Pub Date : 2024-08-24DOI: 10.3390/antibiotics13090800
Guillermo Santamaría-Corral, John Jairo Aguilera-Correa, Jaime Esteban, Meritxell García-Quintanilla
One of the primary opportunistic pathogens that can cause a wide range of diseases is Pseudomonas aeruginosa. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, among other things, the failure of antimicrobial therapies. Due to a variety of virulence factors and host immune system modifications, P. aeruginosa is one of the most significant and common bacteria that colonize wounds and burns. A novel therapeutic option for treating these multidrug-resistant (MDR) bacterial infections is the combination of antibiotics and bacteriophages. This approach has been linked to improved biofilm penetration, a decreased selection of antibiotic and bacteriophage resistance, and an enhanced antibacterial impact. Combining the F1Pa bacteriophage and beta-lactam antibiotics reduced the viability of the mature biofilm of MDR P. aeruginosa strains and suppressed bacterial growth in vitro. F1Pa critically reduced the amount of biofilm that MDR P. aeruginosa clinical strains formed in the in vitro wound model. These findings highlight the bacteriophage F1Pa's therapeutic potential as a prophylactic topical treatment against MDR pseudomonal infections in wounds and burns.
{"title":"Bacteriophage Therapy on an In Vitro Wound Model and Synergistic Effects in Combination with Beta-Lactam Antibiotics.","authors":"Guillermo Santamaría-Corral, John Jairo Aguilera-Correa, Jaime Esteban, Meritxell García-Quintanilla","doi":"10.3390/antibiotics13090800","DOIUrl":"https://doi.org/10.3390/antibiotics13090800","url":null,"abstract":"<p><p>One of the primary opportunistic pathogens that can cause a wide range of diseases is <i>Pseudomonas aeruginosa</i>. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, among other things, the failure of antimicrobial therapies. Due to a variety of virulence factors and host immune system modifications, <i>P. aeruginosa</i> is one of the most significant and common bacteria that colonize wounds and burns. A novel therapeutic option for treating these multidrug-resistant (MDR) bacterial infections is the combination of antibiotics and bacteriophages. This approach has been linked to improved biofilm penetration, a decreased selection of antibiotic and bacteriophage resistance, and an enhanced antibacterial impact. Combining the F1Pa bacteriophage and beta-lactam antibiotics reduced the viability of the mature biofilm of MDR <i>P. aeruginosa</i> strains and suppressed bacterial growth in vitro. F1Pa critically reduced the amount of biofilm that MDR <i>P. aeruginosa</i> clinical strains formed in the in vitro wound model. These findings highlight the bacteriophage F1Pa's therapeutic potential as a prophylactic topical treatment against MDR pseudomonal infections in wounds and burns.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.3390/antibiotics13090802
Jade L L Teng, Elaine Chan, Tsz Tuen Li, Tsz Ying Kwan, Ka Fai Chan, Wing Ho Li, Viki W K Tang, Man Lung Yeung, Susanna K P Lau, Patrick C Y Woo
Due to the increasing resistance of aerobic and facultative anaerobic Gram-negative rods, ceftazidime-avibactam and ceftolozane-tazobactam have been launched in the market in the last few years. In this study, we analyzed the susceptibility pattern of the major aerobic and facultative anaerobic Gram-negative rods in Hong Kong for ceftazidime-avibactam, ceftolozane-tazobactam, four other broad-spectrum antibiotics commonly used in Hong Kong and colistin. For 300 isolates collected from January to December 2021, non-ESBL-producing Enterobacterales, ESBL-producing Enterobacterales and Pseudomonas aeruginosa were highly susceptible to ceftazidime-avibactam (all 100%) and ceftolozane-tazobactam (98.7%, 99.7% and 94.3%). For 32 archived ESBL-producing Klebsiella pneumoniae isolates collected between January 2014 and March 2023, all were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam. For 101 archived carbapenemase-producing Enterobacterales, their susceptibilities to ceftazidime-avibactam and ceftolozane-tazobactam varied depending on the type of carbapenemase produced. Both had high activities against OXA-producing strains (97.1% and 76.5%, respectively) but were 100% resistant for NDM-producing and NDM+OXA-producing strains. All KPC-producing strains were susceptible to ceftazidime-avibactam but resistant to ceftolozane-tazobactam. Ceftazidime-avibactam and ceftolozane-tazobactam are good alternatives for the management of infections caused by ESBL-producing Enterobacterales and selective strains of carbapenemase-producing Enterobacterales in Hong Kong.
