Pub Date : 2024-09-12DOI: 10.1016/j.ijantimicag.2024.107326
Objective
Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear.
Methods
This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10,000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group, n = 12) or the same dose q12h for 7 days (multi-dose group, n = 12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis.
Results
After a single dose the peak concentration (Cmax), area under the curve from 0 to 12 h (AUC0-12h), terminal half-life (T1/2), volume of distribution (Vd), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported.
Conclusions
This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice.
{"title":"Pharmacokinetics and safety of colistin sulfate after single and multiple intravenous doses in healthy Chinese subjects","authors":"","doi":"10.1016/j.ijantimicag.2024.107326","DOIUrl":"10.1016/j.ijantimicag.2024.107326","url":null,"abstract":"<div><h3>Objective</h3><div>Increasing antimicrobial resistance has led to the revival of the polymyxins as a last-resort therapeutic option for multidrug-resistant Gram-negative bacterial infections. A parenteral formulation of colistin sulfate is available solely in China. While the onset of action of IV colistin may occur faster than with its prodrug CMS, its pharmacokinetic (PK) profile remains unclear.</div></div><div><h3>Methods</h3><div>This single-centre, open-label, single- and multi-dose, phase 1 trial examined the PKs and safety of colistin sulfate in healthy Chinese adults. Participants received a single 10,000 units/kg (equivalent to 0.452 mg/kg) dose of colistin sulfate (single-dose group, <em>n</em> = 12) or the same dose q12h for 7 days (multi-dose group, <em>n</em> = 12) via a 2-h IV infusion. Colistin concentrations in plasma and urine were determined using LC-MS/MS, and the PK parameters calculated using non-compartmental analysis.</div></div><div><h3>Results</h3><div>After a single dose the peak concentration (C<sub>max</sub>), area under the curve from 0 to 12 h (AUC<sub>0-12h</sub>), terminal half-life (T<sub>1/2</sub>), volume of distribution (V<sub>d</sub>), and total body clearance (CL) of colistin were 1.08 ± 0.18 mg/L, 4.73 ± 0.89 h·mg/L, 3.65 ± 0.55 h, 16.82 ± 2.70 L, and 3.24 ± 0.51 L/h, respectively. No accumulation of colistin was observed after multiple doses. The cumulative urinary recovery of colistin was 0.9 ± 0.7% within 24 h after multi-dose administration. No nephrotoxicity was reported.</div></div><div><h3>Conclusions</h3><div>This study is the first to report colistin PKs in healthy Chinese subjects after single and multiple doses of colistin sulfate. The PK and safety data are required for optimal dose selection in clinical practice.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286366","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107332
Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing.
{"title":"Past, Present, and Future Biomarkers of Kidney Function and Injury: The Relationship With Antibiotics","authors":"","doi":"10.1016/j.ijantimicag.2024.107332","DOIUrl":"10.1016/j.ijantimicag.2024.107332","url":null,"abstract":"<div><div>Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153963","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107327
Objectives
The aim of this study was to investigate interspecies transfer of resistance gene blaNDM-1 and intraspecies transfer of resistance gene blaKPC-2 in Serratia marcescens, and explore the epidemical and evolutionary characteristics of carbapenemase-producing S. marcescens (CPSM) regionally and globally.
Methods
Interspecies and intraspecies transfer of blaKPC-2- or blaNDM-1 were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.
Results
CPSM S50079 strain, co-carrying blaKPC-2 and blaNDM-1 on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either blaKPC-2 or blaNDM-1. The interspecies transfer of blaNDM-1-carrying plasmid from Providencia rettgeri P50213, producing the identical blaNDM-1-carrying TUs, to S. marcescens S50079K, an S50079 variant via plasmid curing, was identified through blaNDM-1-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of blaKPC-2, mediated by IS26 from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of blaNDM-1 carried by IncX3 plasmid was identified among S. marcescens and Citrobacter freundii as well as Enterobacter hormaechei via plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive S. marcescens strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from blaKPC-2 to both blaKPC-2 and blaNDM-1, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive S. marcescens genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.
