{"title":"Monte Carlo simulation for dosage optimization of the best available therapy for bloodstream infections secondary to carbapenemase-producing Klebsiella pneumoniae in critically ill patients.","authors":"Sujareenoot Suya, Worapong Nasomsong, Wichai Santimaleeworagun, Piraporn Juntanawiwat, Tassananwan Chatreewonanakul, Weerayuth Saelim","doi":"10.1016/j.jgar.2024.10.263","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.10.263","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to use Monte Carlo simulation, based on pharmacokinetic/ pharmacodynamic (PK/PD) targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients.</p><p><strong>Methods: </strong>We collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction (PCR). Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target achievement (PTA) and cumulative fraction of response (CFR).</p><p><strong>Results: </strong>The 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was bla<sub>oxacillinases (OXA)-48-like</sub> (42.6%), followed by bla<sub>New Delhi metallo beta lactamase (NDM)</sub> (29.6%) and coexistence of bla<sub>OXA-48-like</sub> and bla<sub>NDM</sub> (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline-colistin (67.9%), tigecycline-gentamicin (62.2%), and tigecycline-amikacin (51.4%).</p><p><strong>Conclusions: </strong>Tigecycline-colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance (CrCl) of <90 mL/min can raise the CFR target and less nephrotoxicity.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiao Feng, Zhiwei Song, Piaopiao Dai, Huimin Chen, Dakang Hu, Lianhua Yu, Jin Zhang, Xinhua Luo
{"title":"Genomic analysis of IMP-8-producing Enterobacter hormaechei with a novel plasmid pK432-IMP.","authors":"Jiao Feng, Zhiwei Song, Piaopiao Dai, Huimin Chen, Dakang Hu, Lianhua Yu, Jin Zhang, Xinhua Luo","doi":"10.1016/j.jgar.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.11.001","url":null,"abstract":"<p><strong>Background: </strong>Carbapenem-resistant Enterobacter cloacae (CR-ECC) complex has posed significant challenges to the clinical treatment of infections, and Enterobacter hormaechei is the most commonly identified nosocomial pathogen of CR-ECC.</p><p><strong>Methods: </strong>Carbapenemases were detected by the immunocolloidal gold technique. The MIC values were determined by VITEK2. The genome sequence of strain K432 was obtained and analyzed.</p><p><strong>Results: </strong>We isolated the IMP-8-producing E. hormaechei strain K432 from a patient's urine specimen in a Chinese Hospital, which exhibited resistance to multiple antibiotics including ceftazidime, piperacillin/tazobactam, aztreonam, imipenem, meropenem, ciprofloxacin, levofloxacin, minocycline and trimethoprim/sulfamethoxazole. The genome of strain K432 was composed of the chromosome cK432 (4,863 kb) and three plasmids: pK432-IMP (45.8 kb), pK432-TEM (75.6 kb) and pK432-NR (4.8 kb). In K432, six drug-resistant genes were detected, including bla<sub>ACT-7</sub> and fosA on cK432, bla<sub>IMP-8</sub> and qnrS1 on pK432-IMP, bla<sub>SFO-1</sub> and bla<sub>TEM-1</sub> on pK432-TEM. pK432-IMP belonged to a novel incompatibility group, and pK432-TEM was an IncR plasmid. Both of these two plasmids shared similar conserved backbone regions with their reference plasmids, respectively. However, the single accessory regions in these two plasmids were different from their reference plasmids, indicating that new recombination and integration events had occurred in K432.</p><p><strong>Conclusions: </strong>This study provides a comprehensive understanding of the genomic characterization of K432 and identified a novel plasmid for IMP transmission. Further investigation and surveillance are warranted for pK432-IMP-type plasmid. While routine monitoring of MDR E. hormaechei strains is necessary in China.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasmine Eddoubaji, Claudia Aldeia, Dierik H Heg, Edgar I Campos-Madueno, Andrea Endimiani
