Zhaoquan Wang, He Jiang, Xianwu Pang, Jianjun Li, Shujia Liang, Jinghua Huang, Dejian Li, Wenxuan Hou, Ni Chen, Guanghua Lan
Objectives: To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China.
Methods: HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database.
Results: A total of 36 263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions.
Conclusions: HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.
{"title":"Exploring disparities in HIV-1 pretreatment and acquired drug resistance in China from 2003 to 2022.","authors":"Zhaoquan Wang, He Jiang, Xianwu Pang, Jianjun Li, Shujia Liang, Jinghua Huang, Dejian Li, Wenxuan Hou, Ni Chen, Guanghua Lan","doi":"10.1093/jac/dkae260","DOIUrl":"10.1093/jac/dkae260","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the epidemic patterns of pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in HIV-1 sequences from China.</p><p><strong>Methods: </strong>HIV-1 pol sequences and associated epidemiological data were collected from the Los Alamos HIV Sequence Database, NCBI, HIV Gene Sequence Database and PubMed. Genotypic resistance and subtypes were identified using the Stanford HIV Drug Resistance Database.</p><p><strong>Results: </strong>A total of 36 263 sequences from ART-naïve individuals and 1548 sequences from ART-experienced individuals with virological failure were evaluated. PDR prevalence was 6.64%, initially decreasing and then increasing to 7.84% (2018-22) due to NNRTI. Pooled ADR prevalence (44.96%) increased, with NNRTI and NRTI aligning with the overall trend. The percentage of multidrug resistance was more than that of single-drug resistance in PDR and especially ADR annually. PDR was most prevalent in Central China followed by Southwest and North. ADR prevalence was highest in North China followed by Northwest and Southwest. In ADR sequences, high-level resistance was more common, especially in NRTI. PDR sequences exhibited low-level or intermediate resistance, especially PI. Drug resistance mutations revealed distinct patterns in PDR and ADR. CRF01_AE, the predominant subtype in China, exhibited the highest proportions among most ART drugs and drug resistance mutations, with a few exceptions where CRF07_BC (prominent in the Northwest), CRF55_01B and CRF08_BC (prominent in the Southwest) showed the highest proportions.</p><p><strong>Conclusions: </strong>HIV-1 PDR and ADR prevalence in China exhibited diverse epidemiological characteristics, underscoring the importance of ongoing national monitoring of PDR, ADR and subtype; patient education on adherence; and personalized regimens.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751747","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}
Shabbir Simjee, J Scott Weese, Ruby Singh, Darren J Trott, Sabiha Essack, Rungtip Chuanchuen, Shubhi Mehrotra
The similarity of current definitions of 'cross-resistance' and 'co-resistance' continues to cause confusion both in the scientific community as well as in understanding policies and in particular when looking at resistance from a risk assessment perspective. Further, lack of harmonized definitions of these terms in the regulatory space is challenging for interpretation. The purpose of this article is to: (i) provide an overview of the ambiguity in existing terminology related to cross-resistance, co-resistance and co-selection; (ii) emphasize the challenges created by the use of poor terminology in research and scientific literature; and (iii) propose a clear set of harmonized definitions that could be put into use through international regulatory agencies and institutions, such as the World Health Organization, Food and Drug Administration, European Medicines Agency, Center for Disease Control, Committee for Veterinary Medicinal Products, World Organization for Animal Health/Office International des Epizooties and the Food and Agriculture Organization of the United Nations.
