Antimicrobial Agents and Chemotherapy最新文献

{"title":"PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam.","authors":"Melina Ruggiero, Melina García Alonso, Salvador I Drusin, Roque Figueroa-Espinosa, Ivan Jackson Briceño Muñoz, Robert A Bonomo, Gabriel Gutkind, José Di Conza, Diego M Moreno, Pablo Power","doi":"10.1128/aac.00378-26","DOIUrl":"10.1128/aac.00378-26","url":null,"abstract":"<p><p>PER-1-producing <i>Pseudomonas</i> and <i>Acinetobacter</i> and PER-2-producing <i>Enterobacterales</i>, respectively, are increasingly difficult to treat due to combined resistance to antibiotics like ceftazidime, cefiderocol, and ceftazidime/aztreonam-avibactam, among others. PER-14 differs from PER-2 by an S130T substitution. Through combined functional and <i>in silico</i> analyses, we demonstrated that PER-14 is resistant to avibactam and relebactam inhibition while retaining an extended-spectrum activity and the ability to hydrolyze cefiderocol, as the S130T substitution affects the proper binding of the DBOs.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0037826"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534914","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> activity of zoliflodacin against <i>Neisseria gonorrhoeae</i> collected in the United States from 2020 to 2022.","authors":"Sarah M McLeod, Samir H Moussa, Meredith Hackel, Carmen Au, Pierre Daram","doi":"10.1128/aac.00527-26","DOIUrl":"10.1128/aac.00527-26","url":null,"abstract":"<p><p>Zoliflodacin is a first-in-class spiropyrimidinetrione, oral, single-dose antibacterial recently approved by the US FDA for treatment of uncomplicated urogenital gonorrhea. Isolates of <i>Neisseria gonorrhoeae</i> (<i>n</i> = 322) collected in the United States in 2020-2022 by the Centers for Disease Control and Prevention, as well as two ceftriaxone-resistant isolates, were tested for susceptibility to zoliflodacin. All isolates were susceptible to zoliflodacin with MIC_50/90 values of 0.12 µg/mL. Zoliflodacin activity was consistent over time and against ceftriaxone-, ciprofloxacin-, and tetracycline-resistant and azithromycin-non-susceptible isolates.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0052726"},"PeriodicalIF":4.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663501","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":"Recalculation of inhibitor concentration fold-changes for CMY-219: comments on a recent article about CMY-219 conferring resistance to ceftazidime-avibactam.","authors":"Chunlin Feng","doi":"10.1128/aac.00505-26","DOIUrl":"10.1128/aac.00505-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0050526"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306640","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":"Reply to Feng, \"Recalculation of inhibitor concentration fold-changes for CMY-219: comments on a recent article about CMY-219 conferring resistance to ceftazidime-avibactam\".","authors":"Agnès B Jousset, Delphine Girlich, Saoussen Oueslati, Aurélien Birer, Anne Delaval, Caroline Guyot, Ines Rezzoug, Cécile Emeraud, Thierry Naas, Rémy A Bonnin, Laurent Dortet","doi":"10.1128/aac.00523-26","DOIUrl":"10.1128/aac.00523-26","url":null,"abstract":"","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0052326"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306687","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":"Isavuconazole as primary antifungal prophylaxis in pediatric hematological patients: a clinical and pharmacokinetic analysis.","authors":"Francesco Baccelli, Caterina Campoli, Martina Colli, Milo Gatti, Francesca Gottardi, Gennaro Pagano, Francesco Venturelli, Davide Leardini, Edoardo Muratore, Gianluca Bossù, Federico Pea, Pierluigi Viale, Maddalena Giannella, Tamara Belotti, Arcangelo Prete, Riccardo Masetti","doi":"10.1128/aac.00451-26","DOIUrl":"10.1128/aac.00451-26","url":null,"abstract":"<p><p>Invasive fungal diseases (IFDs) are a major threat in pediatric patients with hematologic malignancies (HMs) and hematopoietic stem cell transplantation (HSCT) recipients. Optimal antifungal prophylaxis (AFP) remains a clinical challenge. Isavuconazole (ISA), a broad-spectrum triazole, may offer a safer, more predictable option for AFP in this