{"title":"Antibiotic Susceptibility of Aerobic and Facultative Anaerobic Gram-Negative Rods in Hong Kong and Implications on Usefulness of Ceftazidime-Avibactam and Ceftolozane-Tazobactam.","authors":"Jade L L Teng, Elaine Chan, Tsz Tuen Li, Tsz Ying Kwan, Ka Fai Chan, Wing Ho Li, Viki W K Tang, Man Lung Yeung, Susanna K P Lau, Patrick C Y Woo","doi":"10.3390/antibiotics13090802","DOIUrl":"https://doi.org/10.3390/antibiotics13090802","url":null,"abstract":"<p><p>Due to the increasing resistance of aerobic and facultative anaerobic Gram-negative rods, ceftazidime-avibactam and ceftolozane-tazobactam have been launched in the market in the last few years. In this study, we analyzed the susceptibility pattern of the major aerobic and facultative anaerobic Gram-negative rods in Hong Kong for ceftazidime-avibactam, ceftolozane-tazobactam, four other broad-spectrum antibiotics commonly used in Hong Kong and colistin. For 300 isolates collected from January to December 2021, non-ESBL-producing Enterobacterales, ESBL-producing Enterobacterales and <i>Pseudomonas aeruginosa</i> were highly susceptible to ceftazidime-avibactam (all 100%) and ceftolozane-tazobactam (98.7%, 99.7% and 94.3%). For 32 archived ESBL-producing <i>Klebsiella pneumoniae</i> isolates collected between January 2014 and March 2023, all were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam. For 101 archived carbapenemase-producing Enterobacterales, their susceptibilities to ceftazidime-avibactam and ceftolozane-tazobactam varied depending on the type of carbapenemase produced. Both had high activities against OXA-producing strains (97.1% and 76.5%, respectively) but were 100% resistant for NDM-producing and NDM+OXA-producing strains. All KPC-producing strains were susceptible to ceftazidime-avibactam but resistant to ceftolozane-tazobactam. Ceftazidime-avibactam and ceftolozane-tazobactam are good alternatives for the management of infections caused by ESBL-producing Enterobacterales and selective strains of carbapenemase-producing Enterobacterales in Hong Kong.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.3390/antibiotics13090799
Seongok Kim, Bokyung Son, Hyeryen Kim, Hakdong Shin, Sangryeol Ryu
Salmonella enterica is a major food-borne pathogen causing food poisoning. The use of bacteriophages as alternative biocontrol agents has gained renewed interest due to the rising issue of antibiotic-resistant bacteria. We isolated and characterized three phages targeting Salmonella: SPN3US, SPN3UB, and SPN10H. Morphological and genomic analyses revealed that they belong to the class Caudoviricetes. SPN3UB, SPN3US, and SPN10H specifically target bacterial surface molecules as receptors, including O-antigens of lipopolysaccharides, flagella, and BtuB, respectively. The phages exhibited a broad host range against Salmonella strains, highlighting their potential for use in a phage cocktail. Bacterial challenge assays demonstrated significant lytic activity of the phage cocktail consisting of the three phages against S. typhimurium UK1, effectively delaying the emergence of phage-resistant bacteria. The phage cocktail effectively reduced Salmonella contamination in foods, including milk and pork and chicken meats, during cold storage. These results indicate that a phage cocktail targeting different host receptors could serve as a promising antimicrobial strategy to control Salmonella.
