Pub 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":"2025-10-22","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 : 2025-10-22DOI: 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":"2025-10-22","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}
The Mississippi Public Health Laboratory conducts active surveillance of carbapenem-resistant Enterobacterales (CRE) infections as part of the Antimicrobial Resistance Laboratory Network (ARLN) program implemented by the United States Centers for Disease Control and Prevention (CDC). Here, we describe the prevalence of New Delhi Metallo-β-lactamase (blaNDM) genes in Klebsiella, a major pathogen of the Enterobacterales order linked to nosocomial infections, between January 2022 and June 2025.
Methods
Carbapenemase activity was confirmed using the Modified Carbapenem Inactivation Method (mCIM). PCR was then performed on carbapenemase-positive isolates to detect blaNDM genes. Whole-genome sequencing (WGS) was performed on 35 blaNDM-positive isolates to identify blaNDM gene variants, other antimicrobial resistance (AMR) determinants, virulence factors, and plasmids. Antibiotic susceptibility testing (AST) was determined by the Kirby-Bauer disk diffusion assay.
Results
Among the 35 NDM-positive Klebsiella species, the blaNDM-5 variant was identified in 23 (65.7%) isolates, followed by blaNDM-1 and blaNDM-7 genes which were identified in 6/35 (17%) and 6/35 (17%) cases, respectively. A significant proportion of blaNDM-5 cases also harbored additional β-lactamase genes such as blaSHV family (18/23; 78%) and blaTEM-1 (9/23; 39%) indicating multi-drug resistance. All 23 blaNDM-5-positive isolates were resistant to carbapenems and broad-spectrum cephalosporins, but 13/23 (56.5%) remained susceptible to aztreonam. PlasmidFinder analysis identified IncX3 (20/23) and IncFIB(K) (19/23) as the predominant plasmid replicons among these isolates.
Conclusion
The emergence and spread of bacteria carrying blaNDM-5 gene poses a significant threat to public health in Mississippi. Our dataset warrants further study to investigate the potential role of plasmids in blaNDM-5 dissemination.
{"title":"blaNDM-5 is the predominant variant of blaNDM gene in Klebsiella species detected in Mississippi, USA","authors":"Srimadhav Nallani , Saihou Ceesay , Abiye Iyo, Lucersia Nichols, Daphne Ware, Beata Karolewicz","doi":"10.1016/j.jgar.2025.10.014","DOIUrl":"10.1016/j.jgar.2025.10.014","url":null,"abstract":"<div><h3>Objectives</h3><div>The Mississippi Public Health Laboratory conducts active surveillance of carbapenem-resistant <em>Enterobacterales</em> (CRE) infections as part of the Antimicrobial Resistance Laboratory Network (ARLN) program implemented by the United States Centers for Disease Control and Prevention (CDC). Here, we describe the prevalence of New Delhi Metallo-β-lactamase (<em>bla</em><sub>NDM</sub>) genes in <em>Klebsiella</em>, a major pathogen of the <em>Enterobacterales</em> order linked to nosocomial infections, between January 2022 and June 2025.</div></div><div><h3>Methods</h3><div>Carbapenemase activity was confirmed using the Modified Carbapenem Inactivation Method (mCIM). PCR was then performed on carbapenemase-positive isolates to detect <em>bla</em><sub>NDM</sub> genes. Whole-genome sequencing (WGS) was performed on 35 <em>bla</em><sub>NDM</sub>-positive isolates to identify <em>bla</em><sub>NDM</sub> gene variants, other antimicrobial resistance (AMR) determinants, virulence factors, and plasmids. Antibiotic susceptibility testing (AST) was determined by the Kirby-Bauer disk diffusion assay.</div></div><div><h3>Results</h3><div>Among the 35 NDM-positive <em>Klebsiella</em> species, the <em>bla</em><sub>NDM-5</sub> variant was identified in 23 (65.7%) isolates, followed by <em>bla</em><sub>NDM-1</sub> and <em>bla</em><sub>NDM-7</sub> genes which were identified in 6/35 (17%) and 6/35 (17%) cases, respectively. A significant proportion of <em>bla</em><sub>NDM-5</sub> cases also harbored additional β-lactamase genes such as <em>bla</em><sub>SHV</sub> family (18/23; 78%) and <em>bla</em><sub>TEM-1</sub> (9/23; 39%) indicating multi-drug resistance. All 23 <em>bla</em><sub>NDM-5</sub>-positive isolates were resistant to carbapenems and broad-spectrum cephalosporins, but 13/23 (56.5%) remained susceptible to aztreonam. PlasmidFinder analysis identified IncX3 (20/23) and IncFIB(K) (19/23) as the predominant plasmid replicons among these isolates.</div></div><div><h3>Conclusion</h3><div>The emergence and spread of bacteria carrying <em>bla</em><sub>NDM-5</sub> gene poses a significant threat to public health in Mississippi. Our dataset warrants further study to investigate the potential role of plasmids in <em>bla</em><sub>NDM-5</sub> dissemination.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 282-286"},"PeriodicalIF":3.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354938","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":"2025-10-21","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 : 2025-10-21DOI: 10.1016/j.jgar.2025.10.015
Soumya Deo , Aimeen Sharoze , Meerim Esenbekova , Dawn White , Frank Schweizer , Ramesh Kumar Mani , Bala Kishan Gorityala , Ayush Kumar
Objectives
Farm animals exposed to excessive amounts of antibiotics are reservoirs for antimicrobial-resistance genes and multidrug-resistant bacteria. The goal of this study was to investigate the adjuvant activity of a previously synthesized, proline-rich lipopeptide called C12-PRP in combination with various antibiotics against multidrug-resistant E. coli isolated from chicken and cattle.
