Antimicrobial Agents and Chemotherapy最新文献

{"title":"Increase of macrolide resistance among <i>Streptococcus pyogenes</i> pharyngitis driven by a <i>mef</i>(A)-<i>msr</i>(D)/<i>emm</i>2-ST55 lineage in Portugal (2014-2019).","authors":"Ana Friães, Rafael Mamede, Beatriz Santos, Gina Marrão, José Melo-Cristino, Mario Ramirez","doi":"10.1128/aac.00968-25","DOIUrl":"https://doi.org/10.1128/aac.00968-25","url":null,"abstract":"<p><p>Increases in macrolide resistance occurred recently among <i>Streptococcus pyogenes</i> (Group A <i>Streptococcus</i>, GAS) in some countries. While the importance of monitoring the clinical and molecular epidemiology of non-invasive GAS is increasingly recognized, most surveillance focuses on invasive infections, since culture is rarely performed in tonsillo-pharyngitis. We determined the antimicrobial susceptibility and characterized the macrolide-resistant lineages of 2,002 pharyngeal isolates recovered in a Portuguese hospital in 2014-2019. There were seasonal variations in the numbers of recovered isolates, with peaks shifting between March-July and October-December, but consistently low numbers in August and September. Macrolide-resistant and macrolide-susceptible GAS presented independent seasonal and clonal dynamics, with resistant isolates showing lower genetic diversity and minimal overlap with susceptible lineages. Overall, 84 (4%), 77 (4%), and 52 (3%) isolates were resistant to erythromycin, clindamycin, and tetracycline, respectively. Until 2018, macrolide resistance was mainly due to an internationally disseminated <i>emm</i>77-ST63 lineage carrying <i>erm</i>(A) and <i>tet</i>(O) in ICE<i>Sp2905</i> and an <i>emm</i>75-ST49 lineage carrying <i>mef</i>(A)-<i>msr</i>(D) in a novel ɸ1207.3 variant. In 2019, resistance peaked at 9% due to the rapid expansion of <i>mef</i>(A)-<i>msr</i>(D)-positive <i>emm</i>2-ST55 isolates, replacing previous lineages. Other minor resistant lineages carried mostly <i>erm</i>(B) in a diversity of mobile genetic elements, including <i>emm</i>75-ST150, <i>emm</i>9-ST75, <i>emm</i>11-ST403, <i>emm</i>12-ST36, <i>emm</i>76-ST50, and <i>emm</i>77-ST399 [<i>erm</i>(T)]. Tetracycline resistance was associated with the genes <i>tet</i>(M) and <i>tet</i>(O), in most cases co-located in the same genetic elements as the <i>erm</i> genes. This study reveals clonal changes among macrolide-resistant GAS driving fluctuations in macrolide resistance and associated phenotypes.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0096825"},"PeriodicalIF":4.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olorofim activity against multidrug-resistant <i>Fusarium</i> unveils intra-species and inter-species variability.","authors":"Ruoning Xue, Shenghan Gao, Sybren de Hoog, Anne van Diepeningen, Shaoqin Zhou, Tianyi Xu, Like Fokkens, Ruoyu Li, Lin Bai, Zhe Wan, Paul E Verweij, Yinggai Song","doi":"10.1128/aac.00961-25","DOIUrl":"https://doi.org/10.1128/aac.00961-25","url":null,"abstract":"<p><p>Fungi in the genus <i>Fusarium</i> are plant pathogens but are also capable of causing a wide range of diseases in humans. The intrinsic multi-drug resistance of <i>Fusarium</i> often leads to a poor clinical outcome in patients with severe immune disorders. Olorofim, a member of the orotomide class, is a novel type of antifungal drug that interferes with pyrimidine biosynthesis by inhibiting dihydroorotate dehydrogenase and thereby prevents growth and cell division. In this study, the <i>in vitro</i> activity of olorofim was evaluated against 253 <i>Fusarium</i> isolates, of which 228 isolates belonging to the prevalent complexes involved in human infection, <i>F. solani</i> species complex (SC) and <i>F. fujikuroi</i> SC. All <i>Fusarium</i> isolates underwent species-level identification via multi-locus sequence typing (MLST) targeting <i>RPB1</i>, <i>RPB2</i>, and <i>TEF1</i> loci. Antifungal susceptibility testing was performed using a CLSI M38, 3rd ed. broth microdilution for olorofim. The geometric mean of the MICs of olorofim for all 253 isolates was 0.581 µg/mL, ranging from 0.015 µg/mL to >16 µg/mL. Olorofim demonstrated high MICs against <i>F. solani</i> SC, whereas greater potency (lower MICs) was observed against <i>F. fujikuroi</i> SC. Clinical isolates tended to have higher MIC values than environmental isolates, but this pattern was not consistent across all species complexes. Overall, olorofim demonstrated moderate <i>in vitro</i> activity against <i>Fusarium</i> isolates, suggesting it might be a potential candidate for treating fusarioses caused by multidrug-resistant strains.