Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.jgar.2025.10.011
Sirui Tang , Yuxuan Song , Caipeng Qin , Tao Xu
Objectives
The increasing resistance of gram-negative bacteria in complicated urinary tract infections (cUTI) and acute pyelonephritis (APN) poses major treatment challenges. This study aimed to evaluated the efficacy and safety of novel β-Lactam/β-Lactamase inhibitor combinations compared with conventional antibiotics.
Methods
We systematically searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and FDA.gov for randomized controlled trials (RCTs) published up to July 15, 2025. Eligible studied included patients with cUTI or APN. Primary outcomes were clinical and microbiological response rates at the test-of-cure (TOC) or the end-of-treatment visit. Secondary outcomes included adverse events (AEs), serious AEs (SAEs), and treatment discontinuations due to AEs. Risk of bias was assessed using the Cochran tool.
Results
Eleven RCTs with a total of 4986 patients (2719 in the experimental group and 2267 in the control group) were included. Novel β-Lactam/β-Lactamase inhibitors significantly improved clinical response in the microbiological modified intent-to-treat population (OR = 1.64, 95% CI [1.43–1.88], P < 0.001). The incidence of overall AEs and SAEs was similar between groups, though drug-related AEs were more common in the experimental group (OR = 1.38, 95% CI [1.11–1.72], P = 0.003).
Conclusions
Novel β-Lactam/β-Lactamase inhibitor combinations demonstrated superior efficacy and comparable safety to conventional antibiotics in treating cUTI and APN, particularly at the TOC stage.
背景：复杂性尿路感染（cUTI）和急性肾盂肾炎（APN）中革兰氏阴性菌耐药性的增加给治疗带来了重大挑战。本研究旨在评价新型β-内酰胺/β-内酰胺酶抑制剂联合使用与传统抗生素的疗效和安全性。方法：我们系统地检索PubMed、Embase、Cochrane Library、Web of Science、ClinicalTrials.gov和FDA.gov，检索截至2025年7月15日发表的随机对照试验（RCTs）。符合条件的研究包括cUTI或APN患者。主要结果是临床和治愈试验（TOC）或治疗结束时的微生物反应率。次要结局包括不良事件（ae）、严重ae （sae）和因ae而停止治疗。使用Cochran工具评估偏倚风险。结果：纳入11项随机对照试验，共4986例患者（实验组2719例，对照组2267例）。新型β-内酰胺/β-内酰胺酶抑制剂显著改善了微生物修饰的意图治疗人群的临床反应（OR=1.64, 95% CI[1.43-1.88]）。结论：新型β-内酰胺/β-内酰胺酶抑制剂联合治疗cUTI和APN具有优于传统抗生素的疗效和相当的安全性，特别是在TOC期。
{"title":"Efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations for the treatment of complicated urinary tract infections or acute pyelonephritis: A systematic review and meta-analysis","authors":"Sirui Tang , Yuxuan Song , Caipeng Qin , Tao Xu","doi":"10.1016/j.jgar.2025.10.011","DOIUrl":"10.1016/j.jgar.2025.10.011","url":null,"abstract":"<div><h3>Objectives</h3><div>The increasing resistance of gram-negative bacteria in complicated urinary tract infections (cUTI) and acute pyelonephritis (APN) poses major treatment challenges. This study aimed to evaluated the efficacy and safety of novel β-Lactam/β-Lactamase inhibitor combinations compared with conventional antibiotics.</div></div><div><h3>Methods</h3><div>We systematically searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and FDA.gov for randomized controlled trials (RCTs) published up to July 15, 2025. Eligible studied included patients with cUTI or APN. Primary outcomes were clinical and microbiological response rates at the test-of-cure (TOC) or the end-of-treatment visit. Secondary outcomes included adverse events (AEs), serious AEs (SAEs), and treatment discontinuations due to AEs. Risk of bias was assessed using the Cochran tool.</div></div><div><h3>Results</h3><div>Eleven RCTs with a total of 4986 patients (2719 in the experimental group and 2267 in the control group) were included. Novel β-Lactam/β-Lactamase inhibitors significantly improved clinical response in the microbiological modified intent-to-treat population (OR = 1.64, 95% CI [1.43–1.88], <em>P</em> < 0.001). The incidence of overall AEs and SAEs was similar between groups, though drug-related AEs were more common in the experimental group (OR = 1.38, 95% CI [1.11–1.72], <em>P</em> = 0.003).</div></div><div><h3>Conclusions</h3><div>Novel β-Lactam/β-Lactamase inhibitor combinations demonstrated superior efficacy and comparable safety to conventional antibiotics in treating cUTI and APN, particularly at the TOC stage.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 268-281"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.jgar.2025.10.001
Jiayi Peng , Wenyue Zhang , Ying Shi , Haiqin Jiang , Jingshu Xiong , Youming Mei , Tian Gan , Hongsheng Wang
Objectives
Antimicrobial susceptibility data for cutaneous mycobacteria remain limited. This study investigated the antimicrobial susceptibility patterns and molecular resistance mechanisms of Mycobacterium marinum and Mycobacterium abscessus isolates from a dermatology specialized hospital in China.