{"title":"Redefining cross-resistance, co-resistance and co-selection: beyond confusion?","authors":"Shabbir Simjee, J Scott Weese, Ruby Singh, Darren J Trott, Sabiha Essack, Rungtip Chuanchuen, Shubhi Mehrotra","doi":"10.1093/jac/dkae304","DOIUrl":"10.1093/jac/dkae304","url":null,"abstract":"<p><p>The similarity of current definitions of 'cross-resistance' and 'co-resistance' continues to cause confusion both in the scientific community as well as in understanding policies and in particular when looking at resistance from a risk assessment perspective. Further, lack of harmonized definitions of these terms in the regulatory space is challenging for interpretation. The purpose of this article is to: (i) provide an overview of the ambiguity in existing terminology related to cross-resistance, co-resistance and co-selection; (ii) emphasize the challenges created by the use of poor terminology in research and scientific literature; and (iii) propose a clear set of harmonized definitions that could be put into use through international regulatory agencies and institutions, such as the World Health Organization, Food and Drug Administration, European Medicines Agency, Center for Disease Control, Committee for Veterinary Medicinal Products, World Organization for Animal Health/Office International des Epizooties and the Food and Agriculture Organization of the United Nations.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119866","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":"Correction to: Use of teicoplanin monotherapy for the treatment of enterococcal infective endocarditis: a retrospective and comparative study at a referral centre.","authors":"","doi":"10.1093/jac/dkae317","DOIUrl":"10.1093/jac/dkae317","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086046","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}
T J Harryvan, E Schaftenaar, B T Franssens, D C Melles, R J Rentenaar
{"title":"EUCAST ciprofloxacin area of technical uncertainty in Escherichia coli and Klebsiella pneumoniae using BD Phoenix™ and VITEK® 2 automated susceptibility systems.","authors":"T J Harryvan, E Schaftenaar, B T Franssens, D C Melles, R J Rentenaar","doi":"10.1093/jac/dkae245","DOIUrl":"10.1093/jac/dkae245","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620060","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}
Kerstin Walter, Lindsey H M Te Brake, Ann-Kathrin Lemm, Michael Hoelscher, Elin M Svensson, Christoph Hölscher, Norbert Heinrich
Background: New and shorter regimens against multi-drug resistant tuberculosis (TB) remain urgently needed. To inform treatment duration in clinical trials, this study aimed to identify human pharmacokinetic equivalent doses, antimycobacterial and sterilizing activity of a novel regimen, containing bedaquiline, delamanid, moxifloxacin and sutezolid (BDMU), in the standard mouse model (BALB/c) of Mycobacterium tuberculosis (Mtb) infection.
Methods: Treatment of mice with B25D0.6M200U200, B25D0.6M200, B25D0.6M200(U2003) or H10R10Z150E100 (isoniazid, rifampicin, pyrazinamide, ethambutol, HRZE), started 3 weeks after Mtb infection. Bactericidal activity was assessed after 1, 2, 3 and 4 months of treatment and relapse rates were assessed 3 months after completing treatment durations of 2, 3 and 4 months.
Results: B25D0.6M200U200 generated human equivalent exposures in uninfected BALB/c mice. After 1 month of treatment, a higher bactericidal activity was observed for the B25D0.6M200U200 and the B25D0.6M200 regimen compared to the standard H10R10Z150E100 regimen. Furthermore, 3 months of therapy with both BDM-based regimens resulted in negative lung cultures, whereas all H10R10Z150E100 treated mice were still culture positive. After 3 months of therapy 7% and 13% of mice relapsed receiving B25D0.6M200U200 and B25D0.6M200, respectively, compared to 40% for H10R10Z150E100 treatment showing an increased sterilizing activity of both BDM-based regimens.
Conclusions: BDM-based regimens, with and without sutezolid, have a higher efficacy than the HRZE regimen in the BALB/c model of TB, with some improvement by adding sutezolid. By translating these results to TB patients, this novel BDMU regimen should be able to reduce treatment duration by 25% compared to HRZE therapy.