{"title":"Precision Phage Cocktail Targeting Surface Appendages for Biocontrol of <i>Salmonella</i> in Cold-Stored Foods.","authors":"Seongok Kim, Bokyung Son, Hyeryen Kim, Hakdong Shin, Sangryeol Ryu","doi":"10.3390/antibiotics13090799","DOIUrl":"https://doi.org/10.3390/antibiotics13090799","url":null,"abstract":"<p><p><i>Salmonella enterica</i> is a major food-borne pathogen causing food poisoning. The use of bacteriophages as alternative biocontrol agents has gained renewed interest due to the rising issue of antibiotic-resistant bacteria. We isolated and characterized three phages targeting <i>Salmonella</i>: SPN3US, SPN3UB, and SPN10H. Morphological and genomic analyses revealed that they belong to the class <i>Caudoviricetes</i>. SPN3UB, SPN3US, and SPN10H specifically target bacterial surface molecules as receptors, including O-antigens of lipopolysaccharides, flagella, and BtuB, respectively. The phages exhibited a broad host range against <i>Salmonella</i> strains, highlighting their potential for use in a phage cocktail. Bacterial challenge assays demonstrated significant lytic activity of the phage cocktail consisting of the three phages against <i>S. typhimurium</i> UK1, effectively delaying the emergence of phage-resistant bacteria. The phage cocktail effectively reduced <i>Salmonella</i> contamination in foods, including milk and pork and chicken meats, during cold storage. These results indicate that a phage cocktail targeting different host receptors could serve as a promising antimicrobial strategy to control <i>Salmonella</i>.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.3390/antibiotics13090798
Loredana-Elena Mantea, Cristina-Veronica Moldovan, Mihaela Savu, Laura Gabriela Sarbu, Marius Stefan, Mihail Lucian Birsa
The rapid emergence and spread of multidrug-resistant microorganisms is threatening our ability to treat common infections, with serious medical, social, and economic consequences. Despite substantial progress in the global fight against antibiotic resistance, the number of effective antibiotics is rapidly decreasing, underlying the urgent need to develop novel antimicrobials. In the present study, the green synthesis of novel iodine-substituted tricyclic flavonoids has been accomplished using an eco-friendly reagent, HPW-SiO2, as a cyclization agent for the precursor 3-dithiocarmamic flavanones. In vitro antimicrobial activity of the new compounds was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentrations. All tested compounds displayed potent inhibitory activity against all tested microbial strains, with the lowest MIC values of 0.12 µg/mL and 0.48 µg/mL recorded for compound 5c against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Higher MIC values (7.81 µg/mL) were registered for several flavonoids against Gram-negative bacteria Escherichia coli and Acinetobacter pittii. No inhibitory activity was evidenced against Pseudomonas aeruginosa strain. The highest antifungal activity was displayed by flavonoid 5d against Candida krusei (MIC = 3.9 µg/mL). The same compound also exhibited the most potent bactericidal and fungicidal activity against Bacillus subtilis (0.9 µg/mL) and Staphylococcus aureus (1.97 µg/mL), Candida albicans, and Candida krusei (7.81 µg/mL). Based on the reported results, we believe that the novel iodine-substituted tricyclic flavonoids have good potential to become new antimicrobial agents effective against bacterial and fungal strains, including WHO-priority pathogens.
{"title":"An Eco-Friendly Method to Synthesize Potent Antimicrobial Tricyclic Flavonoids.","authors":"Loredana-Elena Mantea, Cristina-Veronica Moldovan, Mihaela Savu, Laura Gabriela Sarbu, Marius Stefan, Mihail Lucian Birsa","doi":"10.3390/antibiotics13090798","DOIUrl":"https://doi.org/10.3390/antibiotics13090798","url":null,"abstract":"<p><p>The rapid emergence and spread of multidrug-resistant microorganisms is threatening our ability to treat common infections, with serious medical, social, and economic consequences. Despite substantial progress in the global fight against antibiotic resistance, the number of effective antibiotics is rapidly decreasing, underlying the urgent need to develop novel antimicrobials. In the present study, the green synthesis of novel iodine-substituted tricyclic flavonoids has been accomplished using an eco-friendly reagent, HPW-SiO<sub>2</sub>, as a cyclization agent for the precursor 3-dithiocarmamic flavanones. In vitro antimicrobial activity of the new compounds was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentrations. All tested compounds displayed potent inhibitory activity against all tested microbial strains, with the lowest MIC values of 0.12 µg/mL and 0.48 µg/mL recorded for compound <b>5c</b> against Gram-positive bacteria <i>Bacillus subtilis</i> and <i>Staphylococcus aureus</i>. Higher MIC values (7.81 µg/mL) were registered for several flavonoids against Gram-negative bacteria <i>Escherichia coli</i> and <i>Acinetobacter pittii</i>. No inhibitory activity was evidenced against <i>Pseudomonas aeruginosa</i> strain. The highest antifungal activity was displayed by flavonoid <b>5d</b> against <i>Candida krusei</i> (MIC = 3.9 µg/mL). The same compound also exhibited the most potent bactericidal and fungicidal activity against <i>Bacillus subtilis</i> (0.9 µg/mL) and <i>Staphylococcus aureus</i> (1.97 µg/mL), <i>Candida albicans,</i> and <i>Candida krusei</i> (7.81 µg/mL). Based on the reported results, we believe that the novel iodine-substituted tricyclic flavonoids have good potential to become new antimicrobial agents effective against bacterial and fungal strains, including WHO-priority pathogens.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-24DOI: 10.3390/antibiotics13090801
