Pub Date : 2024-08-21DOI: 10.3390/antibiotics13080783
Maria Cristina Bellucci, Carola Romani, Monica Sani, Alessandro Volonterio
In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic-AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity.
{"title":"Dual Antibiotic Approach: Synthesis and Antibacterial Activity of Antibiotic-Antimicrobial Peptide Conjugates.","authors":"Maria Cristina Bellucci, Carola Romani, Monica Sani, Alessandro Volonterio","doi":"10.3390/antibiotics13080783","DOIUrl":"https://doi.org/10.3390/antibiotics13080783","url":null,"abstract":"<p><p>In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic-AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094190","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}
Background: Patients with carbapenem-resistant Enterobacterales (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66-85% of isolates. This study evaluated the efficacy and safety of neomycin for CRE decolonization.
Methods: In this open-label randomized controlled trial, stool/rectal swab samples from high-risk patients were collected and tested for CRE colonization in the GI tract. Patients who had CRE and met eligible criteria were divided into a neomycin group (n = 26; treated with 4.2 g/day neomycin for 5 days) and a control group (n = 26). CRE detection in stool/rectal swabs was performed on days 7 ± 2 and 14 ± 2.
Results: The two groups' baseline characteristics were similar. CRE presence on day 7 ± 2 was significantly lower in the neomycin group (46.2%) than in the control group (80.8%, p = 0.01). Efficacy of neomycin (4.2 g/day for 5 days) for CRE decolonization was 42.8-53.8% by day 7. By day 14 ± 2, the CRE rate in the neomycin group had risen to align with the control group's rate (73.1% vs. 61.5%, p = 0.56). The neomycin group experienced mild, temporary, gastrointestinal side-effects.
Conclusions: Neomycin effectively reduced CRE colonization on day 7 ± 2, but its impact waned by day 14 ± 2. This suggests that neomycin dosage was too low and the duration of treatment was too short for lasting CRE decolonization.
{"title":"Efficacy and Safety of Oral Neomycin for the Decolonization of Carbapenem-Resistant <i>Enterobacterales</i>: An Open-Label Randomized Controlled Trial.","authors":"Lalita Tancharoen, Ananya Srisomnuek, Surapee Tiengrim, Narisara Thamthaweechok, Teerawit Tangkorskul, Visanu Thamlikitkul","doi":"10.3390/antibiotics13080781","DOIUrl":"https://doi.org/10.3390/antibiotics13080781","url":null,"abstract":"<p><strong>Background: </strong>Patients with carbapenem-resistant <i>Enterobacterales</i> (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66-85% of isolates. This study evaluated the efficacy and safety of neomycin for CRE decolonization.</p><p><strong>Methods: </strong>In this open-label randomized controlled trial, stool/rectal swab samples from high-risk patients were collected and tested for CRE colonization in the GI tract. Patients who had CRE and met eligible criteria were divided into a neomycin group (<i>n</i> = 26; treated with 4.2 g/day neomycin for 5 days) and a control group (<i>n</i> = 26). CRE detection in stool/rectal swabs was performed on days 7 ± 2 and 14 ± 2.</p><p><strong>Results: </strong>The two groups' baseline characteristics were similar. CRE presence on day 7 ± 2 was significantly lower in the neomycin group (46.2%) than in the control group (80.8%, <i>p</i> = 0.01). Efficacy of neomycin (4.2 g/day for 5 days) for CRE decolonization was 42.8-53.8% by day 7. By day 14 ± 2, the CRE rate in the neomycin group had risen to align with the control group's rate (73.1% vs. 61.5%, <i>p</i> = 0.56). The neomycin group experienced mild, temporary, gastrointestinal side-effects.</p><p><strong>Conclusions: </strong>Neomycin effectively reduced CRE colonization on day 7 ± 2, but its impact waned by day 14 ± 2. This suggests that neomycin dosage was too low and the duration of treatment was too short for lasting CRE decolonization.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094192","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 : 2024-08-19DOI: 10.3390/antibiotics13080780
Svetlana Iuliana Polianciuc, Alexandra Ciorîță, Maria Loredana Soran, Ildiko Lung, Béla Kiss, Maria Georgia Ștefan, Daniel Corneliu Leucuța, Anca Elena Gurzău, Rahela Carpa, Liora Mihaela Colobațiu, Felicia Loghin
This study evaluates antibiotic residues and bacterial loads in influent and effluent samples from three wastewater treatment plants (WWTPs) in Romania, across four seasons from 2021 to 2022. Analytical methods included solid-phase extraction and high-performance liquid chromatography (HPLC) to quantify antibiotic concentrations, while microbiological assays estimated bacterial loads and assessed antibiotic resistance patterns. Statistical analyses explored the impact of environmental factors such as temperature and rainfall on antibiotic levels. The results showed significant seasonal variations, with higher antibiotic concentrations in warmer seasons. Antibiotic removal efficiency varied among WWTPs, with some antibiotics being effectively removed and others persisting in the effluent, posing high environmental risks and potential for antibiotic resistance development. Bacterial loads were higher in spring and summer, correlating with increased temperatures. Eight bacterial strains were isolated, with higher resistance during warmer seasons, particularly to amoxicillin and clarithromycin.