Conclusions
Interspecies transfer of resistance gene blaNDM-1 and intraspecies transfer of resistance gene blaKPC-2 in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.
{"title":"In-host intra- and inter-species transfer of blaKPC-2 and blaNDM-1 in Serratia marcescens and its local and global epidemiology","authors":"","doi":"10.1016/j.ijantimicag.2024.107327","DOIUrl":"10.1016/j.ijantimicag.2024.107327","url":null,"abstract":"<div><h3>Objectives</h3><div>The aim of this study was to investigate interspecies transfer of resistance gene <em>bla</em><sub>NDM-1</sub> and intraspecies transfer of resistance gene <em>bla</em><sub>KPC-2</sub> in <em>Serratia marcescens</em>, and explore the epidemical and evolutionary characteristics of carbapenemase-producing <em>S. marcescens</em> (CPSM) regionally and globally.</div></div><div><h3>Methods</h3><div>Interspecies and intraspecies transfer of <em>bla</em><sub>KPC-2</sub>- or <em>bla</em><sub>NDM-1</sub> were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.</div></div><div><h3>Results</h3><div>CPSM S50079 strain, co-carrying <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>NDM-1</sub> on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either <em>bla</em><sub>KPC-2</sub> or <em>bla</em><sub>NDM-1</sub>. The interspecies transfer of <em>bla</em><sub>NDM-1</sub>-carrying plasmid from <em>Providencia rettgeri</em> P50213, producing the identical <em>bla</em><sub>NDM-1</sub>-carrying TUs, to <em>S. marcescens</em> S50079K, an S50079 variant <em>via</em> plasmid curing, was identified through <em>bla</em><sub>NDM-1</sub>-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of <em>bla</em><sub>KPC-2</sub>, mediated by IS<em>26</em> from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of <em>bla</em><sub>NDM-1</sub> carried by IncX3 plasmid was identified among <em>S. marcescens</em> and <em>Citrobacter freundii</em> as well as <em>Enterobacter hormaechei via</em> plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive <em>S. marcescens</em> strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from <em>bla</em><sub>KPC-2</sub> to both <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>NDM-1</sub>, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive <em>S. marcescens</em> genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.</div></div><div><h3>Conclusions</h3><div>Interspecies transfer of resistance gene <em>bla</em><sub>NDM-1</sub> and intraspecies transfer of resistance gene <em>bla</em><sub>KPC-2</sub> in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153962","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107335
Background
This study aimed to assess the incidence and risk factors of subsequent carbapenem-resistant Enterobacterales (CRE) infection among rectal carriers, and their association with geographic region and age.
Methods
A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to 31 January 2024). This study is registered with PROSPERO (CRD42023444420).
Results
Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9–25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2–34.5), followed by Europe (20.9%, 95% CI 12.5–30.8) and Asia (19.8%, 95% CI 12.7–27.9). Children had a greater incidence (26.7%, 95% CI 21.3–32.3) than adults (19.8%, 95% CI 14.9–25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (odds ratio [OR] 4.95 95% CI 1.87–13.11). In Europe, admission to the intensive care unit was prominent (OR 2.76 95% CI 1.14–6.65). In the America, the use of a urinary Foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to the intensive care unit was most notable in adults (OR 3.01 95% CI 1.80–5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39–55.47).
Conclusions
Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help in developing more potent prevention and control measures to reduce CRE infection.