Methods
The microbroth dilution method was used to determine the minimum inhibitory concentration of 10 antibiotics against four E. coli isolates. The adjuvant activity of C12-PRP was then tested in combination with the same antibiotics using a checkerboard assay. The best synergistic antibiotic-C12-PRP combinations were tested with the most resistant E. coli isolate using the Galleria mellonella insect infection model. A fluorescence-based membrane permeabilization assay was used to investigate a possible mode of action for C12-PRP.
Results
The four E. coli isolates showed varying resistance to the antibiotics (0.008 µg/mL to ≥256 µg/mL), and overall, the addition of C12-PRP lowered the minimum inhibitory concentration. The two most-potent antibiotic-C12-PRP combinations were with novobiocin and erythromycin showing a susceptibility increase of 128-fold and up to 32–fold, respectively. G. mellonella survival was significantly improved when C12-PRP was included with novobiocin or erythromycin during treatment of infected larvae. Membrane permeabilization of an E. coli isolate was markedly higher in the presence of C12-PRP.
Conclusions
We demonstrated the synergistic ability of C12-PRP to enhance antibiotic activity and reduce the virulence of the veterinary E. coli isolates, strengthening the potential promise of this adjuvant candidate as a therapeutic agent for multidrug-resistant bacteria.
{"title":"Investigating the adjuvant activity of the proline-rich antimicrobial lipopeptide C12-PRP against antimicrobial-resistant veterinary bacterial isolates","authors":"Soumya Deo , Aimeen Sharoze , Meerim Esenbekova , Dawn White , Frank Schweizer , Ramesh Kumar Mani , Bala Kishan Gorityala , Ayush Kumar","doi":"10.1016/j.jgar.2025.10.015","DOIUrl":"10.1016/j.jgar.2025.10.015","url":null,"abstract":"<div><h3>Objectives</h3><div>Farm animals exposed to excessive amounts of antibiotics are reservoirs for antimicrobial-resistance genes and multidrug-resistant bacteria. The goal of this study was to investigate the adjuvant activity of a previously synthesized, proline-rich lipopeptide called C<sub>12</sub>-PRP in combination with various antibiotics against multidrug-resistant <em>E. coli</em> isolated from chicken and cattle.</div></div><div><h3>Methods</h3><div>The microbroth dilution method was used to determine the minimum inhibitory concentration of 10 antibiotics against four <em>E. coli</em> isolates. The adjuvant activity of C<sub>12</sub>-PRP was then tested in combination with the same antibiotics using a checkerboard assay. The best synergistic antibiotic-C<sub>12</sub>-PRP combinations were tested with the most resistant <em>E. coli</em> isolate using the <em>Galleria mellonella</em> insect infection model. A fluorescence-based membrane permeabilization assay was used to investigate a possible mode of action for C<sub>12</sub>-PRP.</div></div><div><h3>Results</h3><div>The four <em>E. coli</em> isolates showed varying resistance to the antibiotics (0.008 µg/mL to ≥256 µg/mL), and overall, the addition of C<sub>12</sub>-PRP lowered the minimum inhibitory concentration. The two most-potent antibiotic-C<sub>12</sub>-PRP combinations were with novobiocin and erythromycin showing a susceptibility increase of 128-fold and up to 32–fold, respectively. <em>G. mellonella</em> survival was significantly improved when C<sub>12</sub>-PRP was included with novobiocin or erythromycin during treatment of infected larvae. Membrane permeabilization of an <em>E. coli</em> isolate was markedly higher in the presence of C<sub>12</sub>-PRP.</div></div><div><h3>Conclusions</h3><div>We demonstrated the synergistic ability of C<sub>12</sub>-PRP to enhance antibiotic activity and reduce the virulence of the veterinary <em>E. coli</em> isolates, strengthening the potential promise of this adjuvant candidate as a therapeutic agent for multidrug-resistant bacteria.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 305-309"},"PeriodicalIF":3.2,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354966","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 : 2025-10-15DOI: 10.1016/j.jgar.2025.10.004
Yuwei Qiu , Dan Cao , Bihan Xu , Xiuzhi Jiang , Xu Dong , Pusheng Xu , Yanghui Xiang , Xin Yuan , Yi Li , Ying Zhang
{"title":"Mutations in the atpE gene and bedaquiline resistance in Mycobacterium avium","authors":"Yuwei Qiu , Dan Cao , Bihan Xu , Xiuzhi Jiang , Xu Dong , Pusheng Xu , Yanghui Xiang , Xin Yuan , Yi Li , Ying Zhang","doi":"10.1016/j.jgar.2025.10.004","DOIUrl":"10.1016/j.jgar.2025.10.004","url":null,"abstract":"","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 232-233"},"PeriodicalIF":3.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313056","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 : 2025-10-14DOI: 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":"2025-10-14","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}
Pub 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":"2025-10-14","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}
Infection prevention using antiseptics is crucial to control the transmission of multidrug-resistant Gram-negative pathogens.