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0096125"},"PeriodicalIF":4.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> evolution of durlobactam resistance in NDM-producing <i>Escherichia coli</i> due to a single mutation in <i>mrdA</i> encoding penicillin-binding protein 2.","authors":"Christi L McElheny, Erika L Butcher, Akito Kawai, Robert M Q Shanks, Ryan K Shields, Yohei Doi","doi":"10.1128/aac.01014-25","DOIUrl":"https://doi.org/10.1128/aac.01014-25","url":null,"abstract":"<p><p>Durlobactam, a diazabicyclooctane β-lactamase inhibitor, exhibits direct antibacterial activity by binding to penicillin-binding protein 2 (PBP2). We generated a mutant strain of New Delhi metallo-β-lactamase-producing <i>Escherichia coli</i> with a durlobactam minimum inhibitory concentration of 2 µg/mL, representing a 16-fold increase from baseline, by exposing it to increasing concentrations of durlobactam. Resistance was attributed to a point mutation in the <i>mrdA</i> gene, resulting in a V522I substitution in PBP2.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0101425"},"PeriodicalIF":4.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of cefiderocol in combination with xeruborbactam versus taniborbactam against cefiderocol-resistant NDM-producing <i>Pseudomonas aeruginosa</i>.","authors":"Kaan Kocer, Truong Nhat My, Bui Tien Sy, Lisa Göpel, Thirumalaisamy P Velavan, Le Huu Song, Silke Peter, Sébastien Boutin, Adesola Olalekan, Dennis Nurjadi","doi":"10.1128/aac.00857-25","DOIUrl":"https://doi.org/10.1128/aac.00857-25","url":null,"abstract":"<p><p>We evaluated the <i>in vitro</i> activity of cefiderocol in combination with either taniborbactam or xeruborbactam against cefiderocol-resistant, <i>bla</i>_NDM-positive <i>Pseudomonas aeruginosa</i> clinical isolates from Vietnam and Nigeria. Taniborbactam restored cefiderocol susceptibility in most isolates (20/21, 95.2%), while xeruborbactam had no effect. Resistance was reversed by dipicolinic acid, which confirmed New-Delhi Metallo-β-Lactamase (NDM-mediated) resistance. One isolate that was unresponsive to taniborbactam carried multiple copies of <i>bla</i>_NDM-1. These findings highlight the species-specific limitations of xeruborbactam in <i>P. aeruginosa</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0085725"},"PeriodicalIF":4.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic epidemiology of Colombian resistant <i>Candida auris</i> isolates.","authors":"Maira Lyseth Alvarado Casas, Jeisson Alejandro Triana Díaz, Efrain Montilla-Escudero, Diego Andrés Prada Cardozo, Patricia Escandón Hernández","doi":"10.1128/aac.00725-25","DOIUrl":"https://doi.org/10.1128/aac.00725-25","url":null,"abstract":"<p><p>Since 2016, <i>Candida auris</i> has been subject to mandatory reporting in Colombia due to its critical public health implications. In this context, a genomic characterization of clinical <i>C. auris</i> isolates collected between 2018 and 2024 through national surveillance led by the Instituto Nacional de Salud (INS) was conducted. Twenty-seven isolates from hospitalized patients across 14 departments were analyzed using next-generation sequencing (NGS) and bioinformatics tools (MycoSNP-nf v1.5, TheiaEuk BLAST, Python script, and MUSCLE, snp_phylogeny) to identify mutations associated with antifungal resistance. The patient group was predominantly male <i>n</i> = 18 (66.7%), with 48% (<i>n</i> = 13) for the older adult age group (>60 years of age). Antifungal susceptibility testing (anidulafungin, fluconazole, and amphotericin B) revealed that five isolates (18.5%) were resistant to a single antifungal, while 22 (81.5%) were resistant to two. All isolates belonged to clade IV (South America) and exhibited genetic divergence ranging from 5 to 127 single-nucleotide polymorphisms (SNPs). Mutations in the <i>ERG11</i> gene were identified in 16 isolates, including Y132F (<i>n</i> = 11), G459S (<i>n</i> = 1), K143R (<i>n</i> = 2), and F444L (<i>n</i> = 1), along with a novel mutation, G445D (<i>n</i> = 1). Four of these 