研究目的本研究旨在评估直肠带菌者继发 CRE 感染的发生率和风险因素，以及它们与地理区域和年龄的关系：对调查直肠带菌者CRE后续感染发生率和/或风险因素的研究进行了荟萃分析，并按地理区域和年龄进行了亚组分析。研究人员检索了 PubMed、Embase、Web of Science 和 Cochrane Library（发表时间从开始到 2024 年 1 月 31 日）。本研究已在 PROSPERO 注册，编号为 CRD42023444420：结果：在确定的 4459 项研究中，纳入了 24 项研究，共有 8188 名 CRE 直肠携带者。CRE后续感染的总发生率为20.6%（95% CI 15.9-25.8）。美国的发病率最高（23.6%，95% CI 14.2-34.5），其次是欧洲（20.9%，95% CI 12.5-30.8）和亚洲（19.8%，95% CI 12.7-27.9）。儿童的发病率（26.7%，95% CI 21.3-32.3）高于成人（19.8%，95% CI 14.9-25.2）。有 14 个因素与随后的 CRE 感染有关。在亚洲，最显著的风险因素是胃炎（OR 4.95 95% CI 1.87-13.11）。在欧洲，入住重症监护室是最重要的因素（OR 2.76 95% CI 1.14-6.65）。在美国，使用输尿导管（OR 4.33 95% CI 1.06-17.70）是主要原因。入住重症监护室在成人中最显著（OR 3.01 95% CI 1.80-5.02），而机械通气在儿童中最显著（OR 15.61 95% CI 4.39-55.47）：结论：直肠带菌者继发 CRE 感染的风险至关重要。结论：直肠携带者继发 CRE 感染的风险至关重要，确定继发感染的风险因素有助于制定更有效的预防和控制措施，减少 CRE 感染。
{"title":"Epidemiology of Subsequent Carbapenem-Resistant Enterobacterales (CRE) Infection Among Rectal Carriers: A Meta-Analysis of Incidence, Risk Factors and Their Association With Geographic Region and Age","authors":"","doi":"10.1016/j.ijantimicag.2024.107335","DOIUrl":"10.1016/j.ijantimicag.2024.107335","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to assess the incidence and risk factors of subsequent carbapenem-resistant Enterobacterales (CRE) infection among rectal carriers, and their association with geographic region and age.</div></div><div><h3>Methods</h3><div>A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to 31 January 2024). This study is registered with PROSPERO (CRD42023444420).</div></div><div><h3>Results</h3><div>Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9–25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2–34.5), followed by Europe (20.9%, 95% CI 12.5–30.8) and Asia (19.8%, 95% CI 12.7–27.9). Children had a greater incidence (26.7%, 95% CI 21.3–32.3) than adults (19.8%, 95% CI 14.9–25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (odds ratio [OR] 4.95 95% CI 1.87–13.11). In Europe, admission to the intensive care unit was prominent (OR 2.76 95% CI 1.14–6.65). In the America, the use of a urinary Foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to the intensive care unit was most notable in adults (OR 3.01 95% CI 1.80–5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39–55.47).</div></div><div><h3>Conclusions</h3><div>Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help in developing more potent prevention and control measures to reduce CRE infection.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153961","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107331
Background
Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating Helicobacter pylori. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis.
Materials and Methods
A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing H. pylori eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis.
Results
Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior H. pylori eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07–1.73; P=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07–1.88; P=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35–0.68, P<0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98–1.64; P=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03–3.00; P=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55–0.75), 92% (95% CI 0.91–0.94) and 93% (95% CI 0.90–0.97), respectively.
Conclusion
VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.
