Pub Date : 2024-09-06DOI: 10.3390/antibiotics13090857
Yuliya Semenova, Assiya Kussainova, Laura Kassym, Ainur Aimurziyeva, Daniil Semenov, Lisa Lim
Background/Objectives: While multiple studies have investigated antibiotic consumption rates, there are few studies on the consumption of systemic antifungals and antiprotozoals. This study aims to fill this gap by providing a comprehensive analysis of nationwide consumption trends in Kazakhstan over a seven-year period (2017–2023). Methods: Defined daily doses per 1000 inhabitants per day were calculated for systemic antifungals (J02 code of the Anatomical Therapeutic Chemical Classification System (ATC)) and antiprotozoals (P01 code of the ATC). Time series analyses were applied to examine historical trends, evaluate the impact of the COVID−19 pandemic, and make future projections until 2030. Results: The total consumption increased over the study period, with an average annual percent change of 1.11% for antifungals and 5.48% for antiprotozoals. Fluconazole was the most consumed antifungal agent, whereas metronidazole was the most consumed antiprotozoal agent. The COVID−19 pandemic had a positive but insignificant effect on the consumption of antifungals and a negative and also insignificant effect on the consumption of antiprotozoals. Forecast modeling indicates that the future trends in antifungal and antiprotozoal consumption until 2030 will largely remain stable, with the exception of antiprotozoal consumption in the hospital sector, which is projected to decline. Conclusions: These findings offer valuable insights into the development and implementation of targeted antimicrobial stewardship programs in Kazakhstan.
{"title":"Consumption Trends of Antifungal and Antiprotozoal Agents for Human Systemic Use in Kazakhstan from 2017 to 2023","authors":"Yuliya Semenova, Assiya Kussainova, Laura Kassym, Ainur Aimurziyeva, Daniil Semenov, Lisa Lim","doi":"10.3390/antibiotics13090857","DOIUrl":"https://doi.org/10.3390/antibiotics13090857","url":null,"abstract":"Background/Objectives: While multiple studies have investigated antibiotic consumption rates, there are few studies on the consumption of systemic antifungals and antiprotozoals. This study aims to fill this gap by providing a comprehensive analysis of nationwide consumption trends in Kazakhstan over a seven-year period (2017–2023). Methods: Defined daily doses per 1000 inhabitants per day were calculated for systemic antifungals (J02 code of the Anatomical Therapeutic Chemical Classification System (ATC)) and antiprotozoals (P01 code of the ATC). Time series analyses were applied to examine historical trends, evaluate the impact of the COVID−19 pandemic, and make future projections until 2030. Results: The total consumption increased over the study period, with an average annual percent change of 1.11% for antifungals and 5.48% for antiprotozoals. Fluconazole was the most consumed antifungal agent, whereas metronidazole was the most consumed antiprotozoal agent. The COVID−19 pandemic had a positive but insignificant effect on the consumption of antifungals and a negative and also insignificant effect on the consumption of antiprotozoals. Forecast modeling indicates that the future trends in antifungal and antiprotozoal consumption until 2030 will largely remain stable, with the exception of antiprotozoal consumption in the hospital sector, which is projected to decline. Conclusions: These findings offer valuable insights into the development and implementation of targeted antimicrobial stewardship programs in Kazakhstan.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196134","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 : 2024-09-06DOI: 10.3390/antibiotics13090853
João Gonçalves Pereira, Joana Fernandes, Tânia Mendes, Filipe André Gonzalez, Susana M. Fernandes
Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by β-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host’s immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy. Consequently, either a fixed dose of antibiotics or a fixed target concentration may be doomed to fail. The role of biomarkers in understanding and monitoring host response to infection is also incompletely defined. Nowadays, with the ever-growing stream of data collected in hospitals, utilizing the most efficient analytical tools may lead to better personalization of therapy. The rise of artificial intelligence and machine learning has allowed large amounts of data to be rapidly accessed and analyzed. These unsupervised learning models can apprehend the data structure and identify homogeneous subgroups, facilitating the individualization of medical interventions. This review aims to discuss the challenges of β-lactam dosing, focusing on its pharmacodynamics and the new challenges and opportunities arising from integrating machine learning algorithms to personalize patient treatment.
