Pub Date : 2024-08-30DOI: 10.3390/antibiotics13090822
Marta Freitas, Paulo Andrade, Ricardo Pinto, Fernanda Trigo, Ana Azevedo, Francisco Almeida
Introduction: Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. Methods: We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. Results: The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia.
{"title":"Variation in Antibiotic Prescription in High-Risk Febrile Neutropenia in Portuguese Hospitals","authors":"Marta Freitas, Paulo Andrade, Ricardo Pinto, Fernanda Trigo, Ana Azevedo, Francisco Almeida","doi":"10.3390/antibiotics13090822","DOIUrl":"https://doi.org/10.3390/antibiotics13090822","url":null,"abstract":"Introduction: Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. Methods: We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. Results: The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.3390/antibiotics13090825
Tilden M. Mitchell, Tin Ho, Liseth Salinas, Thomas VanderYacht, Nikolina Walas, Gabriel Trueba, Jay P. Graham
There is little information available on antibiotic resistance (ABR) within shrimp aquaculture environments. The aim of this study was to investigate the presence of antibiotic resistance genes (ARGs) in shrimp farming operations in Atacames, Ecuador. Water samples (n = 162) and shrimp samples (n = 54) were collected from three shrimp farming operations. Samples were cultured and a subset of isolates that grew in the presence of ceftriaxone, a third-generation cephalosporin, were analyzed using whole-genome sequencing (WGS). Among the sequenced isolates (n = 44), 73% of the isolates contained at least one ARG and the average number of ARGs per isolate was two, with a median of 3.5 ARGs. Antibiotic resistance genes that confer resistance to the β-lactam class of antibiotics were observed in 65% of the sequenced isolates from water (20/31) and 54% of the isolates from shrimp (7/13). We identified 61 different ARGs across the 44 sequenced isolates, which conferred resistance to nine antibiotic classes. Over half of all sequenced isolates (59%, n = 26) carried ARGs that confer resistance to more than one class of antibiotics. ARGs for certain antibiotic classes were more common, including beta-lactams (26 ARGs); aminoglycosides (11 ARGs); chloramphenicol (three ARGs); and trimethoprim (four ARGs). Sequenced isolates consisted of a diverse array of bacterial orders and species, including Escherichia coli (48%), Klebsiella pneumoniae (7%), Aeromonadales (7%), Pseudomonadales (16%), Enterobacter cloacae (2%), and Citrobacter freundii (2%). Many ARGs were shared across diverse species, underscoring the risk of horizontal gene transfer in these environments. This study indicated the widespread presence of extended-spectrum β-lactamase (ESBL) genes in shrimp aquaculture, including blaCTX-M, blaSHV, and blaTEM genes. Increased antibiotic resistance surveillance of shrimp farms and identification of aquaculture operation-level risk factors, such as antibiotic use, will likely be important for mitigating the spread of ARGs of clinical significance.
