLPAR) isolates, and 5 β-lactamase-nonproducing ampicillin-resistant (BLNAR) isolates. PBP3 analysis revealed 22 unique substitutions in BLPACR and BLNAR, potentially contributing to cephem resistance. Notably, novel transposons, Tn<em>7736</em>-Tn<em>7739</em>, which contain critical resistance genes, were discovered. Three strains harboured Tn<em>7739</em>, containing seven resistance genes [<em>aph(3′)-Ia, bla</em><sub>TEM-1</sub>, <em>catA, sul2, strA, strB</em>, and <em>tet</em>(B)], while four other strains carried Tn<em>7736</em>, Tn<em>7737</em>, and Tn<em>7738</em>, each containing three resistance genes [<em>bla</em><sub>TEM-1</sub>, <em>catA</em>, and <em>tet</em>(B)]. The emergence of these novel transposons underscores the alarming threat posed by highly resistant NTHi strains. Our findings indicated that robust surveillance and comprehensive genomic studies are needed to address this growing public health challenge.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132648","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":"Can clinical microbiology laboratories rely on disk diffusion for accurate susceptibility assessment of cefiderocol?","authors":"Patricia Orlandi Barth , Camila Mörschbächer Wilhelm , Dariane Castro Pereira , Afonso Luís Barth","doi":"10.1016/j.ijantimicag.2024.107316","DOIUrl":"10.1016/j.ijantimicag.2024.107316","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132645","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}
Francesc Escrihuela-Vidal , Zaira R. Palacios-Baena , Josune Goikoetxea Agirre , María Teresa Pérez-Rodríguez , José María Reguera Iglesias , Jordi Cuquet Pedragosa , Leticia Sánchez Gómez , Lucía Boix-Palop , Alberto Bahamonde Carrasco , Clara Natera-Kindelán , Jonathan Fernández-Suárez , Alfredo Jover-Sáenz , Alejandro Smithson Amat , Alfonso del Arco Jiménez , Juan Manuel Sánchez Calvo , Andrés Martín-Aspas , Pedro María Martínez Pérez-Crespo , Inmaculada López-Hernández , Jesús Rodríguez-Baño , Luis Eduardo López-Cortés , Isabel Reche
{"title":"Early Antibiotic De-escalation in Patients With Severe Infections Due to Bloodstream Infection by Enterobacterales: A Post Hoc Analysis of a Prospective Multicentre Cohort","authors":"Francesc Escrihuela-Vidal , Zaira R. Palacios-Baena , Josune Goikoetxea Agirre , María Teresa Pérez-Rodríguez , José María Reguera Iglesias , Jordi Cuquet Pedragosa , Leticia Sánchez Gómez , Lucía Boix-Palop , Alberto Bahamonde Carrasco , Clara Natera-Kindelán , Jonathan Fernández-Suárez , Alfredo Jover-Sáenz , Alejandro Smithson Amat , Alfonso del Arco Jiménez , Juan Manuel Sánchez Calvo , Andrés Martín-Aspas , Pedro María Martínez Pérez-Crespo , Inmaculada López-Hernández , Jesús Rodríguez-Baño , Luis Eduardo López-Cortés , Isabel Reche","doi":"10.1016/j.ijantimicag.2024.107317","DOIUrl":"10.1016/j.ijantimicag.2024.107317","url":null,"abstract":"<div><h3>Background</h3><div>Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2.</div></div><div><h3>Methods</h3><div>A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting.</div></div><div><h3>Results</h3><div>Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18–0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32–0.83), and extended-spectrum β-lactamase (ESBL)–producing isolate (aOR = 0.28; 95% CI = 0.17–0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56–3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44–0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39–2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09–1.06). Matched and inverse probability treatment weighting analysis showed similar results.</div></div><div><h3>Conclusions</h3><div>These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132646","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":"Improvement in high-density lipoprotein cholesterol in people with HIV who switched from a tenofovir alafenamide-containing regimen to cabotegravir plus rilpivirine","authors":"Camilla Muccini , Sara Diotallevi , Riccardo Lolatto , Girolamo Piromalli , Vincenzo Spagnuolo , Antonella Castagna","doi":"10.1016/j.ijantimicag.2024.107312","DOIUrl":"10.1016/j.ijantimicag.2024.107312","url":null,"abstract":"","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107120","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}