{"title":"Antibiotic Residues and Resistance in Three Wastewater Treatment Plants in Romania.","authors":"Svetlana Iuliana Polianciuc, Alexandra Ciorîță, Maria Loredana Soran, Ildiko Lung, Béla Kiss, Maria Georgia Ștefan, Daniel Corneliu Leucuța, Anca Elena Gurzău, Rahela Carpa, Liora Mihaela Colobațiu, Felicia Loghin","doi":"10.3390/antibiotics13080780","DOIUrl":"https://doi.org/10.3390/antibiotics13080780","url":null,"abstract":"<p><p>This study evaluates antibiotic residues and bacterial loads in influent and effluent samples from three wastewater treatment plants (WWTPs) in Romania, across four seasons from 2021 to 2022. Analytical methods included solid-phase extraction and high-performance liquid chromatography (HPLC) to quantify antibiotic concentrations, while microbiological assays estimated bacterial loads and assessed antibiotic resistance patterns. Statistical analyses explored the impact of environmental factors such as temperature and rainfall on antibiotic levels. The results showed significant seasonal variations, with higher antibiotic concentrations in warmer seasons. Antibiotic removal efficiency varied among WWTPs, with some antibiotics being effectively removed and others persisting in the effluent, posing high environmental risks and potential for antibiotic resistance development. Bacterial loads were higher in spring and summer, correlating with increased temperatures. Eight bacterial strains were isolated, with higher resistance during warmer seasons, particularly to amoxicillin and clarithromycin.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094180","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 : 2024-08-18DOI: 10.3390/antibiotics13080779
Eric Umehara, Thainá R Teixeira, Rayssa A Cajás, Monique C Amaro, Josué de Moraes, João Henrique G Lago
Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to achieve the World Health Organization (WHO) goal of schistosomiasis elimination. Previous studies reported the promising antiparasitic activity of different terpenoids against Schistosoma mansoni Sambon (Diplostomida: Schistosomatidae). In the present work, the hexane extract from branches of Drimys brasiliensis afforded a diastereomeric mixture of endoperoxide sesquiterpenes, including 3,6-epidioxy-bisabola-1,10-diene (EDBD). This compound was evaluated in vitro and in vivo against S. mansoni. EDBD exhibited a significant reduction in S. mansoni viability in vitro, with an effective concentration (EC50) value of 4.1 µM. Additionally, EDBD demonstrated no toxicity to mammalian cells. In silico analysis predicted good drug-likeness properties, adhering to pharmaceutical industry standards, including favorable ADME profiles. Furthermore, oral treatment of S. mansoni-infected mice with EDBD (400 mg/kg) resulted in a remarkable egg burden reduction (98% and 99% in tissues and feces, respectively) surpassing praziquantel's efficacy. These findings suggest the promising potential of EDBD as a lead molecule for developing a novel schistosomiasis treatment.
