Journal of Antimicrobial Chemotherapy最新文献

{"title":"Pharmacokinetics of abacavir and lamivudine in infants living with HIV with and without rifampicin co-treatment.","authors":"Laize Sílvia Dos Anjos Botas Beca, Vivian Mumbiro, Mutsa Bwakura, Hilda A Mujuru, Shepherd Mudzingwa, Alfredo Tagarro, Sara Domínguez-Rodríguez, Victor Musiime, Damalie Nalwanga, W Chris Buck, Jahit Sacarlal, Chishala Chabala, Bwendo Nduna Chansa, Pablo Rojo, David M Burger, Cinta Moraleda, Tom G Jacobs","doi":"10.1093/jac/dkag281","DOIUrl":"10.1093/jac/dkag281","url":null,"abstract":"<p><strong>Background: </strong>Lamivudine and abacavir are key components of first-line paediatric antiretroviral therapy (ART). Rifampicin is part of drug-sensitive TB treatment in children. Rifampicin induces UDP-glucuronosyltransferases and renal transporters and inhibits gastrointestinal transporters involved in the pharmacokinetics of abacavir and lamivudine, but pharmacokinetic data on this potential interaction in infants are scarce.</p><p><strong>Objective: </strong>To evaluate the effect of rifampicin on the pharmacokinetics of abacavir and lamivudine in infants aged 28-365 days and weighing >3 kg.</p><p><strong>Methods: </strong>This pharmacokinetic sub-study was nested within the EMPIRICAL trial (NCT03915366). Eighteen infants from Mozambique, Uganda, Zambia and Zimbabwe received once-daily fixed-dose abacavir/lamivudine with dolutegravir according to WHO guidelines. Five infants received ART alone and 13 received ART plus rifampicin-based tuberculosis treatment. Abacavir/lamivudine dosing was unchanged during rifampicin co-treatment. Six plasma concentrations were measured over 24 h and analysed using non-compartmental pharmacokinetic analysis.</p><p><strong>Results: </strong>Median (IQR) age and weight were 6.8 (5.2-10.2) months and 6.0 (5.3-6.8) kg, respectively, and were comparable between groups. Abacavir exposure was comparable with and without rifampicin (AUC0-24h: 21.9 versus 21.0 h mg/L; Cmax: 6.2 versus 6.3 mg/L, respectively). Lamivudine exposure was also comparable (AUC0-24h: 12.6 versus 12.4 h mg/LL, respectively). The slightly higher Cmax (2.4 versus 1.9 mg/L) in the rifampicin group is probably due to interindividual variability or increased absorption from rifampicin's inhibition of gastrointestinal drug transporters, and considered not clinically relevant.</p><p><strong>Conclusions: </strong>Rifampicin co-treatment had minimal impact on abacavir and lamivudine pharmacokinetics in infants. Dose adjustment of abacavir/lamivudine is not required during rifampicin-containing tuberculosis treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793387","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":"Clinical characteristics and outcomes of patients with bacteraemia caused by non-carbapenemase-producing, carbapenem-resistant Enterobacterales.","authors":"Sunish Shah, Lloyd G Clarke, Ellen G Kline, Rachel V Marini, Kevin M Squires, Ryan K Shields","doi":"10.1093/jac/dkag267","DOIUrl":"https://doi.org/10.1093/jac/dkag267","url":null,"abstract":"<p><strong>Objectives: </strong>Carbapenem-resistant Enterobacterales (CRE) are classified as carbapenemase- and non-carbapenemase-producing (non-CP) CRE. The purpose of this study was to identify factors associated with meropenem non-susceptible non-CP CRE to help stratify treatment approaches and to report rates of treatment-emergent resistance among patients with non-CP CRE bacteraemia.</p><p><strong>Methods: </strong>This was a retrospective, single-centre study of patients hospitalized between January 2015 and September 2025 with bacteraemia due to Enterobacterales resistant to ertapenem and confirmed to be non-CP. Ertapenem resistance was determined by broth microdilution susceptibility testing. Carbapenemase testing was performed by modified carbapenem-inactivation method, polymerase chain reaction or whole-genome sequencing.