Pub Date : 2026-03-06DOI: 10.1016/j.jgar.2026.03.002
Hongxia Wen, Yu Feng, Zhiyong Zong
Objective: Durlobactam, a diazabicyclooctane β-lactamase inhibitor, can protect meropenem from hydrolysis of KPC and OXA-48 carbapenemases. This study aims to characterize the genome of a carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical strain with high MIC (256 mg/L) of meropenem in the presence of durlobactam.
Methods: The strain was recovered from bile and MICs of meropenem-durlobactam and sulbactam-durlobactam were determined using broth microdilution. Its genome was sequenced using Illumina platform and were analyzed for antimicrobial resistance genes and virulence factors using a set of bioinformatic tools.
Results: The strain belonged to sequence type 11 and capsular type 64, harbored carbapenemase gene blaKPC-2, and carried virulence factors encoding aerobactin, (iutA-iuc), yersiniabactin (irp-ybt) and mucoid regulators (rmpADC and rmpA2), suggesting enhanced virulence. MICs of meropenem-durlobactam and sulbactam-durlobactam against this strain were both 256/4 mg/L.
Conclusion: A KPC-2-producing CRKP with non-susceptibility to meropenem-durlobactam, possibly linking to porin LamB deficiency and absence of outer membrane assembly protein AsmA, was identified. This uncovers a new challenge caused by antimicrobial resistance, calling more surveillance.
{"title":"Failure of durlobactam to restore the susceptibility to meropenem in carbapenem-resistant Klebsiella pneumoniae.","authors":"Hongxia Wen, Yu Feng, Zhiyong Zong","doi":"10.1016/j.jgar.2026.03.002","DOIUrl":"https://doi.org/10.1016/j.jgar.2026.03.002","url":null,"abstract":"<p><strong>Objective: </strong>Durlobactam, a diazabicyclooctane β-lactamase inhibitor, can protect meropenem from hydrolysis of KPC and OXA-48 carbapenemases. This study aims to characterize the genome of a carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical strain with high MIC (256 mg/L) of meropenem in the presence of durlobactam.</p><p><strong>Methods: </strong>The strain was recovered from bile and MICs of meropenem-durlobactam and sulbactam-durlobactam were determined using broth microdilution. Its genome was sequenced using Illumina platform and were analyzed for antimicrobial resistance genes and virulence factors using a set of bioinformatic tools.</p><p><strong>Results: </strong>The strain belonged to sequence type 11 and capsular type 64, harbored carbapenemase gene bla<sub>KPC-2</sub>, and carried virulence factors encoding aerobactin, (iutA-iuc), yersiniabactin (irp-ybt) and mucoid regulators (rmpADC and rmpA2), suggesting enhanced virulence. MICs of meropenem-durlobactam and sulbactam-durlobactam against this strain were both 256/4 mg/L.</p><p><strong>Conclusion: </strong>A KPC-2-producing CRKP with non-susceptibility to meropenem-durlobactam, possibly linking to porin LamB deficiency and absence of outer membrane assembly protein AsmA, was identified. This uncovers a new challenge caused by antimicrobial resistance, calling more surveillance.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377689","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 : 2026-03-03DOI: 10.1016/j.jgar.2026.02.014
Qiang Li, Zhenzhen Dong, Li Ma, Xi Yang
Objectives: This study aimed to delineate the genomic architecture of a ST45-K62 Klebsiella pneumoniae strain identified as the first global isolate co-carrying blaKPC-2 and blaNDM-5.
Methods: Antimicrobial susceptibility was determined using broth microdilution. Whole-genome sequencing was performed using the Illumina HiSeq X-10 and PacBio RS II platforms, and genomic features were analyzed using various bioinformatics tools.
Results: HRKP01 showed resistance to most tested antibiotics, being susceptible only to amikacin. It was classified as sequence type (ST) 45 and K-locus type (K) 62. The genome of HRKP01 consisted of a 5,329,093 bp chromosome and three plasmids of 283,811 bp, 122,964 bp and 57,031 bp in length. Comprehensive sequence analysis revealed 12 antimicrobial resistance genes, including blaKPC-2 and blaNDM-5. Virulence factor screening further demonstrated the presence of numerous virulence-associated genes in this isolate. The blaNDM-5 gene is immediately flanked upstream by ISkox3-IS26-bleMBL at a 2-bp interval, and by Tn3-IS3000-IS5 on the other side at a 14-bp interval. Pan-genome analysis revealed a highly conserved core genome but pronounced accessory genome diversity.
Conclusion: To our knowledge, this is the first genomic report of a ST45-K62 K. pneumoniae isolate harboring both blaKPC-2 and blaNDM-5 genes. The pHRKP01-NDM5 harboring blaNDM-5 contains multiple mobile genetic elements (MGEs).