Laura Gras-Martín, Adrián Plaza-Diaz, Borja Zarate-Tamames, Paula Vera-Artazcoz, Olga H Torres, Carla Bastida, Dolors Soy, Jesús Ruiz-Ramos
(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact. The aim of this systematic review is to identify risk factors among critically ill patients that may exhibit significant pharmacokinetic alterations, compromising treatment efficacy and safety. (2) Methods: The search included the PubMed, Web of Science, and Embase databases. (3) Results: We identified 246 observational studies and ten clinical trials. The most studied risk factors in the literature were renal function, weight, age, sex, and renal replacement therapy. Risk factors with the greatest impact included renal function, weight, renal replacement therapy, age, protein or albumin levels, and APACHE or SAPS scores. (4) Conclusions: The review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets and helps us to recognize the extensive number of risk factors that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes.
{"title":"Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review.","authors":"Laura Gras-Martín, Adrián Plaza-Diaz, Borja Zarate-Tamames, Paula Vera-Artazcoz, Olga H Torres, Carla Bastida, Dolors Soy, Jesús Ruiz-Ramos","doi":"10.3390/antibiotics13090801","DOIUrl":"https://doi.org/10.3390/antibiotics13090801","url":null,"abstract":"<p><p>(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact. The aim of this systematic review is to identify risk factors among critically ill patients that may exhibit significant pharmacokinetic alterations, compromising treatment efficacy and safety. (2) Methods: The search included the PubMed, Web of Science, and Embase databases. (3) Results: We identified 246 observational studies and ten clinical trials. The most studied risk factors in the literature were renal function, weight, age, sex, and renal replacement therapy. Risk factors with the greatest impact included renal function, weight, renal replacement therapy, age, protein or albumin levels, and APACHE or SAPS scores. (4) Conclusions: The review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets and helps us to recognize the extensive number of risk factors that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Necrotic enteritis (NE) is a critical disease affecting broiler health, with Clostridium perfringens as its primary pathogen. Polygonum hydropiper compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE's efficacy against Clostridium perfringens-induced NE and its underlying mechanism remain unclear. This study employed network pharmacology and molecular docking to predict PHCE's potential mechanisms in treating NE, followed by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Clostridium perfringens (C. perf). Subsequently, the effects of various PHCE doses on intestinal damage, antioxidant capacity, and inflammatory factors in C. perf-infected broilers were assessed. Network pharmacology and molecular docking suggested that PHCE's therapeutic mechanism for NE involves the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway, with flavonoids such as quercetin, kaempferol, and isorhamnetin as key active components. PHCE exhibited an MIC of 3.13 mg/mL and an MBC of 12.5 mg/mL against C. perf. High PHCE doses effectively reduced intestinal damage scores in both the jejunum and ileum, accompanied by attenuated intestinal pathological changes. Additionally, the high dose significantly increased superoxide dismutase (SOD) levels while decreasing malondialdehyde (MDA), hydrogen peroxide (H2O2), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in the jejunum and ileum (p < 0.01 or p < 0.05). PHCE also modulated the expression of caspase-1, IL-1β, gasdermin D (GSDMD), and NLRP3 mRNA, key components of the NLRP3 inflammasome signaling pathway, in both intestinal segments. These findings collectively indicate that PHCE protects against C. perf-induced oxidative stress and inflammatory damage in NE. By enhancing antioxidant capacity, PHCE likely reduces oxidative stress and inflammatory responses, subsequently modulating NLRP3 inflammasome signaling pathway key factor expression. Overall, this research provides valuable insights into the protective mechanism of the herbal compound PHCE and its potential benefits for avian health.
