JAC-Antimicrobial Resistance最新文献

{"title":"Incidence, characteristics and risk factors of tigecycline-induced hypoglycaemia: a retrospective study from the real world.","authors":"Bolin Zhu, Liang Liang, Di Chen, Yuanchao Zhu","doi":"10.1093/jacamr/dlaf076","DOIUrl":"10.1093/jacamr/dlaf076","url":null,"abstract":"<p><strong>Objectives: </strong>Tigecycline is widely used in clinic because of its broad spectrum of activity including activity against drug-resistance Gram-positive and -negative microorganisms. Hypoglycaemia is a rare but potentially fatal side effect during treatment with tigecycline. At present, data on tigecycline-induced hypoglycaemia are scarce, and there is a paucity of research summarizing the clinical characteristics and incidence rate of this uncommon adverse effect of tigecycline. The purpose of this study was to assess clinical characteristics and risk factors of tigecycline-associated hypoglycaemia.</p><p><strong>Method: </strong>We performed this retrospective single-centre study of inpatients with tigecycline-induced hypoglycaemia in China between 2018 and 2024. Clinical data were achieved by review of medical records, and patients who met the inclusion criteria but did not develop hypoglycaemia were assigned as controls.</p><p><strong>Results: </strong>We finally identified 14 patients with tigecycline-induced hypoglycaemia. The incidence rate of hypoglycaemia was 1.52% (14/922) in the study population. Tigecycline-induced hypoglycaemia can happen in patients with or without diabetes and develop independent of insulin or antidiabetic drugs. For patients of tigecycline-related hypoglycaemia, intravenous dextrose was effective in the restoration of euglycemia.</p><p><strong>Conclusions: </strong>Health professional should be aware of the potential hypoglycaemia risk and monitor blood glucose level during treatment with tigecycline. For patients developing hypoglycaemia, the blood glucose monitoring should be careful and continuous even after tigecycline withdrawal.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf076"},"PeriodicalIF":3.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of heteroresistance to multiple antibiotics in clinical <i>Klebsiella pneumoniae</i> isolates and combination therapeutic strategies.","authors":"Qiaoyu Zhang, Lirong Wen, Shanshan Li, Linwen Zheng, Yuli Nie, Jiansen Chen","doi":"10.1093/jacamr/dlaf071","DOIUrl":"10.1093/jacamr/dlaf071","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the prevalence of heteroresistance in 201 clinical isolates of <i>Klebsiella pneumoniae</i> to 16 clinically significant antibiotics. Furthermore, to investigate the interaction effects of combination antibiotic therapies for heteroresistant isolates.</p><p><strong>Methods: </strong>Isolates were pre-screened for growth of resistant subpopulations at resistant breakpoint concentrations for each isolate/antibiotic combination. Any strain containing colony growth at the resistant breakpoint was selected as a candidate heteroresistant strain, and population analysis profiling (PAP) tested for confirmation of HR phenotype. Dual PAP and time-kill assay were conducted to assess the efficacy of antibiotic combinations in suppressing resistant subpopulations.</p><p><strong>Results: </strong>Ninety-seven percent of isolates were shown to be heteroresistant to at least one antibiotic. Heteroresistance to at least two antibiotics was exhibited by 72.1% of strains. The prevalence of heteroresistance varied across antibiotics, with proportions ranging from 1.5% for imipenem to 85.1% for polymyxin B. The case of Kp486 was heteroresistant to amikacin, ceftazidime/avibactam, tigecycline and polymyxin B. The resistant subpopulations displayed distinct PAP curves and differences in growth and killing kinetics, indicating independent mechanisms for heteroresistance to each of the four antibiotics. Dual PAP experiments showed enhanced killing effects for combinations of antibiotics. In time-kill experiments, pairwise combinations of four drugs achieved a reduction of 3 to 6 logs within 6 h, preventing regrowth of resistant subpopulations. However, combinations with ampicillin did not enhance the activity of tigecycline, polymyxin B or ceftazidime/avibactam.