{"title":"Analysis of Antibiotic Resistance Genes (ARGs) across Diverse Bacterial Species in Shrimp Aquaculture","authors":"Tilden M. Mitchell, Tin Ho, Liseth Salinas, Thomas VanderYacht, Nikolina Walas, Gabriel Trueba, Jay P. Graham","doi":"10.3390/antibiotics13090825","DOIUrl":"https://doi.org/10.3390/antibiotics13090825","url":null,"abstract":"There is little information available on antibiotic resistance (ABR) within shrimp aquaculture environments. The aim of this study was to investigate the presence of antibiotic resistance genes (ARGs) in shrimp farming operations in Atacames, Ecuador. Water samples (n = 162) and shrimp samples (n = 54) were collected from three shrimp farming operations. Samples were cultured and a subset of isolates that grew in the presence of ceftriaxone, a third-generation cephalosporin, were analyzed using whole-genome sequencing (WGS). Among the sequenced isolates (n = 44), 73% of the isolates contained at least one ARG and the average number of ARGs per isolate was two, with a median of 3.5 ARGs. Antibiotic resistance genes that confer resistance to the β-lactam class of antibiotics were observed in 65% of the sequenced isolates from water (20/31) and 54% of the isolates from shrimp (7/13). We identified 61 different ARGs across the 44 sequenced isolates, which conferred resistance to nine antibiotic classes. Over half of all sequenced isolates (59%, n = 26) carried ARGs that confer resistance to more than one class of antibiotics. ARGs for certain antibiotic classes were more common, including beta-lactams (26 ARGs); aminoglycosides (11 ARGs); chloramphenicol (three ARGs); and trimethoprim (four ARGs). Sequenced isolates consisted of a diverse array of bacterial orders and species, including Escherichia coli (48%), Klebsiella pneumoniae (7%), Aeromonadales (7%), Pseudomonadales (16%), Enterobacter cloacae (2%), and Citrobacter freundii (2%). Many ARGs were shared across diverse species, underscoring the risk of horizontal gene transfer in these environments. This study indicated the widespread presence of extended-spectrum β-lactamase (ESBL) genes in shrimp aquaculture, including blaCTX-M, blaSHV, and blaTEM genes. Increased antibiotic resistance surveillance of shrimp farms and identification of aquaculture operation-level risk factors, such as antibiotic use, will likely be important for mitigating the spread of ARGs of clinical significance.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January–August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus, A. baumannii, Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia, and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients.
{"title":"The Profile of Bacterial Infections in a Burn Unit during and after the COVID-19 Pandemic Period","authors":"Corina Musuroi, Silvia-Ioana Musuroi, Luminita Baditoiu, Zorin Crainiceanu, Delia Muntean, Adela Voinescu, Oana Izmendi, Alexandra Sirmon, Monica Licker","doi":"10.3390/antibiotics13090823","DOIUrl":"https://doi.org/10.3390/antibiotics13090823","url":null,"abstract":"Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January–August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus, A. baumannii, Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia, and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"181 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.3390/antibiotics13090824
Yasser Almogbel, Mugahid A. Mobark, Masaad S. Almutairi, Faisal S. Almogbel, Syed I. Rabbani, Sultan Alhathloul, Shada Alamro, Lateefah Alatallah
The optimal use of antibiotics represents a cornerstone in controlling antibiotic resistance. Strategies such as antibiotic stewardship programs (ASPs) have been developed to influence the rational use of antibiotics. This study evaluated the appropriateness of the empirical use of antibiotics based on antibiotic susceptibility results with the aim of participating effectively in improving local ASPs. In a cross-sectional study conducted at a tertiary hospital in Saudi Arabia, 500 inpatients received empirical antibiotics, and their culture and sensitivity results were included. The appropriateness of the empirical use of antibiotics was determined based on their alignment with the culture and sensitivity results. More than half of the participants (56.4%) were men, and nearly half (43%) were over 61 years old. The empirical uses of antibiotics were appropriately prescribed in 58% of the patients. Ciprofloxacin and ceftriaxone were the most prescribed antibiotics, while vancomycin, piperacillin–tazobactam, and tigecycline were the most appropriately prescribed antibiotics. E. coli was the main microorganism isolated in the susceptibility results and was appropriately prescribed in 59% of the patients. The highest microbial sensitivity was observed for linezolid, vancomycin, and tigecycline. Antibiotics were appropriately prescribed empirically in more than half of the participants. Activating interventional ASP is crucial to fill the gap in prescribing antimicrobials. Considering the expected type of organisms and the local susceptibility pattern is likely to yield a more appropriate empirical use of antibiotics.