setting, but pediatric data are scarce. We retrospectively analyzed pediatric patients (≤18 years) with HM or HSCT who received isavuconazole as primary AFP from January 2021 to April 2025 at a single center. Isavuconazole dosing, therapeutic drug monitoring (TDM), safety, and breakthrough IFD incidence were systematically evaluated in a standardized stewardship framework. Isavuconazole was administered as primary antifungal prophylaxis in 21 patients (median age 9.6 years), 17 (77.3 %) after HSCT. Doses were weight-adjusted (100 or 200 mg/day) with loading over 48 h. No severe adverse events attributable to isavuconazole were reported. No breakthrough IFDs occurred during prophylaxis. Concomitant use of CYP3A4-interacting agents (e.g., ruxolitinib) was not associated with increased toxicity or isavuconazole level alterations. TDM was performed in all patients (188 total measurements); median Cmin was 3.4 mg/L. The target range (1-5 mg/L) was achieved in 95.2% of first TDMs. Dosage adjustments were needed in only 5.9% of cases, indicating consistent pharmacokinetics. In this retrospective cohort of high-risk pediatric hematology patients, isavuconazole used as primary antifungal prophylaxis showed favorable safety, consistent drug exposure, and no breakthrough IFDs. These findings support further prospective evaluation of isavuconazole in pediatric prophylactic strategies.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0045126"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337674","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":"Phage-derived endolysin prevents dissemination of methicillin resistant <i>Staphylococcus aureus</i> during oral co-infection with <i>Candida albicans</i>.","authors":"Katrien Van Dyck, Michel A Hoogenkamp, Fritz Eichenseher, Patrick Van Dijck, Bastiaan P Krom","doi":"10.1128/aac.01812-25","DOIUrl":"10.1128/aac.01812-25","url":null,"abstract":"<p><p>The oral cavity is colonized by many species of bacteria and fungi without causing serious infections of hosts. However, upon loss of homeostasis, some of these colonizers have the potential to invade the host and cause life-threatening infections. The fungus <i>Candida albicans</i> and the gram-positive bacterium <i>Staphylococcus aureus</i> represent well-studied examples. In immunocompromised mice, oral co-colonization with these two species can result in dissemination of <i>S. aureus</i> through the body, causing <i>S. aureus</i> bacteremia and subsequent sepsis. In the proof-of-principle experiments described here, we show effective prevention of dissemination of methicillin-resistant <i>S. aureus</i> (MRSA) using an innovative endolysin-derived chimeric protein, XZ.700. Using the established murine model for oral co-colonization, we evaluated the effect of treatment with XZ.700 in drinking water (<i>ad libitum</i>) and applied as a gel formulation twice a day. XZ.700 did not show any adverse reaction in the mice treated and did not show a reduction of <i>C. albicans</i> colonization. XZ.700 in drinking water completely prevented detectable dissemination of MRSA in co-infected mice and significantly reduced weight loss. The gel formulation showed a trend in decreased MRSA colonization of the tongue and dissemination to the kidneys, although this was not significantly different from the placebo control. Taken together, the results presented here indicate that selective removal of MRSA from the oral cavity of mice with XZ.700 during co-infection with <i>C. albicans</i> is effective in preventing dissemination. Further studies need to show clinical applicability of XZ.700 and related compounds in prevention of sepsis in at-risk patients.