{"title":"Investigating the treatment shortening potential of a combination of bedaquiline, delamanid and moxifloxacin with and without sutezolid, in a murine tuberculosis model with confirmed drug exposures.","authors":"Kerstin Walter, Lindsey H M Te Brake, Ann-Kathrin Lemm, Michael Hoelscher, Elin M Svensson, Christoph Hölscher, Norbert Heinrich","doi":"10.1093/jac/dkae266","DOIUrl":"10.1093/jac/dkae266","url":null,"abstract":"<p><strong>Background: </strong>New and shorter regimens against multi-drug resistant tuberculosis (TB) remain urgently needed. To inform treatment duration in clinical trials, this study aimed to identify human pharmacokinetic equivalent doses, antimycobacterial and sterilizing activity of a novel regimen, containing bedaquiline, delamanid, moxifloxacin and sutezolid (BDMU), in the standard mouse model (BALB/c) of Mycobacterium tuberculosis (Mtb) infection.</p><p><strong>Methods: </strong>Treatment of mice with B25D0.6M200U200, B25D0.6M200, B25D0.6M200(U2003) or H10R10Z150E100 (isoniazid, rifampicin, pyrazinamide, ethambutol, HRZE), started 3 weeks after Mtb infection. Bactericidal activity was assessed after 1, 2, 3 and 4 months of treatment and relapse rates were assessed 3 months after completing treatment durations of 2, 3 and 4 months.</p><p><strong>Results: </strong>B25D0.6M200U200 generated human equivalent exposures in uninfected BALB/c mice. After 1 month of treatment, a higher bactericidal activity was observed for the B25D0.6M200U200 and the B25D0.6M200 regimen compared to the standard H10R10Z150E100 regimen. Furthermore, 3 months of therapy with both BDM-based regimens resulted in negative lung cultures, whereas all H10R10Z150E100 treated mice were still culture positive. After 3 months of therapy 7% and 13% of mice relapsed receiving B25D0.6M200U200 and B25D0.6M200, respectively, compared to 40% for H10R10Z150E100 treatment showing an increased sterilizing activity of both BDM-based regimens.</p><p><strong>Conclusions: </strong>BDM-based regimens, with and without sutezolid, have a higher efficacy than the HRZE regimen in the BALB/c model of TB, with some improvement by adding sutezolid. By translating these results to TB patients, this novel BDMU regimen should be able to reduce treatment duration by 25% compared to HRZE therapy.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897504","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}
C Massip, L Feletti, C V Chagneau, Y Dumont, E Maurin, A Muggeo, M Pichon, M Pompilio, F Buchler, D Halimi, D Dubois
Objectives: Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam.
Methods: We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method.
Results: For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement ≥ 90%; bias ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used.
Conclusions: Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.
目的:对常规实验室方法进行性能评估,以确定肠杆菌对磷霉素(口服)和美西林的敏感性:对常规实验室方法进行性能评估,以确定尿液中分离出的肠杆菌对磷霉素(口服)和美西林的敏感性:我们从有明显菌尿和白细胞尿的妇女的单菌中段尿液样本中收集了 347 株肠杆菌。其中大部分为非大肠埃希菌分离物(即克雷伯氏菌属、柯氏柠檬杆菌、复合泄殖腔肠杆菌和奇异变形杆菌)(n = 298)。根据国际标准化组织 (ISO) 20776-2:2021(或 20776-2:2007,用于圆盘扩散法)与琼脂稀释参考方法进行比较,评估了 VITEK®2、ETEST® 和圆盘扩散法测定磷霉素和美西林敏感性的性能:结果:对于磷霉素检测,VITEK®2和ETEST®接近ISO要求(基本一致度≥90%;偏差±30%)。盘扩散法的分类一致率(CA)和主要误差率均可接受。福斯霉素对复合物大肠杆菌和克雷伯氏菌的活性较低,其 MIC50(抑制 50%受试分离菌生长所需的最低抑菌浓度)与大肠杆菌 EUCAST 分界点(8 毫克/升)相同。对于这些菌种,三种替代技术都高估了 MIC 和耐药性,不符合性能标准。对于肠杆菌科分离菌株的美西林检测,除了奇异变形杆菌外,ETEST® 几乎达到了 ISO 的要求,CA 率在盘扩散法中也是可以接受的。使用 VITEK®2 对科氏菌和大肠杆菌进行检测时,除重大错误率过高外,均达到了 ISO 标准。对于奇异变形杆菌,无论使用哪种常规方法,其结果都是不可接受的:结论:市售检验可替代琼脂稀释法评估肠杆菌科尿液分离物对磷霉素(口服)和美西林的敏感性,但种间差异很大。为了加强我们的结论,还需要进行更多的研究,其中包括更多对磷霉素和美西林耐药的分离物。
