Frontiers in antibiotics最新文献

{"title":"Probiotics beyond the farm: Benefits, costs, and considerations of using antibiotic alternatives in livestock.","authors":"Kyle R Leistikow, Rachelle E Beattie, Krassimira R Hristova","doi":"10.3389/frabi.2022.1003912","DOIUrl":"10.3389/frabi.2022.1003912","url":null,"abstract":"<p><p>The increasing global expansion of antimicrobial resistant infections warrants the development of effective antibiotic alternative therapies, particularly for use in livestock production, an agricultural sector that is perceived to disproportionately contribute to the antimicrobial resistance (AMR) crisis by consuming nearly two-thirds of the global antibiotic supply. Probiotics and probiotic derived compounds are promising alternative therapies, and their successful use in disease prevention, treatment, and animal performance commands attention. However, insufficient or outdated probiotic screening techniques may unintentionally contribute to this crisis, and few longitudinal studies have been conducted to determine what role probiotics play in AMR dissemination in animal hosts and the surrounding environment. In this review, we briefly summarize the current literature regarding the efficacy, feasibility, and limitations of probiotics, including an evaluation of their impact on the animal microbiome and resistome and their potential to influence AMR in the environment. Probiotic application for livestock is often touted as an ideal alternative therapy that might reduce the need for antibiotic use in agriculture and the negative downstream impacts. However, as detailed in this review, limited research has been conducted linking probiotic usage with reductions in AMR in agricultural or natural environments. Additionally, we discuss the methods, including limitations, of current probiotic screening techniques across the globe, highlighting approaches aimed at reducing antibiotic usage and ensuring safe and effective probiotic mediated health outcomes. Based on this information, we propose economic and logistical considerations for bringing probiotic therapies to market including regulatory roadblocks, future innovations, and the significant gaps in knowledge requiring additional research to ensure probiotics are suitable long-term options for livestock producers as an antibiotic alternative therapy.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"1003912"},"PeriodicalIF":0.0,"publicationDate":"2022-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44485793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Grand challenge in antibiotic pharmacology: A major step toward tailored antimicrobial treatment in very complex clinical scenarios of infectious risk management.","authors":"Federico Pea","doi":"10.3389/frabi.2022.1016760","DOIUrl":"10.3389/frabi.2022.1016760","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"1016760"},"PeriodicalIF":0.0,"publicationDate":"2022-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44297300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A whole-genome assay identifies four principal gene functions that confer tolerance of meropenem stress upon <i>Escherichia coli</i>.","authors":"Nicholas M Thomson, A Keith Turner, Muhammad Yasir, Sarah Bastkowski, Martin Lott, Mark A Webber, Ian G Charles","doi":"10.3389/frabi.2022.957942","DOIUrl":"10.3389/frabi.2022.957942","url":null,"abstract":"<p><p>We report here the identification of four gene functions of principal importance for the tolerance of meropenem stress in <i>Escherichia coli</i>: cell division, cell envelope synthesis and maintenance, ATP metabolism, and transcription regulation. The primary mechanism of β-lactam antibiotics such as meropenem is inhibition of penicillin binding proteins, thus interfering with peptidoglycan crosslinking, weakening the cell envelope, and promoting cell lysis. However, recent systems biology approaches have revealed numerous downstream effects that are triggered by cell envelope damage and involve diverse cell processes. Subpopulations of persister cells can also arise, which can survive elevated concentrations of meropenem despite the absence of a specific resistance factor. We used Transposon-Directed Insertion Sequencing with inducible gene expression to simultaneously assay the effects of upregulation, downregulation, and disruption of every gene in a model <i>E. coli</i> strain on survival of exposure to four concentrations of meropenem. Automated Gene Functional Classification and manual categorization highlighted the importance at all meropenem concentrations of genes involved in peptidoglycan remodeling during cell division, suggesting that cell division is the primary function affected by meropenem. Genes involved in cell envelope synthesis and maintenance, ATP metabolism, and transcriptional regulation were generally important at higher meropenem concentrations, suggesting that these three functions are therefore secondary or downstream targets. Our analysis revealed the importance of multiple two-component signal transduction mechanisms, suggesting an as-yet unexplored coordinated transcriptional response to meropenem stress. The inclusion of an inducible, transposon-encoded promoter allowed sensitive detection of genes involved in proton transport, ATP production and tRNA synthesis, for which modulation of expression affects survival in the presence of meropenem: a finding that would not be possible with other technologies. We were also able to suggest new targets for future antibiotic development or for synergistic effects between gene or protein inhibitors and existing antibiotics. Overall, in a single massively parallel assay we were able to recapitulate many of the findings from decades of research into β-lactam antibiotics, add to the list of genes known to be important for meropenem tolerance, and categorize the four principal gene functions involved.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"957942"},"PeriodicalIF":0.0,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46048747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of drug-induced phenotypical resistance: Is isoniazid radicalizing <i>M. tuberculosis</i>?","authors":"Rjh Hammond, Frank Kloprogge, O Della Pasqua, Stephen H Gillespie","doi":"10.3389/frabi.2022.928365","DOIUrl":"10.3389/frabi.2022.928365","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis treatment duration is long and does not guarantee eradication of infection. Shorter treatment regimens are a critical research objective to improve uptake and reduce the risk of relapse and bacterial resistance. The explanation for the need to continue treatment after patients are culture negative remains elusive. We have previously shown that the presence of lipid inclusions in mycobacterial cells is associated with an increase in antibiotic resistance.