背景：新型抑酸药物沃诺普拉赞为根除幽门螺杆菌提供了更多选择。因此，沃诺普拉赞和大剂量阿莫西林双重疗法是否更有效、更安全，需要进行系统分析：对截至 2024 年 5 月 16 日的 PubMed、Embase、Cochrane Library 和 Web of Science 数据库中的文献进行了全面检索。纳入了评估VHA双重疗法与其他疗法相比的幽门螺杆菌根除率、不良事件和依从性的研究。使用RevMan 5.4进行统计分析：结果：共纳入11项研究性临床试验和2项回顾性临床研究，4570个样本。VHA双重疗法具有更高的幽门螺杆菌根除率（ITT：86.0% vs 80.7%，OR=1.36，95%CI 1.07-1.73，P=0.01；PP：90.6% vs 85.7%，OR=1.42，95%CI 1.07-1.88，P=0.02）、更少的不良反应（15.4% vs 27.7%，OR=0.49，95%CI 0.35-0.68，PConclusion）：与指南推荐的疗法相比，VHA 10 天或 14 天双重疗法的疗效和安全性更佳，应优先采用。
{"title":"Efficacy and safety of vonoprazan and high-dose amoxicillin dual therapy in eradicating Helicobacter pylori: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.ijantimicag.2024.107331","DOIUrl":"10.1016/j.ijantimicag.2024.107331","url":null,"abstract":"<div><h3>Background</h3><div>Vonoprazan is a new acid-suppressing drug that provides an additional choice for eradicating <em>Helicobacter pylori</em>. The effectiveness and safety of vonoprazan and high-dose amoxicillin (VHA) dual therapy requires study in a systematic analysis.</div></div><div><h3>Materials and Methods</h3><div>A comprehensive search of the literature from the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to 16 May 2024. Trials comparing <em>H. pylori</em> eradication rates, adverse events, and compliance of VHA dual therapy with that of other therapies were included. RevMan 5.4 was used for statistical analysis.</div></div><div><h3>Results</h3><div>Eleven randomised controlled trials (RCTs) and two retrospective clinical studies with 4570 samples were included. VHA dual therapy had superior <em>H. pylori</em> eradication rates (intention-to-treat [ITT]: 86.0% vs. 80.7%; odds ratio [OR]=1.36; 95% confidence interval [CI] 1.07–1.73; <em>P</em>=0.01; per-protocol [PP]: 90.6% vs. 85.7%; OR=1.42; 95% CI 1.07–1.88; <em>P</em>=0.02), fewer adverse events (15.4% vs. 27.7%; OR=0.49; 95% CI 0.35–0.68, <em>P</em><0.0001), and similar compliance (94.6% vs. 93.2%; OR=1.27; 95% CI 0.98–1.64; <em>P</em>=0.07) compared with other guideline therapies. According to subgroup analysis with PP data, VHA dual therapy is more effective than bismuth quadruple therapy based on proton-pump inhibitors (P-BQT) (93.5% vs. 89.3%; OR=1.76; 95% CI 1.03–3.00; <em>P</em>=0.04). In addition, the eradication rates for 7-day, 10-day and 14-day VHA dual therapy were 65% (95% CI 0.55–0.75), 92% (95% CI 0.91–0.94) and 93% (95% CI 0.90–0.97), respectively.</div></div><div><h3>Conclusion</h3><div>VHA dual therapy for 10 or 14 days showed superior efficacy and safety compared with therapies recommended by the guidelines and should be prioritised for adoption.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286361","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijantimicag.2024.107333
Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.
{"title":"Advances in Virus-Specific T-Cell Therapy for Polyomavirus Infections: A Comprehensive Review","authors":"","doi":"10.1016/j.ijantimicag.2024.107333","DOIUrl":"10.1016/j.ijantimicag.2024.107333","url":null,"abstract":"<div><div>Polyomaviruses are a group of small, non-enveloped, double-stranded DNA viruses that can infect various hosts, including humans. BKPyV causes conditions such as human polyomavirus-associated nephropathy (HPyVAN), human polyomavirus-associated haemorrhagic cystitis (HPyVHC), and human polyomavirus-associated urothelial cancer (HPyVUC). JC polyomavirus (JCPyV), on the other hand, is the causative agent of progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. PML primarily affects immunocompromised individuals, including those with HIV, recipients of certain immunosuppressive therapies, and transplant patients. The treatment options for HPyV infections have been limited, but recent developments in virus-specific T cell (VST) therapy have shown promise. Although VST therapy has shown potential in treating both BKPyV and JCPyV infections, several challenges remain. These include the time-consuming and costly preparation of VSTs, the need for sophisticated production facilities, and uncertainties regarding the optimal cell type and infusion frequency. To the best of our knowledge, 85 patients with haemorrhagic cystitis, 27 patients with BKPyV viremia, 2 patients with BKPyV nephritis, 14 patients with haemorrhagic cystitis and BKPyV viremia, and 32 patients with PML have been treated with VST in the literature. The overall response results were 82 complete response, 33 partial response, 35 no response, and 10 no-outcome-reported. This review underscores the importance of VST therapy as a promising treatment approach for polyomavirus infections, emphasising the need for continued research and clinical trials to refine and expand this innovative immunotherapeutic strategy.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153959","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}
Pub Date : 2024-09-06DOI: 10.1016/j.ijantimicag.2024.107325
Background
Empirical treatment needs to be supported by regional data, but knowledge of interregional differences is currently lacking in China. This study aimed to summarize and map the primary and secondary antibiotic resistance of Helicobacter pylori in different regions of mainland China.