{"title":"Genome analysis of bla<sub>NDM-5</sub> and bla<sub>KPC-2</sub> co-occurrence in ST45-K62 carbapenem-resistant Klebsiella pneumoniae isolate from China.","authors":"Qiang Li, Zhenzhen Dong, Li Ma, Xi Yang","doi":"10.1016/j.jgar.2026.02.014","DOIUrl":"https://doi.org/10.1016/j.jgar.2026.02.014","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to delineate the genomic architecture of a ST45-K62 Klebsiella pneumoniae strain identified as the first global isolate co-carrying bla<sub>KPC-2</sub> and bla<sub>NDM-5</sub>.</p><p><strong>Methods: </strong>Antimicrobial susceptibility was determined using broth microdilution. Whole-genome sequencing was performed using the Illumina HiSeq X-10 and PacBio RS II platforms, and genomic features were analyzed using various bioinformatics tools.</p><p><strong>Results: </strong>HRKP01 showed resistance to most tested antibiotics, being susceptible only to amikacin. It was classified as sequence type (ST) 45 and K-locus type (K) 62. The genome of HRKP01 consisted of a 5,329,093 bp chromosome and three plasmids of 283,811 bp, 122,964 bp and 57,031 bp in length. Comprehensive sequence analysis revealed 12 antimicrobial resistance genes, including bla<sub>KPC-2</sub> and bla<sub>NDM-5</sub>. Virulence factor screening further demonstrated the presence of numerous virulence-associated genes in this isolate. The bla<sub>NDM-5</sub> gene is immediately flanked upstream by ISkox3-IS26-ble<sub>MBL</sub> at a 2-bp interval, and by Tn3-IS3000-IS5 on the other side at a 14-bp interval. Pan-genome analysis revealed a highly conserved core genome but pronounced accessory genome diversity.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first genomic report of a ST45-K62 K. pneumoniae isolate harboring both bla<sub>KPC-2</sub> and bla<sub>NDM-5</sub> genes. The pHRKP01-NDM5 harboring blaNDM-5 contains multiple mobile genetic elements (MGEs).</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365287","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 : 2026-03-01Epub Date: 2026-01-21DOI: 10.1016/j.jgar.2026.01.005
Tae-Min La , Taesoo Kim , Sang-Won Lee , Ji-Yeon Hyeon
Objective
This study reports complete chromosome and pESI-like megaplasmid sequences of multidrug-resistant Salmonella enterica serovar Infantis (S. Infantis) isolates obtained from retail chicken meat in South Korea in 2023 and characterizes their antimicrobial resistance (AMR) gene repertoire and the structural diversity of their pESI-like plasmids.
Methods
Twenty-one multidrug-resistant S. Infantis isolates were subjected to whole-genome sequencing using Illumina NextSeq and Oxford Nanopore MinION platforms. Hybrid assemblies were generated using Trycycler v0.5.0 and corrected using Polypolish v1.2.3. AMR genes were identified, and plasmid structures were reconstructed and visualized using Proksee.
Results
All isolates belonged to sequence type ST32 and carried pESI-like megaplasmid encoding multiple AMR genes. Conserved resistance genes included aac(3)-IVa, aph(4)-Ia, blaCTX-M-65, and tet(A), while ant(3″)-Ia, aph(3′)-Ia, dfrA14, floR, and sul1 were variably present. Comparative plasmid analysis revealed six plasmid structural variants (Types A–F), primarily distinguished by deletions within AMR regions. Type A retained all resistance loci, whereas Types B–F exhibited partial loss of regions harbouring aph(3′)-Ia, dfrA14, floR, or sul1. Comparative plasmid mapping showed that the Korean pESI-like plasmids exhibited high overall structural similarity to internationally reported pESI-like plasmids, including those from the UK and USA.
Conclusions
These complete genome sequences expand the current knowledge of pESI-like plasmid diversity in S. Infantis and highlight their role in the dissemination of multidrug resistance in the poultry sector. Continued genomic surveillance is warranted to monitor the emergence and spread of high-risk S. Infantis clones across the food chain.
{"title":"Complete genome sequences and structural variants of pESI-like plasmids in multidrug-resistant Salmonella Infantis carrying blaCTX-M-65 from retail chicken meat in South Korea","authors":"Tae-Min La , Taesoo Kim , Sang-Won Lee , Ji-Yeon Hyeon","doi":"10.1016/j.jgar.2026.01.005","DOIUrl":"10.1016/j.jgar.2026.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>This study reports complete chromosome and pESI-like megaplasmid sequences of multidrug-resistant <em>Salmonella enterica</em> serovar Infantis (<em>S.</em> Infantis) isolates obtained from retail chicken meat in South Korea in 2023 and characterizes their antimicrobial resistance (AMR) gene repertoire and the structural diversity of their pESI-like plasmids.</div></div><div><h3>Methods</h3><div>Twenty-one multidrug-resistant <em>S</em>. Infantis isolates were subjected to whole-genome sequencing using Illumina NextSeq and Oxford Nanopore MinION platforms. Hybrid assemblies were generated using Trycycler v0.5.0 and corrected using Polypolish v1.2.3. AMR genes were identified, and plasmid structures were reconstructed and visualized using Proksee.</div></div><div><h3>Results</h3><div>All isolates belonged to sequence type ST32 and carried pESI-like megaplasmid encoding multiple AMR genes. Conserved resistance genes included <em>aac(3)-IVa, aph(4)-Ia, bla</em><sub>CTX-M-65</sub>, and <em>tet</em>(A), while <em>ant(3″)-Ia, aph(3′)-Ia, dfrA14, floR,</em> and <em>sul1</em> were variably present. Comparative plasmid analysis revealed six plasmid structural variants (Types A–F), primarily distinguished by deletions within AMR regions. Type A retained all resistance loci, whereas Types B–F exhibited partial loss of regions harbouring <em>aph(3′)-Ia, dfrA14, floR</em>, or <em>sul1</em>. Comparative plasmid mapping showed that the Korean pESI-like plasmids exhibited high overall structural similarity to internationally reported pESI-like plasmids, including those from the UK and USA.</div></div><div><h3>Conclusions</h3><div>These complete genome sequences expand the current knowledge of pESI-like plasmid diversity in <em>S</em>. Infantis and highlight their role in the dissemination of multidrug resistance in the poultry sector. Continued genomic surveillance is warranted to monitor the emergence and spread of high-risk <em>S</em>. Infantis clones across the food chain.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 38-40"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040813","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 : 2026-03-01Epub Date: 2026-01-19DOI: 10.1016/j.jgar.2026.01.006
Atef Oreiby , Samanta Freire , Alaaeldin Mohamed Saad , Mohamed A. Donia , Hazim O. Khalifa , Patrice Nordmann , Laurent Poirel , Mustafa Sadek
Objectives
This study investigates the transmission risk of ESBL producers, carbapenemase producers, polymyxin-resistant, and fosfomycin-resistant Enterobacterales from healthy and sick dogs and cats in Tanta governorate, Nile Delta region, Egypt.