Methods
Antimicrobial susceptibility testing was performed on 200 M. marinum and 50 M. abscessus clinical isolates using broth microdilution method. M. abscessus subspecies were identified through hsp65, erm (41), and rpoB gene sequencing. For M. abscessus isolates, resistance-associated mutations for clarithromycin, amikacin, and fluoroquinolones were analysed by sequencing erm (41), rrl, rrs, gyrA, and gyrB genes.
Results
M. marinum demonstrated high susceptibility (82.5%–100%) to clarithromycin, rifampin, rifabutin, moxifloxacin, linezolid, trimethoprim-sulfamethoxazole, with moderate susceptibility to tetracyclines and ciprofloxacin. Ethambutol showed favourable activity against M. marinum with MIC90 of 2 µg/mL. Among M. abscessus isolates (23 M. abscessus subsp. abscessus, 26 M. abscessus subsp. massiliense, 1 M. abscessus subsp. bolletii), overall susceptibility to clarithromycin and amikacin was 78% and 82%, respectively. Tigecycline and clofazimine were effective against M. abscessus with MIC90 1 and 0.5 µg/mL, respectively. In contrast, M. abscessus isolates demonstrated high-level of resistance to multiple antibiotics, including linezolid, fluoroquinolones, and tetracyclines. M. abscessus subsp. massiliense exhibited higher clarithromycin susceptibility (100%) compared to M. abscessus subsp. abscessus (56.5%). Clarithromycin resistance of M. abscessus isolates correlated with functional T28 sequevar in the erm (41) gene.
Conclusions
Our findings elucidate distinct antimicrobial susceptibility profiles of M. marinum and M. abscessus isolated from cutaneous infection in China, providing critical guidance for clinical treatment. Cutaneous M. abscessus isolates exhibit extensive drug resistance patterns. Subtyping and erm (41) polymorphism detection serve as reliable predictors of clarithromycin resistance in M. abscessus.
{"title":"Antimicrobial susceptibility patterns and genotypic characteristics of Mycobacterium marinum and Mycobacterium abscessus isolated from cutaneous infections: A retrospective study","authors":"Jiayi Peng , Wenyue Zhang , Ying Shi , Haiqin Jiang , Jingshu Xiong , Youming Mei , Tian Gan , Hongsheng Wang","doi":"10.1016/j.jgar.2025.10.001","DOIUrl":"10.1016/j.jgar.2025.10.001","url":null,"abstract":"<div><h3>Objectives</h3><div>Antimicrobial susceptibility data for cutaneous mycobacteria remain limited. This study investigated the antimicrobial susceptibility patterns and molecular resistance mechanisms of <em>Mycobacterium marinum</em> and <em>Mycobacterium abscessus</em> isolates from a dermatology specialized hospital in China.</div></div><div><h3>Methods</h3><div>Antimicrobial susceptibility testing was performed on 200 <em>M. marinum</em> and 50 <em>M. abscessus</em> clinical isolates using broth microdilution method. <em>M. abscessus</em> subspecies were identified through <em>hsp65, erm (41),</em> and <em>rpoB</em> gene sequencing. For <em>M. abscessus</em> isolates, resistance-associated mutations for clarithromycin, amikacin, and fluoroquinolones were analysed by sequencing <em>erm (41), rrl, rrs, gyrA, and gyrB</em> genes.</div></div><div><h3>Results</h3><div><em>M. marinum</em> demonstrated high susceptibility (82.5%–100%) to clarithromycin, rifampin, rifabutin, moxifloxacin, linezolid, trimethoprim-sulfamethoxazole, with moderate susceptibility to tetracyclines and ciprofloxacin. Ethambutol showed favourable activity against <em>M. marinum</em> with MIC<sub>90</sub> of 2 µg/mL. Among <em>M. abscessus</em> isolates (23 <em>M. abscessus subsp. abscessus</em>, 26 <em>M. abscessus subsp. massiliense</em>, 1 <em>M. abscessus subsp. bolletii</em>), overall susceptibility to clarithromycin and amikacin was 78% and 82%, respectively. Tigecycline