Methods
PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wanfang databases were systematically reviewed for studies published between 1 January 2000 and 15 July 2023. Data related to primary and secondary H. pylori antibiotic resistance rates were included. Random-effects models were used to synthesize the pooled resistance rates.
Results
Ultimately, 74 studies were included in the final analysis. A total of 16 provinces reported resistance data. The overall resistance rates of H. pylori in mainland China were 30.72% (95% CI 27.53%–33.99%) to clarithromycin, 70.14% (95% CI 29.53%–37.46%) to metronidazole and 32.98% (95% CI 28.73%–37.37%) to levofloxacin; for amoxicillin, tetracycline, and furazolidone, the rates were 2.41% (95% CI 1.43%–3.60%), 2.53% (95% CI 1.19%–4.28%) and 1.54% (95% CI 0.28%–3.62%), respectively. Spatial and temporal differences were observed. The resistance rates increased after treatment failure; however, secondary resistance to amoxicillin, tetracycline and furazolidone were still low across the vast majority of study regions.
Conclusion
Surveillance of the updated prevalence of antibiotic resistance of H. pylori for different regions is warranted, which should factor into clinical decision making and guideline recommendations.
背景：经验性治疗需要地区数据的支持，但中国目前缺乏对地区间差异的了解。本研究旨在总结和绘制中国大陆不同地区幽门螺杆菌的一级和二级抗生素耐药性图谱：方法：系统检索了 PubMed、EMBASE、Web of Science、中国国家知识基础设施和万方数据库中 2000 年 1 月 1 日至 2023 年 7 月 15 日期间发表的研究。研究纳入了与原发性和继发性幽门螺杆菌抗生素耐药率相关的数据。随机效应模型用于综合计算耐药率：最终，74 项研究被纳入最终分析。16个省份报告了耐药性数据。中国大陆幽门螺杆菌对克拉霉素的总体耐药率为 30.72%（95% CI 27.53%-33.99%），对甲硝唑的耐药率为 70.14%（95% CI 29.53%-37.46%），对左氧氟沙星的耐药率为 32.98%（95% CI 28.73%-37.37%）。37%）；阿莫西林、四环素和呋喃唑酮的发病率分别为 2.41% (95% CI 1.43%-3.60%) 、2.53% (95% CI 1.19%-4.28%) 和 1.54% (95% CI 0.28%-3.62%) 。观察到了空间和时间上的差异。耐药率在治疗失败后有所增加，但在绝大多数研究地区，对阿莫西林、四环素和呋喃唑酮的二次耐药率仍然很低：结论：有必要对不同地区幽门螺杆菌抗生素耐药性的最新流行情况进行监测，并将其纳入临床决策和指南建议中。
{"title":"Antibiotic Resistance of Helicobacter pylori in Mainland China: A Focus on Geographic Differences Through Systematic Review and Meta-Analysis","authors":"","doi":"10.1016/j.ijantimicag.2024.107325","DOIUrl":"10.1016/j.ijantimicag.2024.107325","url":null,"abstract":"<div><h3>Background</h3><div>Empirical treatment needs to be supported by regional data, but knowledge of interregional differences is currently lacking in China. This study aimed to summarize and map the primary and secondary antibiotic resistance of <em>Helicobacter pylori</em> in different regions of mainland China.</div></div><div><h3>Methods</h3><div>PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure and Wanfang databases were systematically reviewed for studies published between 1 January 2000 and 15 July 2023. Data related to primary and secondary <em>H. pylori</em> antibiotic resistance rates were included. Random-effects models were used to synthesize the pooled resistance rates.</div></div><div><h3>Results</h3><div>Ultimately, 74 studies were included in the final analysis. A total of 16 provinces reported resistance data. The overall resistance rates of <em>H. pylori</em> in mainland China were 30.72% (95% CI 27.53%–33.99%) to clarithromycin, 70.14% (95% CI 29.53%–37.46%) to metronidazole and 32.98% (95% CI 28.73%–37.37%) to levofloxacin; for amoxicillin, tetracycline, and furazolidone, the rates were 2.41% (95% CI 1.43%–3.60%), 2.53% (95% CI 1.19%–4.28%) and 1.54% (95% CI 0.28%–3.62%), respectively. Spatial and temporal differences were observed. The resistance rates increased after treatment failure; however, secondary resistance to amoxicillin, tetracycline and furazolidone were still low across the vast majority of study regions.</div></div><div><h3>Conclusion</h3><div>Surveillance of the updated prevalence of antibiotic resistance of <em>H. pylori</em> for different regions is warranted, which should factor into clinical decision making and guideline recommendations.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153960","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}