{"title":"Evaluation of several routine methods for fosfomycin and mecillinam susceptibility testing of Enterobacterales urine isolates.","authors":"C Massip, L Feletti, C V Chagneau, Y Dumont, E Maurin, A Muggeo, M Pichon, M Pompilio, F Buchler, D Halimi, D Dubois","doi":"10.1093/jac/dkae271","DOIUrl":"10.1093/jac/dkae271","url":null,"abstract":"<p><strong>Objectives: </strong>Performance evaluation of routine laboratory methods to determine the susceptibility of Enterobacterales urinary isolates to fosfomycin (oral administration) and mecillinam.</p><p><strong>Methods: </strong>We collected 347 Enterobacterales isolates from monomicrobial midstream urine samples from women with significant bacteriuria and leukocyturia. Mostly non-Escherichia coli isolates (i.e. Klebsiella spp., Citrobacter koseri, Enterobacter cloacae complex and Proteus mirabilis) were included (n = 298). Performance of VITEK®2, ETEST®, and disc diffusion to determine fosfomycin and mecillinam susceptibility was evaluated following International Organization for Standardization (ISO) 20776-2:2021 (or 20776-2:2007 for disc diffusion) in comparison with the agar dilution reference method.</p><p><strong>Results: </strong>For fosfomycin testing, VITEK®2 and ETEST® were close to reaching ISO requirements (essential agreement ≥ 90%; bias ±30%) for C. koseri, E. coli and P. mirabilis. Categorical agreement (CA) and major error rates were acceptable for disc diffusion. Fosfomycin displayed lower activity against E. cloacae complex and Klebsiella spp., with MIC50 (minimum inhibitory concentration required to inhibit the growth of 50% of tested isolates) equal to the E. coli EUCAST breakpoint (8 mg/L). For these species, the three alternative techniques overestimated MICs and resistance, and did not meet performance criteria. For mecillinam testing of Enterobacterales isolates, apart from P. mirabilis, ETEST® nearly fulfilled ISO requirements, and CA rates were acceptable for disc diffusion. ISO criteria were reached for C. koseri and E. coli testing with VITEK®2, apart from too high rates of very major errors. For P. mirabilis, performances were unacceptable, whatever the routine method used.</p><p><strong>Conclusions: </strong>Commercially available tests may serve as alternatives to agar dilution to assess fosfomycin (oral) and mecillinam susceptibility of Enterobacterales urinary isolates, with important interspecies variabilities. Additional studies comprising more fosfomycin- and mecillinam-resistant isolates are needed to strengthen our conclusions.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000002","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}
Milo Gatti, Matteo Rinaldi, Cristiana Laici, Simone Ambretti, Antonio Siniscalchi, Pierluigi Viale, Federico Pea
Objective: To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization.
Methods: Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (fCss) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM fCss/MIC ratio >4 coupled with VBM free area under time-concentration curve (fAUC)/threshold concentration (CT) ratio >24.
Results: Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21-0.79) and 0.40 for VBM (range 0.20-0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one.
Conclusions: The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L.