坏死性肠炎(NE)是影响肉鸡健康的一种严重疾病,其主要病原体是产气荚膜梭菌。根据传统中兽医学原理配制的何首乌复合提取物(PHCE)主要含有具有抗菌、消炎和抗氧化特性的黄酮类化合物。然而,PHCE 对产气荚膜梭菌诱导的 NE 的疗效及其内在机制仍不清楚。本研究采用网络药理学和分子对接法预测了 PHCE 治疗 NE 的潜在机制,并确定了其对产气荚膜梭菌(C. perfringens)的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。随后,评估了不同剂量的 PHCE 对梭状芽孢杆菌感染肉鸡肠道损伤、抗氧化能力和炎症因子的影响。网络药理学和分子对接表明,PHCE对NE的治疗机制涉及NOD样受体热蛋白域相关蛋白3(NLRP3)炎性体信号通路,而槲皮素、山柰醇和异鼠李素等黄酮类化合物是其关键的活性成分。PHCE对C. perf的最小作用浓度为3.13毫克/毫升,最大作用浓度为12.5毫克/毫升。高剂量的PHCE可有效降低空肠和回肠的肠道损伤评分,同时减轻肠道病理变化。此外,高剂量还能显著提高空肠和回肠中的超氧化物歧化酶(SOD)水平,同时降低丙二醛(MDA)、过氧化氢(H2O2)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)(p < 0.01 或 p < 0.05)。PHCE 还调节了两个肠段中 Caspase-1、IL-1β、gasdermin D (GSDMD) 和 NLRP3 mRNA(NLRP3 炎性体信号通路的关键成分)的表达。这些研究结果共同表明,PHCE 可保护东北亚地区免受梭状芽孢杆菌诱导的氧化应激和炎症损伤。通过增强抗氧化能力,PHCE 可能会降低氧化应激和炎症反应,进而调节 NLRP3 炎性体信号通路关键因子的表达。总之,这项研究为了解中草药化合物 PHCE 的保护机制及其对禽类健康的潜在益处提供了宝贵的见解。
{"title":"<i>Polygonum hydropiper</i> Compound Extract Inhibits <i>Clostridium perfringens</i>-Induced Intestinal Inflammatory Response and Injury in Broiler Chickens by Modulating NLRP3 Inflammasome Signaling.","authors":"Jinwu Zhang, Chunzi Peng, Maojie Lv, Shisen Yang, Liji Xie, Jiaxun Feng, Yingyi Wei, Tingjun Hu, Jiakang He, Zhixun Xie, Meiling Yu","doi":"10.3390/antibiotics13090793","DOIUrl":"https://doi.org/10.3390/antibiotics13090793","url":null,"abstract":"<p><p><i>Necrotic enteritis</i> (<i>NE</i>) is a critical disease affecting broiler health, with <i>Clostridium perfringens</i> as its primary pathogen. <i>Polygonum hydropiper</i> compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE's efficacy against <i>Clostridium perfringens</i>-induced <i>NE</i> and its underlying mechanism remain unclear. This study employed network pharmacology and molecular docking to predict PHCE's potential mechanisms in treating NE, followed by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against <i>Clostridium perfringens</i> (<i>C. perf</i>). Subsequently, the effects of various PHCE doses on intestinal damage, antioxidant capacity, and inflammatory factors in <i>C. perf</i>-infected broilers were assessed. Network pharmacology and molecular docking suggested that PHCE's therapeutic mechanism for <i>NE</i> involves the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway, with flavonoids such as quercetin, kaempferol, and isorhamnetin as key active components. PHCE exhibited an MIC of 3.13 mg/mL and an MBC of 12.5 mg/mL against <i>C. perf</i>. High PHCE doses effectively reduced intestinal damage scores in both the jejunum and ileum, accompanied by attenuated intestinal pathological changes. Additionally, the high dose significantly increased superoxide dismutase (SOD) levels while decreasing malondialdehyde (MDA), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in the jejunum and ileum (<i>p</i> < 0.01 or <i>p</i> < 0.05). PHCE also modulated the expression of caspase-1, IL-1β, gasdermin D (GSDMD), and NLRP3 mRNA, key components of the NLRP3 inflammasome signaling pathway, in both intestinal segments. These findings collectively indicate that PHCE protects against <i>C. perf</i>-induced oxidative stress and inflammatory damage in <i>NE</i>. By enhancing antioxidant capacity, PHCE likely reduces oxidative stress and inflammatory responses, subsequently modulating NLRP3 inflammasome signaling pathway key factor expression. Overall, this research provides valuable insights into the protective mechanism of the herbal compound PHCE and its potential benefits for avian health.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.3390/antibiotics13090791
Sophie Reissier, Carine Couzigou, Romain Courseau, Elise Aubert, Alban Le Monnier, Eric Bonnet, Peter Upex, Pierre-Emmanuel Moreau, Guillaume Riouallon, Julie Lourtet-Hascoët
Objective: The objective was to compare the microbiological characteristics and treatment of early and late surgical site infections (SSIs) in instrumented spinal surgery.