抗生素的优化使用是控制抗生素耐药性的基石。抗生素监管计划（ASPs）等策略的制定旨在影响抗生素的合理使用。本研究评估了根据抗生素药敏结果经验性使用抗生素的适当性，目的是有效参与改进当地的 ASP。在沙特阿拉伯一家三级医院进行的横断面研究中，500 名住院病人接受了经验性抗生素治疗，其培养和药敏结果均被纳入研究范围。根据培养和药敏结果确定经验性使用抗生素的适当性。半数以上（56.4%）的参与者为男性，近一半（43%）的参与者年龄在 61 岁以上。58%的患者在经验性使用抗生素时处方得当。环丙沙星和头孢曲松是处方量最大的抗生素，而万古霉素、哌拉西林-他唑巴坦和替加环素则是处方量最适当的抗生素。大肠杆菌是药敏结果中分离出的主要微生物，59%的患者可适当处方大肠杆菌。利奈唑胺、万古霉素和替加环素的微生物敏感性最高。半数以上的参与者在经验处方中使用了抗生素。启动介入性 ASP 对于填补抗菌药物处方的空白至关重要。考虑到预期的生物类型和当地的药敏模式，很可能会更恰当地根据经验使用抗生素。
{"title":"The Appropriateness of Empirical Uses of Antibiotics Based on Antimicrobial Susceptibility Results for Inpatients at a Tertiary Hospital in Saudi Arabia","authors":"Yasser Almogbel, Mugahid A. Mobark, Masaad S. Almutairi, Faisal S. Almogbel, Syed I. Rabbani, Sultan Alhathloul, Shada Alamro, Lateefah Alatallah","doi":"10.3390/antibiotics13090824","DOIUrl":"https://doi.org/10.3390/antibiotics13090824","url":null,"abstract":"The optimal use of antibiotics represents a cornerstone in controlling antibiotic resistance. Strategies such as antibiotic stewardship programs (ASPs) have been developed to influence the rational use of antibiotics. This study evaluated the appropriateness of the empirical use of antibiotics based on antibiotic susceptibility results with the aim of participating effectively in improving local ASPs. In a cross-sectional study conducted at a tertiary hospital in Saudi Arabia, 500 inpatients received empirical antibiotics, and their culture and sensitivity results were included. The appropriateness of the empirical use of antibiotics was determined based on their alignment with the culture and sensitivity results. More than half of the participants (56.4%) were men, and nearly half (43%) were over 61 years old. The empirical uses of antibiotics were appropriately prescribed in 58% of the patients. Ciprofloxacin and ceftriaxone were the most prescribed antibiotics, while vancomycin, piperacillin–tazobactam, and tigecycline were the most appropriately prescribed antibiotics. E. coli was the main microorganism isolated in the susceptibility results and was appropriately prescribed in 59% of the patients. The highest microbial sensitivity was observed for linezolid, vancomycin, and tigecycline. Antibiotics were appropriately prescribed empirically in more than half of the participants. Activating interventional ASP is crucial to fill the gap in prescribing antimicrobials. Considering the expected type of organisms and the local susceptibility pattern is likely to yield a more appropriate empirical use of antibiotics.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.3390/antibiotics13090821
Claudia Patricia Barrera Patiño, Jennifer Machado Soares, Kate Cristina Blanco, Vanderlei Salvador Bagnato
Recent studies introduced the importance of using machine learning algorithms in research focused on the identification of antibiotic resistance. In this study, we highlight the importance of building solid machine learning foundations to differentiate antimicrobial resistance among microorganisms. Using advanced machine learning algorithms, we established a methodology capable of analyzing the FTIR structural profile of the samples of Streptococcus pyogenes and Streptococcus mutans (Gram-positive), as well as Escherichia coli and Klebsiella pneumoniae (Gram-negative), demonstrating cross-sectional applicability in this focus on different microorganisms. The analysis focuses on specific biomolecules—Carbohydrates, Fatty Acids, and Proteins—in FTIR spectra, providing a multidimensional database that transcends microbial variability. The results highlight the ability of the method to consistently identify resistance patterns, regardless of the Gram classification of the bacteria and the species involved, reinforcing the premise that the structural characteristics identified are universal among the microorganisms tested. By validating this approach in four distinct species, our study proves the versatility and precision of the methodology used, in addition to bringing support to the development of an innovative protocol for the rapid and safe identification of antimicrobial resistance. This advance is crucial for optimizing treatment strategies and avoiding the spread of resistance. This emphasizes the relevance of specialized machine learning bases in effectively differentiating between resistance profiles in Gram-negative and Gram-positive bacteria to be implemented in the identification of antibiotic resistance. The obtained result has a high potential to be applied to clinical procedures.