{"title":"Biliary pharmacokinetic/pharmacodynamic analysis of continuous infusion meropenem/vaborbactam in a case series of orthotopic liver transplant recipients.","authors":"Milo Gatti, Matteo Rinaldi, Cristiana Laici, Simone Ambretti, Antonio Siniscalchi, Pierluigi Viale, Federico Pea","doi":"10.1093/jac/dkae261","DOIUrl":"10.1093/jac/dkae261","url":null,"abstract":"<p><strong>Objective: </strong>To analyse the biliary pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) meropenem-vaborbactam (MEM-VBM) in a case series of orthotopic liver transplant (OLT) recipients being treated for Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) related biliary tract infections (BTIs) or as preemptive therapy of KPC-Kp rectal colonization.</p><p><strong>Methods: </strong>Critical OLT recipients receiving CI MEM-VBM (2 g/2 g q8h over 8 h) because of KPC-Kp related BTIs or as preemptive therapy of KPC-Kp rectal colonization, having Kehr's tube positioned and undergoing simultaneous therapeutic drug monitoring of MEM and VBM in plasma and bile were retrospectively assessed. Bile-to-plasma ratio of free steady-state concentrations (fCss) of MEM and VBM was used for assessing biliary penetration. Optimal joint MEM-VBM PK/PD target attainment was defined as MEM fCss/MIC ratio >4 coupled with VBM free area under time-concentration curve (fAUC)/threshold concentration (CT) ratio >24.</p><p><strong>Results: </strong>Overall, four critical OLT recipients were included. Median bile-to-plasma ratio was 0.32 for MEM (range 0.21-0.79) and 0.40 for VBM (range 0.20-0.77). Biliary MEM-VBM joint PK/PD target attainment was optimal in 3/4 OLT recipients and quasi-optimal in the other one.</p><p><strong>Conclusions: </strong>The 1:1 proportion between MEM and VBM concentrations was maintained unchanged in the bile, allowing us to assume that the efficacy of MEM-VBM may be appropriate even in the treatment of BTIs. CI administration was an effective strategy for attaining aggressive biliary joint PK/PD targets against pathogens with an MIC up to 2 mg/L.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859778","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}
Catriona L Halliday, Enoch Tay, Wendy Green, Derek Law, Ronald Lopez, Silvia Faris, Lauren Meehan, Emma Harvey, Mike Birch, Sharon C A Chen
Background: New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non-Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data.
Objectives: Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital.
Materials and methods: Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific).
Results: A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25-0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4->8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species.
Conclusions: Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus, L. prolificans, Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava.
背景:需要新的抗真菌剂来减轻对唑类耐药曲霉菌和非曲霉菌的耐药性。新型奥罗托咪唑--奥罗非姆(F2G,英国曼彻斯特)对曲霉菌(包括耐唑曲霉菌、多孔菌和头孢菌属)具有很强的杀真菌活性,但开发奥罗非姆特异性临床断点/流行病学临界值需要可靠的 MIC 数据:在澳大利亚的一家医院中,与标准抗真菌药相比,确定奥罗芬对霉菌病原体的体外活性:采用 CLSI M38-A3 标准测定了 507 个临床霉菌分离株的奥罗芬 MIC。使用 Sensititre™ YeastOne YO10 和 AUSNMRCI 面板(Thermo-Fisher Scientific)测定两性霉素 B、阿尼妥芬、泊沙康唑、伏立康唑和异武康唑的 MIC:结果:严格意义上的烟曲霉是最常见的菌种(33.3%),其次是增殖酵母菌(18.3%)、Scedosporium(11.4%)和镰刀菌(6%)。除乌斯季曲霉(1 毫克/升)外,奥罗芬对所有曲霉的 MIC 值均小于 0.25 毫克/升(MIC90 为 0.25 毫克/升);对 9 种抗唑/非野生型烟曲霉的 MIC 值介于 0.008 至 0.125 毫克/升之间。Olorofim 对 L. prolificans 的 MIC90 为 0.5 毫克/升,对 Scedosporium 属的 MIC90 为 0.25-0.5 毫克/升,对 F. solani 复合物的 MIC90 为 8 毫克/升,但对 F. oxysporum 和 F. proliferatum 复合物的模式 MIC 分别为 0.25 和 0.008 毫克/升。对于 Verruconis gallopava(n = 10),Olorofim 的 MIC90 为 0.06 mg/L(伏立康唑的 MIC90 为 2 mg/L,异戊唑的 MIC 为 4->8 mg/L)。Olorofim 对包括 Exophiala 菌在内的其他脱霉菌几乎没有活性:结论:Olorofim 对曲霉菌属(包括耐唑曲霉菌属)、L. prolificans、Scedosporium 菌属和一些镰刀菌属具有很高的活性,对 V. gallopava 菌属也有很强的活性。