{"title":"Artificial Intelligence to Close the Gap between Pharmacokinetic/Pharmacodynamic Targets and Clinical Outcomes in Critically Ill Patients: A Narrative Review on Beta Lactams","authors":"João Gonçalves Pereira, Joana Fernandes, Tânia Mendes, Filipe André Gonzalez, Susana M. Fernandes","doi":"10.3390/antibiotics13090853","DOIUrl":"https://doi.org/10.3390/antibiotics13090853","url":null,"abstract":"Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by β-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host’s immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy. Consequently, either a fixed dose of antibiotics or a fixed target concentration may be doomed to fail. The role of biomarkers in understanding and monitoring host response to infection is also incompletely defined. Nowadays, with the ever-growing stream of data collected in hospitals, utilizing the most efficient analytical tools may lead to better personalization of therapy. The rise of artificial intelligence and machine learning has allowed large amounts of data to be rapidly accessed and analyzed. These unsupervised learning models can apprehend the data structure and identify homogeneous subgroups, facilitating the individualization of medical interventions. This review aims to discuss the challenges of β-lactam dosing, focusing on its pharmacodynamics and the new challenges and opportunities arising from integrating machine learning algorithms to personalize patient treatment.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196111","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 : 2024-09-06DOI: 10.3390/antibiotics13090855
Dorota Grabek-Lejko, Mariusz Worek
The purpose of this study was to isolate, identify, and evaluate the antibacterial and probiotic potential of bacteria from honeydew honey collected in Poland. Isolates (189 colonies from 10 honey samples) were evaluated for their antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica, and then identified by MALDI-TOF-MS. The isolates with the greatest antimicrobial properties were screened for their probiotic potential. The total number of bacteria isolated from honey did not exceed the value of 2.5 × 102 CFU/mL. The Bacillus pumilus/altitudinis, B. licheniformis, and Bacillus cereus groups were the dominant identified bacteria. Almost 16% of the isolates expressed antibacterial potential against three pathogenic bacteria, over 20% against two, while almost 34% of the isolates did not inhibit any. The survival rate of the isolates under gastrointestinal tract conditions was higher after 4 h of exposure to bile salts (>60% survival rate for 66.66% of the isolates), while at pH 2.0, it was lower (>50% survival rate for 44% of the isolates). The most resistant isolate B. pumilus/altitudinis survived at a rate of 77% at low pH and 108% with bile salts. These results confirmed that honeydew honey is a promising reservoir of bacteria that produces metabolites with antimicrobial and probiotic potential.
{"title":"Honeydew Honey as a Reservoir of Bacteria with Antibacterial and Probiotic Properties","authors":"Dorota Grabek-Lejko, Mariusz Worek","doi":"10.3390/antibiotics13090855","DOIUrl":"https://doi.org/10.3390/antibiotics13090855","url":null,"abstract":"The purpose of this study was to isolate, identify, and evaluate the antibacterial and probiotic potential of bacteria from honeydew honey collected in Poland. Isolates (189 colonies from 10 honey samples) were evaluated for their antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica, and then identified by MALDI-TOF-MS. The isolates with the greatest antimicrobial properties were screened for their probiotic potential. The total number of bacteria isolated from honey did not exceed the value of 2.5 × 102 CFU/mL. The Bacillus pumilus/altitudinis, B. licheniformis, and Bacillus cereus groups were the dominant identified bacteria. Almost 16% of the isolates expressed antibacterial potential against three pathogenic bacteria, over 20% against two, while almost 34% of the isolates did not inhibit any. The survival rate of the isolates under gastrointestinal tract conditions was higher after 4 h of exposure to bile salts (>60% survival rate for 66.66% of the isolates), while at pH 2.0, it was lower (>50% survival rate for 44% of the isolates). The most resistant isolate B. pumilus/altitudinis survived at a rate of 77% at low pH and 108% with bile salts. These results confirmed that honeydew honey is a promising reservoir of bacteria that produces metabolites with antimicrobial and probiotic potential.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196112","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 : 2024-09-06DOI: 10.3390/antibiotics13090854
Yindi Xiong, Herman W. Barkema, Jingyue Yang, John P. Kastelic, Diego B. Nobrega, Xiaoping Li, Xiaofang Tong, Zhenying Fan, Jian Gao