{"title":"Machine Learning in FTIR Spectrum for the Identification of Antibiotic Resistance: A Demonstration with Different Species of Microorganisms","authors":"Claudia Patricia Barrera Patiño, Jennifer Machado Soares, Kate Cristina Blanco, Vanderlei Salvador Bagnato","doi":"10.3390/antibiotics13090821","DOIUrl":"https://doi.org/10.3390/antibiotics13090821","url":null,"abstract":"Recent studies introduced the importance of using machine learning algorithms in research focused on the identification of antibiotic resistance. In this study, we highlight the importance of building solid machine learning foundations to differentiate antimicrobial resistance among microorganisms. Using advanced machine learning algorithms, we established a methodology capable of analyzing the FTIR structural profile of the samples of Streptococcus pyogenes and Streptococcus mutans (Gram-positive), as well as Escherichia coli and Klebsiella pneumoniae (Gram-negative), demonstrating cross-sectional applicability in this focus on different microorganisms. The analysis focuses on specific biomolecules—Carbohydrates, Fatty Acids, and Proteins—in FTIR spectra, providing a multidimensional database that transcends microbial variability. The results highlight the ability of the method to consistently identify resistance patterns, regardless of the Gram classification of the bacteria and the species involved, reinforcing the premise that the structural characteristics identified are universal among the microorganisms tested. By validating this approach in four distinct species, our study proves the versatility and precision of the methodology used, in addition to bringing support to the development of an innovative protocol for the rapid and safe identification of antimicrobial resistance. This advance is crucial for optimizing treatment strategies and avoiding the spread of resistance. This emphasizes the relevance of specialized machine learning bases in effectively differentiating between resistance profiles in Gram-negative and Gram-positive bacteria to be implemented in the identification of antibiotic resistance. The obtained result has a high potential to be applied to clinical procedures.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.3390/antibiotics13090814
Addisu D. Teklemariam, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Ishtiaq Qadri, Turki Alamri, Ahmed Esmael, Steve Harakeh
The journal retracts the article, “Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa”, cited above [...]
{"title":"RETRACTED: Teklemariam et al. Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa. Antibiotics 2023, 12, 497","authors":"Addisu D. Teklemariam, Rashad R. Al-Hindi, Mona G. Alharbi, Ibrahim Alotibi, Sheren A. Azhari, Ishtiaq Qadri, Turki Alamri, Ahmed Esmael, Steve Harakeh","doi":"10.3390/antibiotics13090814","DOIUrl":"https://doi.org/10.3390/antibiotics13090814","url":null,"abstract":"The journal retracts the article, “Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa”, cited above [...]","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.3390/antibiotics13090818
Jeffrey W. Kwong, Michael Abramowicz, Klaus Dieter Kühn, Christian Foelsch, Erik N. Hansen
