[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-455928-105":59,"doc-detail-455928-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","simulated-endocardial-vegetation-model-highlights-the-complexity-of-high-inoculum-infections-among-beta-lactamase-producing-organisms-editorial-commentary","Simulated endocardial vegetation model highlights the complexity of high-inoculum infections among β-lactamase-producing organisms - Editorial Commentary","","Susceptibility testing and PK/PD analysis are often based on standard inocula (10^5–10^6 CFU), which may poorly predict outcomes in high-bacterial-burden infections, particularly those driven by β-lactamase–producing organisms. Using a 96-h simulated endocardial vegetation model, clinically relevant antibiotic exposures were assessed across Enterobacter cloacae complex isolates, linking pharmacodynamic efficacy, resistance emergence, and β-lactamase expression; MIC values frequently failed to reflect model efficacy. The commentary emphasizes inoculum effects, biofilm-associated resistance, and limitations of standard MIC breakpoints for endocarditis.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/simulated-endocardial-vegetation-model-highlights-the-complexity-of-high-inoculum-infections-among-beta-lactamase-producing-organisms-editorial-commentary/455928/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/simulated-endocardial-vegetation-model-highlights-the-complexity-of-high-inoculum-infections-among-beta-lactamase-producing-organisms-editorial-commentary/455928.png","ImageObject",300,407,{"name":92,"@type":93},"Taylor Morgan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why may standard susceptibility testing poorly predict treatment success in high-inoculum infections?","Question",{"text":113,"@type":114},"Standard inoculum-based susceptibility testing (10^5–10^6 CFU) may not capture how antibiotic exposure/response relationships change at higher bacterial burdens, especially in infections involving β-lactamase–mediated resistance and biofilm formation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What did the 96-h simulated endocardial vegetation model evaluate?",{"text":118,"@type":114},"It assessed pharmacodynamic efficacy, resistance emergence, and β-lactamase expression after clinically relevant, human-simulated antibiotic exposures against three Enterobacter cloacae complex isolates.",{"name":120,"@type":111,"acceptedAnswer":121},"How did MIC values relate to bactericidal efficacy in the model?",{"text":122,"@type":114},"MIC values were often poorly predictive; some antibiotics failed to achieve bactericidal activity at 96 h despite MIC-based expectations, while other combinations showed inoculum-dependent differences in killing.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},455928,1790791774,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":39,"preview_page_count":4},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","| Antimicrobial Chemotherapy | Commentary  \nSimulated endocardial vegetation model highlights the complexity of high-inoculum infections among β-lactamaseproducing organisms  \nAndrew J. Fratoni1  \nAUTHOR AFFILIATION See affiliation list on p. 3.  \nABSTRACT Conventionally, susceptibility testing and pharmacokinetic/pharmacodynamic relationships are determined using standard inoculum (i.e., 105–106 CFU) . These may be poorly predictive of efficacy for high-inoculum infections, especially amongst β-lactamase-producing organisms. A. J. Kunz-Coyne, R. Gray, E. May, H. Curry, et al. (Antimicrob Agents Chemother 69:e01170-25, 2025, [https://doi.org/10.1128/](https://doi.org/10.1128/)[ ](https://doi.org/10.1128/)[aac.01170-25](aac.01170-25)) used a 96-h simulated endocardial vegetation model to describe pharmacodynamic efficacy, resistance emergence, and β-lactamase expression that resulted after clinically relevant exposures of antibiotics against three Enterobacter cloacae complex isolates, demonstrating that MIC values were often poorly predictive of efficacy in the model.  \nKEYWORDS infective endocarditis, Enterobacter, beta-lactamases, beta-lactams  \nE nterobacter cloacae complex (ECC) is not often high on the list of frequently  \nencountered pathogens responsible for infective endocarditis. Unfortunately, reported treatment outcomes leave something to be desired (1) . ECC is a key member of AmpC-producing gram-negative organisms (2) . While MIC testing, in vitro time kill experiments, and in vivo pharmacokinetic/pharmacodynamic (PK/PD) infection models traditionally operate with starting inoculums from 105 to 106 CFU/mL, it is vital to consider how antibiotic exposure/response relationships might differ at higher bacterial burdens, such as those observed in deep-seated infections like endocarditis.  \nKunz-Coyne and colleagues employed a 96-h simulated endocardial vegetation endocarditis model to describe pharmacodynamic efficacy, resistance emergence, and β-lactamase expression that resulted after clinically relevant, human-simulated exposures of cefepime, ertapenem, meropenem (with and without vaborbactam), and ceftazidime-avibactam were administered against three ECC isolates (3). All three isolates originated from the CDC and FDA Antimicrobial Resistance Isolate Bank. CDC 0008 and 0060 express ACT-15 and-89, respectively, AmpC β-lactamases that are inherent to ECC. CDC 0032 also expresses ACT-16 but additionally has other acquired β-lactamase genes, KPC-3 and TEM-1 . Generally speaking, based on these genotypic profiles, cefepime or a carbapenem would be considered reasonable therapeutic options for 0008 and 0060, while one of the aforementioned BL/BLIs could be considered for 0032. However, considering the impact of a high-inoculum infection raises uncertainty and leads one to question whether standard antibiotic selections are best suited for these types of clinical scenarios.  \nIn their endocarditis model, cefepime 2 g q8h as either 30-min intermittent infusion (II) or 3-h extended infusion (EI) failed to achieve bactericidal activity (i.e., ≥3 log 10CFU/g reduction) at 96 h and resulted in multi-fold MIC increases in all three ECC isolates, while changes in gene expression were mixed. As would be expected based on the presence of  \nEditor Pranita D. Tamma, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA  \nAddress correspondence to Andrew J. Fratoni, [andrew.fratoni@hhchealth.org](andrew.fratoni@hhchealth.org).  \nA.J. F. received research funding from Qpex Biopharma.  \nviews expressed in this article do necessarily  \nKPC-3, ECC 0032 showed net growth on meropenem monotherapy, with an approximate 15-fold uptick in ACT-16 induction. Meropenem yielded reductions of −2.9 and −4.6 log 10CFU/g against EC 0060 with II and EI, respectively, suggesting additional efficacy with prolonged infusion. In the same isolate, ertapenem demonstrated modest (−1.9 log 10CFU/g) reductions at 96 h with an ","cbCaichJOflQNPOt","https://ap.wps.com/l/cbCaichJOflQNPOt","pdf",140825,"English","# Antimicrobial Chemotherapy Commentary\n## Rationale: limits of standard inoculum testing\n## Study design: 96-h simulated endocardial vegetation model\n## Isolate profiles and expected therapy\n## Drug performance under high inoculum\n## Implications for breakpoints and clinical decision-making","[{\"question\":\"Why may standard susceptibility testing poorly predict treatment success in high-inoculum infections?\",\"answer\":\"Standard inoculum-based susceptibility testing (10^5–10^6 CFU) may not capture how antibiotic exposure/response relationships change at higher bacterial burdens, especially in infections involving β-lactamase–mediated resistance and biofilm formation.\"},{\"question\":\"What did the 96-h simulated endocardial vegetation model evaluate?\",\"answer\":\"It assessed pharmacodynamic efficacy, resistance emergence, and β-lactamase expression after clinically relevant, human-simulated antibiotic exposures against three Enterobacter cloacae complex isolates.\"},{\"question\":\"How did MIC values relate to bactericidal efficacy in the model?\",\"answer\":\"MIC values were often poorly predictive; some antibiotics failed to achieve bactericidal activity at 96 h despite MIC-based expectations, while other combinations showed inoculum-dependent differences in killing.\"}]","Simulated endocardial vegetation model highlights the complexity of high-inoculum infections among β-lactamase-producing organisms - Editorial Commentary | PDF",1790744696]