{"title":"EDBD-3,6-Epidioxy-1,10-Bisaboladiene-An Endoperoxide Sesquiterpene Obtained from <i>Drimys brasiliensis</i> (Winteraceae) Exhibited Potent Preclinical Efficacy against <i>Schistosoma mansoni</i> Infection.","authors":"Eric Umehara, Thainá R Teixeira, Rayssa A Cajás, Monique C Amaro, Josué de Moraes, João Henrique G Lago","doi":"10.3390/antibiotics13080779","DOIUrl":"https://doi.org/10.3390/antibiotics13080779","url":null,"abstract":"<p><p>Schistosomiasis, a neglected tropical disease impacting over 250 million individuals globally, remains a major public health challenge due to its prevalence and significant impact on affected communities. Praziquantel, the sole available treatment, highlights the urgency of the need for novel anthelmintic agents to achieve the World Health Organization (WHO) goal of schistosomiasis elimination. Previous studies reported the promising antiparasitic activity of different terpenoids against <i>Schistosoma mansoni</i> Sambon (Diplostomida: Schistosomatidae). In the present work, the hexane extract from branches of <i>Drimys brasiliensis</i> afforded a diastereomeric mixture of endoperoxide sesquiterpenes, including 3,6-epidioxy-bisabola-1,10-diene (EDBD). This compound was evaluated in vitro and in vivo against <i>S. mansoni.</i> EDBD exhibited a significant reduction in <i>S. mansoni</i> viability in vitro, with an effective concentration (EC<sub>50</sub>) value of 4.1 µM. Additionally, EDBD demonstrated no toxicity to mammalian cells. In silico analysis predicted good drug-likeness properties, adhering to pharmaceutical industry standards, including favorable ADME profiles. Furthermore, oral treatment of <i>S. mansoni</i>-infected mice with EDBD (400 mg/kg) resulted in a remarkable egg burden reduction (98% and 99% in tissues and feces, respectively) surpassing praziquantel's efficacy. These findings suggest the promising potential of EDBD as a lead molecule for developing a novel schistosomiasis treatment.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094191","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 : 2024-08-17DOI: 10.3390/antibiotics13080778
Li Tan, Rong Ma, Adam J Katz, Nicole Levi
The family of ESKAPE pathogens is comprised of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter. Together they are the main contributors of nosocomial infections and are well established for their ability to "escape" antibiotics. Farnesol is an FDA-approved cosmetic and flavoring agent with significant anti-biofilm properties. In a proprietary emulsion, farnesol has been shown to be capable of disrupting S. aureus, P. aeruginosa, and A. baumannii biofilms. The current work demonstrates that this farnesol emulsion reduces the number of viable bacteria, while also leading to reductions in biomass, of the other three ESKAPE pathogens: Enterococcus faecium, Klebsiella pneumoniae, and Enterobacter, both in vitro and in an ex vivo human skin model. A concentration of 0.5 mg/mL was effective for impeding biofilm development of all three bacteria, while 1 mg/mL for E. faecium and K. pneumoniae, or 0.2 mg/mL for E. cloacae, was able to kill bacteria in established biofilms. Contrary to antibiotics, no resistance to farnesol was observed for E. faecium or K. pneumoniae. The results indicate that farnesol is effective for direct cell killing and also has the ability to induce biofilm detachment from surfaces, as confirmed using Live/Dead image analysis. Our findings confirm that farnesol emulsion is an effective broad-spectrum agent to impede ESKAPE biofilms.