</p><p><strong>Conclusions: </strong>Heteroresistance in clinical <i>K. pneumoniae</i> is common and can complicate treatment outcomes. The effects of combination antibiotic therapy depend on the heteroresistance of bacteria to both drugs.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf071"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between antibiotic use in hospitals and residual antibiotic concentrations in hospital effluents: a pilot study.","authors":"Fatima Zahra Deedat, Andile Mbuso Faya, Bhekumuzi Prince Gumbi, Deanne Mary Graham Johnston, Rajshekhar Karpoormath, Sabiha Yusuf Essack","doi":"10.1093/jacamr/dlaf070","DOIUrl":"10.1093/jacamr/dlaf070","url":null,"abstract":"<p><strong>Objective: </strong>To analyse the possible association between hospital antibiotic use and residual antibiotic concentrations in wastewater effluents, with the aim of evaluating wastewater surveillance as a potential alternative antimicrobial use monitoring system (AlAUMS).</p><p><strong>Methods: </strong>The study was conducted at a Regional Hospital in South Africa and followed an observational, quantitative and correlational design. The hospital use of selected antibiotics was determined using consumption data as a proxy and calculated using the WHO Anatomic Therapeutic Chemical (ATC) and DDD methodology. Selected antibiotics in the hospital effluent were analysed by solid-phase extraction (SPE) and quantified by GC-MS. Spearman's rank correlation coefficient and <i>P</i> values were calculated to determine the possible association between antibiotic use and residual antibiotic concentrations as an AlAUMS.</p><p><strong>Findings: </strong>The highest mean antibiotic use in the hospital was for oral sulfamethoxazole (6.71 DDD/100 bed days), followed by parenteral cefazolin (3.15 DDD/100 bed days). The highest mean antibiotic concentration in the hospital effluent was for sulfamethoxazole (34.57 μg/L) followed by cefazolin (25.32 μg/L). A strong positive correlation was observed for sulfamethoxazole (<i>R</i>s = 0.86) and a moderate positive correlation for cefazolin (<i>R</i>s = 0.50). However, none were statistically significant.</p><p><strong>Conclusions: </strong>The positive correlation displayed between the use of cefazolin and sulfamethoxazole and their concentrations in wastewater indicates a potential association between antibiotic use and residual antibiotic concentrations in hospital settings suggesting that wastewater surveillance is a promising proxy for conventional antibiotic use surveillance. Further studies are necessary to validate these results before wastewater surveillance can be implemented as an AlAUMS.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf070"},"PeriodicalIF":3.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic characterization of multidrug-resistant tuberculosis in Shanghai, China: antibiotic resistance, virulence and transmission.","authors":"Yang Guo, Jing Lu, Peipei Jin, Zhipeng Qiu, Fangyou Yu, Yan Zhu, Jiayuan Huang","doi":"10.1093/jacamr/dlaf064","DOIUrl":"10.1093/jacamr/dlaf064","url":null,"abstract":"<p><strong>Objectives: </strong>Whole-genome sequencing (WGS) was employed to investigate antibiotic resistance, virulence and transmission profiles of multidrug-resistant tuberculosis (MDR-TB) isolates from Shanghai, China.</p><p><strong>Methods: </strong>A total of 306 MDR-TB clinical isolates were collected from Shanghai Pulmonary Hospital and underwent phenotypic drug susceptibility testing (DST) for common anti-TB drugs and WGS. Combined 778 published bacterial sequences, we performed phylogenetic analysis, resistance and virulence gene identification to understand the genetic relationships and resistance mechanisms among those strains.