</p><p><strong>Aim: </strong>We investigate the bactericidal effect of isoniazid and rifampicin on the expression of lipid inclusions and characterize the degree of the associated phenotypic antibiotic resistance to a range of anti-tuberculosis agents in current use.</p><p><strong>Methods: </strong>Antibiotic killing effect for both <i>M. tuberculosis</i> and <i>M. komossense</i> were investigated by both hollow fiber bioreactor (HFS) studies and static time kill curve (STKC) experiments. Following STKC cultures were stained with resazurin, Sytox green and Nile red to establish their live/dead (resazurin positive/Sytox positive) and lipid inclusion status, respectively. In addition, <i>M. komossense</i> was studied in the hollow fiber bioreactor model (HFS) and exposed to isoniazid (H) and rifampicin (R). The MIC of current antituberculosis agents for cells from the treated hollow fiber experiments were tested.</p><p><strong>Results: </strong>Antibiotic killing was similar for both species. For <i>M. komossense</i>; isoniazid was ineffective at the established MIC (1 mg/L) in the hollow fiber bioreactor but rifampicin reduced the viable count rapidly at MIC (0.4 mg/L). When the two drugs were combined at their respective MICs the killing effect was significant and greater than separately. Cells exposed to isoniazid (1x and 9x MIC) for 168 h showed considerable numbers of recoverable viable cells when compared with a combination of 1x MIC R & H where there were no viable cells detectable. For both drugs the number of lipid body positive cells increased over time and this effect was most pronounced for isoniazid and was associated with phenotypic resistance to multiple anti-tuberculosis drugs.</p><p><strong>Conclusion: </strong>Our results showed that isoniazid is a potent stimulator of lipid body accumulation, culture persistence, and phenotypic resistance to multiple anti-tuberculosis drugs. These findings emphasize the importance of understanding mechanisms of drug-drug interactions and phenotypic resistance in regimen building.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"928365"},"PeriodicalIF":0.0,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47849827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of extended-spectrum beta-lactamase producing Enterobacteriaceae in Qatar: A 3-year hospital-based study.","authors":"Musaed Alsamawi, Anwar I Joudeh, Yaseer Eldeeb, Ayman Al-Dahshan, Fahmi Khan, Wissam Ghadban, Muna Almaslamani, Abdulatif Alkhal","doi":"10.3389/frabi.2022.980686","DOIUrl":"10.3389/frabi.2022.980686","url":null,"abstract":"<p><strong>Background: </strong>The incidence of ESBL infections is exponentially increasing with variable prevalence among geographical areas and treatment settings. Identifying local prevalence rate and patient-related factors will help in earlier recognition and initiation of appropriate antibiotics treatment of patients with ESBL infections.</p><p><strong>Methods: </strong>Retrospective analysis of all positive cultures for ESBL producing Enterobacteriaceae collected in Al-Khor hospital from January 2010 to December 2012. ESBL bacterial isolates reported as cephalosporin-resistant or ESBL using the automated VITEK Gram-Negative Susceptibility System with cards GNS 206 and 121 were screened for ESBL detection using the disk diffusion method in keeping with the Clinical and Laboratory Standards Institute. Both descriptive and analytic statistics were applied when appropriate, and univariate analysis was used to identify significant factors.</p><p><strong>Results: </strong>Most of the ESBL-producing bacterial isolates were <i>E. coli</i>, which were also resistant to other classes of antimicrobials. Meropenem, amikacin and nitrofurantoin retained good coverage to most isolates. Klebsiella pneumonia infection was most likely associated with diabetes mellitus (<i>p</i> = 0.004), hospital-acquired infection (<i>p</i> = 0.046) and with more severe infection (<i>p</i> = 0.006). ESBL associated hospital-acquired infections were more likely to occur in older patients, those with comorbidities and with invasive device use. ESBL-associated urinary tract infections were most commonly community-acquired while ESBL associated respiratory tract infections were acquired from hospitals (<i>p</i> = < 0.001). Factors associated with mortality include treatment in the ICU (OR 104.8 [9.82-1116.96] <i>p</i> < 0.001), sepsis/septic shock (OR 20.80 (5.68-76.12) <i>p</i> < 0.001), hospital-acquired infections (OR 8.80 [1.88-41.16] <i>p</i> = 0.006) and bacteremia (OR 8.80 [1.63-47.5] <i>p</i> = 0.013).</p><p><strong>Conclusion: </strong>Multiple risk factors were associated with ESBL infections both in the community and hospital setting. Prediction tools are needed to improve the protocol of appropriate empiric antibiotic selection while preserving antimicrobial stewardship recommendations.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"980686"},"PeriodicalIF":0.0,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43931137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Grand challenge of antibiotics resistance: A global, multidisciplinary effort is needed.","authors":"Jianping Xie","doi":"10.3389/frabi.2022.984076","DOIUrl":"10.3389/frabi.2022.984076","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"984076"},"PeriodicalIF":0.0,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43663269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Antimicrobial Treatment Assessment of <i>Serratia marcescens</i> Bacteremia and Endocarditis.","authors":"Douglas Slain, Catessa Howard, C Garret Cooper","doi":"10.3389/frabi.2022.942721","DOIUrl":"10.3389/frabi.2022.942721","url":null,"abstract":"<p><p>We assessed the treatment of <i>Serratia marcescens</i> bacteremia and endocarditis in one of the largest single center studies. We could not identify an advantage with any particular antibiotic treatment regimen in this study. Induction of AmpC or selection of ESBL organisms was not displayed by any of the organisms.</p>","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"3 1","pages":"942721"},"PeriodicalIF":0.0,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91258606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Field Grand Challenge Frontiers in Antibiotics.","authors":"Stephen Henry Gillespie","doi":"10.3389/frabi.2022.897071","DOIUrl":"10.3389/frabi.2022.897071","url":null,"abstract":"","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":"897071"},"PeriodicalIF":0.0,"publicationDate":"2022-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43622168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}