Introduction: Prosthetic joint infections (PJIs) are difficult to treat and represent a significant burden to the healthcare system. Two-stage revision surgery with placement of an antibiotic-loaded cement spacer is currently the gold standard for treatment in the United States for late-onset infections. We evaluate the efficacy of varying doses of vancomycin added to antibiotic-containing acrylic cement spacers and discuss the biomechanical and antimicrobial properties of using high versus low doses of vancomycin in cement spacers in the hip and knee. Materials and Methods: Commercially available Copal cement containing either gentamicin and clindamycin (G + C) or gentamicin and vancomycin (G + V) was prepared with the manual addition of low (2 g) and high (6 g) doses of vancomycin. In vitro mechanical testing was then carried out according to ISO 5833 and DIN 53435, as well as inhibition zone assays against common PJI pathogens. Additionally, inhibition zone assays were conducted on two commercially available prefabricated spacers containing gentamicin: Copal Exchange G and Cemex Spacer-K. Results: In biomechanical testing, Copal G + V with the addition of 6 g of vancomycin failed to meet the ISO standard. Copal G + C and Copal G + V with low and high dosages of vancomycin were all effective against the tested pathogens and displayed constant efficacy for a duration of 42 days. High doses of vancomycin showed significantly lower mechanical stability. Moreover, Copal Exchange G showed significantly larger inhibition zones across 42 days. Discussion: While higher concentrations of vancomycin appear to improve the antimicrobial efficacy of cement, they also reduce its mechanical stability. Despite its smoother surface, the Copal Exchange G spacer exhibits large inhibition zones after 1 day and maintains consistently large inhibition zones over 6 weeks. Thus, it may be preferred for use in two-stage revision surgery. Conclusion: Copal Exchange G is more effective than Cemex Spacer K against S. aureus and E. coli. The manual addition of vancomycin to cement containing double antibiotics is very effective. The influence on ISO compression is low, the ISO bending modulus is increased, and ISO bending, DIN bending, and DIN impact, are reduced.
导言：人工关节感染（PJIs）难以治疗，给医疗系统带来了沉重负担。目前，在美国，两阶段翻修手术和植入抗生素骨水泥垫片是治疗晚期感染的金标准。我们评估了在含抗生素的丙烯酸骨水泥垫片中添加不同剂量万古霉素的疗效，并讨论了在髋关节和膝关节骨水泥垫片中使用高剂量和低剂量万古霉素的生物力学和抗菌特性。材料和方法：制备含有庆大霉素和克林霉素（G + C）或庆大霉素和万古霉素（G + V）的市售 Copal 骨水泥，并手动添加低剂量（2 克）和高剂量（6 克）的万古霉素。然后根据 ISO 5833 和 DIN 53435 标准进行了体外机械测试，并对常见的 PJI 病原体进行了抑制区检测。此外，还对两种含有庆大霉素的市售预制垫片进行了抑菌区检测：Copal Exchange G 和 Cemex Spacer-K。结果在生物力学测试中，添加了 6 克万古霉素的 Copal G + V 未达到 ISO 标准。添加了低剂量和高剂量万古霉素的 Copal G + C 和 Copal G + V 均能有效抵抗受测病原体，并在 42 天的持续时间内显示出稳定的功效。高剂量万古霉素的机械稳定性明显较低。此外，Copal Exchange G 在 42 天内的抑菌区明显更大。讨论：虽然高浓度的万古霉素似乎能提高骨水泥的抗菌效果，但同时也会降低其机械稳定性。尽管Copal Exchange G垫片的表面更光滑，但它在1天后就显示出较大的抑菌区，并在6周内持续保持较大的抑菌区。因此，在两阶段翻修手术中，它可能是首选。结论：Copal Exchange G 比 Cemex Spacer K 对金黄色葡萄球菌和大肠杆菌更有效。在含有双重抗生素的骨水泥中手动添加万古霉素非常有效。对ISO压缩的影响较小，ISO弯曲模量增加，ISO弯曲、DIN弯曲和DIN冲击降低。
{"title":"High and Low Dosage of Vancomycin in Polymethylmethacrylate Cements: Efficacy and Mechanical Properties","authors":"Jeffrey W. Kwong, Michael Abramowicz, Klaus Dieter Kühn, Christian Foelsch, Erik N. Hansen","doi":"10.3390/antibiotics13090818","DOIUrl":"https://doi.org/10.3390/antibiotics13090818","url":null,"abstract":"Introduction: Prosthetic joint infections (PJIs) are difficult to treat and represent a significant burden to the healthcare system. Two-stage revision surgery with placement of an antibiotic-loaded cement spacer is currently the gold standard for treatment in the United States for late-onset infections. We evaluate the efficacy of varying doses of vancomycin added to antibiotic-containing acrylic cement spacers and discuss the biomechanical and antimicrobial properties of using high versus low doses of vancomycin in cement spacers in the hip and knee. Materials and Methods: Commercially available Copal cement containing either gentamicin and clindamycin (G + C) or gentamicin and vancomycin (G + V) was prepared with the manual addition of low (2 g) and high (6 g) doses of vancomycin. In vitro mechanical testing was then carried out according to ISO 5833 and DIN 53435, as well as inhibition zone assays