</p><p><strong>Results: </strong>WGS determination, supported by DST, revealed high resistance rates for isoniazid (83.66%) and rifampicin (90.20%) among the MDR-TB isolates. Key resistance-associated mutations included <i>katG</i> Ser315Thr for isoniazid, <i>rpoB</i> mutations for rifampicin, and <i>embB</i> Met306Val for ethambutol. WGS demonstrated >90% concordance with culture-based DST for most drugs, except ethambutol that showed a 76.80% concordance. Analyses of virulence factors and phylogenetics revealed the genetically homogeneous, endemic MDR-TB population in Shanghai, with no evidence of recent transmission.</p><p><strong>Conclusions: </strong>This study highlights the genetic homogeneity and endemic nature of MDR-TB in Shanghai, providing insights into key resistance mechanisms of TB.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf064"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking Antimicrobial Resistant Organisms Timely: a workflow validation study for successive core-genome SNP-based nosocomial transmission analysis.","authors":"Kotaro Aoki, Kohji Komori, Tetsuo Yamaguchi, Sohei Harada, Mayumi Tsukada, Hinako Murakami, Kazuhiro Tateda","doi":"10.1093/jacamr/dlaf069","DOIUrl":"10.1093/jacamr/dlaf069","url":null,"abstract":"<p><strong>Background and objectives: </strong>Effective infection prevention and control (IPC) interventions in hospitals require timely information to determine the potential transmission of antimicrobial-resistant (AMR) organisms. We proposed and developed a successive core-genome SNP (cgSNP)-based phylogenetic analysis workflow, 'Tracking Antimicrobial Resistant Organisms Timely' (TAROT), using the Oxford Nanopore Technologies (ONT) sequencer for MRSA, and compared the results with those obtained using the Illumina sequencer.</p><p><strong>Methods: </strong>We have developed a TAROT workflow for successive phylogenetic analysis using ONT data. We sequenced 34 MRSA strains isolated from Toho University Omori Medical Center using MinION (ONT) and MiSeq (Illumina). Each strain's ONT data were inputted into TAROT (TAROT-ONT), and successive cgSNP-based phylogenetic analyses were conducted. Illumina data were processed with a batched cgSNP-based phylogenetic analysis. Assembly-based analysis identified AMR genes, AMR mutations and virulence genes.</p><p><strong>Results: </strong>MinION generated an average sequence depth of 262× for the ST8 reference genome within 3 h. TAROT-ONT successively generated 11 phylogenetic trees for 14 ST8 strains, 7 trees for 10 ST1 strains and 2 trees for 5 ST5 strains. Highly suspected transmission pairs (pairwise cgSNP< 5) were detected in trees #6 through #11 for ST8, trees #3, #5 and #7 for ST1, and tree #2 for ST5. Differences in pairwise cgSNP value between TAROT-ONT and Illumina ranged from zero to two within pairs with fewer than 20 cgSNPs using Illumina. TAROT-ONT bioinformatic analysis for each strain required 5-42 min. The identification of AMR genes, mutations and virulence genes showed high concordance between ONT and Illumina.</p><p><strong>Conclusions: </strong>TAROT-ONT can facilitate effective IPC intervention for MRSA nosocomial transmissions by providing timely feedback through successive phylogenetic analyses based on cgSNPs.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf069"},"PeriodicalIF":3.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility of 24 h continuous-infusion cefiderocol administered by elastomeric pump in attaining an aggressive PK/PD target in the treatment of NDM-producing <i>Klebsiella pneumoniae</i> otomastoiditis.","authors":"Stella Babich, Pier Giorgio Cojutti, Milo Gatti, Federico Pea, Stefano Di Bella, Jacopo Monticelli","doi":"10.1093/jacamr/dlaf066","DOIUrl":"10.1093/jacamr/dlaf066","url":null,"abstract":"<p><strong>Objectives: </strong>Cefiderocol has emerged as a key treatment for managing MDR infections, and its time-dependent pharmacodynamics are optimized by prolonged infusion to maintain time above the MIC (<i>T</i> _> MIC). Whereas recent stability studies have shown cefiderocol remains stable up to 72 h in elastomeric pumps, its use in 24 h continuous infusions (CIs) for outpatient parenteral antibiotic therapy (OPAT) is undocumented. This case highlights its suitability for 24 h CI via elastomeric pumps in an OPAT setting, supported by therapeutic drug monitoring (TDM) to ensure optimal treatment efficacy.