Methods: Those patients admitted for SSIs in a single center between January 2010 and December 2022 were included. The subjects were divided into early (eSSIs) and late (lSSIs) SSIs, and demographic, microbiological, treatment, and follow-up data were collected.
Results: Instrumented spinal surgery was performed in 2136 patients. Ninety-six cases of infections were identified (prevalence = 4.5%), with 47.9% eSSIs and 52.1% lSSIs. In 58.7% of the cases, the eSSIs were monomicrobial: Staphylococcus aureus (37%) and Enterobacterales (33.3%) were the main bacteria involved. In 66% of the cases, the lSSIs, were monomicrobial: Cutibacterium acnes (30.3%) and staphylococci were predominant. Enterobacterales were isolated in more than 70% of the polymicrobial samples in both the eSSIs and lSSIs. The treatment of the eSSIs mostly consisted of lavage-debridement surgery associated with antibiotic treatment, while the treatment of the lSSIs combined hardware removal or replacement and long-duration antibiotic treatment. A negative outcome was observed in 17.1% of the eSSIs and 5.7% of the lSSIs. Enterobacterales were associated with negative outcomes of eSSIs.
Conclusions: Enterobacterales were found in most of the polymicrobial infections regardless of the time of infection onset. Further large studies should be conducted to precisely determine the management and prevention regarding the increasing Gram-negative bacteria SSIs.
{"title":"Microbiological Profile of Instrumented Spinal Infections: 10-Year Study at a French Spine Center.","authors":"Sophie Reissier, Carine Couzigou, Romain Courseau, Elise Aubert, Alban Le Monnier, Eric Bonnet, Peter Upex, Pierre-Emmanuel Moreau, Guillaume Riouallon, Julie Lourtet-Hascoët","doi":"10.3390/antibiotics13090791","DOIUrl":"https://doi.org/10.3390/antibiotics13090791","url":null,"abstract":"<p><strong>Objective: </strong>The objective was to compare the microbiological characteristics and treatment of early and late surgical site infections (SSIs) in instrumented spinal surgery.</p><p><strong>Methods: </strong>Those patients admitted for SSIs in a single center between January 2010 and December 2022 were included. The subjects were divided into early (eSSIs) and late (lSSIs) SSIs, and demographic, microbiological, treatment, and follow-up data were collected.</p><p><strong>Results: </strong>Instrumented spinal surgery was performed in 2136 patients. Ninety-six cases of infections were identified (prevalence = 4.5%), with 47.9% eSSIs and 52.1% lSSIs. In 58.7% of the cases, the eSSIs were monomicrobial: <i>Staphylococcus aureus</i> (37%) and Enterobacterales (33.3%) were the main bacteria involved. In 66% of the cases, the lSSIs, were monomicrobial: <i>Cutibacterium acnes</i> (30.3%) and staphylococci were predominant. Enterobacterales were isolated in more than 70% of the polymicrobial samples in both the eSSIs and lSSIs. The treatment of the eSSIs mostly consisted of lavage-debridement surgery associated with antibiotic treatment, while the treatment of the lSSIs combined hardware removal or replacement and long-duration antibiotic treatment. A negative outcome was observed in 17.1% of the eSSIs and 5.7% of the lSSIs. Enterobacterales were associated with negative outcomes of eSSIs.</p><p><strong>Conclusions: </strong>Enterobacterales were found in most of the polymicrobial infections regardless of the time of infection onset. Further large studies should be conducted to precisely determine the management and prevention regarding the increasing Gram-negative bacteria SSIs.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.3390/antibiotics13090792
Teresa López-Viñau, Montserrat Muñoz-Rosa, Lidia Mª Ruiz-Lara, Lucrecia García-Martínez, Isabel Machuca, Irene Gracia-Ahufinger, Rafael Ruiz Montero, Juan José Castón, Ángela Cano, Elisa Ruiz-Arabi, José Ramón Del Prado, Inmaculada Salcedo, Luis Martínez-Martínez, Julián Torre-Cisneros
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of -66.19% (95% CI -87.03 to -45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of -88.14% (95% CI; -100.4 to -75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect.