and clofazimine were effective against <em>M. abscessus</em> with MIC<sub>90</sub> 1 and 0.5 µg/mL, respectively. In contrast, <em>M. abscessus</em> isolates demonstrated high-level of resistance to multiple antibiotics, including linezolid, fluoroquinolones, and tetracyclines. <em>M. abscessus subsp. massiliense</em> exhibited higher clarithromycin susceptibility (100%) compared to <em>M. abscessus subsp. abscessus</em> (56.5%). Clarithromycin resistance of <em>M. abscessus</em> isolates correlated with functional T28 sequevar in the <em>erm (41)</em> gene.</div></div><div><h3>Conclusions</h3><div>Our findings elucidate distinct antimicrobial susceptibility profiles of <em>M. marinum</em> and <em>M. abscessus</em> isolated from cutaneous infection in China, providing critical guidance for clinical treatment. Cutaneous <em>M. abscessus</em> isolates exhibit extensive drug resistance patterns. Subtyping and <em>erm (41)</em> polymorphism detection serve as reliable predictors of clarithromycin resistance in <em>M. abscessus</em>.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 240-247"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-23DOI: 10.1016/j.jgar.2025.10.010
Yonggeun Cho , Kyung-Wook Hong , Min-Kyoung Shin , Sunjoo Kim , Jung-Hyun Byun
{"title":"Rapid clonal replacement by ST773 with NDM-1 among carbapenem-resistant Pseudomonas aeruginosa in South Korea","authors":"Yonggeun Cho , Kyung-Wook Hong , Min-Kyoung Shin , Sunjoo Kim , Jung-Hyun Byun","doi":"10.1016/j.jgar.2025.10.010","DOIUrl":"10.1016/j.jgar.2025.10.010","url":null,"abstract":"","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 287-289"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-27DOI: 10.1016/j.jgar.2025.10.021
Isidora Manríquez-Cuadra , Maximiliano Matus-Köhler , Alejandro Aguayo-Reyes , Mario Quezada-Aguiluz , Felipe Morales-Leon , Gerardo González-Rocha , Andrés Opazo-Capurro
Introduction
Carbapenem- and third-generation cephalosporin-resistant Enterobacterales, including the Citrobacter freundii complex, are classified as a World Health Organization ‘critical priority’ due to their public health threat. This study reports a C. freundii complex isolate (Cit-107) co-harbouring the blaNDM-1, blaCTX-M-30, armA, rmtC, and rmtD genes, recovered from a rectal swab in 2022 in Concepción, Chile.
Methods
Antimicrobial susceptibility was assessed via disk diffusion. Whole-genome sequencing was performed using the Illumina NextSeq 2000 platform and annotated with Bakta. In silico analyses included JSpeciesWS, PubMLST, ABRicate, AMRFinderPlus, and MOB-suite. Phylogenetic analysis of Cit-107 and 50 C. freundii complex genomes from the Americas was conducted using IQ-TREE and visualized with iTOL.
Results
Cit-107 was resistant to clinically relevant antibiotics, such as carbapenems, cephalosporins, aminoglycosides, and fluoroquinolones. It belongs to sequence type (ST) ST112 and carries multiple resistance genes: blaNDM-1, blaCTX-M-30, mcr-9.1, armA, rmtC, and rmtD. The blaNDM-1 gene was embedded in a Tn125-like transposon contained in an IncC-type plasmid alongside the blaCTX-M-30, rmtC, and tet(G) genes. The blaCTX-M-30 was harboured in an IncN-type plasmid, while armA, msr(E), and mph(E) were co-carried in an IncHI2A-type plasmid. Phylogenetic analysis revealed Cit-107 as a divergent lineage within the C. freundii complex.
Conclusions
This is the first report of a carbapenem-resistant C. freundii complex isolate carrying blaNDM-1 in Chile alongside multiple antibiotic-resistance genes harboured in several plasmid types. Its unique resistome and phylogenetic profile underscore the need for surveillance of emerging multidrug-resistant C. freundii strains in clinical settings.