</p><p><strong>Results: </strong>Among 60 patients who met the inclusion criteria, the median (IQR) age was 63 years (57-73), 33% (20/60) were female and 18% (11/60) were organ transplant recipients. Patients infected with meropenem non-susceptible non-CP CRE were more likely to have prior meropenem exposure [60% (10/15) versus 13% (8/45), P < 0.001] and have breakthrough bacteraemia [60% (9/15) versus 29% (13/45), P = 0.031]. Treatment-emergent resistance developed in 16% (4/24) and 0% (0/15) of patients treated with meropenem and ceftazidime-avibactam, respectively.</p><p><strong>Conclusions: </strong>These exploratory data provide new insights into clinical factors associated with meropenem non-susceptible non-CP CRE and support future investigations into the comparative-effectiveness of meropenem versus beta-lactam/beta-lactamase inhibitors for the treatment of meropenem-susceptible non-CP CRE.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678344","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":"Antimicrobial resistance in Neisseria gonorrhoeae isolates at the Bangrak STIs Center, Bangkok, Thailand and WGS of antimicrobial-resistant isolates, 2018-23.","authors":"Porntip Paopang, Pongsathorn Sangprasert, Daniel Golparian, Natnaree Girdthep, Nutchaya Jintana, Supawadee Sonnak, Padchara Sangsuk, Thewarkrith Bunpan, Magnus Unemo, Rossaphorn Kittiyaowamarn","doi":"10.1093/jac/dkag260","DOIUrl":"10.1093/jac/dkag260","url":null,"abstract":"<p><strong>Objectives: </strong>Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern, particularly due to increasing resistance to the last remaining monotherapy, ceftriaxone, in several Asian countries. We examined the AMR of gonococcal isolates obtained at the Bangrak STIs Center, Bangkok, Thailand in 2018-23, and used WGS on isolates resistant to ceftriaxone, cefixime and/or azithromycin.</p><p><strong>Methods: </strong>Genital and extragenital swabs from males, females and transgender women were cultured. Etest (five antimicrobials) and EUCAST breakpoints (v16.0), or disc diffusion method (ciprofloxacin) were used to determine AMR. WGS was performed using Illumina NextSeq 550.</p><p><strong>Results: </strong>In 2018-23, 765 gonococcal isolates from 739 patients were cultured. Resistance to ceftriaxone, cefixime, azithromycin, tetracycline and ciprofloxacin was 0.5%, 0.8%, 1.7%, 83.7% and 95.7%, respectively. Ceftriaxone-resistant isolates, all resistant also to cefixime, were first detected in 2023 (n = 3, 1.2%). Additional cefixime-resistant isolates were found in 2022 (n = 2, 1.4%). Azithromycin-resistant isolates first emerged in 2020 (n = 1, 0.9%) and increased to nine (3.7%) isolates in 2023. All ceftriaxone-resistant isolates contained penA-60.001, but cefixime resistance was additionally caused by penA-34.019 and penA-10.001. All azithromycin-resistant isolates had 23S rRNA mutations and/or mosaic/semi-mosaic MtrD (subunit of the MtrCDE efflux pump).</p><p><strong>Conclusions: </strong>Resistance to ceftriaxone, cefixime and azithromycin has emerged in gonococcal strains circulating in Bangkok, Thailand, and resistance appears to be increasing. Resistance to these last options for monotherapy or dual therapy emphasize the need for strengthened national culture-based and genomic surveillance to prevent the spread of MDR and XDR strains in Thailand and globally, and implementation of the novel oral treatments, i.e. zoliflodacin and gepotidacin.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669394","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":"Antimicrobial-loaded PMMA bone cement: time for good practice recommendations.","authors":"Tariq Azamgarhi, Herbert Gbejuade, Ryan A Hamilton, Simon Warren, Elizabeth S R Darley, Mark Gilchrist, Erden Ali, Félix-Antoine Garneau-Picard, Jason C J Webb","doi":"10.1093/jac/dkag261","DOIUrl":"10.1093/jac/dkag261","url":null,"abstract":"<p><p>Antimicrobial-loaded PMMA bone cement has been used since the 1970s as both a fixation material and a local antimicrobial reservoir. Its clinical roles differ between prophylaxis in primary