Methods
A total of 206 different samples were collected from healthy and sick pets. Samples were screened for different resistance mechanisms using mSuperCarba, SuperPolymyxin, ChromID ESBL, and SuperFOS selective plates. Antimicrobial susceptibility testing was performed using disk diffusion and broth microdilution techniques. Phenotypic confirmation of resistance traits was done using various rapid diagnostic tests. PCR screening was performed for ESBLs, carbapenemases, mcr, and fosA genes. Molecular typing and clonality evaluation were also performed.
Results
Isolates (Escherichia coli, n = 17 and Enterobacter cloacae, n = 1) showing acquired multidrug resistance phenotype were identified in 13 animals, accounting for 25% of the total cases. Production of ESBLs was the most prevalent resistance mechanism, with the corresponding producers predominantly carrying the blaCTX-M-15 gene (92.3%), whereas the blaSHV-12 gene was identified in a single isolate. The blaNDM-5 carbapenemase gene was identified in three E. coli isolates, those latter sharing the same sequence type (ST361). A single colistin-resistant E. coli was isolated and carried both mcr-1 and blaCTX-M-15, whereas a fosfomycin-resistant E. coli isolate coproduced fosA5 and SHV-12. Notably, 69.2% of resistant bacteria were isolated from sick pets compared with 30.7% in healthy ones. E. coli isolates showed various sequence types, with ESBL-producing strains belonging to seven different STs and NDM-5 enzyme producers belonging to ST361.
Conclusions
This study highlights significant antimicrobial resistance in companion animals and the potential risk for zoonotic transmission.
{"title":"Occurrence of ESBL and carbapenemase producers and polymyxin- and fosfomycin-resistant Enterobacterales among pets in a veterinary clinic, Egypt","authors":"Atef Oreiby , Samanta Freire , Alaaeldin Mohamed Saad , Mohamed A. Donia , Hazim O. Khalifa , Patrice Nordmann , Laurent Poirel , Mustafa Sadek","doi":"10.1016/j.jgar.2026.01.006","DOIUrl":"10.1016/j.jgar.2026.01.006","url":null,"abstract":"<div><h3>Objectives</h3><div>This study investigates the transmission risk of ESBL producers, carbapenemase producers, polymyxin-resistant, and fosfomycin-resistant Enterobacterales from healthy and sick dogs and cats in Tanta governorate, Nile Delta region, Egypt.</div></div><div><h3>Methods</h3><div>A total of 206 different samples were collected from healthy and sick pets. Samples were screened for different resistance mechanisms using mSuperCarba, SuperPolymyxin, ChromID ESBL, and SuperFOS selective plates. Antimicrobial susceptibility testing was performed using disk diffusion and broth microdilution techniques. Phenotypic confirmation of resistance traits was done using various rapid diagnostic tests. PCR screening was performed for ESBLs, carbapenemases, <em>mcr</em>, and <em>fosA</em> genes. Molecular typing and clonality evaluation were also performed.</div></div><div><h3>Results</h3><div>Isolates (<em>Escherichia coli</em>, n = 17 and <em>Enterobacter cloacae</em>, n = 1) showing acquired multidrug resistance phenotype were identified in 13 animals, accounting for 25% of the total cases. Production of ESBLs was the most prevalent resistance mechanism, with the corresponding producers predominantly carrying the <em>bla</em><sub>CTX-M-15</sub> gene (92.3%), whereas the <em>bla</em><sub>SHV-12</sub> gene was identified in a single isolate. The <em>bla</em><sub>NDM-5</sub> carbapenemase gene was identified in three <em>E. coli</em> isolates, those latter sharing the same sequence type (ST361). A single colistin-resistant <em>E. coli</em> was isolated and carried both <em>mcr-1</em> and <em>bla</em><sub>CTX-M-15</sub>, whereas a fosfomycin-resistant <em>E. coli</em> isolate coproduced <em>fosA5</em> and SHV-12. Notably, 69.2% of resistant bacteria were isolated from sick pets compared with 30.7% in healthy ones. <em>E. coli</em> isolates showed various sequence types, with ESBL-producing strains belonging to seven different STs and NDM-5 enzyme producers belonging to ST361.</div></div><div><h3>Conclusions</h3><div>This study highlights significant antimicrobial resistance in companion animals and the potential risk for zoonotic transmission.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 49-54"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018513","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 : 2026-03-01Epub Date: 2026-01-20DOI: 10.1016/j.jgar.2026.01.004
Qin Tang , Yuting Sun , Fei Yan , Lu Lin , Huarong Yu , Jinxing Chen
Research Background
mecA-positive MRSA is generally assumed to be broadly non-susceptible to β-lactams. Reports of penicillin-susceptible MRSA (PS-MRSA) challenge this view. We describe CDSYY2023, a cefoxitin-resistant yet penicillin-susceptible MRSA carrying three mecA substitutions (S225R, K239E, E246G) and a novel sequence type, ST9332.
Methods
The strain was recovered from the sputum of a hospitalised older adult with dementia and identified as S. aureus by MALDI-TOF MS (Autobio MS1000). Susceptibility testing followed CLSI procedures on VITEK 2 with parallel Mueller–Hinton edge tests (cefoxitin, penicillin). Key readouts were verified by Etest and independently confirmed at a referral laboratory. Whole-genome sequencing (Illumina HiSeq 2500) was assembled de novo with SOAPdenovo2. Functional annotation used COG/GO/KEGG; resistance and virulence genes were queried against CARD and VFDB. MLST was assigned and registered via PUBMLST.