{"title":"Genomic characterization of a carbapenem-resistant Citrobacter freundii complex strain co-carrying blaNDM-1, blaCTX-M-30, armA, rmtC, and rmtD from Chile","authors":"Isidora Manríquez-Cuadra , Maximiliano Matus-Köhler , Alejandro Aguayo-Reyes , Mario Quezada-Aguiluz , Felipe Morales-Leon , Gerardo González-Rocha , Andrés Opazo-Capurro","doi":"10.1016/j.jgar.2025.10.021","DOIUrl":"10.1016/j.jgar.2025.10.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Carbapenem- and third-generation cephalosporin-resistant <em>Enterobacterales</em>, including the <em>Citrobacter freundii</em> complex, are classified as a World Health Organization ‘critical priority’ due to their public health threat. This study reports a <em>C. freundii</em> complex isolate (Cit-107) co-harbouring the <em>bla</em><sub>NDM-1</sub>, <em>bla</em><sub>CTX-M-30</sub>, <em>armA, rmtC</em>, and <em>rmtD</em> genes, recovered from a rectal swab in 2022 in Concepción, Chile.</div></div><div><h3>Methods</h3><div>Antimicrobial susceptibility was assessed via disk diffusion. Whole-genome sequencing was performed using the Illumina NextSeq 2000 platform and annotated with Bakta. <em>In silico</em> analyses included JSpeciesWS, PubMLST, ABRicate, AMRFinderPlus, and MOB-suite. Phylogenetic analysis of Cit-107 and 50 <em>C. freundii</em> complex genomes from the Americas was conducted using IQ-TREE and visualized with iTOL.</div></div><div><h3>Results</h3><div>Cit-107 was resistant to clinically relevant antibiotics, such as carbapenems, cephalosporins, aminoglycosides, and fluoroquinolones. It belongs to sequence type (ST) ST112 and carries multiple resistance genes: <em>bla</em><sub>NDM-1</sub>, <em>bla</em><sub>CTX-M-30</sub>, <em>mcr-9.1, armA, rmtC</em>, and <em>rmtD</em>. The <em>bla</em><sub>NDM-1</sub> gene was embedded in a Tn<em>125</em>-like transposon contained in an IncC-type plasmid alongside the <em>bla</em><sub>CTX-M-30</sub>, <em>rmtC</em>, and <em>tet(G)</em> genes. The <em>bla</em><sub>CTX-M-30</sub> was harboured in an IncN-type plasmid, while <em>armA, msr(E)</em>, and <em>mph(E)</em> were co-carried in an IncHI2A-type plasmid. Phylogenetic analysis revealed Cit-107 as a divergent lineage within the <em>C. freundii</em> complex.</div></div><div><h3>Conclusions</h3><div>This is the first report of a carbapenem-resistant <em>C. freundii</em> complex isolate carrying <em>bla</em><sub>NDM-1</sub> in Chile alongside multiple antibiotic-resistance genes harboured in several plasmid types. Its unique resistome and phylogenetic profile underscore the need for surveillance of emerging multidrug-resistant <em>C. freundii</em> strains in clinical settings.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 290-293"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-14DOI: 10.1016/j.jgar.2025.10.005
Jinfeng Lu , Aiping Zhou , Dongjiang Wang , Shuang Wan , Yuting Yang , Na Lv , Jun Li , Guoping Wu
Objective
The emergence of multidrug-resistant bacteria alongside the extensive spread of opportunistic pathogens with a diversity of serotypes threatens public health. Fitness cost and morphological variation are hypothesised to result from O-antigen diversity and lipid A modification, whereas these reconfigurations within lipopolysaccharides (LPS) confer polymyxin resistance.
Methods
In this study, a multidrug-resistant Escherichia coli named EcE.CRE.COL was isolated from a patient undergoing therapeutic laparoscope for liver cancer. Antibiotic susceptibility was measured using the VITEK 2 system (bioMérieux, Marcy-l'Étoile, France), and whole-genome sequencing revealed a chromosome and three plasmids (namely pEcE.CRE.COL015, pEcE.CRE.COL016, and pEcE.CRE.COL032). Comparative genomics was then conducted to identify genetic determinants accounting for multi-drug resistance.
Results
This isolate exhibited characteristic resistance to carbapenems and polymyxin. Interestingly, pEcE.CRE.COL015 and pEcE.CRE.COL032 were shown to harbour blaNDM-5 and mcr-1, accounting for corresponding antimicrobial resistance. We consequently proposed an evolutionary pattern for the spread of mcr-1, demonstrating that transposon-like architecture could play a key role in the dissemination of polymyxin resistance driven by mcr-1. In addition, a novel serotype gene cluster related to defective O-antigen synthesis was determined, likely resulting from a genetic insertion. SDS-PAGE indicated LPS defectiveness within this isolate, suggesting a variable charge on the membrane surface of EcE.CRE.COL.