arthroplasty and treatment of established infection, particularly during revision surgery and through the use of temporary spacers. Commercially manufactured products offer more predictable handling, but bespoke admixing may be considered when resistant or unusual organisms are encountered. This Viewpoint argues that such practice requires clearer governance. Cement formulation, antimicrobial choice, dose and mixing technique influence elution, bioactivity, mechanical strength and toxicity. Local delivery may support antimicrobial stewardship, but prolonged low-level elution could theoretically select for resistance if poorly planned. We propose a cautious, evidence-informed framework to support multidisciplinary decision-making and the development of PMMA-specific antimicrobial guidance.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793374","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":"Phenotypic and biochemical characterization of the class C β-lactamase, PAC-1.","authors":"Otávio Hallal Ferreira Raro, Stefano Mancini, Jacqueline Findlay, Helena M B Seth-Smith, Muhammad Ali Syed, Adrian Egli, Patrice Nordmann, Laurent Poirel","doi":"10.1093/jac/dkag291","DOIUrl":"10.1093/jac/dkag291","url":null,"abstract":"<p><strong>Background: </strong>The class C β-lactamase, PAC-1, was originally described as acquired in Pseudomonas aeruginosa clinical isolates from south Asia, the corresponding gene being chromosomally located and embedded within a Tn1721-like transposon. Despite its association with high-level resistance to cephalosporins and β-lactam/β-lactamase inhibitor combinations, data on its full hydrolytic profile and kinetic parameters have not yet been comprehensively characterized.</p><p><strong>Objectives: </strong>To characterize the susceptibility profile and hydrolytic kinetics of PAC-1, with a particular focus on cefiderocol hydrolysis, and the activity of novel β-lactam/β-lactamase inhibitor combinations.</p><p><strong>Methods: </strong>The blaPAC-1 allele was cloned into vector pUCP24 and expressed in Escherichia coli TOP10 and Pseudomonas aeruginosa PAO1, respectively. MICs were determined by broth microdilution and interpreted according to EUCAST guidelines. PAC-1 was purified, and steady-state kinetic measurements of selected β-lactams were determined. IC50 values were determined for the β-lactamase inhibitors avibactam, taniborbactam, xeruborbactam and zidebactam. WGS was performed to characterize the genetic environment of the blaPAC-1 gene.</p><p><strong>Results: </strong>PAC-1 conferred broad resistance to penicillins, broad-spectrum cephalosporins and cefiderocol, while carbapenems remained unaffected. Kinetic analyses confirmed high catalytic efficiency against cefotaxime and aztreonam, but no hydrolysis of imipenem. Avibactam, relebactam and vaborbactam failed to inhibit PAC-1 (IC50 > 1000 µM), whereas xeruborbactam and zidebactam showed potent inhibitory activities (IC50 = 1.0 and 0.6 µM, respectively). A chromosomally located Tn1721-like transposon was identified carrying the blaPAC-1 gene in P. aeruginosa ST4936.</p><p><strong>Conclusions: </strong>PAC-1 is not inhibited by avibactam and hydrolyses a broad range of β-lactams including the novel cephalosporin cefiderocol. The combination cefiderocol/zidebactam was the most active against PAC-1. Transposon-mediated dissemination across distinct lineages warrants continued epidemiological surveillance of PAC-type β-lactamases.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812795","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":"Humanizing meropenem dosage regimens by co-administration of cilastatin in an immunocompetent mouse bloodstream infection model of Acinetobacter baumannii based on a novel quantitative matching framework.","authors":"Yuanyuan Jiao, Jun Yan, Dhruvitkumar S Sutaria, Michael Vicchiarelli, Peggy Lu, Xindi Shan, Yinzhi Lang, Taehyung Kim, Zeferino Reyna, Brad Spellberg, Robert A Bonomo, George L Drusano, Arnold Louie, Brian M Luna, Jürgen B Bulitta","doi":"10.1093/jac/dkag274","DOIUrl":"https://doi.org/10.1093/jac/dkag274","url":null,"abstract":"<p><strong>Background: </strong>Meropenem is commonly used to treat serious bacterial infections, but its short half-life in mice impedes achieving human-like drug exposure profiles. This study aimed to create humanized meropenem dosage regimens in immunocompetent mice with bloodstream infections by Acinetobacter baumannii.