Background: In China’s expanding dairy industry, a lack of oversight regarding antimicrobial use and increasing antimicrobial resistance are evident. Selective treatments of dairy cows for clinical mastitis or dry cow therapy are proposed to promote judicious antimicrobial use without adversely impacting cattle health. These approaches have been successfully implemented on farms in other countries. Methods: On 28 October 2023, a 2-day in-person seminar was held in Beijing, China, on selective antimicrobial treatments of dairy cows for clinical mastitis or dry cow therapy on large Chinese dairy farms. Concurrently, a qualitative study involving 15 technical managers from the 13 largest Chinese dairy groups used focus group discussions and questionnaires to explore perspectives on selective treatments of dairy cows for clinical mastitis or dry cow therapy. The main outcomes assessed were opinions and concerns regarding implementing selective antimicrobial treatments. Results: Although there was diversity of cognition on AMR and selective treatments, the technical managers were generally positive regarding adoption of selective treatments. However, they expressed a need for more evidence and tools, including anticipated economic impacts, effects of delaying treatment until diagnosis, accurate interpretation of milk recording data, safe use of internal teat sealants, and spread of pathogens. Participants stressed the need for awareness, staff training, farm management, and China-specific standards, suggesting large-scale trials to assess efficacy of selective treatments. Conclusion: The findings revealed key challenges and barriers currently impeding selective AMU practices. These insights could inform efforts to promote judicious AMU on farms through targeted treatment regimens, reducing mounting selective pressure driving resistance.
{"title":"Antimicrobial Resistance and Use on Chinese Dairy Farms: Awareness and Opinions Regarding Selective Treatments of Farm Managers","authors":"Yindi Xiong, Herman W. Barkema, Jingyue Yang, John P. Kastelic, Diego B. Nobrega, Xiaoping Li, Xiaofang Tong, Zhenying Fan, Jian Gao","doi":"10.3390/antibiotics13090854","DOIUrl":"https://doi.org/10.3390/antibiotics13090854","url":null,"abstract":"Background: In China’s expanding dairy industry, a lack of oversight regarding antimicrobial use and increasing antimicrobial resistance are evident. Selective treatments of dairy cows for clinical mastitis or dry cow therapy are proposed to promote judicious antimicrobial use without adversely impacting cattle health. These approaches have been successfully implemented on farms in other countries. Methods: On 28 October 2023, a 2-day in-person seminar was held in Beijing, China, on selective antimicrobial treatments of dairy cows for clinical mastitis or dry cow therapy on large Chinese dairy farms. Concurrently, a qualitative study involving 15 technical managers from the 13 largest Chinese dairy groups used focus group discussions and questionnaires to explore perspectives on selective treatments of dairy cows for clinical mastitis or dry cow therapy. The main outcomes assessed were opinions and concerns regarding implementing selective antimicrobial treatments. Results: Although there was diversity of cognition on AMR and selective treatments, the technical managers were generally positive regarding adoption of selective treatments. However, they expressed a need for more evidence and tools, including anticipated economic impacts, effects of delaying treatment until diagnosis, accurate interpretation of milk recording data, safe use of internal teat sealants, and spread of pathogens. Participants stressed the need for awareness, staff training, farm management, and China-specific standards, suggesting large-scale trials to assess efficacy of selective treatments. Conclusion: The findings revealed key challenges and barriers currently impeding selective AMU practices. These insights could inform efforts to promote judicious AMU on farms through targeted treatment regimens, reducing mounting selective pressure driving resistance.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"187 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196109","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}
Introduction: We assessed the efficacy of taurolidine lock (TL) in preventing catheter-related bloodstream infections (CRBSIs) and related hospitalizations in children with parenteral nutrition (PN) in the home setting. Methods: This study is a retrospective case series study. All children with intestinal failure in a single center in southern Israel who were administered PN and treated with TL between 2017 and 2024 were included. The rates of CRBSI episodes, related hospitalizations and pathogen distribution in the pre-TL and post-TL periods were compared. Results: Overall, 14 patients were included. The median pre-TL and post-TL periods were 990 and 1260 days, respectively. The rate of CRBSI episodes due to bacterial infection per 1000 days declined by 45%, from 6.2 to 3.7, with p = 0.0008, while fungal CRBSI rates were low (<10% of all positive cultures) and did not decline significantly. Similarly, the hospitalization episode rate per 1000 days declined by 41%, from 7.6 to 4.5, with p = 0.001. Conclusions: Taurolidine lock treatment for children with central-line PN resulted in a substantial decrease in CRBSI episodes and related hospitalizations.