Conclusions
Collectively, the co-occurrence of plasmid-borne mcr-1 and blaNDM-5 was determined, with genetic variations in LPS biosynthesis genes potentially contributing to a synergistic change in bacterial surface charge and corresponding electrostatics to polymyxin.
{"title":"Convergence of genetic variants in MCR-1 and O-antigen conferring polymyxin resistance and fitness cost","authors":"Jinfeng Lu , Aiping Zhou , Dongjiang Wang , Shuang Wan , Yuting Yang , Na Lv , Jun Li , Guoping Wu","doi":"10.1016/j.jgar.2025.10.005","DOIUrl":"10.1016/j.jgar.2025.10.005","url":null,"abstract":"<div><h3>Objective</h3><div>The emergence of multidrug-resistant bacteria alongside the extensive spread of opportunistic pathogens with a diversity of serotypes threatens public health. Fitness cost and morphological variation are hypothesised to result from O-antigen diversity and lipid A modification, whereas these reconfigurations within lipopolysaccharides (LPS) confer polymyxin resistance.</div></div><div><h3>Methods</h3><div>In this study, a multidrug-resistant <em>Escherichia coli</em> named EcE.CRE.COL was isolated from a patient undergoing therapeutic laparoscope for liver cancer. Antibiotic susceptibility was measured using the VITEK 2 system (bioMérieux, Marcy-l'Étoile, France), and whole-genome sequencing revealed a chromosome and three plasmids (namely pEcE.CRE.COL015, pEcE.CRE.COL016, and pEcE.CRE.COL032). Comparative genomics was then conducted to identify genetic determinants accounting for multi-drug resistance.</div></div><div><h3>Results</h3><div>This isolate exhibited characteristic resistance to carbapenems and polymyxin. Interestingly, pEcE.CRE.COL015 and pEcE.CRE.COL032 were shown to harbour <em>bla</em><sub>NDM-5</sub> and <em>mcr-1</em>, accounting for corresponding antimicrobial resistance. We consequently proposed an evolutionary pattern for the spread of <em>mcr-1</em>, demonstrating that transposon-like architecture could play a key role in the dissemination of polymyxin resistance driven by <em>mcr-1</em>. In addition, a novel serotype gene cluster related to defective O-antigen synthesis was determined, likely resulting from a genetic insertion. SDS-PAGE indicated LPS defectiveness within this isolate, suggesting a variable charge on the membrane surface of EcE.CRE.COL.</div></div><div><h3>Conclusions</h3><div>Collectively, the co-occurrence of plasmid-borne <em>mcr-1</em> and <em>bla</em><sub>NDM-5</sub> was determined, with genetic variations in LPS biosynthesis genes potentially contributing to a synergistic change in bacterial surface charge and corresponding electrostatics to polymyxin.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 228-231"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-14DOI: 10.1016/j.jgar.2025.10.009
Charles Baulier , Marion Giry , Manuel Etienne , Julien Kallout , Kévin Alexandre
Introduction
The hollow-fibre infection model (HFIM) is an in vitro model used to study pharmacokinetic/pharmacodynamic (PK/PD) interactions between antibiotics and bacteria. However, its external validity remains poorly assessed. This study aimed to identify PK/PD targets and experimental variables associated with bacterial killing and prevention of resistance emergence during β-lactam treatment in HFIM.
Methods
Systematic review of studies using HFIM and β-lactams, with literature search conducted in 4 databases, following PRISMA guidelines. After a quality assessment (modified ToxRtools scale) of the included studies, univariate and multivariate analyses identified factors associated with the prevention of resistance emergence. CART analysis determined values of PK/PD indices best predicting this outcome.
Results
Of the 497 screened studies, 41 were included. A total of 367 experiments were analysed, mainly involving Pseudomonas aeruginosa (51%) and carbapenems (46%). Antibiotic exposure through minimal or steady-state free concentrations (fCmin,ss/MIC) (OR 0.78, 95% CI [0.70–0.85], P < 0.001), the initial inoculum size (OR 1.48, 95% CI [1.08–2.06], P = 0.017) and the use of a combination therapy (OR 0.33, CI [0.17–0.64], P = 0.001) remained significantly associated with resistance emergence in multivariate analysis. For carbapenems in monotherapy, the prevention of resistance emergence was likely with fCmin,ss/MIC > 5.7.
Conclusions
Stringent PK/PD indices thresholds were necessary to prevent resistance emergence in HFIM experiments.