16 isolates also harbored mutations in the <i>TAC1B</i> gene (P595H, <i>n</i> = 3; S611P, <i>n</i> = 1), and one isolate carried a single <i>TAC1B</i> mutation (S195G). Additionally, three isolates presented the S639F mutation in the <i>FKS1</i> gene. Notably, seven isolates showed phenotypic resistance without any known resistance mutations. These findings are concerning, as the antifungals involved are critical for treating invasive <i>Candida</i> infections. The study highlights the need for ongoing genomic surveillance to complement phenotypic testing and enhance strategies for antifungal resistance control, ultimately informing therapeutic decision-making and drug development.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0072525"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> and <i>in vivo</i> study of the inhibition of ubiquinone biosynthesis in <i>Leishmania (Leishmania) amazonensis</i> using the combination of buparvaquone and 4-nitrobenzoate as a strategy for the discovery of new therapeutic targets.","authors":"Juliana Tonini Mesquita, Gabriel Cândido Moura, Tainá Cavalcante, Jenicer Kazumi Umada Yokoyama Yasunaka, Manoel Aparecido Peres, Claudia Blanes Angeli, Noemi Nosomi Taniwaki, Beatriz Simonsen Stolf, Giuseppe Palmisano, Alejandro Miguel Katzin","doi":"10.1128/aac.00824-25","DOIUrl":"https://doi.org/10.1128/aac.00824-25","url":null,"abstract":"<p><p>Leishmaniasis is a parasitic disease caused by several species of the genus <i>Leishmania,</i> considered one of the most dangerous neglected tropical diseases in the world. Treatment options are limited and toxicity exists, requiring an urgent search for new therapies. <i>Leishmania</i> differs from mammalian cells by having unique mitochondria, which have been considered an important therapeutic target. Ubiquinone is found in the inner membrane of mitochondria and plays a critical role in the electron transport chain, which is essential for cell viability. The combination of buparvaquone and 4-nitrobenzoate seems an interesting option due to their action on these targets. The aim of the present work was to investigate the effects of this combination against <i>Leishmania (Leishmania) amazonensis</i> infections <i>in vitro</i> and <i>in vivo</i> and to elucidate the possible mechanism of action of 4-nitrobenzoate. The results showed that the drug combination tested in promastigotes has an additive or indifferent effect. In the intracellular amastigotes, when buparvaquone was tested with fixed concentrations of 4-nitrobenzoate, concentrations that had no effect alone potentiated the effect of buparvaquone by two to four times. The mechanism of action of 4-nitrobenzoate in promastigote forms suggests a reduction in ubiquinone 6 levels, an alteration in mitochondrial membrane potential, and an increase in reactive oxygen species. <i>In vivo</i> treatment with a topical formulation (buparvaquone 0.1% and 4-nitrobenzoate 0.1%) in infected mice showed a reduction in parasite burden of 57% compared to the control group, suggesting that this combination may represent a promising therapeutic strategy for future treatment of this disease.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0082425"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TLR7 agonist vesatolimod does not measurably induce SIV expression in macaques receiving combination antiretroviral therapy initiated during chronic infection.","authors":"Adrienne E Swanstrom, Kelli Oswald, Randy Fast, Rebecca Shoemaker, James A Thomas, Cathi Pyle, Michael Hull, William J Bosche, Yuan Li, Matthew W Breed, Joshua A Kramer, Duncan Donohue, Charles M Trubey, Claire Deleage, Romas Geleziunas, Jeffrey D Lifson, Gregory Q Del Prete","doi":"10.1128/aac.01073-25","DOIUrl":"https://doi.org/10.1128/aac.01073-25","url":null,"abstract":"<p><p>Lim et al. previously reported that TLR7 agonist (Vesatolimod [VES] or the related compound GS-986) administration to SIVmac251-infected macaques receiving combination antiretroviral therapy (cART) led to transient plasma viral load (PVL) increases, viral DNA (vDNA) reductions in blood and tissues, and, in some animals, extended viral remission after treatment cessation (S. Y. Lim, C. E. Osuna, P. T. Hraber, J. Hesselgesser, et al., Sci Transl Med 10:eaao4521, 2018, https://doi.org/10.1126/scitranslmed.aao4521). However, in