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0181225"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248927","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":"Cefiderocol nonsusceptibility among carbapenem-resistant <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>: data from the 2024 Antimicrobial Testing Leadership and Surveillance (ATLAS) program.","authors":"Po-Wei Chiu, Jiun-Ling Wang, Shun-Chung Hsueh, Nan-Yao Lee, Yu-Tsung Huang, Wen-Chien Ko, Po-Ren Hsueh","doi":"10.1128/aac.00634-26","DOIUrl":"10.1128/aac.00634-26","url":null,"abstract":"<p><p>We evaluated cefiderocol activity against carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) and carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB), characterized the β-lactamase gene profiles of cefiderocol-nonsusceptible CRPA by metallo-β-lactamase (MBL) subtype, and assessed cross-resistance with comparator agents. Cefiderocol minimum inhibitory concentrations (MICs) for 890 CRPA and 1,063 CRAB isolates from the 2024 Antimicrobial Testing Leadership and Surveillance (ATLAS) program were determined by broth microdilution using iron-depleted cation-adjusted Mueller-Hinton broth. Cefiderocol nonsusceptibility was defined as MIC ≥ 8 mg/L per CLSI (intermediate + resistant). DTRPA was defined as nonsusceptible to all anti-pseudomonal β-lactams and fluoroquinolones; DTRAB was defined as nonsusceptible to carbapenems, ampicillin-sulbactam, and fluoroquinolones, reflecting species-specific susceptibility panels. CRPA isolates underwent molecular screening for <i>bla</i>_NDM, <i>bla</i>_VIM, <i>bla</i>_IMP, serine carbapenemase, and ESBL genes; genotype data were not available for <i>A. baumannii</i>. Cefiderocol susceptibility was 93.9% for CRPA and 88.5% for CRAB, respectively (nonsusceptibility 6.1% and 11.5%, respectively; OR = 2.01, <i>P</i> < 0.001); nonsusceptibility among DTRPA and DTRAB was 8.1% and 11.7%, respectively. Among 54 cefiderocol-nonsusceptible CRPA, 41 (76%) harbored no detectable carbapenemase gene. Nonsusceptibility among MBL-positive CRPA was exclusively attributable to <i>bla</i>_NDM producers (27.7%, 13/47); <i>bla</i>_VIM-positive (<i>n</i> = 68) and <i>bla</i>_IMP-positive (<i>n</i> = 21) isolates were uniformly susceptible. Among cefiderocol-nonsusceptible CRPA, 98.1% were co-resistant to ceftazidime-avibactam and 96.3% to ceftolozane-tazobactam.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0063426"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429622","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":"NagX, a periplasmic β-<i>N</i>-acetylglucosaminidase, contributes to NagZ-independent β-lactamase expression in <i>Stenotrophomonas maltophilia</i>.","authors":"En-Wei Hu, Po-Cheng Kuo, Li-Hua Li, Chen-Syuan Yen, Cheng-Chih Hsu, Tsuey-Ching Yang","doi":"10.1128/aac.00243-26","DOIUrl":"10.1128/aac.00243-26","url":null,"abstract":"<p><p>Beta-lactam resistance in <i>Stenotrophomonas maltophilia</i> is primarily mediated by the expression of L1 and L2 β-lactamases. L1/L2 expression is closely linked to peptidoglycan recycling through the AmpNG-NagZ-AmpR pathway, in which NagZ plays a dominant role for L1/L2 expression. Although a NagZ-independent β-lactamase expression has been suggested, its molecular basis remains unclear. Here, we identify NagX, a periplasmic β-<i>N</i>-acetylglucosaminidase, as a key contributor to the NagZ-independent β-lactamase pathway. Using <i>S. maltophilia</i> KJ and its derived <i>nagZ</i> in-frame deletion mutant, KJΔNagZ, we confirm the presence of NagZ-independent β-lactamase expression and an additional β-<i>N</i>-acetylglucosaminidase in addition to NagZ. Determination of β-lactamase and β-<i>N</i>-acetylglucosaminidase activities in various engineered strains of <i>S. maltophilia</i> KJ demonstrated that NagX is a periplasmic β-<i>N</i>-acetylglucosaminidase and drives NagZ-independent β-lactamase expression in an AmpNG- and AmpR-dependent manner. To reveal how NagX processes the released peptidoglycan sacculus, the periplasmic muropeptides profile of wild-type KJ, KJΔAmpNG (an <i>ampNG</i> mutant), and KJΔAmpNGΔNagX (an <i>ampNG</i> and <i>nagX</i> double mutant) were determined by LC-MS/MS. The results demonstrated that NagX can remove the <i>N</i>-acetylglucosamine (GlcNAc) moiety from the GlcNAc-anhMurNAc-peptide and GlcNAc-anhMurNAc, yielding anhMurNAc-peptide and anhMurNAc, respectively. AmpNG permease system shuttled GlcNAc-anhMurNAc-peptide, GlcNAc-anhMurNAc, and anhMurNAc-peptide from periplasm to cytosol. Then, the anhMurNAc-peptide served as activator ligands that cooperate with AmpR to induce β-lactamase expression. Our findings uncover a novel NagX-AmpNG-AmpR circuit underlying NagZ-independent β-lactamase expression in <i>S. maltophilia</i>.