{"title":"Pharmacokinetic/pharmacodynamic targets of ß-lactams associated with bacterial killing and suppression of the resistance emergence in the hollow fiber infection model: A systematic review","authors":"Charles Baulier , Marion Giry , Manuel Etienne , Julien Kallout , Kévin Alexandre","doi":"10.1016/j.jgar.2025.10.009","DOIUrl":"10.1016/j.jgar.2025.10.009","url":null,"abstract":"<div><h3>Introduction</h3><div>The hollow-fibre infection model (HFIM) is an in vitro model used to study pharmacokinetic/pharmacodynamic (PK/PD) interactions between antibiotics and bacteria. However, its external validity remains poorly assessed. This study aimed to identify PK/PD targets and experimental variables associated with bacterial killing and prevention of resistance emergence during β-lactam treatment in HFIM.</div></div><div><h3>Methods</h3><div>Systematic review of studies using HFIM and β-lactams, with literature search conducted in 4 databases, following PRISMA guidelines. After a quality assessment (modified ToxRtools scale) of the included studies, univariate and multivariate analyses identified factors associated with the prevention of resistance emergence. CART analysis determined values of PK/PD indices best predicting this outcome.</div></div><div><h3>Results</h3><div>Of the 497 screened studies, 41 were included. A total of 367 experiments were analysed, mainly involving <em>Pseudomonas aeruginosa</em> (51%) and carbapenems (46%). Antibiotic exposure through minimal or steady-state free concentrations (<em>f</em>C<sub>min,ss</sub>/MIC) (OR 0.78, 95% CI [0.70–0.85], <em>P</em> < 0.001), the initial inoculum size (OR 1.48, 95% CI [1.08–2.06], <em>P</em> = 0.017) and the use of a combination therapy (OR 0.33, CI [0.17–0.64], <em>P</em> = 0.001) remained significantly associated with resistance emergence in multivariate analysis. For carbapenems in monotherapy, the prevention of resistance emergence was likely with <em>f</em>C<sub>min,ss</sub>/MIC > 5.7.</div></div><div><h3>Conclusions</h3><div>Stringent PK/PD indices thresholds were necessary to prevent resistance emergence in HFIM experiments.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 220-227"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aims to optimize carbapenem dosing strategies in febrile neutropenic (FN) patients by evaluating the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) using Monte Carlo simulations based on published population PK (PopPK) models and real-world covariate data.
Methods
A systematic review of published PopPK studies on carbapenems in FN patients was conducted to obtain relevant PK parameters. In parallel, retrospective clinical data from FN patients treated at the First Affiliated Hospital of Wenzhou Medical University between January 2022 and April 2024 were collected to provide covariates for Monte Carlo simulation. Monte Carlo simulations were then performed to evaluate the PTA for various dosing regimens. Dosing regimens were assessed based on achieving a PTA of ≥ 90%.
Results
A total of 96 studies were screened, of which 4 met the inclusion criteria. Separately, real-world covariate data were obtained from 163 FN patients to inform the Monte Carlo simulations. The simulation results showed that standard label dosages of carbapenems administered over 0.5-h infusions failed to consistently achieve a PTA ≥ 90% at the current CLSI breakpoint of 1 mg/L for Enterobacterales. Notably, increasing the dose did not consistently improve PTA, whereas extending the infusion duration to 3 h or using continuous infusion strategy markedly enhanced the likelihood of attaining the PK/PD target.
Conclusion
Standard carbapenem dosing with 0.5-h infusions may lead to suboptimal exposure in FN patients. Prolonging the infusion duration is an effective strategy to improve PTA and optimize efficacy.