{"title":"In vitro activity of olorofim against 507 filamentous fungi including antifungal drug-resistant strains at a tertiary laboratory in Australia: 2020-2023.","authors":"Catriona L Halliday, Enoch Tay, Wendy Green, Derek Law, Ronald Lopez, Silvia Faris, Lauren Meehan, Emma Harvey, Mike Birch, Sharon C A Chen","doi":"10.1093/jac/dkae267","DOIUrl":"10.1093/jac/dkae267","url":null,"abstract":"<p><strong>Background: </strong>New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non-Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data.</p><p><strong>Objectives: </strong>Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital.</p><p><strong>Materials and methods: </strong>Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific).</p><p><strong>Results: </strong>A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25-0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4->8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species.</p><p><strong>Conclusions: </strong>Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus, L. prolificans, Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893489","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}
Sonia Nina Coccitto, Francesca Romana Massacci, Marzia Cinthi, Elisa Albini, Lucilla Cucco, Marta Paniccià, Giovanni Pezzotti, Silvia Di Lodovico, Mara Di Giulio, Xiang-Dang Du, Chiara Francesca Magistrali, Andrea Brenciani, Eleonora Giovanetti
{"title":"Novel optrA-carrying integrative and conjugative element in a porcine Streptococcus suis, Italy.","authors":"Sonia Nina Coccitto, Francesca Romana Massacci, Marzia Cinthi, Elisa Albini, Lucilla Cucco, Marta Paniccià, Giovanni Pezzotti, Silvia Di Lodovico, Mara Di Giulio, Xiang-Dang Du, Chiara Francesca Magistrali, Andrea Brenciani, Eleonora Giovanetti","doi":"10.1093/jac/dkae354","DOIUrl":"https://doi.org/10.1093/jac/dkae354","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347116","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}
Bin Du, Wei Zhang, Yang Wang, Yue-E Wu, Ya-Hui Zhang, John van den Anker, Guo-Xiang Hao, Wei Zhao
Objectives: The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures.
Methods: Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (n = 1000) were performed using NONMEM.
Results: A total of 86 samples of 30 adolescents (12-17 years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0-24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3 m2, where a fixed loading dose (LD) is preferred when BSA ≥ 1.3 m2 and a BSA-based LD is preferred when BSA < 1.3 m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70 mg/day and MD 70 mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1 mg/L. Furthermore, an LD of 70 mg/day and MD of 60 mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1 mg/L in the virtual population.
Conclusions: Our study proposed optimized dosing regimens of caspofungin based on AUC0-24/MIC90 or Ctrough, which may support further individualized treatment.
{"title":"Optimal dosing regimen of caspofungin in adolescents with allogeneic haematopoietic stem cell transplantation.","authors":"Bin Du, Wei Zhang, Yang Wang, Yue-E Wu, Ya-Hui Zhang, John van den Anker, Guo-Xiang Hao, Wei Zhao","doi":"10.1093/jac/dkae276","DOIUrl":"10.1093/jac/dkae276","url":null,"abstract":"<p><strong>Objectives: </strong>The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures.</p><p><strong>Methods: </strong>Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (n = 1000) were performed using NONMEM.</p><p><strong>Results: </strong>A total of 86 samples of 30 adolescents (12-17 years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0-24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3 m2, where a fixed loading dose (LD) is preferred when BSA ≥ 1.3 m2 and a BSA-based LD is preferred when BSA < 1.3 m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70 mg/day and MD 70 mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1 mg/L. Furthermore, an LD of 70 mg/day and MD of 60 mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1 mg/L in the virtual population.</p><p><strong>Conclusions: </strong>Our study proposed optimized dosing regimens of caspofungin based on AUC0-24/MIC90 or Ctrough, which may support further individualized treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906696","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}