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0024326"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468369","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":"Comparative analysis of disk diffusion and microscan versus broth microdilution methods for determining antimicrobial susceptibility of cefepime and piperacillin-tazobactam in <i>Escherichia coli</i> isolates carrying <i>bla</i>_OXA-1.","authors":"Marta Carretero-Ledesma, Carlos Saúco-Carballo, Ana Velázquez Escudero, Inmaculada López-Hernández, Inés Portillo-Calderón, Lorena López-Cerero, José Manuel Rodríguez-Martínez, Jesús Rodríguez Baño, Álvaro Pascual, Fernando Docobo-Pérez","doi":"10.1128/aac.00300-26","DOIUrl":"10.1128/aac.00300-26","url":null,"abstract":"<p><p>Routine susceptibility testing often misses resistance in <i>bla</i>_OXA-1-producing <i>E. coli</i>, risking therapeutic failure. Among 165 clinical isolates from the Spanish multicenter cohort, MicroScan and disk diffusion versus reference broth microdilution yielded suboptimal categorical agreement (73.9%-86.7%) for piperacillin-tazobactam (PTZ) and cefepime (FEP). MicroScan PTZ very major errors (30%) indicate resistance underestimation; disk diffusion PTZ major errors (23%) and both methods FEP major errors (8.3%-13.8%) indicate resistance overestimation. These errors justify cautious interpretation of routine susceptibility results.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0030026"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337624","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":"Sustained high prevalence of multiple antimalarial drug resistance markers in Uganda in 2023-2024.","authors":"Thomas Katairo, Victor Asua, Francis D Semakuba, Bienvenu Nsengimaana, Shahiid Kiyaga, Nicholas Hathaway, Kathryn Murie, Stephen Tukwasibwe, Innocent Wiringilimaana, Jackie Nakasaanyaa, Caroline Mwubaha, Karen B Achom, Trevor E Esilu, Alisen Ayitewalah, Monica Mbabazi, Kisakye D Kabbale, Jerry Mulondo, Eric Watyekele, Andrés Aranda-Diaz, Catherine S Maiteki, Jimmy Opigo, Grant Dorsey, Samuel L Nsobya, Moses R Kamya, Bosco B Agaba, Isaac Ssewanyana, Bryan Greenhouse, Philip J Rosenthal, Jessica Briggs, Melissa D Conrad","doi":"10.1128/aac.00361-26","DOIUrl":"10.1128/aac.00361-26","url":null,"abstract":"<p><p>The emergence and spread of drug resistance threaten malaria control in Uganda. This study reports new data on key polymorphisms associated with antimalarial drug sensitivity at 32 malaria reference centers in Uganda in 2023 and 2024. Ten thousand thirty samples were collected from patients aged >6 months presenting with uncomplicated falciparum malaria and sequenced using the MAD⁴HatTeR panel and Illumina platforms; of these, 8,518 passed quality control and were analyzed. Multiple validated or candidate K13 mutations associated with artemisinin partial resistance were detected at ≥20% prevalence at one or more sites across multiple timepoints. The K13 mutations A675V and C469Y predominated in northern Uganda, P441L was most common in western Uganda, and R561H and C469F were confined to southwestern Uganda. After rapid increases in earlier years, prevalences of K13 mutations plateaued at most sites, with A675V, C469Y, and P441L reaching maximum site prevalences of 40%, 58%, and 46%, respectively. Prevalence of the chloroquine resistance marker CRT K76T was generally low but increased substantially at three sites in northwestern Uganda, rising to 38% at the last timepoint, with CRT H97L, newly reported in Africa, following a similar trend. The antifolate resistance quintuple mutant haplotype remained highly prevalent nationwide. In addition, DHPS A581G and DHFR I164L, markers of higher-level antifolate resistance, were most common in southwestern Uganda with prevalences up to 64% and 76%, respectively; DHFR I164L also expanded into central and eastern regions. These results highlight continued geographic heterogeneity and underscore the need for continued, nationwide molecular surveillance to guide treatment and chemoprevention policies.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0036126"},"PeriodicalIF":4.2,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249014","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}