{"title":"The Effectiveness of Taurolidine Antimicrobial Locks in Preventing Catheter-Related Bloodstream Infections (CRBSIs) in Children Receiving Parenteral Nutrition: A Case Series","authors":"Galina Ling, Shalom Ben-Shimol, Siham Elamour, Raouf Nassar, Eyal Kristal, Rotem Shalev, Gadi Howard, Baruch Yerushalmi, Slava Kogan, Moshe Shmueli","doi":"10.3390/antibiotics13090847","DOIUrl":"https://doi.org/10.3390/antibiotics13090847","url":null,"abstract":"Introduction: We assessed the efficacy of taurolidine lock (TL) in preventing catheter-related bloodstream infections (CRBSIs) and related hospitalizations in children with parenteral nutrition (PN) in the home setting. Methods: This study is a retrospective case series study. All children with intestinal failure in a single center in southern Israel who were administered PN and treated with TL between 2017 and 2024 were included. The rates of CRBSI episodes, related hospitalizations and pathogen distribution in the pre-TL and post-TL periods were compared. Results: Overall, 14 patients were included. The median pre-TL and post-TL periods were 990 and 1260 days, respectively. The rate of CRBSI episodes due to bacterial infection per 1000 days declined by 45%, from 6.2 to 3.7, with p = 0.0008, while fungal CRBSI rates were low (<10% of all positive cultures) and did not decline significantly. Similarly, the hospitalization episode rate per 1000 days declined by 41%, from 7.6 to 4.5, with p = 0.001. Conclusions: Taurolidine lock treatment for children with central-line PN resulted in a substantial decrease in CRBSI episodes and related hospitalizations.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196137","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 : 2024-09-05DOI: 10.3390/antibiotics13090850
Christina N. Banti, Sotiris K. Hadjikakou
This Special Issue entitled “Silver and Gold Compounds as Antibiotics” covers a selection of recent research and review articles focused on biological inorganic chemistry [...]
{"title":"Silver and Gold Compounds as Antibiotics","authors":"Christina N. Banti, Sotiris K. Hadjikakou","doi":"10.3390/antibiotics13090850","DOIUrl":"https://doi.org/10.3390/antibiotics13090850","url":null,"abstract":"This Special Issue entitled “Silver and Gold Compounds as Antibiotics” covers a selection of recent research and review articles focused on biological inorganic chemistry [...]","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196141","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 : 2024-09-05DOI: 10.3390/antibiotics13090845
Chloe M. Burford-Gorst, Stephen P. Kidd
Staphylococcus aureus is a bacterial species that is commonly found colonising healthy individuals but that presents a paradoxical nature: simultaneously, it can migrate within the body and cause a range of diseases. Many of these become chronic by resisting immune responses, antimicrobial treatment, and medical intervention. In part, this ability to persist can be attributed to the adoption of multiple cell types within a single cellular population. These dynamics in the S. aureus cell population could be the result of its interplay with host cells or other co-colonising bacteria—often coagulase-negative Staphylococcal (CoNS) species. Further understanding of the unique traits of S. aureus alternative cell types, the drivers for their selection or formation during disease, as well as their presence even during non-pathological colonisation could advance the development of diagnostic tools and drugs tailored to target specific cells that are eventually responsible for chronic infections.