Results
The draft genome is ∼2 750 950 bp (GC 32.94%), with no plasmids, encoding 2521 CDSs, 55 tRNAs and 19 rRNAs. MLST designated ST9332. Phenotypically, VITEK 2 and MH edge tests agreed on cefoxitin resistance (17 mm), while penicillin remained susceptible (25 mm; Etest MIC 0.032 µg/mL), contrary to expectations for a mecA-positive background. Genomics revealed the triple mecA substitutions noted above and no definitive evidence of blaZ. The resistome/virulome included multiple efflux and regulatory elements.
Conclusions
CDSYY2023 is a PS-MRSA with triple-substituted mecA on a novel MLST background (ST9332). Its penicillin-susceptible/cefoxitin-resistant profile likely reflects a specific mecA sequence/regulatory context, highlighting the limits of relying solely on cefoxitin-based screening to infer β-lactam behaviour.
研究背景：meca阳性MRSA通常被认为对β-内酰胺不敏感。青霉素敏感MRSA （PS-MRSA）的报道挑战了这一观点。我们描述了CDSYY2023，这是一种对头孢西丁耐药但对青霉素敏感的MRSA，携带三个mecA替换（S225R, K239E, E246G）和一种新的序列类型ST9332。方法：从1例住院老年痴呆患者的痰液中分离得到该菌株，经MALDI-TOF MS （Autobio MS1000）鉴定为金黄色葡萄球菌。采用CLSI程序对VITEK 2进行平行Mueller-Hinton边缘试验（头孢西丁、青霉素）的药敏试验。关键读数由Etest验证，并在转诊实验室独立确认。全基因组测序（Illumina HiSeq 2500）用SOAPdenovo2重新组装。功能注释采用COG/GO/KEGG；对CARD和VFDB的抗性和毒力基因进行了查询。MLST通过PUBMLST进行分配和注册。结果：该草图基因组约2,750,950 bp (GC 32.94%)，不含质粒，编码2,521个cds， 55个trna和19个rnas。MLST指定为ST9332。表型上，VITEK 2和MH边缘试验一致显示头孢西丁耐药（17 mm），而青霉素仍然敏感（25 mm；测试MIC 0.032µg/mL），与meca阳性背景的预期相反。基因组学揭示了上述三个mecA替换，没有明确的blaZ证据。抵抗组/病毒组包括多种外排和调控元件。结论：CDSYY2023是一种具有新型MLST背景（ST9332）的三取代mecA的PS-MRSA。其青霉素敏感/头孢西丁耐药谱可能反映了特定的mecA序列/调控背景，突出了仅依靠基于头孢西丁的筛选推断β-内酰胺行为的局限性。
{"title":"Genomic analysis of a penicillin-susceptible, methicillin-resistant Staphylococcus aureus (ST9332) harboring triple mecA substitutions","authors":"Qin Tang , Yuting Sun , Fei Yan , Lu Lin , Huarong Yu , Jinxing Chen","doi":"10.1016/j.jgar.2026.01.004","DOIUrl":"10.1016/j.jgar.2026.01.004","url":null,"abstract":"<div><h3>Research Background</h3><div><em>mecA</em>-positive MRSA is generally assumed to be broadly non-susceptible to β-lactams. Reports of penicillin-susceptible MRSA (PS-MRSA) challenge this view. We describe CDSYY2023, a cefoxitin-resistant yet penicillin-susceptible MRSA carrying three <em>mecA</em> substitutions (S225R, K239E, E246G) and a novel sequence type, ST9332.</div></div><div><h3>Methods</h3><div>The strain was recovered from the sputum of a hospitalised older adult with dementia and identified as <em>S. aureus</em> by MALDI-TOF MS (Autobio MS1000). Susceptibility testing followed CLSI procedures on VITEK 2 with parallel Mueller–Hinton edge tests (cefoxitin, penicillin). Key readouts were verified by Etest and independently confirmed at a referral laboratory. Whole-genome sequencing (Illumina HiSeq 2500) was assembled de novo with SOAPdenovo2. Functional annotation used COG/GO/KEGG; resistance and virulence genes were queried against CARD and VFDB. MLST was assigned and registered via PUBMLST.</div></div><div><h3>Results</h3><div>The draft genome is ∼2 750 950 bp (GC 32.94%), with no plasmids, encoding 2521 CDSs, 55 tRNAs and 19 rRNAs. MLST designated ST9332. Phenotypically, VITEK 2 and MH edge tests agreed on cefoxitin resistance (17 mm), while penicillin remained susceptible (25 mm; Etest MIC 0.032 µg/mL), contrary to expectations for a <em>mecA</em>-positive background. Genomics revealed the triple <em>mecA</em> substitutions noted above and no definitive evidence of <em>blaZ</em>. The resistome/virulome included multiple efflux and regulatory elements.</div></div><div><h3>Conclusions</h3><div>CDSYY2023 is a PS-MRSA with triple-substituted <em>mecA</em> on a novel MLST background (ST9332). Its penicillin-susceptible/cefoxitin-resistant profile likely reflects a specific <em>mecA</em> sequence/regulatory context, highlighting the limits of relying solely on cefoxitin-based screening to infer β-lactam behaviour.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 20-26"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029678","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 : 2026-03-01Epub Date: 2026-01-21DOI: 10.1016/j.jgar.2026.01.007
Bing Lv, Xin Zhang, Hui Xu, Changying Lin, Ying Huang, Mei Qu, Daitao Zhang, Quanyi Wang
Objectives
This study aimed to investigate the prevalence of diarrhoeagenic Escherichia coli (DEC) among outpatients in Beijing, and to analyse the antimicrobial susceptibility profiles and antimicrobial resistance gene characteristics of the isolated strains.