{"title":"Farnesol Emulsion as an Effective Broad-Spectrum Agent against ESKAPE Biofilms.","authors":"Li Tan, Rong Ma, Adam J Katz, Nicole Levi","doi":"10.3390/antibiotics13080778","DOIUrl":"https://doi.org/10.3390/antibiotics13080778","url":null,"abstract":"<p><p>The family of ESKAPE pathogens is comprised of <i>Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa</i>, and <i>Enterobacter</i>. Together they are the main contributors of nosocomial infections and are well established for their ability to \"escape\" antibiotics. Farnesol is an FDA-approved cosmetic and flavoring agent with significant anti-biofilm properties. In a proprietary emulsion, farnesol has been shown to be capable of disrupting <i>S. aureus, P. aeruginosa</i>, and <i>A. baumannii</i> biofilms. The current work demonstrates that this farnesol emulsion reduces the number of viable bacteria, while also leading to reductions in biomass, of the other three ESKAPE pathogens: <i>Enterococcus faecium, Klebsiella pneumoniae,</i> and <i>Enterobacter,</i> both in vitro and in an ex vivo human skin model. A concentration of 0.5 mg/mL was effective for impeding biofilm development of all three bacteria, while 1 mg/mL for <i>E. faecium</i> and <i>K. pneumoniae</i>, or 0.2 mg/mL for <i>E. cloacae,</i> was able to kill bacteria in established biofilms. Contrary to antibiotics, no resistance to farnesol was observed for <i>E. faecium</i> or <i>K. pneumoniae</i>. The results indicate that farnesol is effective for direct cell killing and also has the ability to induce biofilm detachment from surfaces, as confirmed using Live/Dead image analysis. Our findings confirm that farnesol emulsion is an effective broad-spectrum agent to impede ESKAPE biofilms.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094195","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 : 2024-08-16DOI: 10.3390/antibiotics13080774
Marwa Nabil Sayed Abdelaziz, Mahmoud Gamaleldin Zayda, Aye Thida Maung, Mohamed El-Telbany, Tahir Noor Mohammadi, Su Zar Chi Lwin, Khin Zar Linn, Chen Wang, Lu Yuan, Yoshimitsu Masuda, Ken-Ichi Honjoh, Takahisa Miyamoto
Bacillus cereus sensu stricto is a foodborne pathogen that causes food poisoning. Their spore and biofilm-forming abilities persist in various environments and foods. This study investigated the prevalence, virulence, antibiotic resistance, and genetic diversity of B. cereus s. s. strains isolated from various food samples. Of 179 samples, 22.34% were positive for B. cereus s. s., with significantly high detection rates in milk products and raw chicken meat. Forty strains were isolated from positive samples. Matrix-assisted laser desorption ionization/time of flight mass spectrometry analysis revealed nine distinct clusters and multi-locus sequence typing revealed 34 sequence types including 23 novel sequences, demonstrating high genetic diversity among the isolates. PCR analysis revealed that all the strains contained at least one toxin gene, but none contained the cytK gene. Antibiotic resistance tests revealed that all isolates were classified as multidrug-resistant, with high resistance levels, particularly to β-lactam antibiotics and vancomycin, but were susceptible to gentamicin. All isolates showed variations in biofilm formation. This study highlights the significant public health risk due to B. cereus s. s. and underscores the need for stringent monitoring and control measures in food production to manage antimicrobial resistance and ensure food safety.
{"title":"Genetic Characterization, Antibiotic Resistance, and Virulence Genes Profiling of <i>Bacillus cereus</i> Strains from Various Foods in Japan.","authors":"Marwa Nabil Sayed Abdelaziz, Mahmoud Gamaleldin Zayda, Aye Thida Maung, Mohamed El-Telbany, Tahir Noor Mohammadi, Su Zar Chi Lwin, Khin Zar Linn, Chen Wang, Lu Yuan, Yoshimitsu Masuda, Ken-Ichi Honjoh, Takahisa Miyamoto","doi":"10.3390/antibiotics13080774","DOIUrl":"https://doi.org/10.3390/antibiotics13080774","url":null,"abstract":"<p><p><i>Bacillus cereus sensu stricto</i> is a foodborne pathogen that causes food poisoning. Their spore and biofilm-forming abilities persist in various environments and foods. This study investigated the prevalence, virulence, antibiotic resistance, and genetic diversity of <i>B. cereus s. s.</i> strains isolated from various food samples. Of 179 samples, 22.34% were positive for <i>B. cereus s. s.</i>, with significantly high detection rates in milk products and raw chicken meat. Forty strains were isolated from positive samples. Matrix-assisted laser desorption ionization/time of flight mass spectrometry analysis revealed nine distinct clusters and multi-locus sequence typing revealed 34 sequence types including 23 novel sequences, demonstrating high genetic diversity among the isolates. PCR analysis revealed that all the strains contained at least one toxin gene, but none contained the <i>cytK</i> gene. Antibiotic resistance tests revealed that all isolates were classified as multidrug-resistant, with high resistance levels, particularly to β-lactam antibiotics and vancomycin, but were susceptible to gentamicin. All isolates showed variations in biofilm formation. This study highlights the significant public health risk due to <i>B. cereus s. s.</i> and underscores the need for stringent monitoring and control measures in food production to manage antimicrobial resistance and ensure food safety.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11351997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094197","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 : 2024-08-16DOI: 10.3390/antibiotics13080777