{"title":"Phenotypic Variation in Staphylococcus aureus during Colonisation Involves Antibiotic-Tolerant Cell Types","authors":"Chloe M. Burford-Gorst, Stephen P. Kidd","doi":"10.3390/antibiotics13090845","DOIUrl":"https://doi.org/10.3390/antibiotics13090845","url":null,"abstract":"Staphylococcus aureus is a bacterial species that is commonly found colonising healthy individuals but that presents a paradoxical nature: simultaneously, it can migrate within the body and cause a range of diseases. Many of these become chronic by resisting immune responses, antimicrobial treatment, and medical intervention. In part, this ability to persist can be attributed to the adoption of multiple cell types within a single cellular population. These dynamics in the S. aureus cell population could be the result of its interplay with host cells or other co-colonising bacteria—often coagulase-negative Staphylococcal (CoNS) species. Further understanding of the unique traits of S. aureus alternative cell types, the drivers for their selection or formation during disease, as well as their presence even during non-pathological colonisation could advance the development of diagnostic tools and drugs tailored to target specific cells that are eventually responsible for chronic infections.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196136","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}
This study focused on the discovery of the antimicrobial peptide (AMP) derived from mangrove bacteria. The most promising isolate, NNS5-6, showed the closest taxonomic relation to Paenibacillus thiaminolyticus, with the highest similarity of 74.9%. The AMP produced by Paenibacillus thiaminolyticus NNS5-6 exhibited antibacterial activity against various Gram-negative pathogens, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. The peptide sequence consisted of 13 amino acids and was elucidated as Val-Lys-Gly-Asp-Gly-Gly-Pro-Gly-Thr-Val-Tyr-Thr-Met. The AMP mainly exhibited random coil and antiparallel beta-sheet structures. The stability study indicated that this AMP was tolerant of various conditions, including proteolytic enzymes, pH (1.2–14), surfactants, and temperatures up to 40 °C for 12 h. The AMP demonstrated 4 µg/mL of MIC and 4–8 µg/mL of MBC against both pathogens. Time-kill kinetics showed that the AMP acted in a time- and concentration-dependent manner. A cell permeability assay and scanning electron microscopy revealed that the AMP exerted the mode of action by disrupting bacterial membranes. Additionally, nineteen biosynthetic gene clusters of secondary metabolites were identified in the genome. NNS5-6 was susceptible to various commonly used antibiotics supporting the primary safety requirement. The findings of this research could pave the way for new therapeutic approaches in combating antibiotic-resistant pathogens.
{"title":"Unveiling a New Antimicrobial Peptide with Efficacy against P. aeruginosa and K. pneumoniae from Mangrove-Derived Paenibacillus thiaminolyticus NNS5-6 and Genomic Analysis","authors":"Namfa Sermkaew, Apichart Atipairin, Sucheewin Krobthong, Chanat Aonbangkhen, Yodying Yingchutrakul, Jumpei Uchiyama, Nuttapon Songnaka","doi":"10.3390/antibiotics13090846","DOIUrl":"https://doi.org/10.3390/antibiotics13090846","url":null,"abstract":"This study focused on the discovery of the antimicrobial peptide (AMP) derived from mangrove bacteria. The most promising isolate, NNS5-6, showed the closest taxonomic relation to Paenibacillus thiaminolyticus, with the highest similarity of 74.9%. The AMP produced by Paenibacillus thiaminolyticus NNS5-6 exhibited antibacterial activity against various Gram-negative pathogens, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. The peptide sequence consisted of 13 amino acids and was elucidated as Val-Lys-Gly-Asp-Gly-Gly-Pro-Gly-Thr-Val-Tyr-Thr-Met. The AMP mainly exhibited random coil and antiparallel beta-sheet structures. The stability study indicated that this AMP was tolerant of various conditions, including proteolytic enzymes, pH (1.2–14), surfactants, and temperatures up to 40 °C for 12 h. The AMP demonstrated 4 µg/mL of MIC and 4–8 µg/mL of MBC against both pathogens. Time-kill kinetics showed that the AMP acted in a time- and concentration-dependent manner. A cell permeability assay and scanning electron microscopy revealed that the AMP exerted the mode of action by disrupting bacterial membranes. Additionally, nineteen biosynthetic gene clusters of secondary metabolites were identified in the genome. NNS5-6 was susceptible to various commonly used antibiotics supporting the primary safety requirement. The findings of this research could pave the way for new therapeutic approaches in combating antibiotic-resistant pathogens.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196138","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 : 2024-09-05DOI: 10.3390/antibiotics13090844
Hanne Lazla Rafael de Queiroz Macêdo, Lara Limeira de Oliveira, David Nattan de Oliveira, Karitas Farias Alves Lima, Isabella Macário Ferro Cavalcanti, Luís André de Almeida Campos
Flavonoids are secondary metabolites that exhibit remarkable biological activities, including antimicrobial properties against Klebsiella pneumoniae, a pathogen responsible for several serious nosocomial infections. However, oral administration of these compounds faces considerable challenges, such as low bioavailability and chemical instability. Thus, the encapsulation of flavonoids in nanosystems emerges as a promising strategy to mitigate these limitations, offering protection against degradation; greater solubility; and, in some cases, controlled and targeted release. Different types of nanocarriers, such as polymeric nanoparticles, liposomes, and polymeric micelles, among others, have shown potential to increase the antimicrobial efficacy of flavonoids by reducing the therapeutic dose required and minimizing side effects. In addition, advances in nanotechnology enable co-encapsulation with other therapeutic agents and the development of systems responsive to more specific stimuli, optimizing treatment. In this context, the present article provides an updated review of the literature on flavonoids and the main nanocarriers used for delivering flavonoids with antibacterial properties against Klebsiella pneumoniae.