</p><p><strong>Patient/case description: </strong>A 31-year-old male developed right-sided otomastoiditis caused by <i>Klebsiella pneumoniae</i> producing New Delhi MBL (NDM). Given the resistance profile and the need for prolonged therapy, cefiderocol was initiated at a daily dose of 6 g, administered by 24 h CI using an elastomeric pump. TDM was performed on Days 17 and 45 to assess plasma concentrations.</p><p><strong>Results: </strong>TDM confirmed steady-state concentrations (<i>C</i> _ss 25.2-28.1 mg/L), achieving optimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment such as 100% <i>T</i> _{> 4-6 MIC} (free [<i>f</i>]<i>C</i> _ss/MIC 10.58-11.80). Significant clinical improvement avoided the need for planned surgery, with no adverse events reported from the venous catheter, antibiotic therapy or elastomeric pump.</p><p><strong>Conclusions: </strong>This approach underscores the feasibility and efficacy of cefiderocol administered by 24 h CI by means of an elastomeric pump and supported by real-time TDM in achieving an aggressive PK/PD target for the treatment of otomastoiditis due to NDM-producing <i>K. pneumoniae</i>.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf066"},"PeriodicalIF":3.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significant reduction in antibiotic prescription rates in Japan following implementation of the national action plan on antimicrobial resistance (2016-20): a 9-year interrupted time-series analysis.","authors":"Hideki Hashimoto, Naoki Kanda, Hiromasa Yoshimoto, Kazuo Goda, Naohiro Mitsutake, Shuji Hatakeyama","doi":"10.1093/jacamr/dlaf062","DOIUrl":"10.1093/jacamr/dlaf062","url":null,"abstract":"<p><strong>Background: </strong>Research on the effectiveness of Japan's national action plan on antimicrobial resistance, including among individuals with HIV, remains scarce.</p><p><strong>Objectives: </strong>To evaluate the impact of policies on antibiotic prescription practices.</p><p><strong>Methods: </strong>Outpatient oral antibiotic prescription data from 2012 to 2020 were extracted from a national claims database comprising >98% of the Japanese population. Prescription rates were stratified according to antibiotic class, diagnosis and HIV status. An interrupted time-series analysis was performed to assess the impact of the national action plan.</p><p><strong>Results: </strong>An average of 129,989,400 prescriptions were issued annually (1024 per 1000 population-years). Between 2012 and 2020, the oral antibiotic prescription rate decreased by 54%. The prescription rate showed a significant downward trend post-intervention (additional annual reduction in incidence rate ratio, 0.889; 95% confidence interval, 0.889-0.990). However, broad-spectrum antibiotics (third-generation cephalosporins, macrolides and fluoroquinolones) remained prevalent, comprising 84.7% and 71.4% of prescriptions in 2012 and 2020, respectively. Antibiotic prescriptions during outpatient visits for pharyngitis, sinusitis, bronchitis and viral upper respiratory infections decreased significantly (rate ratios = 0.66, 0.76, 0.51 and 0.49, respectively). The antibiotic prescription rate was ∼2.5-fold higher in individuals with HIV than in those without.</p><p><strong>Conclusions: </strong>Antibiotic prescription rates significantly decreased following the implementation of the national action plan. However, a sharp decline in 2020, likely due to the coronavirus disease pandemic, requires continued rebound monitoring. Reducing broad-spectrum oral antibiotic overuse remains a critical focus.