Anastácia Nikolaos Deonas, Lucas Marcelino Dos Santos Souza, Gabriel Jonathan Sousa Andrade, Jennifer Germiniani-Cardozo, Débora Dahmer, Admilton Gonçalves de Oliveira, Gerson Nakazato, José Marcelo Domingues Torezan, Renata Katsuko Takayama Kobayashi
Given the urgent need for novel methods to control the spread of multidrug-resistant microorganisms, this study presents a green synthesis approach to produce silver nanoparticles (AgNPs) using the bark extract from Anadenanthera colubrina (Vell.) Brenan var. colubrina. The methodology included obtaining the extract and characterizing the AgNPs, which revealed antimicrobial activity against MDR bacteria. A. colubrina species is valued in indigenous and traditional medicine for its medicinal properties. Herein, it was employed to synthesize AgNPs with effective antibacterial activity (MIC = 19.53-78.12 μM) against clinical isolates from the ESKAPEE group, known for causing high hospitalization costs and mortality rates. Despite its complexity, AgNP synthesis is an affordable method with minimal environmental impacts and risks. Plant-synthesized AgNPs possess unique characteristics that affect their biological activity and cytotoxicity. In this work, A. colubrina bark extract resulted in the synthesis of nanoparticles measuring 75.62 nm in diameter, with a polydispersity index of 0.17 and an average zeta potential of -29 mV, as well as low toxicity for human erythrocytes, with a CC50 value in the range of 961 μM. This synthesis underscores its innovative potential owing to its low toxicity, suggesting applicability across several areas and paving the way for future research.
{"title":"Green Synthesis of Silver Nanoparticle from <i>Anadenanthera colubrina</i> Extract and Its Antimicrobial Action against ESKAPEE Group Bacteria.","authors":"Anastácia Nikolaos Deonas, Lucas Marcelino Dos Santos Souza, Gabriel Jonathan Sousa Andrade, Jennifer Germiniani-Cardozo, Débora Dahmer, Admilton Gonçalves de Oliveira, Gerson Nakazato, José Marcelo Domingues Torezan, Renata Katsuko Takayama Kobayashi","doi":"10.3390/antibiotics13080777","DOIUrl":"https://doi.org/10.3390/antibiotics13080777","url":null,"abstract":"<p><p>Given the urgent need for novel methods to control the spread of multidrug-resistant microorganisms, this study presents a green synthesis approach to produce silver nanoparticles (AgNPs) using the bark extract from <i>Anadenanthera colubrina</i> (Vell.) Brenan var. colubrina. The methodology included obtaining the extract and characterizing the AgNPs, which revealed antimicrobial activity against MDR bacteria. <i>A. colubrina</i> species is valued in indigenous and traditional medicine for its medicinal properties. Herein, it was employed to synthesize AgNPs with effective antibacterial activity (MIC = 19.53-78.12 μM) against clinical isolates from the ESKAPEE group, known for causing high hospitalization costs and mortality rates. Despite its complexity, AgNP synthesis is an affordable method with minimal environmental impacts and risks. Plant-synthesized AgNPs possess unique characteristics that affect their biological activity and cytotoxicity. In this work, <i>A. colubrina</i> bark extract resulted in the synthesis of nanoparticles measuring 75.62 nm in diameter, with a polydispersity index of 0.17 and an average zeta potential of -29 mV, as well as low toxicity for human erythrocytes, with a CC<sub>50</sub> value in the range of 961 μM. This synthesis underscores its innovative potential owing to its low toxicity, suggesting applicability across several areas and paving the way for future research.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094198","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}