multiple subsequent studies, TLR7 agonist administration in SIV or SHIV-infected macaques on cART did not induce measurable virus expression. Notably, these studies utilized earlier cART initiation, lengthier cART treatment before TLR7 agonist administration, different sampling time points, and/or less sensitive virologic assays compared to the Lim study. We hypothesized that study design and assay differences may have led to these apparently discrepant results due to quantitative or qualitative differences in the established viral reservoirs and/or a reduced capacity to detect virus induction. To more closely capture the Lim study conditions, we initiated cART at 65 days post-infection in 10 SIVmac239M-infected rhesus macaques. Six received VES (0.15 mg/kg orally, every 2 weeks for six doses), while four received vehicle control. Although VES treatment induced expected transient increases in interferon-stimulated gene expression and immune cell phenotypic changes, it did not lead to measurable PVL increases in peripheral or hepatic portal vein blood using a highly sensitive PVL assay or increases in cell-associated vRNA:vDNA ratios, nor to measurable reductions in vDNA in blood or tissues. These results align with recent clinical data and confirm that TLR7 agonist treatment does not reliably induce significant virus expression <i>in vivo</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0107325"},"PeriodicalIF":4.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefazolin population pharmacokinetics in children undergoing maintenance hemodialysis for kidney failure.","authors":"Romain Berthaud, Saïk Urien, Saoussen Krid, Frantz Foissac, Mehdi Oualha, Michaël Thy, Olivia Boyer, Agathe Béranger, Déborah Hirt, Sihem Benaboud, Jean-Marc Tréluyer, Naïm Bouazza","doi":"10.1128/aac.00451-25","DOIUrl":"https://doi.org/10.1128/aac.00451-25","url":null,"abstract":"<p><p>We aimed to develop a population pharmacokinetic model of cefazolin in children undergoing maintenance hemodialysis for kidney failure and simulate dosing regimens to optimize patients' exposure. Cefazolin plasma concentrations were quantified using high-performance liquid chromatography. A non-linear mixed-effect modeling approach was used to investigate cefazolin pharmacokinetics. Optimal dosing regimens were determined using Monte Carlo simulations targeting 100% of the time a free plasma concentration four times above the minimum inhibitory concentration (MIC) and total plasma concentration less than 80 mg/L (100% fT > 4 × MIC and <i>C</i> < 80 mg/L). Eighty-three samples were analyzed from six patients aged 1.3-14.6 years and weighing 11.4-51 kg. A one-compartment model with first-order elimination best fitted the data, with a significant between-subject variability (BSV). Body weight (BW), using the allometric rule, was a significant predictor of residual elimination clearance (CL) and volume of distribution (Vd), while dialysis membrane surface area (DMSA) explained almost all the BSV on dialysis clearance (CLdial). The parameter relationships were Vd_<i>i</i>(L) = 14.6 × (BW<i>_i</i>/70), CL_i(L/h) = 0.186 × (BW<i>_i</i>/70)^0.75, CLdial_<i>i</i>(L/h)=1.98 × (DMSA<i>_i</i>/1)^1.26, CLtot_i = CL<i>_i +</i> CLdial_DMSA<i>_i</i>, where the subscript <i>i</i> denotes the <i>i</i>^th patient's covariate value. Dosing regimens were simulated for six CL ranges, targeting two concentration intervals: 40-80 mg/L and 20-80 mg/L for MIC of 2 and 1 mg/L, respectively. In children on maintenance hemodialysis for kidney failure, due to the persistence of a large unexplained BSV on CL that substantially affects them, optimal dosing regimen would not be accurately determined a priori and should be individually determined using therapeutic drug monitoring, taking BW, DMSA, and CL into account.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT02539407.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0045125"},"PeriodicalIF":4.