Pub Date : 2024-09-06DOI: 10.1016/j.ijantimicag.2024.107330
Background
The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear.
Methods
Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses.
Results
Patients were classified into two groups: Clostridioides difficile infection (CDI, n = 39) and non-CDI AAD (n = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of C. difficile in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (Enterococcus, Klebsiella, Corynebacterium, Pseudomonas, and Anaerofustis) or negatively (Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium, and Dorea). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20–4.99).
Conclusion
This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients.
{"title":"Dysbiosis of the gut microbiota is associated with in-hospital mortality in patients with antibiotic-associated diarrhoea: A metagenomic analysis","authors":"","doi":"10.1016/j.ijantimicag.2024.107330","DOIUrl":"10.1016/j.ijantimicag.2024.107330","url":null,"abstract":"<div><h3>Background</h3><div>The increasing incidence of antibiotic-associated diarrhoea (AAD) is a serious health care problem. Dysbiosis of the gut microbiota is suspected to play a role in the pathogenesis of AAD, but its impact on the clinical outcomes of patients remains unclear.</div></div><div><h3>Methods</h3><div>Between May and October 2022, 210 patients with AAD admitted to a university hospital and 100 healthy controls were recruited. DNA extraction from stool specimens and shotgun sequencing were performed. Machine learning was conducted to assess profiling at different taxonomic levels and to select variables for multivariable analyses.</div></div><div><h3>Results</h3><div>Patients were classified into two groups: <em>Clostridioides difficile</em> infection (CDI, <em>n</em> = 39) and non-CDI AAD (<em>n</em> = 171). The in-hospital mortality rate for the patients was 20.0%, but the presence of <em>C. difficile</em> in the gut microbiota was not associated with mortality. Machine learning showed that taxonomic profiling at the genus level best reflected patient prognosis. The in-hospital mortality of patients was associated with the relative abundance of specific gut microbial genera rather than alpha-diversity: each of the five genera correlated either positively (<em>Enterococcus, Klebsiella, Corynebacterium, Pseudomonas</em>, and <em>Anaerofustis</em>) or negatively (<em>Bifidobacterium, Bacteroides, Streptococcus, Faecalibacterium</em>, and <em>Dorea</em>). Genes for vancomycin resistance were significantly associated with in-hospital mortality in patients with AAD (adjusted hazard ratios, 2.45; 95% CI, 1.20–4.99).</div></div><div><h3>Conclusion</h3><div>This study demonstrates the potential utility of metagenomic studies of the gut microbial community as a biomarker for prognosis prediction in AAD patients.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145568","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}
Pub Date : 2024-09-06DOI: 10.1016/j.ijantimicag.2024.107329
Background
The use of matrix-assisted laser desorption/ionisation-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and the presence of mecA gene among Staphylococcus aureus.