Intra-abdominal infections (IAIs) account for a major cause of morbidity and mortality, representing the second most common sepsis-related death with a hospital mortality of 23-38%. Prompt identification of sepsis source, appropriate resuscitation, and early treatment with the shortest delay possible are the cornerstones of management of IAIs and are associated with a more favorable clinical outcome. The aim of source control is to reduce microbial load by removing the infection source and it is achievable by using a wide range of procedures, such as definitive surgical removal of anatomic infectious foci, percutaneous drainage and toilette of infected collections, decompression, and debridement of infected and necrotic tissue or device removal, providing for the restoration of anatomy and function. Damage control surgery may be an option in selected septic patients. Intra-abdominal infections can be classified as uncomplicated or complicated causing localized or diffuse peritonitis. Early clinical evaluation is mandatory in order to optimize diagnostic testing and establish a therapeutic plan. Prognostic scores could serve as helpful tools in medical settings for evaluating both the seriousness and future outlook of a condition. The patient's conditions and the potential progression of the disease determine when to initiate source control. Patients can be classified into three groups based on disease severity, the origin of infection, and the patient's overall physical health, as well as any existing comorbidities. In recent decades, antibiotic resistance has become a global health threat caused by inappropriate antibiotic regimens, inadequate control measures, and infection prevention. The sepsis prevention and infection control protocols combined with optimizing antibiotic administration are crucial to improve outcome and should be encouraged in surgical departments. Antibiotic and antifungal regimens in patients with IAIs should be based on the resistance epidemiology, clinical conditions, and risk for multidrug resistance (MDR) and Candida spp. infections. Several challenges still exist regarding the effectiveness, timing, and patient stratification, as well as the procedures for source control. Antibiotic choice, optimal dosing, and duration of therapy are essential to achieve the best treatment. Promoting standard of care in the management of IAIs improves clinical outcomes worldwide. Further trials and stronger evidence are required to achieve optimal management with the least morbidity in the clinical care of critically ill patients with intra-abdominal sepsis.
{"title":"Source Control and Antibiotics in Intra-Abdominal Infections.","authors":"Raffaele Bova, Giulia Griggio, Carlo Vallicelli, Giorgia Santandrea, Federico Coccolini, Luca Ansaloni, Massimo Sartelli, Vanni Agnoletti, Francesca Bravi, Fausto Catena","doi":"10.3390/antibiotics13080776","DOIUrl":"https://doi.org/10.3390/antibiotics13080776","url":null,"abstract":"<p><p>Intra-abdominal infections (IAIs) account for a major cause of morbidity and mortality, representing the second most common sepsis-related death with a hospital mortality of 23-38%. Prompt identification of sepsis source, appropriate resuscitation, and early treatment with the shortest delay possible are the cornerstones of management of IAIs and are associated with a more favorable clinical outcome. The aim of source control is to reduce microbial load by removing the infection source and it is achievable by using a wide range of procedures, such as definitive surgical removal of anatomic infectious foci, percutaneous drainage and toilette of infected collections, decompression, and debridement of infected and necrotic tissue or device removal, providing for the restoration of anatomy and function. Damage control surgery may be an option in selected septic patients. Intra-abdominal infections can be classified as uncomplicated or complicated causing localized or diffuse peritonitis. Early clinical evaluation is mandatory in order to optimize diagnostic testing and establish a therapeutic plan. Prognostic scores could serve as helpful tools in medical settings for evaluating both the seriousness and future outlook of a condition. The patient's conditions and the potential progression of the disease determine when to initiate source control. Patients can be classified into three groups based on disease severity, the origin of infection, and the patient's overall physical health, as well as any existing comorbidities. In recent decades, antibiotic resistance has become a global health threat caused by inappropriate antibiotic regimens, inadequate control measures, and infection prevention. The sepsis prevention and infection control protocols combined with optimizing antibiotic administration are crucial to improve outcome and should be encouraged in surgical departments. Antibiotic and antifungal regimens in patients with IAIs should be based on the resistance epidemiology, clinical conditions, and risk for multidrug resistance (MDR) and Candida spp. infections. Several challenges still exist regarding the effectiveness, timing, and patient stratification, as well as the procedures for source control. Antibiotic choice, optimal dosing, and duration of therapy are essential to achieve the best treatment. Promoting standard of care in the management of IAIs improves clinical outcomes worldwide. Further trials and stronger evidence are required to achieve optimal management with the least morbidity in the clinical care of critically ill patients with intra-abdominal sepsis.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094212","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}
