Antimicrobial Agents and Chemotherapy最新文献

{"title":"The <i>ahpC</i> c-54t compensatory mutation is not always a valid surrogate for isoniazid resistance in <i>Mycobacterium tuberculosis</i>.","authors":"Viktória Szél, Jody E Phelan, Sophia B Georghiou, David L Dolinger, Taane G Clark, Stefan Niemann, Lilla K Lőrinczi, Claudio U Köser","doi":"10.1128/aac.00265-25","DOIUrl":"10.1128/aac.00265-25","url":null,"abstract":"<p><p>Thirteen commercial genotypic antimicrobial susceptibility assays interrogate mutations upstream of <i>ahpC</i> to infer isoniazid resistance for <i>Mycobacterium tuberculosis</i>. We demonstrate that relying on one of these compensatory mutations (i.e., <i>ahpC</i> c-54t)-rather than causative resistance mutations in <i>katG</i> that <i>ahpC</i> compensates for-can result in systematic false-resistant results for isoniazid with the Cepheid Xpert MTB/XDR and suboptimal treatment. The WHO mutation catalog should be refined to address this scenario.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0026525"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974749","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":"Individual target pharmacokinetic/pharmacodynamic attainment rates among cefepime-treated patients admitted to the ICU with hospital-acquired pneumonia with and without ECMO.","authors":"Adrian Valadez, Marta Zurawska, Emma Harlan, Marc H Scheetz, MIchael N Neely, Paul R Yarnold, Mengjia Kang, Erin Korth, Francisco Martinez, Bridget Giblin, Helen K Donnelly, Kay Dedicatoria, Rachel Medernach, Sophia Nozick, Alan R Hauser, Egon A Ozer, Estefani Diaz, Alexander V Misharin, Richard G Wunderink, Nathaniel J Rhodes","doi":"10.1128/aac.00102-25","DOIUrl":"10.1128/aac.00102-25","url":null,"abstract":"<p><p>Cefepime (FEP) is used for hospital- and ventilator-associated pneumonia when <i>Pseudomonas aeruginosa</i> is involved. However, its pharmacokinetics (PK) in severe pneumonia necessitating extracorporeal membrane oxygenation (ECMO) remain unclear. This single-center, prospective study enrolled 70 mechanically ventilated patients with suspected pneumonia (<i>n</i> = 9 on ECMO), excluding those on renal replacement therapy. Dosing followed institutional renal function-based protocols. Plasma concentrations were quantified by liquid chromatography-tandem mass spectrometry, and a two-compartment PK model was developed using <i>Pmetrics</i> for R, with volume of distribution (Vd) scaled to body weight and ECMO status, and clearance (CL) scaled to renal function. Target attainment was calculated from Bayesian posterior predictions, and Monte Carlo simulations evaluated the cumulative fraction of response (CFR) for regimens of 2 g IV every 8 h, administered as either 0.5 h intermittent or 4 h extended infusion with or without a 2 or 3 g loading dose (LD) (0.5 h). Success was defined as achieving 100% <i>f</i>T _>1xMIC within 24 h for 80% of isolates. Seventy patients (60% male, <i>n</i> = 9 ECMO) contributed 114 plasma samples (1-14 per patient). The model fit the data well. ECMO was associated with a 2.8-fold increase in Vd without altering CL. Monte Carlo simulations demonstrated that standard dosing without an LD failed to achieve CFR ≥ 80% in ECMO patients. Incorporating a 3 g but not 2 g LD restored CFR to ≥80% in ECMO. ECMO significantly increased FEP Vd in intensive care unit patients, suggesting sub-optimal target attainment at higher minimum inhibitory concentrations. A 3 g LD appears essential for target attainment, underscoring the need for revised dosing strategies in ECMO.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0010225"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075552","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":"Population pharmacokinetics and dosing optimization of teicoplanin in renal transplant patients.","authors":"Yangang Zhou, Jiawei Peng, Ping Xu, Feng Wang, Jun Xi, Hedong Zhang, Shanbiao Hu, Han Yan, Liang Tan, Hualin Cai, Bikui Zhang, Gongbin Lan","doi":"10.1128/aac.01568-24","DOIUrl":"10.1128/aac.01568-24","url":null,"abstract":"<p><p>The objectives of this study were to investigate the population pharmacokinetic (PK) characteristics of teicoplanin in renal transplant patients and to provide recommendations for optimal teicoplanin dosing regimens. A total of 99 renal transplant patients with 386 plasma samples were enrolled (306 in development and 80 in validation). A population PK analysis and simulations were performed to identify the optimal teicoplanin doses needed to provide an 80% probability of target attainment at 72 h and 168 h using both a trough concentration target of >15 µg/mL and the ratio of 24 h area under the concentration-time curve to the minimum inhibitory concentration >610.4. Teicoplanin was well described by a two-compartment PK model. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance, and peripheral compartment volume were 0.711 L/h, 11.3 L, 4.22 L/h, and 35.2 L, respectively. Creatinine clearance (CrCL) was the only covariate that significantly affected teicoplanin clearance. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and CrCL-based individual dosing regimens are recommended for both loading dose and maintaining dose. Higher-than-standard teicoplanin doses are necessary to achieve prompt and appropriate drug exposure in renal transplant patients.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0156824"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961977","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>Plasmodium falciparum Kelch-13</i> artemisinin partial resistance markers in Fort Portal, Western Uganda, 2024.","authors":"Welmoed van Loon, Emma Schallenberg, Emmanuel Mande, Patrick Musinguzi, Paul Ngobi, Sharon Atukunda, John Rubaihayo, Frank P Mockenhaupt","doi":"10.1128/aac.01755-24","DOIUrl":"10.1128/aac.01755-24","url":null,"abstract":"<p><p>In Fort Portal, Uganda, artemisinin resistance-associated mutations in <i>Plasmodium falciparum Kelch13</i> (<i>n</i> = 126) were present in 4.8% (675V, 561H, and 441L). A mutation of unknown relevance, 490T, occurred in 9.5%. <i>PfMDR1</i> variants suggested increased lumefantrine tolerance (N86, 100%). Mutation 500N was absent, and 199S occurred in 12.8%. The latter is of unknown relevance. These data indicate an incipient emergence of artemisinin resistance in a crucial location between Rwandan and Ugandan resistance hotspots and hardly affected DR Congo.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0175524"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957320","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":"Outcomes after suppressive antimicrobial therapy for prosthetic joint infection: a prospective cohort study.","authors":"Craig Aboltins, Christopher Lemoh, Mani Suleiman, Alex Soriano, Joshua Davis, Laurens Manning","doi":"10.1128/aac.01784-24","DOIUrl":"10.1128/aac.01784-24","url":null,"abstract":"<p><p>The objective of this study was to describe the use of and outcomes after suppressive antimicrobial therapy (SAT) in a large prospective peri-prosthetic joint infection (PJI) cohort. SAT was defined as antimicrobial therapy continuing beyond 12 months from PJI diagnosis or where there was an early intention for SAT. The primary outcome was \"treatment failure\" at 24 months, defined as any of (i) clinical evidence of (ii) further surgery for or (iii) death from PJI. Secondary outcomes included quality of life (QOL) scores using Short Form 12 (SF-12) and Oxford hip (OHS) and knee (OKS) scores. SAT was prescribed for 223 of 720 (31.0%) in the cohort. Patients prescribed SAT were more likely to be older, have comorbidities, chronic PJI, higher C-reactive protein, sinus tract, or be treated with debridement and implant retention. The most frequently prescribed antimicrobials for SAT were ciprofloxacin (64 [21%]), amoxicillin (42 [14%]), and rifampicin (35 [12%]). Treatment failure was more common in the SAT group (75/185 [40.1%] vs 85/447 [19.0%]). After propensity score-adjusted analysis, SAT remained associated with higher rates of treatment failure (aOR 2.48, 95% CI [1.66-3.72]). Although 24-month QOL scores were lower in the SAT group, there were similar improvements from baseline in functional joint scores in SAT and non-SAT groups (OHS median interquartile range [IQR] +8.5 [19.0] vs +7.0 [22.0]; <i>P</i> = 0.78 and OKS +8.0 [20.0] vs +7.0 [22.0]; <i>P</i> = 0.53). SAT use for PJI is common, and in this study, it was not associated with improved outcomes. Identifying patients most likely to benefit from SAT should be explored in carefully designed controlled trials.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0178424"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969306","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":"Emergence of KPC-8-producing <i>K. pneumoniae</i> infection without prior exposure to ceftazidime/avibactam: the threat of <i>de novo</i> infections by ceftazidime/avibactam-resistant KPC variants.","authors":"María Alejandra Mateo-Vargas, Salud Rodríguez-Pallares, Jorge Arca-Suárez, Lorena López-Cerero, Manuel Rodríguez-Iglesias, Fátima Galán-Sánchez","doi":"10.1128/aac.01494-24","DOIUrl":"10.1128/aac.01494-24","url":null,"abstract":"<p><p><i>De novo</i> infections caused by ceftazidime/avibactam-resistant KPC variants are rarely reported. We characterize the evolution of a KPC-8-producing <i>Klebsiella pneumoniae</i> strain involved in a primary infection without previous ceftazidime/avibactam treatment. During a 15-month follow-up, changes in carbapenem susceptibility due to porin alterations were observed, remaining susceptible to meropenem/vaborbactam, imipenem/relebactam, and cefiderocol. High- and low-permeability recombinant <i>Escherichia coli</i> isolates analysis revealed that, unlike the widespread ceftazidime/avibactam-resistant variant KPC-31, KPC-8 confers ceftazidime/avibactam resistance without decreasing carbapenemase activity.