</p><p><strong>Methods: </strong>Cilastatin was administered to prolong the meropenem half-life in mice and match the concentration-time profiles of meropenem in patients. An integrated population pharmacokinetic model was developed to characterize the concentration-dependent inhibition of meropenem clearance by cilastatin. Murine dosage regimens were humanized based on a novel matching framework. Firstly, meropenem plasma concentrations in mice should remain within the 5th to 95th percentiles of plasma concentrations for meropenem monotherapy in critically ill patients. Secondly, the free-time-above-MIC versus MIC profiles of meropenem in mice should match those in patients.</p><p><strong>Results: </strong>The meropenem half-life in mice increased from 22.2 min without cilastatin to 57.7 min at high cilastatin concentrations. Cilastatin inhibited the meropenem clearance half-maximally at 0.230 mg/L. Subcutaneous doses of 53/10 mg/kg meropenem/cilastatin at 0 h and 26/10 mg/kg at 3 h in mice, both repeated every 8 h, resulted in well-matched pharmacokinetic profiles to those of 2 g meropenem infusions over 30 min at the same dosing interval in patients.</p><p><strong>Conclusions: </strong>Co-administration of cilastatin substantially prolonged the meropenem half-life in mice and enabled humanized meropenem dosage regimens with six doses per day to stay within the 5th and 95th percentiles of plasma concentrations in patients. This novel framework to humanize murine dosage regimens is based on quantitative matching criteria and supports translational research by achieving clinically relevant exposure profiles in mice.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760168","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":"Antibiotic consumption in HIV and PrEP populations with and without sexually transmitted infections: a population-based observational study.","authors":"Adrián Valls-Carbó, Raquel Siguín, Alberto Delgado-Iribarren, Rocío Manzano, Inés Armenteros-Yeguas, Yolanda Campanero, Santiago Fernández-Castelao, Sergio Sabogal, Claudia Dorta-Hernández, Vicente Estrada","doi":"10.1093/jac/dkag228","DOIUrl":"10.1093/jac/dkag228","url":null,"abstract":"<p><strong>Background: </strong>Antimicrobial resistance is driven by antibiotic exposure. People living with HIV (PLWH) and PrEP users face high STI rates, but the magnitude of cumulative antibiotic exposure in these populations compared with the general population has not been well characterized.</p><p><strong>Methods: </strong>This retrospective study (Madrid, 2024-2025) linked pharmacy and microbiology records of 562 325 adults. Participants were categorized into: (A) PLWH or PrEP users with documented rectal STI episodes in the context of active sexual health follow-up; (B) PrEP/PLWH without STIs; and (C) general population controls. Consumption was measured in Defined Daily Doses per 1000 persons-day (DHD) using propensity score overlap weights.</p><p><strong>Results: </strong>Antibiotic use was significantly higher in Group A (95.3%) compared to Group B (35.4%) and Group C (27.3%) (P < 0.001). After weighting, individuals with documented rectal STI episodes (Group A) exhibited a markedly higher overall antibiotic exposure compared with general population controls (Group C) (adjusted rate ratio [RR]-DHD 4.67, 95% CI 4.41-4.94), driven by tetracyclines (RR-DHD 23.7), corresponding to a population rate equivalent to ∼1.1 seven-day doxycycline courses per person-year (a population-level metric, not an individual estimate). Group B consumption was 33% higher than controls (P = 0.004). Direct comparison confirmed that Group A's tetracycline use was 5.6-fold higher than Group B's (P < 0.001).