Pseudomonas aeruginosa is an opportunistic pathogen in humans and a frequent cause of severe nosocomial infections and fatal infections in immunocompromised individuals. Its ability to form biofilms has been the main driving force behind its resistance to almost all conventional antibiotics, thereby limiting treatment efficacy. In an effort to discover novel therapeutic agents to fight P. aeruginosa-associated biofilm infections, the truncated analogs of scorpion venom-derived peptide IsCT were synthesized and their anti-biofilm properties were examined. Among the investigated peptides, the IsCT-Δ6-8 peptide evidently showed the most potential anti-P. aeruginosa biofilm activity and the effect was not due to bacterial growth inhibition. The IsCT-Δ6-8 peptide also exhibited inhibitory activity against the production of pyocyanin, an important virulence factor of P. aeruginosa. Furthermore, the IsCT-Δ6-8 peptide significantly suppressed the production of inflammatory mediators nitric oxide and interleukin-6 in P. aeruginosa LPS-induced macrophages. Due to its low cytotoxicity to mammalian cells, the IsCT-Δ6-8 peptide emerges as a promising candidate with significant anti-biofilm and anti-inflammatory properties. These findings highlight its potential application in treating P. aeruginosa-related biofilm infections.
{"title":"Anti-Biofilm and Anti-Inflammatory Properties of the Truncated Analogs of the Scorpion Venom-Derived Peptide IsCT against <i>Pseudomonas aeruginosa</i>.","authors":"Pornpimon Jantaruk, Kittitat Teerapo, Supattra Charoenwutthikun, Sittiruk Roytrakul, Duangkamol Kunthalert","doi":"10.3390/antibiotics13080775","DOIUrl":"https://doi.org/10.3390/antibiotics13080775","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> is an opportunistic pathogen in humans and a frequent cause of severe nosocomial infections and fatal infections in immunocompromised individuals. Its ability to form biofilms has been the main driving force behind its resistance to almost all conventional antibiotics, thereby limiting treatment efficacy. In an effort to discover novel therapeutic agents to fight <i>P. aeruginosa</i>-associated biofilm infections, the truncated analogs of scorpion venom-derived peptide IsCT were synthesized and their anti-biofilm properties were examined. Among the investigated peptides, the IsCT-Δ6-8 peptide evidently showed the most potential anti-<i>P. aeruginosa</i> biofilm activity and the effect was not due to bacterial growth inhibition. The IsCT-Δ6-8 peptide also exhibited inhibitory activity against the production of pyocyanin, an important virulence factor of <i>P. aeruginosa</i>. Furthermore, the IsCT-Δ6-8 peptide significantly suppressed the production of inflammatory mediators nitric oxide and interleukin-6 in <i>P. aeruginosa</i> LPS-induced macrophages. Due to its low cytotoxicity to mammalian cells, the IsCT-Δ6-8 peptide emerges as a promising candidate with significant anti-biofilm and anti-inflammatory properties. These findings highlight its potential application in treating <i>P. aeruginosa</i>-related biofilm infections.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094179","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 : 2024-08-15DOI: 10.3390/antibiotics13080773
Anfal Kara, Chiara Massaro, Giovanni M Giammanco, Rosa Alduina, Naouel Boussoualim
Urinary tract infections (UTIs) caused by Escherichia coli represent a significant public health concern due to the high virulence and antimicrobial resistance exhibited by these pathogens. This study aimed to analyze the phylogenetic diversity and antibiotic resistance profiles of Uropathogenic E. coli (UPEC) strains isolated from UTI patients in Algeria, focusing on virulence factors such as extended β-lactamase (ESBL) production, biofilm formation, and hemolytic activity. Phylogenetic grouping of 86 clinical imipenem resistant E. coli isolates showed the prevalence of group B2 (48.9%), followed by groups E (22.1%), unknown (12.8%), A (8.1%), and B1 (4.7%), and Clade I, D, Clade I, or Clade II (1.2%). The highest resistance rates were observed towards amoxicillin (86.04%), ticarcillin (82.55%), piperacillin (73.25%), nitrofurantoin (84.88%), and trimethoprim-sulfamethoxazole (51.16%). Notably, 69.8% of UPEC strains were multidrug-resistant (MDR) and 23.2% were extensively drug-resistant (XDR). Additionally, 48.9%, 42%, and 71% of strains demonstrated ESBL production, hemolytic activity, and weak biofilm production, respectively. Continuous monitoring and characterization of UPEC strains are essential to track the spread of the most resistant and virulent phylogenetic groups over time, facilitating rapid therapeutic decisions to treat infections and prevent the emergence of new resistant organisms, helping choose the most effective antibiotics and reducing treatment failure.