Methods
From 2021 to 2024, DEC strains were collected from outpatient specimens. After isolation and identification, the minimum inhibitory concentration (MIC) method was used to assess their susceptibility to 16 antibiotics. Whole-genome sequencing was conducted for further analysis.
Results
Among the 1209 DEC strains, the highest resistance rates were observed for ampicillin (63.28%) and tetracycline (45.57%). In contrast, significantly lower rates were found for tigecycline (0.41%), amikacin (0.66%), meropenem (3.97%), ertapenem (6.70%), ceftazidime (7.20%), and ciprofloxacin (9.26%). The 0–5 age group demonstrated higher resistance rates to most antibiotics compared with other age groups. Multi-locus sequence typing revealed significant genetic diversity among all strains, with the predominant sequence types identified as ST10 (5.96%), ST1491 (5.21%), ST4 (4.22%), and ST48 (3.47%). Among 111 fluoroquinolone-resistant strains, chromosomal mutations in gyrA and parC genes were predominant (56.76%). Among 612 cephalosporin-resistant isolates, the blaCTX−M gene was the most prevalent resistance gene (30.72%).
Conclusions
DEC infections and the spread of resistance genes pose a significant health threat, especially in children. Consequently, there is an urgent need to enhance the surveillance and research of resistance genes and to promote the rational use of antibiotics.
{"title":"Antimicrobial susceptibility analysis of diarrhoeagenic Escherichia coli isolated from outpatients in Beijing, from 2021 to 2024","authors":"Bing Lv, Xin Zhang, Hui Xu, Changying Lin, Ying Huang, Mei Qu, Daitao Zhang, Quanyi Wang","doi":"10.1016/j.jgar.2026.01.007","DOIUrl":"10.1016/j.jgar.2026.01.007","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to investigate the prevalence of diarrhoeagenic <em>Escherichia coli</em> (DEC) among outpatients in Beijing, and to analyse the antimicrobial susceptibility profiles and antimicrobial resistance gene characteristics of the isolated strains.</div></div><div><h3>Methods</h3><div>From 2021 to 2024, DEC strains were collected from outpatient specimens. After isolation and identification, the minimum inhibitory concentration (MIC) method was used to assess their susceptibility to 16 antibiotics. Whole-genome sequencing was conducted for further analysis.</div></div><div><h3>Results</h3><div>Among the 1209 DEC strains, the highest resistance rates were observed for ampicillin (63.28%) and tetracycline (45.57%). In contrast, significantly lower rates were found for tigecycline (0.41%), amikacin (0.66%), meropenem (3.97%), ertapenem (6.70%), ceftazidime (7.20%), and ciprofloxacin (9.26%). The 0–5 age group demonstrated higher resistance rates to most antibiotics compared with other age groups. Multi-locus sequence typing revealed significant genetic diversity among all strains, with the predominant sequence types identified as ST10 (5.96%), ST1491 (5.21%), ST4 (4.22%), and ST48 (3.47%). Among 111 fluoroquinolone-resistant strains, chromosomal mutations in <em>gyrA</em> and <em>parC</em> genes were predominant (56.76%). Among 612 cephalosporin-resistant isolates, the <em>bla</em><sub>CTX−M</sub> gene was the most prevalent resistance gene (30.72%).</div></div><div><h3>Conclusions</h3><div>DEC infections and the spread of resistance genes pose a significant health threat, especially in children. Consequently, there is an urgent need to enhance the surveillance and research of resistance genes and to promote the rational use of antibiotics.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 1-8"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040836","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 : 2026-03-01Epub Date: 2026-01-27DOI: 10.1016/j.jgar.2026.01.010
Vitus Silago , Benson R. Kidenya , Katarina Oravcova , Louise Matthews , Conjester I. Mtemisika , Stephen E. Mshana , Heike Claus , Jeremiah Seni
Background
Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) represent major clinical threats globally. Genomic epidemiological data remain scarce in low- and middle-income countries, limiting a comprehensive understanding of antimicrobial-resistant pathogen diversity and clonal distribution. The present study investigated the genomic epidemiology of ESBL-EC and ESBL-KP isolates in Mwanza, Tanzania.
Methods
This cross-sectional hospital-based study employed whole-genome sequencing to characterise ESBL-EC (n = 39) and ESBL-KP (n = 49) isolated from patients with bloodstream, urinary tract, and wound infections at a zonal referral hospital between June 2019–June 2020 and March–August 2023.
Results
Thirteen sequence types (STs) were identified among ESBL-EC, predominantly ST131 (30.7%) and ST648 (28.2%). ESBL-KP comprised 15 STs, with ST2390 (24.5%) and ST17 (18.4%) being the most common. The blaCTX−M-15 gene was detected in 87.2% of ESBL-EC and 95.9% of ESBL-KP. IncFII was the dominant plasmid replicon in ESBL-EC (63.9%) and ESBL-KP (83.7%), while repB was detected exclusively in ESBL-KP (28.6%), particularly among ST2390. ESBL-EC showed significantly higher resistance to ciprofloxacin (P < 0.01), whereas ESBL-KP demonstrated higher resistance to gentamicin and piperacillin-tazobactam (both P < 0.01). The cgMLST-based Neighbour-Joining phylogenetic analysis revealed substantial genetic diversity and identified clonal clusters involving the high-risk clone ESBL-EC ST131. Clusters of ESBL-EC ST131 and ST648 were observed across medical and neonatology wards, while ESBL-KP ST2390 clusters were mainly confined to neonatology wards.