目前,耐碳酸培南肺炎克雷伯菌(CR-Kp)已成为全球严重关切的问题。抗菌药物管理计划(ASP)是克服耐药性的关键策略之一。然而,有关 ASPs 的长期临床和生态影响的证据却很少。一个多学科团队在一家 CR-Kp 流行的医院进行了为期 6 年的多方面干预。我们评估了 ASP 对碳青霉烯类药物使用、发病密度 (ID) 和医院获得性 CR-Kp 感染粗死亡率的每月长期影响。我们还监测了可能与 CR-Kp 感染率和医疗活动指标相关的其他变量。长期来看,碳青霉烯类药物的使用量持续减少,干预前的预期趋势消耗值与计划实施六年后的预期趋势消耗值之间的差值为-66.19%(95% CI -87.03至-45.34)。CR-Kp的ID也显著下降并长期保持不变,在研究期结束时,相对降幅为-88.14%(95% CI;-100.4至-75.85)。干预后,14 天和 28 天的 CR-Kp 粗死亡率显著下降,六年后保持稳定。感染控制指标趋势保持稳定。这种混合 ASP 有助于降低 CR-Kp 的高感染率和死亡率,取得了持续的生态和临床效果。
{"title":"Long-Term Clinical and Ecological Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Infections in a High-Endemic Hospital.","authors":"Teresa López-Viñau, Montserrat Muñoz-Rosa, Lidia Mª Ruiz-Lara, Lucrecia García-Martínez, Isabel Machuca, Irene Gracia-Ahufinger, Rafael Ruiz Montero, Juan José Castón, Ángela Cano, Elisa Ruiz-Arabi, José Ramón Del Prado, Inmaculada Salcedo, Luis Martínez-Martínez, Julián Torre-Cisneros","doi":"10.3390/antibiotics13090792","DOIUrl":"https://doi.org/10.3390/antibiotics13090792","url":null,"abstract":"<p><p>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of -66.19% (95% CI -87.03 to -45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of -88.14% (95% CI; -100.4 to -75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.3390/antibiotics13090795
Kafayath Fabiyi, Kevin Sintondji, Jerrold Agbankpe, Phenix Assogba, Hornel Koudokpon, Boris Lègba, Elodie Gbotche, Lamine Baba-Moussa, Victorien Dougnon
The conventional treatment of bacterial infections with antibiotics is becoming increasingly ineffective due to the emergence of multidrug-resistant (MDR) pathogens. This literature review explores the potential of bacteriophages as an alternative or adjunctive therapy to antibiotics in combating MDR infections in Africa. This analysis focuses on current research regarding the integration of phage therapy into African healthcare, highlighting its challenges and opportunities. This review begins with the AMR crisis and the need for new treatments, then covers the history, mechanisms, benefits, and limitations of phage therapy. Key African studies are summarized, identifying major obstacles such as regulatory issues, infrastructure, and research standardization. Research efforts in West Africa that have made notable progress in bacteriophage research are highlighted. This review concludes with recommendations for policymakers, researchers, and healthcare professionals to enhance the development and use of phage therapy in Africa, aiming to reduce antibiotic resistance and improve patient outcomes. By addressing the identified challenges and leveraging the unique advantages of phages, there is potential to significantly mitigate the impact of antibiotic resistance and improve patient outcomes in Africa.