Methods
This in vitro study aimed to evaluate: (1) the susceptibility to octenidine (OCT) of 104 Pseudomonas aeruginosa (including multidrug-resistant) clinical isolates; (2) whether resistant mutants can be obtained by applying selective pressure using increasing concentrations of OCT and colistin (COL); (3) the genetic basis of underlying resistance mechanisms; (4) the co-lateral effects on various antibiotics and chlorhexidine (CHX); and (5) the efficacy of OCT-based products in mutant strains according to EN13727.
Results
OCT showed high activity against all isolates. Long-term exposure of four P. aeruginosa strains to OCT resulted in five mutants predominantly exhibiting mutations in genes involved in the regulation of efflux pumps. No co-lateral effect of the OCT mutants on CHX, COL or any other antibiotics was detected. OCT as well as OCT-based products were still fully effective in all OCT mutants under “dirty conditions” within a 1 min contact time. Using COL as a selective molecule, four mutants exhibiting decreased susceptibility to COL were identified that harboured mutations in pmrB. Cross-resistance to gentamicin was observed in two mutants, but not to OCT, CHX or any other antibiotics.
Conclusions
Rare mutations triggered within P. aeruginosa by OCT during long-term in vitro exposure showed no impact on the efficacy of OCT and did not select for other antiseptic or antibiotic cross-resistance.
{"title":"Colistin- and octenidine-induced selective pressure on Pseudomonas aeruginosa clinical isolates in vitro: Antimicrobial activity and mechanisms of cross-resistance","authors":"Samanta Freire , Otávio Hallal Ferreira Raro , Patrice Nordmann , Laurent Poirel","doi":"10.1016/j.jgar.2025.10.008","DOIUrl":"10.1016/j.jgar.2025.10.008","url":null,"abstract":"<div><h3>Objective</h3><div>Infection prevention using antiseptics is crucial to control the transmission of multidrug-resistant Gram-negative pathogens.</div></div><div><h3>Methods</h3><div>This in vitro study aimed to evaluate: (1) the susceptibility to octenidine (OCT) of 104 <em>Pseudomonas aeruginosa</em> (including multidrug-resistant) clinical isolates; (2) whether resistant mutants can be obtained by applying selective pressure using increasing concentrations of OCT and colistin (COL); (3) the genetic basis of underlying resistance mechanisms; (4) the co-lateral effects on various antibiotics and chlorhexidine (CHX); and (5) the efficacy of OCT-based products in mutant strains according to EN13727.</div></div><div><h3>Results</h3><div>OCT showed high activity against all isolates. Long-term exposure of four <em>P. aeruginosa</em> strains to OCT resulted in five mutants predominantly exhibiting mutations in genes involved in the regulation of efflux pumps. No co-lateral effect of the OCT mutants on CHX, COL or any other antibiotics was detected. OCT as well as OCT-based products were still fully effective in all OCT mutants under “dirty conditions” within a 1 min contact time. Using COL as a selective molecule, four mutants exhibiting decreased susceptibility to COL were identified that harboured mutations in <em>pmrB</em>. Cross-resistance to gentamicin was observed in two mutants, but not to OCT, CHX or any other antibiotics.</div></div><div><h3>Conclusions</h3><div>Rare mutations triggered within <em>P. aeruginosa</em> by OCT during long-term in vitro exposure showed no impact on the efficacy of OCT and did not select for other antiseptic or antibiotic cross-resistance.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 209-214"},"PeriodicalIF":3.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308248","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}
A clinical isolate of Acinetobacter spp. MS5394 carrying a novel GES-type β-lactamase gene, blaGES-24, was first identified in 2013. This study aimed to characterize the genetic and phenotypic features of GES-24.