{"title":"Refining the gut colonization Zophobas morio larvae model using an oral administration of multidrug-resistant Escherichia coli.","authors":"Yasmine Eddoubaji, Claudia Aldeia, Dierik H Heg, Edgar I Campos-Madueno, Andrea Endimiani","doi":"10.1016/j.jgar.2024.10.262","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.10.262","url":null,"abstract":"<p><strong>Background: </strong>The darkling beetle Zophobas morio can be implemented as an alternative in vivo model to study different intestinal colonization aspects. Recently, we showed that its larvae can be colonized by multidrug-resistant Escherichia coli strains administered via contaminated food (for 7 days) for a total experimental duration of 28 days.</p><p><strong>Method: </strong>In the present work, we aimed to shorten the model to 14 days (T14) by administering the previously used CTX-M-15 ESBL-producing ST131 Escherichia coli strain Ec-4901.28 via a single oral administration (5 µL dose of 10<sup>8</sup> CFU/mL) , using a blunt 26s-gauge needle connected to a 250 μL gastight syringe. Force-feeding was performed either without or with (larvae placed on ice for 10 minutes before injection) anesthesia. In addition, phage-treated larvae were orally injected with 10 µL of INTESTI bacteriophage cocktail (∼10<sup>5-6</sup> PFU/mL) on days 4 (T4) and 7 (T7) .</p><p><strong>Results: </strong>Growth curve analyses showed that, while larvae rapidly became colonized with Ec-4901.28 (T1, ∼10<sup>6-7</sup> CFU/mL) , only those anesthetized maintained a high bacterial load (∼10<sup>2-3</sup>vs. ∼10<sup>5-6</sup> CFU/mL) and survival rate (76% vs. 99%; P<0.001) by T14. Moreover, bacteriophage administration to anesthetized larvae significantly reduced the bacterial count of INTESTI-susceptible Ec-4901.28 at T14 (5.17 × 10<sup>5</sup>vs. 2.26 × 10<sup>4,</sup> for non-treated and phage-treated larvae, respectively; P=0.04) .</p><p><strong>Conclusion: </strong>The methodological refinements applied to establish the intestinal colonization model simplify the use of Z. morio larvae, facilitate prompt evaluation of novel decolonization approaches and reduce experiments involving vertebrate animals in accordance with the Replacement, Reduction and Refinement principles.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Romane Milleville, Linda Hadjadj, Jean-Marc Rolain, Sophie Alexandra Baron
{"title":"Study of the mechanisms of heteroresistance to colistin in a strain of Enterobacter cloacae by random mutagenesis.","authors":"Romane Milleville, Linda Hadjadj, Jean-Marc Rolain, Sophie Alexandra Baron","doi":"10.1016/j.jgar.2024.10.260","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.10.260","url":null,"abstract":"<p><p>Enterobacter cloacae complex belong to a group for which colistin resistance is not well documented, due to their frequent heteroresistance. Previous studies have examined the role of the two-component systems PhoP-PhoQ and its negative regulator mgrB or the arnBCADTEF operon. We investigated the molecular basis of colistin heteroresistance using genome analysis and random mutagenesis in a strain of Enterobacter cloacae and identified the arnA gene as responsible for colistin resistance.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tasnime Abdo Ahmad, Samar El Houjeiry, Souha S Kanj, Ghassan M Matar, Esber S Saba
{"title":"From Forgotten Cure to Modern Medicine: The Resurgence of Bacteriophage Therapy.","authors":"Tasnime Abdo Ahmad, Samar El Houjeiry, Souha S Kanj, Ghassan M Matar, Esber S Saba","doi":"10.1016/j.jgar.2024.10.259","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.10.259","url":null,"abstract":"<p><strong>Objectives: </strong>The unregulated use of antibiotics has led to the rise of antibiotic-resistant bacterial strains. This study explores bacteriophage therapy as an alternative treatment, highlighting its history, significance, and advancements in Europe, the USA, and the Middle East.</p><p><strong>Methods: </strong>A comprehensive literature review on bacteriophage therapy was conducted, focusing on its development, clinical trials, and patient treatment applications. The study also examined challenges, limitations, criteria for ideal phage selection, and manipulation techniques.</p><p><strong>Results: </strong>The USA and several European countries have advanced in phage therapy, progressing from clinical trials to patient treatment, while Middle Eastern countries are still in the early stages. Bacteriophages offer specificity, abundance, and minimal side effects, but challenges like safety concerns and potential resistance limit their widespread use.</p><p><strong>Conclusion: </strong>Bacteriophage therapy shows promise as an antibiotic alternative but faces safety and resistance challenges. Continued research and better regulatory frameworks, especially in the Middle East, are needed to realize its potential.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicolas Lauwerier, Claire Duployez, Rémi Le Guern, Frédéric Wallet, Caroline Loïez