由于耐多药(MDR)病原体的出现,用抗生素治疗细菌感染的传统方法越来越无效。本文献综述探讨了噬菌体作为抗生素的替代或辅助疗法在非洲抗击 MDR 感染的潜力。分析的重点是目前有关将噬菌体疗法纳入非洲医疗保健的研究,强调其挑战和机遇。本综述从 AMR 危机和对新疗法的需求入手,然后介绍了噬菌体疗法的历史、机制、益处和局限性。综述了非洲的主要研究,指出了主要障碍,如监管问题、基础设施和研究标准化。重点介绍了西非在噬菌体研究方面取得显著进展的研究工作。本综述最后向政策制定者、研究人员和医疗保健专业人员提出了建议,以促进噬菌体疗法在非洲的发展和使用,从而减少抗生素耐药性并改善患者的治疗效果。通过应对已确定的挑战并利用噬菌体的独特优势,有可能大大减轻抗生素耐药性的影响并改善非洲患者的治疗效果。
{"title":"Harnessing Bacteriophages to Combat Antibiotic-Resistant Infections in Africa: A Comprehensive Review.","authors":"Kafayath Fabiyi, Kevin Sintondji, Jerrold Agbankpe, Phenix Assogba, Hornel Koudokpon, Boris Lègba, Elodie Gbotche, Lamine Baba-Moussa, Victorien Dougnon","doi":"10.3390/antibiotics13090795","DOIUrl":"https://doi.org/10.3390/antibiotics13090795","url":null,"abstract":"<p><p>The conventional treatment of bacterial infections with antibiotics is becoming increasingly ineffective due to the emergence of multidrug-resistant (MDR) pathogens. This literature review explores the potential of bacteriophages as an alternative or adjunctive therapy to antibiotics in combating MDR infections in Africa. This analysis focuses on current research regarding the integration of phage therapy into African healthcare, highlighting its challenges and opportunities. This review begins with the AMR crisis and the need for new treatments, then covers the history, mechanisms, benefits, and limitations of phage therapy. Key African studies are summarized, identifying major obstacles such as regulatory issues, infrastructure, and research standardization. Research efforts in West Africa that have made notable progress in bacteriophage research are highlighted. This review concludes with recommendations for policymakers, researchers, and healthcare professionals to enhance the development and use of phage therapy in Africa, aiming to reduce antibiotic resistance and improve patient outcomes. By addressing the identified challenges and leveraging the unique advantages of phages, there is potential to significantly mitigate the impact of antibiotic resistance and improve patient outcomes in Africa.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.3390/antibiotics13090794
Ki Ha Min, Koung Hee Kim, Mi-Ran Ki, Seung Pil Pack
The emergence of drug resistance genes and the detrimental health effects caused by the overuse of antibiotics are increasingly prominent problems. There is an urgent need for effective strategies to antibiotics or antimicrobial resistance in the fields of biomedicine and therapeutics. The pathogen-killing ability of antimicrobial peptides (AMPs) is linked to their structure and physicochemical properties, including their conformation, electrical charges, hydrophilicity, and hydrophobicity. AMPs are a form of innate immune protection found in all life forms. A key aspect of the application of AMPs involves their potential to combat emerging antibiotic resistance; certain AMPs are effective against resistant microbial strains and can be modified through peptide engineering. This review summarizes the various strategies used to tackle antibiotic resistance, with a particular focus on the role of AMPs as effective antibiotic agents that enhance the host's immunological functions. Most of the recent studies on the properties and impregnation methods of AMPs, along with their biomedical applications, are discussed. This review provides researchers with insights into the latest advancements in AMP research, highlighting compelling evidence for the effectiveness of AMPs as antimicrobial agents.
{"title":"Antimicrobial Peptides and Their Biomedical Applications: A Review.","authors":"Ki Ha Min, Koung Hee Kim, Mi-Ran Ki, Seung Pil Pack","doi":"10.3390/antibiotics13090794","DOIUrl":"https://doi.org/10.3390/antibiotics13090794","url":null,"abstract":"<p><p>The emergence of drug resistance genes and the detrimental health effects caused by the overuse of antibiotics are increasingly prominent problems. There is an urgent need for effective strategies to antibiotics or antimicrobial resistance in the fields of biomedicine and therapeutics. The pathogen-killing ability of antimicrobial peptides (AMPs) is linked to their structure and physicochemical properties, including their conformation, electrical charges, hydrophilicity, and hydrophobicity. AMPs are a form of innate immune protection found in all life forms. A key aspect of the application of AMPs involves their potential to combat emerging antibiotic resistance; certain AMPs are effective against resistant microbial strains and can be modified through peptide engineering. This review summarizes the various strategies used to tackle antibiotic resistance, with a particular focus on the role of AMPs as effective antibiotic agents that enhance the host's immunological functions. Most of the recent studies on the properties and impregnation methods of AMPs, along with their biomedical applications, are discussed. This review provides researchers with insights into the latest advancements in AMP research, highlighting compelling evidence for the effectiveness of AMPs as antimicrobial agents.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11429172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}