{"title":"A reappraisal of carbapenems dosing in febrile neutropenic patients","authors":"Sun-Ting Qin , Meng-Yu Kong , Rui-Yun Ling , Jing Fu , Yao-Jie Chen , Yu-Han Zeng , Dan-Na Jiang , Xiu-Hua Zhang , Xu-Ben Yu , Hai-Na Zhang","doi":"10.1016/j.jgar.2025.10.006","DOIUrl":"10.1016/j.jgar.2025.10.006","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to optimize carbapenem dosing strategies in febrile neutropenic (FN) patients by evaluating the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) using Monte Carlo simulations based on published population PK (PopPK) models and real-world covariate data.</div></div><div><h3>Methods</h3><div>A systematic review of published PopPK studies on carbapenems in FN patients was conducted to obtain relevant PK parameters. In parallel, retrospective clinical data from FN patients treated at the First Affiliated Hospital of Wenzhou Medical University between January 2022 and April 2024 were collected to provide covariates for Monte Carlo simulation. Monte Carlo simulations were then performed to evaluate the PTA for various dosing regimens. Dosing regimens were assessed based on achieving a PTA of ≥ 90%.</div></div><div><h3>Results</h3><div>A total of 96 studies were screened, of which 4 met the inclusion criteria. Separately, real-world covariate data were obtained from 163 FN patients to inform the Monte Carlo simulations. The simulation results showed that standard label dosages of carbapenems administered over 0.5-h infusions failed to consistently achieve a PTA ≥ 90% at the current CLSI breakpoint of 1 mg/L for <em>Enterobacterales</em>. Notably, increasing the dose did not consistently improve PTA, whereas extending the infusion duration to 3 h or using continuous infusion strategy markedly enhanced the likelihood of attaining the PK/PD target.</div></div><div><h3>Conclusion</h3><div>Standard carbapenem dosing with 0.5-h infusions may lead to suboptimal exposure in FN patients. Prolonging the infusion duration is an effective strategy to improve PTA and optimize efficacy.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 248-259"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-11DOI: 10.1016/j.jgar.2025.09.001
Andrés Ceballos-Garzon, Carolina Firacative
{"title":"In vitro evaluation of Ibrexafungerp against clinical and environmental isolates of cryptococcus neoformans and cryptococcus gattii","authors":"Andrés Ceballos-Garzon, Carolina Firacative","doi":"10.1016/j.jgar.2025.09.001","DOIUrl":"10.1016/j.jgar.2025.09.001","url":null,"abstract":"","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 84-85"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-08-27DOI: 10.1016/j.jgar.2025.08.012
Min Woo Kang, Shin Young Ahn
Objective
Methicillin‑resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in intensive care units (ICUs) carry high mortality, and although vancomycin remains standard treatment, daptomycin and linezolid may benefit specific subgroups. This study evaluates the mortality reduction associated with vancomycin, daptomycin, and linezolid using a deep learning–based causal inference model.
Methods
Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV databases, including 270 ICU patients with MRSA BSI. A deep learning-based causal inference model was used to assess the treatment effect of linezolid, daptomycin, and vancomycin on in-hospital mortality. Multivariable logistic regression was employed to identify patient characteristics associated with the effectiveness of each antibiotic.
Results
The deep learning-based model predicted that vancomycin, daptomycin, and linezolid reduced mortality by 15.86% (17.90% to 13.82%), 9.68% (11.83% to 7.53%), and 10.74% (12.64% to 8.84%), respectively, with vancomycin showing the greatest reduction. The average treatment effect for in-hospital mortality reduction with vancomycin was significantly greater than that with linezolid and daptomycin (both P < 0.001). Multivariable logistic regression for treatment effects revealed that vancomycin was particularly effective in patients of advanced age, those with chronic liver disease, and those with end-stage kidney disease, while it was less effective in patients with congestive heart failure or cancer. Daptomycin exhibited superior efficacy over vancomycin in patients with cancer, and linezolid was more effective in patients with cancer, hypertension, and congestive heart failure.
Conclusion
This study highlights linezolid and daptomycin treatment in select subgroups, while a deep learning–based model enables personalised antibiotic recommendations for ICU treatment strategies.
{"title":"Optimising personalised antibiotic treatment for methicillin-resistant Staphylococcus aureus bloodstream infections in ICU patients using a deep learning–based causal inference approach","authors":"Min Woo Kang, Shin Young Ahn","doi":"10.1016/j.jgar.2025.08.012","DOIUrl":"10.1016/j.jgar.2025.08.012","url":null,"abstract":"<div><h3>Objective</h3><div>Methicillin‑resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in intensive care units (ICUs) carry high mortality, and although vancomycin remains standard treatment, daptomycin and linezolid may benefit specific subgroups. This study evaluates the mortality reduction associated with vancomycin, daptomycin, and linezolid using a deep learning–based causal inference model.</div></div><div><h3>Methods</h3><div>Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV databases, including 270 ICU patients with MRSA BSI. A deep learning-based causal inference model was used to assess the treatment effect of linezolid, daptomycin, and vancomycin on in-hospital mortality. Multivariable logistic regression was employed to identify patient characteristics associated with the effectiveness of each antibiotic.</div></div><div><h3>Results</h3><div>The deep learning-based model predicted that vancomycin, daptomycin, and linezolid reduced mortality by 15.86% (17.90% to 13.82%), 9.68% (11.83% to 7.53%), and 10.74% (12.64% to 8.84%), respectively, with vancomycin showing the greatest reduction. The average treatment effect for in-hospital mortality reduction with vancomycin was significantly greater than that with linezolid and daptomycin (both <em>P</em> < 0.001). Multivariable logistic regression for treatment effects revealed that vancomycin was particularly effective in patients of advanced age, those with chronic liver disease, and those with end-stage kidney disease, while it was less effective in patients with congestive heart failure or cancer. Daptomycin exhibited superior efficacy over vancomycin in patients with cancer, and linezolid was more effective in patients with cancer, hypertension, and congestive heart failure.</div></div><div><h3>Conclusion</h3><div>This study highlights linezolid and daptomycin treatment in select subgroups, while a deep learning–based model enables personalised antibiotic recommendations for ICU treatment strategies.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 70-76"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-16DOI: 10.1016/j.jgar.2025.09.002
Claudia Stange , Rogers Kalyetsi , Judith Owokuhaisa , Moses Ntaro , Arthur Leon , Paul R. Hunter , Andreas Tiehm , Edgar M. Mulogo
Objective
The aim of this study was to estimate the prevalence of antimicrobial resistance in the population of Mbarara through analysis of wastewater and determine the effectiveness of wastewater treatment in reducing discharge of antibiotic-resistant bacteria and antibiotic resistance genes into the environment.