{"title":"Rapid immunochromatographic detection of carbapenemases directly from positive blood cultures in patients colonized by carbapenemase-producing bacteria.","authors":"Nicolas Lauwerier, Claire Duployez, Rémi Le Guern, Frédéric Wallet, Caroline Loïez","doi":"10.1016/j.jgar.2024.10.261","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.10.261","url":null,"abstract":"<p><strong>Objectives: </strong>Carbapenem resistance is increasing worldwide. Earlier detection of this resistance, combined with appropriate treatment, could improve the prognosis of bloodstream infection. This study aims to evaluate the detection of carbapenemase producing gram-negative bacteria directly from positive blood cultures to quickly adapt antibiotic therapy before the results of antibiotic susceptibility testing are available.</p><p><strong>Method: </strong>A prospective single-center study was conducted over a five-month period at Lille University Hospital. Carbapenemase detection by immunochromatographic testing was performed directly from positive blood cultures with gram-negative rods of thirty-five patients previously colonized with carbapenemase-producing bacteria.</p><p><strong>Results: </strong>Among these thirty-five positive blood cultures, 15 carbapenemase-producing strains were directly detected, mainly OXA-48 and NDM. This rapid procedure provided results in less than one hour, compared to several hours for conventional methods. Of the patients with infections caused by carbapenemase-producing isolates, 67% (10 patients) received inappropriate empiric treatment, highlighting the potential of the rapid test to adjust antibiotic therapy sooner.</p><p><strong>Conclusions: </strong>Carbapenemase detection by immunochromatographic testing directly on blood culture pellets is reliable and can lead to early adaptation of antibiotic therapy in these severe infections.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
González-Espinosa Francisco, Di Pilato Vincenzo, Calabrese Luca, Costa Elisa, Costa Agustina, Gutkind Gabriel, Cejas Daniela, Radice Marcela
{"title":"Integral genomic description of bla<sub>NDM-5</sub>-harbouring plasmids recovered from Enterobacterales in Argentina.","authors":"González-Espinosa Francisco, Di Pilato Vincenzo, Calabrese Luca, Costa Elisa, Costa Agustina, Gutkind Gabriel, Cejas Daniela, Radice Marcela","doi":"10.1016/j.jgar.2024.10.258","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.10.258","url":null,"abstract":"<p><strong>Objective: </strong>To characterise four bla<sub>NDM-5</sub>-harbouring plasmids recovered in Enterobacterales isolated in Argentina.</p><p><strong>Methods: </strong>DNA was sequenced by Illumina and Oxford Nanopore technologies, assembled using Unicycler, analysed using PlasmidFinder, MOB-Typer, IslandViewer4 and Resfinder, and visualised by Proksee and Clinker. bla<sub>NDM-5</sub>-harbouring plasmids were compared with deposited similar ones using PLSDB.</p><p><strong>Results: </strong>two plasmids belonged to incompatibility group IncFII where bla<sub>NDM-5</sub> was located in a previously described genetic context, immersed in an antimicrobial resistance island (ARI). Local IncFII plasmids displayed high similarity (≥ 90% shared hashes (sh)) with four deposited in PLSDB. The other two local plasmids belonged to the multi-replicon group IncFIB-HI1B, harbouring bla<sub>NDM-5</sub> in a novel variant of the genetic context. Both multi-replicon plasmids, presented two ARI, one containing bla<sub>NDM-5</sub> in addition to other ARM; and the second ARI carrying bla<sub>CTX-M-15</sub> and a class 1 integron. Plasmids deposited in PLSDB showed low similarity to local multi-replicon plasmids. The most similar plasmids (n:5) displayed less than 60% sh showing the same Inc groups but lacking ARM.</p><p><strong>Conclusion: </strong>This study broadens the limited understanding of bla<sub>NDM-5</sub>-harbouring plasmids in Latin America. Furthermore, it represents the first description of bla<sub>NDM-5</sub> in a novel variant of the common genetic platform and its location in multi-replicon IncFIB-IncHI1B plasmids, which were not previously associated with any antimicrobial resistance marker (ARM).</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasir R Khan, Jorge A Hernandez, Subhashinie Kariyawasam, Garry Butcher, Daniel M Czyz, Abraham J Pellissery, Thomas Denagamage