Methods
The complete genome of A. nosocomialis MS5394 was sequenced using Illumina MiSeq and Oxford Nanopore technologies. Plasmid pAC-GES-24 was analysed for resistance gene content and sequence. Site-directed mutagenesis was used to examine the functional role of amino acid substitutions at positions 62, 104, and 170 in GES-24. Antimicrobial susceptibility testing was performed in E. coli expressing different GES variants.
Results
The blaGES-24, is on a ∼153-kb plasmid pAC-GES-24. The complete nucleotide sequence of the pAC-GES-24 indicated that the backbone sequence was possibly a hybrid of two independent plasmids, pNDM-AP_882 and pOXA-588-AP_882, carrying blaNDM and blaOXA, respectively, from Acinetobacter pitti AP_882 isolated in Malaysia. A comparison of the amino acid sequence of GES-24 with that of highly homologous GES identified three amino acid differences at ambler positions 62, 104, and 170. Phenotypic investigation of E. coli producing GES-24 in comparison with E. coli producing GES variants at Ambler positions 62, 104, and 170 under isogenic conditions confirmed that GES-24 is a β-lactamase that possesses carbapenemase activity but is relatively weak in hydrolysing CTX, CAZ, AZT, and CFPM when compared to the other GES-type tested.
Conclusions
GES-24 represents a GES-type β-lactamase with carbapenemase activity but relatively weak hydrolytic activity against certain β-lactams. The genetic analysis suggests that the plasmid carrying blaGES-24 may have evolved from a hybrid plasmid.
{"title":"Plasmid-mediated blaGES-24 in Acinetobacter nosocomialis: Genetic context and resistance profile","authors":"Raita Yano , Shizuo Kayama , Masato Suzuki , Koji Yahara , Junzo Hisatsune , Liansheng Yu , Chika Arai , Taijiro Sueda , Shinya Takahashi , Yumiko Koba , Hiroki Ohge , Motoyuki Sugai","doi":"10.1016/j.jgar.2025.10.003","DOIUrl":"10.1016/j.jgar.2025.10.003","url":null,"abstract":"<div><h3>Objectives</h3><div>A clinical isolate of <em>Acinetobacter</em> spp. MS5394 carrying a novel GES-type β-lactamase gene, <em>bla</em><sub>GES</sub><sub>-24</sub>, was first identified in 2013. This study aimed to characterize the genetic and phenotypic features of GES-24.</div></div><div><h3>Methods</h3><div>The complete genome of <em>A. nosocomialis</em> MS5394 was sequenced using Illumina MiSeq and Oxford Nanopore technologies. Plasmid pAC-GES-24 was analysed for resistance gene content and sequence. Site-directed mutagenesis was used to examine the functional role of amino acid substitutions at positions 62, 104, and 170 in GES-24. Antimicrobial susceptibility testing was performed in <em>E. coli</em> expressing different GES variants.</div></div><div><h3>Results</h3><div>The <em>bla</em><sub>GES-24,</sub> is on a ∼153-kb plasmid pAC-GES-24. The complete nucleotide sequence of the pAC-GES-24 indicated that the backbone sequence was possibly a hybrid of two independent plasmids, pNDM-AP_882 and pOXA-588-AP_882, carrying <em>bla</em><sub>NDM</sub> and <em>bla</em><sub>OXA</sub>, respectively, from <em>Acinetobacter pitti</em> AP_882 isolated in Malaysia. A comparison of the amino acid sequence of GES-24 with that of highly homologous GES identified three amino acid differences at ambler positions 62, 104, and 170. Phenotypic investigation of <em>E. coli</em> producing GES-24 in comparison with <em>E. coli</em> producing GES variants at Ambler positions 62, 104, and 170 under isogenic conditions confirmed that GES-24 is a β-lactamase that possesses carbapenemase activity but is relatively weak in hydrolysing CTX, CAZ, AZT, and CFPM when compared to the other GES-type tested.</div></div><div><h3>Conclusions</h3><div>GES-24 represents a GES-type β-lactamase with carbapenemase activity but relatively weak hydrolytic activity against certain β-lactams. The genetic analysis suggests that the plasmid carrying <em>bla</em><sub>GES-24</sub> may have evolved from a hybrid plasmid.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"45 ","pages":"Pages 202-208"},"PeriodicalIF":3.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145301453","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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