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf062"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The S862C amino acid change in CpMrr1 confers fluconazole resistance in <i>Candida parapsilosis</i>.","authors":"Iacopo Franconi, Noemi Poma, Cosmeri Rizzato, Lorenzo Maltinti, Marco Falcone, Arianna Tavanti, Antonella Lupetti","doi":"10.1093/jacamr/dlaf051","DOIUrl":"10.1093/jacamr/dlaf051","url":null,"abstract":"<p><strong>Background: </strong><i>Candida parapsilosis</i> is an opportunistic pathogen with increasing rates of resistance to fluconazole and voriconazole. Recently, in an outbreak at the Azienda Ospedaliero-Universitaria Pisana, a new amino acid substitution, S862C in the CpMrr1 protein, was found only in azole-resistant strains. The contribution of this mutation to the acquisition of an azole-resistant phenotype was investigated in this study.</p><p><strong>Methods: </strong>Antifungal resistance in <i>C. parapsilosis</i> clinical strains isolated from the outbreak (<i>n</i> = 16) was tested by the broth microdilution method and Etest strip. WGS and Sanger sequencing analyses were used for the detection of SNPs. A CRISPR-Cas9-based genome editing strategy was used to induce the C2585G substitution in the <i>CpMRR1</i> gene of susceptible <i>C. parapsilosis</i> isolates to investigate its role in the acquisition of azole resistance.</p><p><strong>Results: </strong>The A395T and the newly found C2585G substitution in the <i>CpMRR1</i> gene were present in all resistant isolates, but not in the susceptible ones. Such mutations were later induced in the <i>C. parapsilosis</i> reference strain ATCC 22019 and in two azole-susceptible clinical isolates in homozygosis, and in heterozygosis only for ATCC 22019 and one azole-susceptible clinical isolate. Both heterozygous and homozygous mutants carrying the C2585G mutation were fluconazole resistant, with some clones also presenting intermediate susceptibility or resistance to voriconazole.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study to report the effect on azole resistance of a novel C2585G nucleotide substitution in the <i>CpMRR1</i> gene found in clinical isolates recovered during an outbreak of azole-resistant <i>C. parapsilosis</i> in a healthcare setting.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf051"},"PeriodicalIF":3.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-carriage of diverse vancomycin-resistant <i>Enterococcus faecium</i> ST80-lineages by 70% of patients in an Irish hospital.","authors":"Nicole L Kavanagh, Peter M Kinnevey, Grainne I Brennan, Brian O'Connell, Richard V Goering, David C Coleman","doi":"10.1093/jacamr/dlaf065","DOIUrl":"10.1093/jacamr/dlaf065","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin-resistant <i>Enterococcus faecium</i> (VREfm) are significant nosocomial pathogens. Irish VREfm comprise diverse <i>vanA</i>-encoding ST80-complex type (CT) lineages. Recent studies indicate that within-patient VREfm diversity could confound surveillance. This study investigated the intra-host VREfm genetic diversity among colonized Irish hospital patients.</p><p><strong>Methods: </strong>Rectal VREfm (<i>n</i> = 150) from 10 patients (15 isolates each) were investigated by WGS, core-genome MLST and split <i>k-mer</i> (SKA)-SNP analysis. Plasmids and <i>vanA</i>-transposons from 39 VREfm representative of CTs identified were resolved by hybrid assembly of short-read (Illumina) and long-read (Oxford Nanopore Technologies) sequences. Plasmid relatedness was assessed based on Mash distances. Thirty vancomycin-susceptible <i>E. faecium</i> (VSEfm) from four VREfm-positive patients were also investigated.</p><p><strong>Results: </strong>All isolates were clade A1 and most were ST80 (VREfm, 147/150; VSEfm, 25/30). Seventy-percent of patients (7/10) harboured either two (<i>n</i> = 4), three (<i>n</i> = 2) or four (<i>n</i> = 1) VREfm CTs. Individual patient isolate pairs from different CTs differed significantly (median SKA-SNPs 2933), but differences were minimal between isolate pairs of the same CT (median SKA-SNPs 0). In total, 193 plasmids were identified in 39 VREfm investigated. Near-identical plasmids (≥99.5% average nucleotide identity) were identified in divergent CTs from multiple patients. Most VREfm (28/39, 72%) harboured <i>vanA</i> on closely related transferable, linear plasmids. Divergent CTs within individual patients harboured either indistinguishable <i>vanA</i>-transposons or <i>vanA</i>-transposons with distinct organizational iterations. Four VSEfm from different CTs investigated harboured similar plasmids to VREfm.