Conclusion
This study highlights clonal clusters, the first report of ESBL-KP ST2390, and the predominance of the virulent high-risk clone ESBL-EC ST131 in Mwanza, Tanzania. Underscoring the critical need for reinforced infection control strategies and genomic surveillance.
{"title":"Genomic epidemiology of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Mwanza, Tanzania","authors":"Vitus Silago , Benson R. Kidenya , Katarina Oravcova , Louise Matthews , Conjester I. Mtemisika , Stephen E. Mshana , Heike Claus , Jeremiah Seni","doi":"10.1016/j.jgar.2026.01.010","DOIUrl":"10.1016/j.jgar.2026.01.010","url":null,"abstract":"<div><h3>Background</h3><div>Extended-spectrum beta-lactamase-producing <em>Escherichia coli</em> (ESBL-EC) and <em>Klebsiella pneumoniae</em> (ESBL-KP) represent major clinical threats globally. Genomic epidemiological data remain scarce in low- and middle-income countries, limiting a comprehensive understanding of antimicrobial-resistant pathogen diversity and clonal distribution. The present study investigated the genomic epidemiology of ESBL-EC and ESBL-KP isolates in Mwanza, Tanzania.</div></div><div><h3>Methods</h3><div>This cross-sectional hospital-based study employed whole-genome sequencing to characterise ESBL-EC (<em>n</em> = 39) and ESBL-KP (<em>n</em> = 49) isolated from patients with bloodstream, urinary tract, and wound infections at a zonal referral hospital between June 2019–June 2020 and March–August 2023.</div></div><div><h3>Results</h3><div>Thirteen sequence types (STs) were identified among ESBL-EC, predominantly ST131 (30.7%) and ST648 (28.2%). ESBL-KP comprised 15 STs, with ST2390 (24.5%) and ST17 (18.4%) being the most common. The <em>bla</em><sub>CTX−M-15</sub> gene was detected in 87.2% of ESBL-EC and 95.9% of ESBL-KP. IncFII was the dominant plasmid replicon in ESBL-EC (63.9%) and ESBL-KP (83.7%), while repB was detected exclusively in ESBL-KP (28.6%), particularly among ST2390. ESBL-EC showed significantly higher resistance to ciprofloxacin (<em>P</em> < 0.01), whereas ESBL-KP demonstrated higher resistance to gentamicin and piperacillin-tazobactam (both <em>P</em> < 0.01). The cgMLST-based Neighbour-Joining phylogenetic analysis revealed substantial genetic diversity and identified clonal clusters involving the high-risk clone ESBL-EC ST131. Clusters of ESBL-EC ST131 and ST648 were observed across medical and neonatology wards, while ESBL-KP ST2390 clusters were mainly confined to neonatology wards.</div></div><div><h3>Conclusion</h3><div>This study highlights clonal clusters, the first report of ESBL-KP ST2390, and the predominance of the virulent high-risk clone ESBL-EC ST131 in Mwanza, Tanzania. Underscoring the critical need for reinforced infection control strategies and genomic surveillance.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 55-63"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086035","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 : 2026-03-01Epub Date: 2026-02-01DOI: 10.1016/j.jgar.2026.01.011
Juan Yuan , Yarong Yang , Yi Zhang , Jun Wang , Bin Xue , Fangzhi He , Wenjuan Zhao , Shuyue Tang , Zengguo Wang , Xinxin Zhu
Objective
To assess the efficacy and influencing factors of sulfamethoxazole–trimethoprim (SXT) in children with pertussis in regions with a high prevalence of macrolide-resistant Bordetella pertussis (MRBP).
Methods
A total of 317 PCR-confirmed pediatric pertussis cases treated with SXT were retrospectively analyzed. Patients were categorized into short-term (5–7 days, n = 93) and long-term (10–14 days, n = 65) treatment groups. Clinical outcomes, adverse events, and potential predictors of treatment response were analyzed.
Results
The median interval from symptom onset to SXT initiation was 12 days (IQR: 9–15). Following SXT therapy, 243 patients (76.7%) achieved clinical remission, 68 (21.4%) showed partial improvement, and 6 (1.9%) experienced no relief, without clinical deterioration. Multivariate analysis identified nucleic acid negative conversion as a independent predictor of clinical remission (OR, 5.14, 95% CI: 2.66–9.88, p < 0.001). Compared to the short-course group, the long-course group demonstrated significantly higher rates of both clinical remission (83.1% vs. 66.7%, p = 0.022) and nucleic acid clearance (87.7% vs. 71.0%, p = 0.013). No serious adverse events were reported. Skin lesions were the most frequent adverse events (5.1%), with no significant difference between groups (3.2% vs. 7.7%, p = 0.373).
Conclusions
SXT effectively alleviates clinical symptoms of pertussis in children in high MRBP prevalence regions. Nucleic acid negative conversion predicts clinical remission. An extended SXT course (10–14 days) demonstrates superior efficacy to a shorter course (5–7 days). No serious adverse events were observed; skin lesions were the most common side effect.