{"title":"Nanostructures for Delivery of Flavonoids with Antibacterial Potential against Klebsiella pneumoniae","authors":"Hanne Lazla Rafael de Queiroz Macêdo, Lara Limeira de Oliveira, David Nattan de Oliveira, Karitas Farias Alves Lima, Isabella Macário Ferro Cavalcanti, Luís André de Almeida Campos","doi":"10.3390/antibiotics13090844","DOIUrl":"https://doi.org/10.3390/antibiotics13090844","url":null,"abstract":"Flavonoids are secondary metabolites that exhibit remarkable biological activities, including antimicrobial properties against Klebsiella pneumoniae, a pathogen responsible for several serious nosocomial infections. However, oral administration of these compounds faces considerable challenges, such as low bioavailability and chemical instability. Thus, the encapsulation of flavonoids in nanosystems emerges as a promising strategy to mitigate these limitations, offering protection against degradation; greater solubility; and, in some cases, controlled and targeted release. Different types of nanocarriers, such as polymeric nanoparticles, liposomes, and polymeric micelles, among others, have shown potential to increase the antimicrobial efficacy of flavonoids by reducing the therapeutic dose required and minimizing side effects. In addition, advances in nanotechnology enable co-encapsulation with other therapeutic agents and the development of systems responsive to more specific stimuli, optimizing treatment. In this context, the present article provides an updated review of the literature on flavonoids and the main nanocarriers used for delivering flavonoids with antibacterial properties against Klebsiella pneumoniae.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196135","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 : 2024-09-05DOI: 10.3390/antibiotics13090849
Yong Kyun Kim, Gaeun Kang, Dae Young Zang, Dong Hwan Lee
This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free (f) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions (fT>MIC). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40%fT>MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100%fT>MIC or a 90%PTA for 100%fT>4MIC, higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets.
本研究旨在建立美罗培南在健康成人中的群体药代动力学（PK）模型，并探索肾功能正常患者的最佳给药方案。研究人员采集了 12 名健康参与者的 PK 样本，并采用非室分析和非线性混合效应模型对其进行了分析。使用双室模型分析了美罗培南的 PK 曲线，发现血清肌酐水平是影响总清除率的重要协变量。利用该模型进行了蒙特卡罗模拟，为用药建议提供依据。美罗培南疗效的目标指数被定义为在稳态条件下，24 小时内游离（f）药物浓度超过最小抑菌浓度（MIC）的累积百分比（fT>MIC）。这些模拟结果表明，目前每 8 小时输注 1 克、每次 30 分钟的剂量方案在 MIC 为 MIC 时，40%fT>MIC 的达标概率 (PTA) 为 90%，100%fT>4MIC 的达标概率 (PTA) 为 90%。这些结果突出表明，需要根据模型进行精确给药，以提高美罗培南在不同 MIC 水平和治疗靶点上的疗效。
{"title":"Precision Dosing of Meropenem in Adults with Normal Renal Function: Insights from a Population Pharmacokinetic and Monte Carlo Simulation Study","authors":"Yong Kyun Kim, Gaeun Kang, Dae Young Zang, Dong Hwan Lee","doi":"10.3390/antibiotics13090849","DOIUrl":"https://doi.org/10.3390/antibiotics13090849","url":null,"abstract":"This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free (f) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions (fT>MIC). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40%fT>MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100%fT>MIC or a 90%PTA for 100%fT>4MIC, higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196140","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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