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0149424"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966679","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":"Prevalence and characteristics of tigecycline- and carbapenem-resistant <i>adeN</i>-truncated <i>Acinetobacter baumannii</i>: a genomic epidemiological analysis.","authors":"Ying Zhang, Beibei Zhou, Jingchun Kong, Panjie Hu, Haifeng Liu, Deyi Zhao, Jianzhong Ye, Qingxia Fu, Tieli Zhou, Changrui Qian","doi":"10.1128/aac.01843-24","DOIUrl":"10.1128/aac.01843-24","url":null,"abstract":"<p><p><i>adeN</i>-truncated <i>Acinetobacter baumannii</i> (ATAB) isolates are associated with elevated tigecycline resistance and enhanced virulence, yet its epidemic dynamics and genomic features remain poorly understood. This study aimed to investigate the epidemiology of ATAB isolates, identify infection risk factors, and assess their impact on patient prognosis. The prevalence of ATAB isolates in a tertiary care teaching hospital (Wenzhou, China) from January 2018 to December 2022 was determined via polymerase chain reaction (PCR) screening. Whole-genome sequencing and genomic analysis were conducted to explore the epidemiology and genomic characteristics of 254 ATAB isolates. Clinical data analysis was performed to identify risk factors for ATAB infection and its correlation with patient prognosis. The results of local sample analysis showed that <i>adeN</i> truncation was identified in 26.5% (486/1834) of the patient isolates, with the monthly prevalence peaking at 64.9% (24/37). The capsular types of ATAB isolates were primarily KL2, whereas <i>adeN</i>-complete isolates exhibited a greater capsular diversity. ATAB could evolve within the hospital and lead to multiple nosocomial clonal transmissions. Most ATAB isolates exhibited co-resistance to carbapenems and tigecycline. ICU admission and use of immunosuppressants were significant risk factors for ATAB isolate infection. Patients infected with ATAB isolates had significantly higher 28-day all-cause mortality (32.8%, 20/61) compared to those infected with <i>adeN</i>-complete isolates (11.5%, 7/61, <i>P</i> < 0.01). Bioinformatics analysis of the 18,946 completed and draft <i>A. baumannii</i> genome assemblies from the GenBank database showed that ATAB isolates were widely prevalent worldwide. This study highlights the importance of early identification and monitoring of ATAB isolates as a critical marker for hospital infection control.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0184324"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974521","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":"Regulation of phosphatidylinositol-(4,5)-bisphosphate and active-Rho1p levels and distribution is crucial for correct spatio-temporal cytokinesis and echinocandin responses in <i>Candida albicans</i>.","authors":"Hassan Badrane, M Hong Nguyen, Cornelius J Clancy","doi":"10.1128/aac.01900-24","DOIUrl":"10.1128/aac.01900-24","url":null,"abstract":"<p><p><i>Candida</i> species cause severe infections like invasive candidiasis, which annually affects 1.5 million people worldwide and causes close to 1 million deaths. <i>Candida albicans</i> is the predominant cause of candidiasis. We previously showed that Eps15-Homology domain-containing protein Irs4p binds 5-phosphatase enzyme Inp51p to regulate plasma membrane levels of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P₂) in <i>C. albicans</i>. Indeed, deletion of <i>IRS4</i> or <i>INP51</i> led to elevated levels of PI(4,5)P₂ and the presence of abnormal intracellular membranous PI(4,5)P₂ patches. We demonstrated an interplay between PI(4,5)P₂ and septins to regulate the PKC-Mkc1 cell wall integrity pathway, echinocandin and cell wall stress responses, and virulence during candidiasis. To gain insights into the nature of these abnormal patches, we used fluorescent protein tagging and live-cell imaging to follow their nascency. We show that these abnormal patches tightly correlate with cytokinesis, as they predominantly arise close to the site and time of cell division. We further demonstrate that these patches colocalize PI(4,5)P₂ with actomyosin ring components Act1p and Myo1p, which form its core, and active Rho1p, a small GTPase that plays a regulatory role. Additionally, activation of Rho1p was altered in <i>irs4</i> and <i>inp51</i> mutants compared to wild-type strain, with over-activation or down-activation during early exponential or stationary phase, respectively. Wild-type cells exposed to 4× MIC of the echinocandin caspofungin show abnormal PI(4,5)P₂ patches that colocalize with the same cytokinesis components as above, except that they are transient. Taken together, our results support a model in which PI(4,5)P₂ plays a pivotal role, along with Rho1p, in the correct execution of cytokinesis and response to caspofungin.