目的：评价磺胺甲恶唑-甲氧苄啶（SXT）在大环内酯耐药百日咳（MRBP）高发地区儿童百日咳的疗效及影响因素。方法：回顾性分析317例经pcr证实的小儿百日咳经sst治疗的病例。将患者分为短期治疗组（5 ~ 7天，n=93）和长期治疗组（10 ~ 14天，n=65）。分析临床结果、不良事件和治疗反应的潜在预测因素。结果：从症状出现到SXT开始的中位时间间隔为12天（IQR 9-15）。经SXT治疗后，243例（76.7%）患者临床缓解，68例（21.4%）患者部分改善，6例（1.9%）患者无缓解，无临床恶化。多变量分析发现核酸阴性转化是临床缓解的独立预测因子（OR 5.14, 95% CI 2.66-9.88, p < 0.001）。与短疗程组相比，长疗程组的临床缓解率（83.1%比66.7%,p=0.022）和核酸清除率（87.7%比71.0%,p=0.013）均显著高于短疗程组。无严重不良事件报告。皮肤损害是最常见的不良事件（5.1%），组间差异无统计学意义（3.2% vs. 7.7%, p = 0.373）。结论：SXT可有效缓解MRBP高发地区儿童百日咳的临床症状。核酸阴性转化预测临床缓解。延长SXT疗程（10-14天）比缩短疗程（5-7天）更有效。未观察到严重不良事件；皮肤损伤是最常见的副作用。
{"title":"Clinical efficacy of trimethoprim-sulfamethoxazole treatment for pediatric pertussis in macrolide-resistant endemic regions: A retrospective cohort study","authors":"Juan Yuan , Yarong Yang , Yi Zhang , Jun Wang , Bin Xue , Fangzhi He , Wenjuan Zhao , Shuyue Tang , Zengguo Wang , Xinxin Zhu","doi":"10.1016/j.jgar.2026.01.011","DOIUrl":"10.1016/j.jgar.2026.01.011","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the efficacy and influencing factors of sulfamethoxazole–trimethoprim (SXT) in children with pertussis in regions with a high prevalence of macrolide-resistant <em>Bordetella pertussis</em> (MRBP).</div></div><div><h3>Methods</h3><div>A total of 317 PCR-confirmed pediatric pertussis cases treated with SXT were retrospectively analyzed. Patients were categorized into short-term (5–7 days, <em>n</em> = 93) and long-term (10–14 days, <em>n</em> = 65) treatment groups. Clinical outcomes, adverse events, and potential predictors of treatment response were analyzed.</div></div><div><h3>Results</h3><div>The median interval from symptom onset to SXT initiation was 12 days (IQR: 9–15). Following SXT therapy, 243 patients (76.7%) achieved clinical remission, 68 (21.4%) showed partial improvement, and 6 (1.9%) experienced no relief, without clinical deterioration. Multivariate analysis identified nucleic acid negative conversion as a independent predictor of clinical remission (OR, 5.14, 95% CI: 2.66–9.88, <em>p</em> < 0.001). Compared to the short-course group, the long-course group demonstrated significantly higher rates of both clinical remission (83.1% vs. 66.7%, <em>p</em> = 0.022) and nucleic acid clearance (87.7% vs. 71.0%, <em>p</em> = 0.013). No serious adverse events were reported. Skin lesions were the most frequent adverse events (5.1%), with no significant difference between groups (3.2% vs. 7.7%, <em>p</em> = 0.373).</div></div><div><h3>Conclusions</h3><div>SXT effectively alleviates clinical symptoms of pertussis in children in high MRBP prevalence regions. Nucleic acid negative conversion predicts clinical remission. An extended SXT course (10–14 days) demonstrates superior efficacy to a shorter course (5–7 days). No serious adverse events were observed; skin lesions were the most common side effect.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 33-37"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105845","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 spread of high-risk extensively drug-resistant (XDR) Pseudomonas aeruginosa (Pa) clones is a global threat to public health. In Morocco, data on circulating clones and genomic features of Pa isolates are lacking. Accordingly, this study performed whole-genome sequencing (Illumina NextSeq500) of 18 Pa isolates from hospitals (n = 10) and the community (n = 8) to identify their sequence type (ST) affiliation, antimicrobial resistance determinants, virulence factors, and phylogenetic relationships.
Methods
Isolates were selected based on alarming resistance profiles from strains collected in Casablanca, Morocco, between January and December 2021.
Results
These isolates were assigned sequence type 773 (n = 11), 308 (n = 5), and 233 (n = 1), in addition to a novel ST4902 for one hospital isolate. Carbapenem resistance in hospital isolates was primarily attributed to acquired carbapenemases (NDM-1 in ST773 and ST308 clones). In contrast, resistance in one hospital (CSPa93) and one community isolate (cSPa43) was associated with mutations in the outer membrane protein. Fluoroquinolone resistance correlated with the carriage of qnrVC1 and crpP genes, along with mutations in the quinolone resistance-determining regions. The isolates also carried diverse aminoglycoside modifying enzymes and 16S rRNA methyltransferase genes. Genomic analysis also identified multiple virulence genes in these isolates, notably exoU in ST308 and ST773 isolates. Phylogenetic analysis further revealed hospital-adapted strains being genetically related to each other and to community strains.
Conclusion
This first genomic investigation of circulating XDR Pa clones in both hospital and community settings in Morocco using whole-genome sequencing highlights the urgent need for enhanced surveillance and targeted strategies to contain the spread of XDR high-risk clones.