Methods
Hospital, municipal, and treated wastewater (collected on 10 different dates) from Mbarara, Uganda, were analysed for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli using a culture-based method and selected clinically relevant antibiotic resistance genes using quantitative PCR.
Results
The finding of this study demonstrated that 30.6% of the total E. coli were ESBL producers, constituting a high proportion compared to studies in other countries. Furthermore, the investigation revealed the widespread distribution of the carbapenemase gene blaCMY-2 within the population. The comparative study of the inflow and outflow of the waste stabilisation pond system, which is used for wastewater treatment, demonstrated a log reduction of 1.9–2.4 for coliform bacteria and total as well as ESBL-producing E. coli. Conversely, the wastewater treatment was associated with an increase of the antibiotic resistance genes sul1 and tetC.
Conclusions
The study shows that the waste stabilisation pond system is releasing significant amounts of coliform bacteria, E. coli, ESBL-producing E. coli, somatic bacteriophages, and antibiotic resistance genes into the Rwizi River. We also demonstrated that wastewater-based surveillance is a cost-effective method of obtaining information on the prevalence of AMR in the population, especially in countries where clinical surveillance is limited due to a lack of resources and infrastructure.
{"title":"Monitoring of antimicrobial resistance in hospital, municipal, and treated wastewater in Mbarara, Uganda","authors":"Claudia Stange , Rogers Kalyetsi , Judith Owokuhaisa , Moses Ntaro , Arthur Leon , Paul R. Hunter , Andreas Tiehm , Edgar M. Mulogo","doi":"10.1016/j.jgar.2025.09.002","DOIUrl":"10.1016/j.jgar.2025.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study was to estimate the prevalence of antimicrobial resistance in the population of Mbarara through analysis of wastewater and determine the effectiveness of wastewater treatment in reducing discharge of antibiotic-resistant bacteria and antibiotic resistance genes into the environment.</div></div><div><h3>Methods</h3><div>Hospital, municipal, and treated wastewater (collected on 10 different dates) from Mbarara, Uganda, were analysed for extended-spectrum beta-lactamase (ESBL)-producing <em>Escherichia coli</em> using a culture-based method and selected clinically relevant antibiotic resistance genes using quantitative PCR.</div></div><div><h3>Results</h3><div>The finding of this study demonstrated that 30.6% of the total <em>E. coli</em> were ESBL producers, constituting a high proportion compared to studies in other countries. Furthermore, the investigation revealed the widespread distribution of the carbapenemase gene <em>bla</em><sub>CMY-2</sub> within the population. The comparative study of the inflow and outflow of the waste stabilisation pond system, which is used for wastewater treatment, demonstrated a log reduction of 1.9–2.4 for coliform bacteria and total as well as ESBL-producing <em>E. coli</em>. Conversely, the wastewater treatment was associated with an increase of the antibiotic resistance genes <em>sul1</em> and <em>tet</em>C.</div></div><div><h3>Conclusions</h3><div>The study shows that the waste stabilisation pond system is releasing significant amounts of coliform bacteria, <em>E. coli</em>, ESBL-producing <em>E. coli</em>, somatic bacteriophages, and antibiotic resistance genes into the Rwizi River. We also demonstrated that wastewater-based surveillance is a cost-effective method of obtaining information on the prevalence of AMR in the population, especially in countries where clinical surveillance is limited due to a lack of resources and infrastructure.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 100-106"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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