</p><p><strong>Conclusion: </strong>VREfm within-host diversity is highly prevalent in Irish hospital patients, which complicates surveillance. Linear plasmids play an important role in the emergence of Irish VREfm.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 3","pages":"dlaf065"},"PeriodicalIF":3.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1 cross-resistance to second-generation non-nucleoside reverse transcriptase inhibitors among individuals failing antiretroviral therapy in Cameroon: implications for the use of long-acting treatment regimens in low- and middle-income countries.","authors":"Davy-Hyacinthe Gouissi Anguechia, Yagai Bouba, Ezechiel Ngoufack Jagni Semengue, Desire Takou, Collins Ambe Chenwi, Vincent Kamaël Mekel, Grace Angong Beloumou, Alex Durand Nka, Aude Christelle Ka'e, Sandrine Claire Ndjeyep Djupsa, Vittorio Colizzi, Nicaise Ndembi, Alexis Ndjolo, Dora Mbanya, Carlo-Federico Perno, Joseph Fokam","doi":"10.1093/jacamr/dlaf059","DOIUrl":"https://doi.org/10.1093/jacamr/dlaf059","url":null,"abstract":"<p><strong>Background: </strong>Several long-acting antiretroviral treatment regimens contain second-generation non-nucleoside reverse transcriptase inhibitors (2ndGenNNRTI). As first-generation NNRTIs (1stGenNNRTI) exhibit some cross-resistance with 2ndGenNNRTI, we sought to evaluate the rate of acquired cross-resistance to 2ndGenNNRTI and its determinants at treatment failure in a typical low- and middle-income country (LMIC) such as Cameroon.</p><p><strong>Patients and methods: </strong>A facility-based cross-sectional study was conducted among patients failing first-/second-line regimens between 2019 and 2023 in Cameroon. HIV-1 Sanger sequencing was performed on plasma and resistance-associated mutations (RAMs) to etravirine, rilpivirine and doravirine were interpreted using HIVdb program v.9.5.0 (HIVdb penalty scores were,  ≥60, high resistance; 15-59, intermediate resistance and  <15, susceptible) and the IAS-USA 2022 list.</p><p><strong>Results: </strong>Overall, 653 individuals previously exposed to 1stGenNNRTI were enrolled [median (IQR) age 39 (26-46) years and viraemia 59 370 (10 442-244 916) copies/mL]. Importantly, 361 participants were on 1stGenNNRTI-based first-line and 292 on protease inhibitor-based second-line regimen. NNRTIs RAMs were found in up to 90.64% of individuals, with 36.45% having more than three RAMs. Concerning 2ndGenNNRTIs, 77.18% of individuals harboured RAMs conferring high or intermediate-level resistance, with the predicted efficacy of etravirine, doravirine and rilpivirine being 47.17%, 33.23% and 32.31%, respectively. Major 2ndGenNNRTIs RAMs were driven by Y181C (23.74%), K101E (8.57%), Y188L (8.42%) and H221Y (8.42%), while minor RAMs were A98G (18.83%), G190A (18.68%) and P225H (14.70%). A higher prevalence of RAMs was observed in those failing first-line versus second line (81.71% versus 71.57%, respectively, <i>P</i> < 0.001), driven predominantly by the difference in doravirine-RAMs [first line (72.85%) versus second line (59.58%), <i>P</i> < 0.001].</p><p><strong>Conclusions: </strong>Among patients failing treatment in Cameroon, there is a high-level of cross-resistance to 2ndGenNNRTI due to wide exposure to 1stGenNNRTI. Thus, in LMICs sharing similar programmatic features, the use of NNRTI-sparing regimens should be prioritized as a public health approach, while second-generation-NNRTI long-acting regimens should be guided by genotyping or for clients without previous exposure to NNRTIs.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 2","pages":"dlaf059"},"PeriodicalIF":3.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}