against common PJI pathogens. Additionally, inhibition zone assays were conducted on two commercially available prefabricated spacers containing gentamicin: Copal Exchange G and Cemex Spacer-K. Results: In biomechanical testing, Copal G + V with the addition of 6 g of vancomycin failed to meet the ISO standard. Copal G + C and Copal G + V with low and high dosages of vancomycin were all effective against the tested pathogens and displayed constant efficacy for a duration of 42 days. High doses of vancomycin showed significantly lower mechanical stability. Moreover, Copal Exchange G showed significantly larger inhibition zones across 42 days. Discussion: While higher concentrations of vancomycin appear to improve the antimicrobial efficacy of cement, they also reduce its mechanical stability. Despite its smoother surface, the Copal Exchange G spacer exhibits large inhibition zones after 1 day and maintains consistently large inhibition zones over 6 weeks. Thus, it may be preferred for use in two-stage revision surgery. Conclusion: Copal Exchange G is more effective than Cemex Spacer K against S. aureus and E. coli. The manual addition of vancomycin to cement containing double antibiotics is very effective. The influence on ISO compression is low, the ISO bending modulus is increased, and ISO bending, DIN bending, and DIN impact, are reduced.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.3390/antibiotics13090815
Olga Pacios, Soraya Herrera-Espejo, Lucía Armán, Clara Ibarguren-Quiles, Lucía Blasco, Inés Bleriot, Laura Fernández-García, Concha Ortiz-Cartagena, María Paniagua, Antonio Barrio-Pujante, Belén Aracil, José Miguel Cisneros, María Eugenia Pachón-Ibáñez, María Tomás
The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.
由于细菌更容易克服单药治疗而非多药治疗，因此将多种治疗策略结合起来通常被视为降低耐药率的好方法。当多个靶点和亚群都受到影响时，这种策略尤其具有吸引力，肺炎克雷伯氏菌的持久细胞就是这种情况，它是一种能在抗生素暴露下短暂存活的细菌亚群。这项研究的目的是评估一种重新利用的抗癌药物--丝裂霉素 C 与肺炎克雷伯氏菌溶菌噬菌体 vB_KpnM-VAC13 在体外结合使用的潜力，以及它在体内小鼠模型中对两种临床分离的肺炎克雷伯氏菌病原体的安全性，其中一种病原体表现出亚胺培南持久细胞表型。同时，我们还利用人体软骨细胞系 T/C28a2 验证了该浓度的丝裂霉素 C 无毒性。我们使用细胞毒性测定法和流式细胞仪检测了这些人体细胞的存活率。
{"title":"Mitomycin C as an Anti-Persister Strategy against Klebsiella pneumoniae: Toxicity and Synergy Studies","authors":"Olga Pacios, Soraya Herrera-Espejo, Lucía Armán, Clara Ibarguren-Quiles, Lucía Blasco, Inés Bleriot, Laura Fernández-García, Concha Ortiz-Cartagena, María Paniagua, Antonio Barrio-Pujante, Belén Aracil, José Miguel Cisneros, María Eugenia Pachón-Ibáñez, María Tomás","doi":"10.3390/antibiotics13090815","DOIUrl":"https://doi.org/10.3390/antibiotics13090815","url":null,"abstract":"The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.3390/antibiotics13090816
Jayaram Lakshmaiah Narayana, Abraham Fikru Mechesso, Imran Ibni Gani Rather, D. Zarena, Jinghui Luo, Jingwei Xie, Guangshun Wang
This review describes the discovery, structure, activity, engineered constructs, and applications of KR-12, the smallest antibacterial peptide of human cathelicidin LL-37, the production of which can be induced under sunlight or by vitamin D. It is a moonlighting peptide that shows both antimicrobial and immune-regulatory effects. Compared to LL-37, KR-12 is extremely appealing due to its small size, lack of toxicity, and narrow-spectrum antimicrobial activity. Consequently, various KR-12 peptides have been engineered to tune peptide activity and stability via amino acid substitution, end capping, hybridization, conjugation, sidechain stapling, and backbone macrocyclization. We also mention recently discovered peptides KR-8 and RIK-10 that are shorter than KR-12. Nano-formulation provides an avenue to targeted delivery, controlled release, and increased bioavailability. In addition, KR-12 has been covalently immobilized on biomaterials/medical implants to prevent biofilm formation. These constructs with enhanced potency and stability are demonstrated to eradicate drug-resistant pathogens, disrupt preformed biofilms, neutralize endotoxins, and regulate host immune responses. Also highlighted are the safety and efficacy of these peptides in various topical and systemic animal models. Finaly, we summarize the achievements and discuss future developments of KR-12 peptides as cosmetic preservatives, novel antibiotics, anti-inflammatory peptides, and microbiota-restoring agents.