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic blockade of <i>Pseudomonas aeruginosa</i> type III secretion by a monoclonal antibody targeting the pore size-determining domain of PcrV.","authors":"Yu Zhang, Shiyu Guo, Liwen Jiang, Siqi Wang, Weitong Hou, Xiran Qiu, Hui Shen, Maomao An","doi":"10.1128/aac.00405-25","DOIUrl":"10.1128/aac.00405-25","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> bloodstream infections carry mortality rates exceeding 60%, with escalating antibiotic resistance dramatically limiting therapeutic options. The type III secretion system (T3SS), a virulence apparatus delivering cytotoxic effectors via PcrV-dependent translocation pores, represents a therapeutic target. Here, we developed a monoclonal antibody (5C8) targeting the central domain (H106-D173) of PcrV, which regulates translocation pore size. 5C8 demonstrated sub-nanomolar affinity (KD = 0.32 nM) via biolayer interferometry and broad neutralization efficacy against clinical isolates (IC₅₀: 0.32-1.47 μg/mL). In murine bloodstream infection models, 5C8 conferred improved survival against cytotoxic (<i>exoU⁺</i>) and invasive (<i>exoS⁺</i>) strains (<i>P</i> < 0.01 vs controls), reducing bacterial loads in lungs/kidneys by 1.5-log₁₀ colony-forming unit (<i>P</i> < 0.01) and suppressing interleukin-6 levels by 60-82% (<i>P</i> < 0.01). Mechanistic studies revealed 5C8's dual action: blocking effector release (ExoU/ExoT reduced by 41-88% via liquid chromatography-mass spectrometry) and constricting T3SS pores below 1.2 nm (carbohydrate exclusion assay). Molecular docking identified D125/K129/Y145 as critical binding residues, validated by alanine scanning and mutant construction. Humanized Hu5C8 retained potency (KD = 0.55 nM) with extended half-life (t_1/2 = 91.26 h) through Fc receptor engineering. As an inhibitor targeting the pore size-determining domain of PcrV, 5C8 disrupts virulence through a novel dual mechanism, providing a paradigm-shifting strategy against multidrug-resistant <i>P. aeruginosa</i>, bridging a critical gap in sepsis management.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0040525"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of resistance markers of artemisinin, partner drugs, and sulfadoxine-pyrimethamine in Nanyumbu and Masasi Districts, Tanzania between 2020 and 2021.","authors":"Richard O Mwaiswelo, Bruno P Mmbando, Frank Chacky, Fabrizio Molteni, Ally Mohamed, Samwel Lazaro, Bushukatale Samuel, Cristina V Ariani, Sonia Gonçalves, Eleanor Drury, Billy Ngasala","doi":"10.1128/aac.01751-24","DOIUrl":"10.1128/aac.01751-24","url":null,"abstract":"<p><p>Regular monitoring of the emergence and spread of <i>Plasmodium falciparum</i> markers of resistance against artemisinin, partner drugs, sulfadoxine, and pyrimethamine is important for the treatment and prevention of malaria in Tanzania. Blood samples were collected from febrile and non-febrile children aged 3 to 59 months in Masasi and Nanyumbu Districts between 2020 and 2021. The samples were subjected to molecular analysis for markers of artemisinin, partner drugs, sulfadoxine, and pyrimethamine resistance, including <i>Plasmodium falciparum</i> kelch (<i>Pfk</i>) 13 gene, <i>P. falciparum</i> chloroquine resistance transporter gene (<i>Pfcrt</i>), <i>P. falciparum</i> multidrug resistance gene (<i>Pfmdr</i>) 1, <i>P. falciparum</i> dihydrofolate reductase (<i>Pfdhfr</i>), and <i>P. falciparum</i> dihydropteroate synthase (<i>Pfdhps</i>). A total of 531 blood samples were involved in the analysis. None of the <i>P. falciparum</i> isolates analyzed for <i>Pfk13</i> carried any of the validated markers of artemisinin resistance. <i>Pfcrt</i> CVMNK wild-type haplotype occurred in 88.9% (271/305) of the parasites, and the mutant CVIET haplotype occurred only in 0.7% (2/305). Conversely, the majority of the parasites (24.2% [48/198]) were carrying <i>Pfmdr1</i> NFD haplotype, followed by the wild-type haplotype NYD (19.1% (39/198), and the rest were mixed infections. Quintuple mutation <b><u>IRN</u></b>I-S<b><u>GE</u></b>AA occurred in 54.4% (62/114), and sextuple mutation <b><u>IRN</u></b>I-<b><u>F</u></b>AK<b><u>GS</u></b> occurred only in 0.9% (1/114) of the parasites. No parasite carried any of the validated markers of artemisinin resistance; however, the prevalence of <i>Pfcrt</i> and <i>Pfmdr1</i> resistance markers against the partner drugs reached the saturation point. Sextuple <i>Pfdhfr-Pfdhps</i> mutations occurred only in one patient; therefore, SP remains efficacious for IPTp in the Districts.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0175124"},"PeriodicalIF":4.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}