</p><p><strong>Conclusions: </strong>PLWH and PrEP users with documented rectal STI episodes experience markedly higher antibiotic exposure than the general population, driven primarily by tetracycline use. This disproportionate exposure in a small, identifiable subgroup supports targeted antimicrobial stewardship strategies in sexual health and HIV care settings, including systematic consumption monitoring, individualized doxy-PEP counselling, and integration of STI-focused populations into national AMR surveillance frameworks.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793348","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":"Impact of modified microbiology reporting on the treatment of low-risk AmpC Enterobacterales infections: a multi-centre controlled interrupted time series study.","authors":"Marie-Félixe Granger, Marion Elligsen, Janine McCready, Xena X Li, Robert A Kozak, Jerome A Leis, Philip W Lam","doi":"10.1093/jac/dkag269","DOIUrl":"10.1093/jac/dkag269","url":null,"abstract":"<p><strong>Objectives: </strong>We assessed the impact of a modified microbiology report and cascade that selectively reported narrower-spectrum β-lactams for low-risk AmpC Enterobacterales (AmpC-E).</p><p><strong>Methods: </strong>We conducted a controlled interrupted time series analysis to assess the proportion of patients receiving ceftriaxone or piperacillin/tazobactam on the fourth day of antibiotic treatment for low-risk AmpC-E infection (Serratia marcescens, Morganella morganii, Providencia spp., Citrobacter koseri) compared with a high-risk AmpC-E (Enterobacter cloacae complex, Klebsiella aerogenes, Citrobacter freundii) control group. Secondary outcomes included a pre-post measurement of antibiotic use on the fourth day of therapy, death at 30 days, and recurrent infection at 90 days.</p><p><strong>Results: </strong>Patients with low-risk AmpC-E infections were more likely to receive ceftriaxone or piperacillin/tazobactam compared with high-risk AmpC-E controls [incidence rate ratio (IRR) 39.8, 95% CI 1.8-871.7, P = 0.02]. There was an upward shift and trend in ceftriaxone and piperacillin/tazobactam use during the implementation period in the low-risk AmpC-E group compared with the control group (IRR 3.3, 95% CI 0.9-11.9, P = 0.07 and slope 1.3, 95% CI 1.0-1.8, P = 0.10), with an associated reduction in fluoroquinolone use. During the implementation period, 30 day mortality (13.8% versus 12.1%, P = 0.70) and recurrent infection at 90 days (6.4% versus 5.7%, P = 0.83) were similar between low-risk and high-risk AmpC-E groups.</p><p><strong>Conclusions: </strong>Modification of microbiology reporting for low-risk AmpC Enterobacterales infections to selectively report narrower-spectrum β-lactams resulted in a rapid and sustained increase in use of ceftriaxone and piperacillin/tazobactam across two hospitals. Aligning this microbiology reporting with guidelines would have scalable impact on hospital antimicrobial stewardship.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669519","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":"Epidemiology of KPC-producing Enterobacterales isolated from 2019 to 2023 in France.","authors":"Lamia Rouabah, Sarah Ronsin, Axelle Vasseur, Inès Rezzoug, Sandrine Bernabeu, Aurélien Birer, Cécile Emeraud, Thierry Naas, Rémy A Bonnin, Laurent Dortet, Agnès B Jousset","doi":"10.1093/jac/dkag273","DOIUrl":"10.1093/jac/dkag273","url":null,"abstract":"<p><strong>Objectives: </strong>The global spread of Klebsiella pneumoniae carbapenemase (KPC)-type carbapenemases has historically been driven by clonal group CG258, but increasing clonal diversification has recently been reported. We aimed to provide a comprehensive phenotypic and genomic characterization of KPC-producing Enterobacterales referred to French National Center (NRC) for Antimicrobial Resistance between 2019 and 2023.