{"title":"Origami of KR-12 Designed Antimicrobial Peptides and Their Potential Applications","authors":"Jayaram Lakshmaiah Narayana, Abraham Fikru Mechesso, Imran Ibni Gani Rather, D. Zarena, Jinghui Luo, Jingwei Xie, Guangshun Wang","doi":"10.3390/antibiotics13090816","DOIUrl":"https://doi.org/10.3390/antibiotics13090816","url":null,"abstract":"This review describes the discovery, structure, activity, engineered constructs, and applications of KR-12, the smallest antibacterial peptide of human cathelicidin LL-37, the production of which can be induced under sunlight or by vitamin D. It is a moonlighting peptide that shows both antimicrobial and immune-regulatory effects. Compared to LL-37, KR-12 is extremely appealing due to its small size, lack of toxicity, and narrow-spectrum antimicrobial activity. Consequently, various KR-12 peptides have been engineered to tune peptide activity and stability via amino acid substitution, end capping, hybridization, conjugation, sidechain stapling, and backbone macrocyclization. We also mention recently discovered peptides KR-8 and RIK-10 that are shorter than KR-12. Nano-formulation provides an avenue to targeted delivery, controlled release, and increased bioavailability. In addition, KR-12 has been covalently immobilized on biomaterials/medical implants to prevent biofilm formation. These constructs with enhanced potency and stability are demonstrated to eradicate drug-resistant pathogens, disrupt preformed biofilms, neutralize endotoxins, and regulate host immune responses. Also highlighted are the safety and efficacy of these peptides in various topical and systemic animal models. Finaly, we summarize the achievements and discuss future developments of KR-12 peptides as cosmetic preservatives, novel antibiotics, anti-inflammatory peptides, and microbiota-restoring agents.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The propagation of antibiotic resistance in environments, particularly aquatic environments that serve as primary pathways for antibiotic resistance genes (ARGs), poses significant health risks. The impact of nutrients, as key determinants of bacterial growth and metabolism, on the propagation of ARGs, particularly extracellular ARGs (eARGs), remains poorly understood. In this study, we collected microorganisms from the Yangtze River and established a series of microcosms to investigate how variations in nutrient levels and delivery frequency affect the relative abundance of intracellular ARGs (iARGs) and eARGs in bacterial communities. Our results show that the relative abundance of 7 out of 11 representative eARGs in water exceeds that of iARGs, while 8 iARGs dominate in biofilms. Notably, iARGs and eARGs consistently exhibited opposite responses to nutrient variation. When nutrient levels increased, iARGs in the water also increased, with the polluted group (COD = 333.3 mg/L, COD:N:P = 100:3:0.6, m/m) and the eutrophic group (COD = 100 mg/L, COD:N:P = 100:25:5, m/m) showing 1.2 and 3.2 times higher levels than the normal group (COD = 100 mg/L, COD:N:P = 100:10:2, m/m), respectively. In contrast, eARGs decreased by 6.7% and 8.4% in these groups. On the other hand, in biofilms, higher nutrient levels