{"title":"High-risk Pseudomonas aeruginosa clones ST308, ST773, and ST233 associated with carbapenem-resistant and extensively drug-resistant isolates from hospital and community settings in Casablanca, Morocco","authors":"Ihssane Benzaarate , Fatima El Otmani , Aboubakr Khazaz , Francois Lebreton , Sylvain Brisse , Kaotar Nayme","doi":"10.1016/j.jgar.2025.12.012","DOIUrl":"10.1016/j.jgar.2025.12.012","url":null,"abstract":"<div><h3>Objectives</h3><div>The spread of high-risk extensively drug-resistant (XDR) <em>Pseudomonas aeruginosa</em> (Pa) clones is a global threat to public health. In Morocco, data on circulating clones and genomic features of Pa isolates are lacking. Accordingly, this study performed whole-genome sequencing (Illumina NextSeq500) of 18 Pa isolates from hospitals (n = 10) and the community (n = 8) to identify their sequence type (ST) affiliation, antimicrobial resistance determinants, virulence factors, and phylogenetic relationships.</div></div><div><h3>Methods</h3><div>Isolates were selected based on alarming resistance profiles from strains collected in Casablanca, Morocco, between January and December 2021.</div></div><div><h3>Results</h3><div>These isolates were assigned sequence type 773 (n = 11), 308 (n = 5), and 233 (n = 1), in addition to a novel ST4902 for one hospital isolate. Carbapenem resistance in hospital isolates was primarily attributed to acquired carbapenemases (NDM-1 in ST773 and ST308 clones). In contrast, resistance in one hospital (CSPa93) and one community isolate (cSPa43) was associated with mutations in the outer membrane protein. Fluoroquinolone resistance correlated with the carriage of <em>qnrVC1</em> and <em>crpP</em> genes, along with mutations in the quinolone resistance-determining regions. The isolates also carried diverse aminoglycoside modifying enzymes and 16S rRNA methyltransferase genes. Genomic analysis also identified multiple virulence genes in these isolates, notably <em>exoU</em> in ST308 and ST773 isolates. Phylogenetic analysis further revealed hospital-adapted strains being genetically related to each other and to community strains.</div></div><div><h3>Conclusion</h3><div>This first genomic investigation of circulating XDR Pa clones in both hospital and community settings in Morocco using whole-genome sequencing highlights the urgent need for enhanced surveillance and targeted strategies to contain the spread of XDR high-risk clones.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 41-48"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917575","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 : 2026-03-01Epub Date: 2026-02-09DOI: 10.1016/j.jgar.2026.01.016
Ziyan Chen , Chunhua Peng , Fangrui Liang , Sailan Wang , Lu Lai , Qin Ai , Zaixing Chen , Shuai Zheng , Yanyan Liu , Xiaohui Huang
Objectives
This study sought to compare the pharmacokinetic-pharmacodynamic (PK/PD) targets of linezolid against methicillin-resistant Staphylococcus aureus (MRSA) in monotherapy versus combination with fosfomycin.
Methods
We assessed the antibacterial effect of linezolid plus fosfomycin, followed by determination of the mutant prevention concentrations (MPCs) under both individual and combined regimens. Next, using a neutropenic murine thigh infection model, we determined the pharmacokinetics of linezolid and evaluated its efficacy following administration as monotherapy or in combination with fosfomycin. PK/PD analysis was subsequently conducted using an Emax model. Finally, we compared the %fT>MPC (the percentage of the dosing interval during which free drug concentrations exceeded the MPC) of linezolid between its monotherapy and combination therapy with fosfomycin.
Results
Combination therapy enhanced bactericidal activity against MRSA and reduced the MPCs of the agents, thereby narrowing the mutant selection window (MSW). Addition of fosfomycin significantly improved linezolid efficacy in the MRSA thigh infection model. For linezolid, the fAUC/MIC values required for stasis, 1-log10 kill, and 2-log10 kill were 18.01, 47.87, and 225.07, respectively. When administered together, fosfomycin reduced the required fAUC/MIC of linezolid by 1.4–6.4-fold. At equivalent linezolid doses, combination therapy increased linezolid %fT>MPC by 1.7–4.8-fold.
Conclusions
Combined linezolid and fosfomycin therapy enhances in vivo anti-MRSA efficacy, reduces the risk of resistance emergence, and lowers the exposure requirements for linezolid.
{"title":"Pharmacokinetic/pharmacodynamic integration of linezolid alone and in combination with fosfomycin against methicillin-resistant Staphylococcus aureus in a neutropenic murine thigh infection model","authors":"Ziyan Chen , Chunhua Peng , Fangrui Liang , Sailan Wang , Lu Lai , Qin Ai , Zaixing Chen , Shuai Zheng , Yanyan Liu , Xiaohui Huang","doi":"10.1016/j.jgar.2026.01.016","DOIUrl":"10.1016/j.jgar.2026.01.016","url":null,"abstract":"<div><h3>Objectives</h3><div>This study sought to compare the pharmacokinetic-pharmacodynamic (PK/PD) targets of linezolid against methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) in monotherapy versus combination with fosfomycin.</div></div><div><h3>Methods</h3><div>We assessed the antibacterial effect of linezolid plus fosfomycin, followed by determination of the mutant prevention concentrations (MPCs) under both individual and combined regimens. Next, using a neutropenic murine thigh infection model, we determined the pharmacokinetics of linezolid and evaluated its efficacy following administration as monotherapy or in combination with fosfomycin. PK/PD analysis was subsequently conducted using an <em>E</em><sub>max</sub> model. Finally, we compared the %<em>f</em>T>MPC (the percentage of the dosing interval during which free drug concentrations exceeded the MPC) of linezolid between its monotherapy and combination therapy with fosfomycin.</div></div><div><h3>Results</h3><div>Combination therapy enhanced bactericidal activity against MRSA and reduced the MPCs of the agents, thereby narrowing the mutant selection window (MSW). Addition of fosfomycin significantly improved linezolid efficacy in the MRSA thigh infection model. For linezolid, the <em>f</em>AUC/MIC values required for stasis, 1-log<sub>10</sub> kill, and 2-log<sub>10</sub> kill were 18.01, 47.87, and 225.07, respectively. When administered together, fosfomycin reduced the required <em>f</em>AUC/MIC of linezolid by 1.4–6.4-fold. At equivalent linezolid doses, combination therapy increased linezolid %<em>f</em>T>MPC by 1.7–4.8-fold.</div></div><div><h3>Conclusions</h3><div>Combined linezolid and fosfomycin therapy enhances in vivo anti-MRSA efficacy, reduces the risk of resistance emergence, and lowers the exposure requirements for linezolid.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"47 ","pages":"Pages 64-72"},"PeriodicalIF":3.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165708","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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