Materials and Methods
Antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of S. aureus were analysed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical centre (CS database). Five ML classifiers were used to analyse performance metrics. The Shapley value quantified the predictive contribution of individual features.
Results
The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant S. aureus (ORSA) compared with all S. aureus and oxacillin-susceptible S. aureus (OSSA) in both databases. In DRIAMS, Multilayer Perceptron (MLP) was associated with excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In the CS database, Ada and Light Gradient Boosting Machine (LightGBM) showed excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86). Mass-to-charge ratio (m/z) features of 2411–2414 and 2429–2432 correlated with clindamycin resistance, whereas 5033–5036 was linked to erythromycin resistance in DRIAMS. In the CS database, overlapping features of 2423–2426, 4496–4499, and 3764–3767 simultaneously predicted the presence of mecA and oxacillin resistance.
Conclusion
The predictive performance of antimicrobial resistance against S. aureus using MALDI-TOF MS depends on database characteristics and the ML algorithm selected. Specific and overlapping mass spectra features are excellent predictive markers for mecA and specific antimicrobial resistance.
背景：基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）与机器学习（ML）的结合被用于预测抗菌药耐药性。本研究评估了 MALDI-TOF MS 与各种 ML 分类器配对的有效性，并建立了预测金黄色葡萄球菌抗菌药耐药性和 mecA 基因存在情况的最佳模型：利用MALDI-TOF质谱法抗菌药耐药性数据库（DRIAMS）和一个医疗中心（CS数据库）的数据，分析了金黄色葡萄球菌对一级抗生素和MALDI-TOF MS的抗菌药耐药性。五种 ML 分类器用于分析性能指标。Shapley 值量化了单个特征的预测贡献：结果：在这两个数据库中，LightGBM 在预测耐奥沙西林金黄色葡萄球菌（ORSA）对大多数 1 级抗生素的抗菌性方面表现优于所有金黄色葡萄球菌和对奥沙西林敏感的金黄色葡萄球菌（OSSA）。在 DRIAMS 数据库中，MLP 对克林霉素（0.74/0.81/0.90）、四环素（0.86/0.87/0.94）和三甲双氨-磺胺甲噁唑（0.95/0.72/0.97）具有出色的预测性能，以准确率/AUROC/AUPR 表示。在 CS 数据库中，Ada 和 LightGBM 分别对红霉素（0.97/0.92/0.86）和四环素（0.68/0.79/0.86）保持了卓越的性能。在 DRIAMS 中，2,411-2,414 和 2,429-2,432 的质荷比（m/z）特征与克林霉素耐药性相关，而 5,033-5,036 与红霉素耐药性相关。在 CS 数据库中，2,423-2,426、4,496-4,499 和 3,764-3,767 个重叠特征同时预测了 mecA 的存在和对奥沙西林的耐药性：结论：使用 MALDI-TOF MS 预测金黄色葡萄球菌抗菌药耐药性的性能取决于数据库特征和所选的 ML 算法。特定和重叠的 MS 特征是预测 mecA 和特定抗菌素耐药性的极佳标记。
{"title":"Accurate prediction of antimicrobial resistance and genetic marker of Staphylococcus aureus clinical isolates using MALDI-TOF MS and machine learning – across DRIAMS and Taiwan database","authors":"","doi":"10.1016/j.ijantimicag.2024.107329","DOIUrl":"10.1016/j.ijantimicag.2024.107329","url":null,"abstract":"<div><h3>Background</h3><div>The use of matrix-assisted laser desorption/ionisation-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and the presence of <em>mecA</em> gene among <em>Staphylococcus aureus</em>.</div></div><div><h3>Materials and Methods</h3><div>Antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of <em>S. aureus</em> were analysed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical centre (CS database). Five ML classifiers were used to analyse performance metrics. The Shapley value quantified the predictive contribution of individual features.