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0190024"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963842","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 the double deletion ΔG242-T243 in KPC-2 in the effectiveness of ceftazidime-avibactam and imipenem-relebactam.","authors":"Florencia Brunetti, Gabriel Gutkind, Lin Gao, Shozeb Haider, Robert A Bonomo, Pablo Power","doi":"10.1128/aac.01915-24","DOIUrl":"10.1128/aac.01915-24","url":null,"abstract":"<p><p>Combinations of β-lactam-diazabicyclooctane inhibitors (DBOs) like ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) have shown efficacy in treating KPC-2-producing <i>Klebsiella pneumoniae</i>. However, CZA-resistant <i>K. pneumoniae</i> strains have been identified, often linked to substitutions and/or insertions/deletions in three different loops of KPC: (i) the Ω-loop region (amino acids 164-179), (ii) the 237-243 loop; and (iii) the 266-275 loop. This study investigates the impact of the double deletion ΔG242-T243 present in KPC-14. Our results demonstrate that the lower effectiveness of CZA against KPC-14 can be explained by both increased hydrolysis of ceftazidime and a lower affinity and acylation rate by avibactam. In contrast, the IMR combination was efficient in restoring susceptibility to the KPC-14 producing-clone. Although we also observed a lower affinity and acylation rate for relebactam in KPC-14, this reduction in affinity was accompanied by a loss in the carbapenemase activity, finally resulting in an IMR susceptibility phenotype for KPC-14. Expansion of the substrate profile of KPC-14 toward ceftazidime is associated with a trade-off for carbapenems, other penicillins, and cephalosporins, as well as a higher inhibition by clavulanic acid compared to KPC-2. This study provides a better understanding of how deletions in the 237-243 loop affect the effectiveness of novel DBO-combinations and supports the hypothesis that these mutations result in CZA resistance by other different biochemical mechanisms than mutations in the Ω-loop.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0191524"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959700","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 susceptibility and genetic mechanisms of resistance of <i>Ureaplasma</i> isolates in North America between 2012 and 2023.","authors":"Joshua T Waites, Donna M Crabb, Amy E Ratliff, Ken B Waites, Li Xiao","doi":"10.1128/aac.01868-24","DOIUrl":"10.1128/aac.01868-24","url":null,"abstract":"<p><p>We analyzed antimicrobial susceptibilities of 415 <i>Ureaplasma</i> isolates from various sample types derived from different regions of the United States and Canada from 2012 to 2023 and investigated the genetic mechanisms of antimicrobial resistance. Minimum inhibitory concentration (MIC) ranges for erythromycin, tetracycline, and levofloxacin were 0.063-256, 0.016-64, and 0.063-32 µg/mL, respectively. MIC₅₀ values for erythromycin, tetracycline, and levofloxacin were 2, 0.25, and 1 µg/mL, and MIC₉₀ values were 4, 1, and 2 µg/mL, respectively. According to Clinical and Laboratory Standards Institute breakpoints, there were 61 (14.7%) isolates resistant to one or more drugs, and resistance rates for erythromycin, tetracycline, and levofloxacin were 2.4% (10/415), 6.5% (27/413), and 6.7% (28/415), respectively. Four isolates (1.0%) were resistant to two drugs. Mutations in domain V of 23S rRNA, mainly A2058G (<i>Escherichia coli</i> numbering), and/or in the <i>rpl</i>D gene encoding ribosomal protein L4 were identified in most erythromycin-resistant isolates. <i>Tet</i>(M) was detected in all isolates with tetracycline MIC ≥4 µg/mL but absent in 64.7% (11/17) of isolates with MIC of 2 µg/mL. For fluoroquinolone-resistant isolates, C248T (S83L) and G259A (E87K) mutations in <i>parC</i> were identified in most cases (23/26). In summary, erythromycin, tetracycline, and levofloxacin are still effective <i>in vitro</i> against most <i>Ureaplasma</i> isolates in North America.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0186824"},"PeriodicalIF":4.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969305","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}