</p><p><strong>Materials and methods: </strong>A total of 419 KPC-producing Enterobacterales were referred to the French NRC for Antimicrobial Resistance. Antimicrobial susceptibility testing was performed by broth microdilution. Whole-genome sequencing was conducted for 404 isolates. AMR gene detection, MLST and SNP-based phylogeny were used to analyse resistance mechanisms, clonal structure and outbreak dynamics.</p><p><strong>Results: </strong>KPC-producing Enterobacterales accounted for ∼2% of all carbapenemase-producing Enterobacterales. The K. pneumoniae species complex represented 86% (363/419) of isolates. KPC-3 predominated (328/419, 78%), followed by KPC-2 (87/419, 21%). Additional carbapenemases were detected in 11 isolates. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam showed high in vitro activity (97.8%, 95.8% and 97.9% susceptibility, respectively). MLST of 353 K. pneumoniae genomes identified 45 sequence types (STs); ST307 predominated (39.4%) and was associated with a major outbreak in northern France. ST147 (8.8%) and ST512 (7.6%) were also prevalent. Fifteen isolates from ST11, ST39, ST101, and ST395 had high virulence score of 4 (iuc-positive).</p><p><strong>Conclusions: </strong>KPC-producing K. pneumoniae referred to the French NRC show marked clonal diversification. The emergence of resistant isolates and convergent resistance-virulence profiles underscore the need for sustained genomic surveillance.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722882","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":"Synergy between orally bioavailable antibiotics and dalbavancin against MRSA.","authors":"Ethan Ahrendt, Melanie C L Foreman, Brian J Werth","doi":"10.1093/jac/dkag264","DOIUrl":"10.1093/jac/dkag264","url":null,"abstract":"<p><strong>Background: </strong>We have shown that dalbavancin exposure can select for mutants with reduced susceptibilities to vancomycin and daptomycin, and several clinical cases of such resistance have been documented. Synergistic antimicrobial combinations may reduce resistance selection and enhance the activity of dalbavancin for deep-seated infections. Since the key advantage of dalbavancin is its infrequent dosing, the objective of this study was to evaluate whether orally bioavailable antibiotics typically dosed ≤ twice daily were synergistic with dalbavancin.</p><p><strong>Methods: </strong>Using five isogenic S. aureus strain pairs (susceptible parent strain and a dalbavancin-selected resistant strain), we assessed for synergy between dalbavancin and cefadroxil, trimethoprim, doxycycline, moxifloxacin, and clarithromycin by standard time-kill methods.</p><p><strong>Results: </strong>Cefadroxil was synergistic with dalbavancin against every strain tested. When combined with dalbavancin, trimethoprim was synergistic against 6/8 trimethoprim-susceptible strains, moxifloxacin was synergistic against 6/10 strains, doxycycline was synergistic against 2 strains but antagonistic against 2 strains, and clarithromycin was synergistic against 2/6 clarithromycin-susceptible strains. All other interactions were indifferent.</p><p><strong>Conclusions: </strong>Cefadroxil is a first-generation cephalosporin, like cephalexin, but with a longer half-life that allows for a typical 12-h dosing interval. In our study, we found that synergy between cefadroxil and dalbavancin was common regardless of susceptibility to cefadroxil or dalbavancin, suggesting that this might be a promising companion agent to add to dalbavancin in patients with deep-seated infections that may benefit from synergistic activity to enhance bactericidal effects. Trimethoprim/sulfamethoxazole and moxifloxacin may improve activity and are unlikely to be antagonistic. Clarithromycin and doxycycline seem least likely to offer a benefit.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":"81 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701348","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}