led to an increase in eARGs by 1.5 and 1.7 times, while iARGs decreased by 17.5% and 50.1% in the polluted and eutrophic groups compared to the normal group. Moreover, while increasing the frequency of nutrient delivery (from 1 time/10 d to 20 times/10 d) generally did not favor iARGs in either water or biofilm, it selectively enhanced eARGs in both. To further understand these dynamics, we developed an ARGs-nutrient model by integrating the Lotka–Volterra and Monod equations. The results highlight the complex interplay of bacterial growth, nutrient availability, and mechanisms such as horizontal gene transfer and secretion influencing ARGs’ propagation, driving the opposite trend between these two forms of ARGs. This contrasting response between iARGs and eARGs contributes to a dynamic balance that stabilizes bacterial resistance levels amid nutrient fluctuations. This study offers helpful implications regarding the persistence of bacterial resistance in the environment.
{"title":"Contrasting Dynamics of Intracellular and Extracellular Antibiotic Resistance Genes in Response to Nutrient Variations in Aquatic Environments","authors":"Lele Liu, Xinyi Zou, Yuan Cheng, Huihui Li, Xueying Zhang, Qingbin Yuan","doi":"10.3390/antibiotics13090817","DOIUrl":"https://doi.org/10.3390/antibiotics13090817","url":null,"abstract":"The propagation of antibiotic resistance in environments, particularly aquatic environments that serve as primary pathways for antibiotic resistance genes (ARGs), poses significant health risks. The impact of nutrients, as key determinants of bacterial growth and metabolism, on the propagation of ARGs, particularly extracellular ARGs (eARGs), remains poorly understood. In this study, we collected microorganisms from the Yangtze River and established a series of microcosms to investigate how variations in nutrient levels and delivery frequency affect the relative abundance of intracellular ARGs (iARGs) and eARGs in bacterial communities. Our results show that the relative abundance of 7 out of 11 representative eARGs in water exceeds that of iARGs, while 8 iARGs dominate in biofilms. Notably, iARGs and eARGs consistently exhibited opposite responses to nutrient variation. When nutrient levels increased, iARGs in the water also increased, with the polluted group (COD = 333.3 mg/L, COD:N:P = 100:3:0.6, m/m) and the eutrophic group (COD = 100 mg/L, COD:N:P = 100:25:5, m/m) showing 1.2 and 3.2 times higher levels than the normal group (COD = 100 mg/L, COD:N:P = 100:10:2, m/m), respectively. In contrast, eARGs decreased by 6.7% and 8.4% in these groups. On the other hand, in biofilms, higher nutrient levels led to an increase in eARGs by 1.5 and 1.7 times, while iARGs decreased by 17.5% and 50.1% in the polluted and eutrophic groups compared to the normal group. Moreover, while increasing the frequency of nutrient delivery (from 1 time/10 d to 20 times/10 d) generally did not favor iARGs in either water or biofilm, it selectively enhanced eARGs in both. To further understand these dynamics, we developed an ARGs-nutrient model by integrating the Lotka–Volterra and Monod equations. The results highlight the complex interplay of bacterial growth, nutrient availability, and mechanisms such as horizontal gene transfer and secretion influencing ARGs’ propagation, driving the opposite trend between these two forms of ARGs. This contrasting response between iARGs and eARGs contributes to a dynamic balance that stabilizes bacterial resistance levels amid nutrient fluctuations. This study offers helpful implications regarding the persistence of bacterial resistance in the environment.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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