</div></div><div><h3>Results</h3><div>The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant <em>S. aureus</em> (ORSA) compared with all <em>S. aureus</em> and oxacillin-susceptible <em>S. aureus</em> (OSSA) in both databases. In DRIAMS, Multilayer Perceptron (MLP) was associated with excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In the CS database, Ada and Light Gradient Boosting Machine (LightGBM) showed excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86). Mass-to-charge ratio (m/z) features of 2411–2414 and 2429–2432 correlated with clindamycin resistance, whereas 5033–5036 was linked to erythromycin resistance in DRIAMS. In the CS database, overlapping features of 2423–2426, 4496–4499, and 3764–3767 simultaneously predicted the presence of <em>mecA</em> and oxacillin resistance.</div></div><div><h3>Conclusion</h3><div>The predictive performance of antimicrobial resistance against <em>S. aureus</em> using MALDI-TOF MS depends on database characteristics and the ML algorithm selected. Specific and overlapping mass spectra features are excellent predictive markers for <em>mecA</em> and specific antimicrobial resistance.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145566","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}
Pub Date : 2024-09-05DOI: 10.1016/j.ijantimicag.2024.107321
Background
Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear.
Objectives
To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam.
Methods
This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed.
Results
A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013–1.093), presence in the ICU (aOR 2.704, 95% CI 1.071–6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797–11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n = 77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089–1.155).
Conclusion
In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.
背景：头孢他啶/阿维巴坦是治疗耐碳青霉烯类肠杆菌（CRE）的首选药物之一。然而，头孢他啶/阿维巴坦与另一种抗生素联合使用的益处仍不明确：确定在使用头孢他啶/阿维巴坦治疗CRE感染期间与治疗失败相关的变量，并评估氨基糖苷类药物与头孢他啶/阿维巴坦联合使用的效果：这是一项回顾性队列研究，研究对象是2015年至2021年间在134个退伍军人事务（VA）机构中接受头孢他啶/阿维巴坦治疗的CRE培养阳性患者。主要结果是 30 天死亡率，次要结果是院内死亡率。此外，还对接受氨基糖苷类药物治疗的患者进行了亚分析：结果：共纳入 303 名患者。30天和住院总死亡率分别为12.5%和24.1%。年龄（aOR 1.052，95% CI 1.013-1.093）、是否住在重症监护室（aOR 2.704，95% CI 1.071-6.830）、开始使用头孢他啶/阿维巴坦前是否使用过氨基糖苷类药物（aOR 4.512，95% CI 1.797-11.327）与 30 天死亡率有独立关联。在接受氨基糖苷类药物治疗的亚组患者（77人）中，与头孢他啶/阿维巴坦合用氨基糖苷类药物的30天死亡率aOR为0.321（95% CI，0.089-1.155）：在使用头孢他啶/阿维巴坦治疗CRE感染的退伍军人中，年龄增大、接受过氨基糖苷类药物治疗以及在进行指数培养时身处重症监护室与30天死亡率升高有关。在接受氨基糖苷类药物治疗的患者中，与头孢他啶/阿维巴坦联合使用可降低30天死亡率，这表明这种联合用药可用于治疗病情较重患者的CRE感染。
{"title":"Ceftazidime/avibactam alone or in combination with an aminoglycoside for treatment of carbapenem-resistant Enterobacterales infections: A retrospective cohort study","authors":"","doi":"10.1016/j.ijantimicag.2024.107321","DOIUrl":"10.1016/j.ijantimicag.2024.107321","url":null,"abstract":"<div><h3>Background</h3><div>Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear.</div></div><div><h3>Objectives</h3><div>To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed.</div></div><div><h3>Results</h3><div>A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013–1.093), presence in the ICU (aOR 2.704, 95% CI 1.071–6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797–11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n = 77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089–1.155).</div></div><div><h3>Conclusion</h3><div>In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.</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":"142145567","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}
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