{"title":"Exposure factors associated with antimicrobial resistance and identification of management practices for preharvest mitigation along the broiler production systems: a systematic review.","authors":"Yasir R Khan, Jorge A Hernandez, Subhashinie Kariyawasam, Garry Butcher, Daniel M Czyz, Abraham J Pellissery, Thomas Denagamage","doi":"10.1016/j.jgar.2024.09.010","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.09.010","url":null,"abstract":"<p><strong>Objectives: </strong>This systematic review aims to [1] determine the risk of AMR development associated with AMU and other exposure factors in broiler, and [2] identify the best management practices to mitigate preharvest AMR development in enteric bacteria along the broiler production.</p><p><strong>Methods: </strong>Study selection criteria was PECO/PICO framework and included broiler (population), AMU or other management practices (exposure or intervention), organic or antibiotic-free production (comparator), and presence of AMR-enteric bacteria/genes (outcome). Peer-reviewed primary research studies were searched in PubMed on December 19, 2022, and AGRICOLA, Embase, Scopus, and Web of Science on February 10, 2023. The risk of bias in studies was assessed using modified ROBIS-E risk of bias assessment tool. Results were synthesized and presented narratively according to PRISMA-2020 guidelines.</p><p><strong>Results: </strong>205/2699 studies were subjected to full-text review, and fifteen included in the final synthesis. Enteric bacteria Escherichia coli, Salmonella and Campylobacter exhibited AMR and multidrug resistance (MDR) against several critically important antimicrobials (aminoglycoside, cephalosporin, chloramphenicol, macrolide, penicillin, quinolone, tetracycline, and sulfonamide) for human health. The risk of AMR development in bacteria is potentially higher with AMU in broiler production. Substandard farm management practices, poor biosecurity measures, and conventional production system are also associated with dissemination of AMR in bacteria.</p><p><strong>Conclusion: </strong>Findings indicate, AMU exposure is associated with considerably higher risks of AMR development in enteric bacteria. Antimicrobial stewardship, organic/antibiotic-free broiler production, good farm management practices, and high-level biosecurity measures can substantially mitigate preharvest AMR development in enteric bacteria. However, most of the studies are cross-sectional and therefore, causal inference cannot be established.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genome sequence of a ST65 hypervirulent Klebsiella pneumoniae isolate carrying mcr-8 from China.","authors":"Weili Zhang, Hao Xu, Yaling Li, Ruishan Liu, Danfeng Lou","doi":"10.1016/j.jgar.2024.09.006","DOIUrl":"https://doi.org/10.1016/j.jgar.2024.09.006","url":null,"abstract":"<p><strong>Objectives: </strong>In this study, we report the complete genome sequence of a ST65 hypervirulent Klebsiella pneumoniae isolate carrying mcr-8 from China. The aim was to investigate its molecular characteristics and resistant mechanism.</p><p><strong>Methods: </strong>A colistin-resistant hvKP was isolated from an inpatient in China. The whole genome was sequenced on Illumina NovaSeq 6000 and long-read ONT platforms. de novo assembly was conducted using SPAdes and Unicycler. S1 nuclease pulsed-field gel electrophoresis, Southern-blot, and antimicrobial susceptibility testing were performed. Sequence type, antimicrobial resistance and virulence-related genes were predicted from the sequence. The circular maps of multiple plasmids comparisons were drawn by the BLAST Ring Image.</p><p><strong>Results: </strong>The complete genome sequence of K. pneumoniae ACESH00926 consists of one chromosome and two plasmids. ACESH00926 belongs to K2 ST65 according to the MLST scheme. ACESH00926 showed high resistance to colistin (MIC > 8 µg/mL). Several ARGs were identified, including mobile colistin-resistant gene mcr-8 which was located in an IncFIl(K)/IncFIA(HI1) type plasmid. The bigger plasmid was a pK244-like virulence plasmid. It carrying a series of virulence genes, such as the regulator of the mucoid phenotype (rmpA and rmpA2), salmochelin siderophore biosynthesis (iroB), ABC transporter (iroC), ferric aerobactin receptor (iutA), aerobactin siderophore biosynthesis protein (iucC), and aerobactin synthetase (iucA) encoded genes. And another plasmid carrying mcr-8 with a conserved genetic context (dgkA-sasA-copR-mcr-8-ccdA-ccdB-xerD-repE-parM-umuC-lexA-klcA).</p><p><strong>Conclusions: </strong>It is necessary to emphasize the necessity of monitoring a combination of colistin-resistant and hypervirulent Klebsiella pneumoniae strains in the future.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}