由大肠埃希菌引起的尿路感染(UTI)是一个重大的公共卫生问题,因为这些病原体具有很强的毒力和抗菌药耐药性。本研究旨在分析从阿尔及利亚尿路感染患者中分离出的尿路致病性大肠杆菌(UPEC)菌株的系统发育多样性和抗生素耐药性特征,重点关注毒力因素,如扩展β-内酰胺酶(ESBL)的产生、生物膜的形成和溶血活性。对 86 个临床亚胺培南耐药大肠杆菌分离物进行的系统发育分组显示,B2 群(48.9%)的流行率最高,其次是 E 群(22.1%)、未知群(12.8%)、A 群(8.1%)和 B1 群(4.7%),以及 I 群、D 群、I 群或 II 群(1.2%)。阿莫西林(86.04%)、替卡西林(82.55%)、哌拉西林(73.25%)、硝基呋喃妥因(84.88%)和三甲双氨-磺胺甲噁唑(51.16%)的耐药率最高。值得注意的是,69.8%的 UPEC 菌株具有多重耐药性(MDR),23.2%具有广泛耐药性(XDR)。此外,分别有 48.9%、42% 和 71% 的菌株表现出 ESBL 生产、溶血活性和弱生物膜生产。对 UPEC 菌株的持续监测和特征描述对于追踪耐药性最强、毒性最大的系统发育群的长期传播至关重要,有助于快速做出治疗感染的决定,防止出现新的耐药生物,帮助选择最有效的抗生素,减少治疗失败。
{"title":"Phylogenetic Diversity, Antibiotic Resistance, and Virulence of <i>Escherichia coli</i> Strains from Urinary Tract Infections in Algeria.","authors":"Anfal Kara, Chiara Massaro, Giovanni M Giammanco, Rosa Alduina, Naouel Boussoualim","doi":"10.3390/antibiotics13080773","DOIUrl":"https://doi.org/10.3390/antibiotics13080773","url":null,"abstract":"<p><p>Urinary tract infections (UTIs) caused by <i>Escherichia coli</i> represent a significant public health concern due to the high virulence and antimicrobial resistance exhibited by these pathogens. This study aimed to analyze the phylogenetic diversity and antibiotic resistance profiles of Uropathogenic <i>E. coli</i> (UPEC) strains isolated from UTI patients in Algeria, focusing on virulence factors such as extended β-lactamase (ESBL) production, biofilm formation, and hemolytic activity. Phylogenetic grouping of 86 clinical imipenem resistant <i>E. coli</i> isolates showed the prevalence of group B2 (48.9%), followed by groups E (22.1%), unknown (12.8%), A (8.1%), and B1 (4.7%), and Clade I, D, Clade I, or Clade II (1.2%). The highest resistance rates were observed towards amoxicillin (86.04%), ticarcillin (82.55%), piperacillin (73.25%), nitrofurantoin (84.88%), and trimethoprim-sulfamethoxazole (51.16%). Notably, 69.8% of UPEC strains were multidrug-resistant (MDR) and 23.2% were extensively drug-resistant (XDR). Additionally, 48.9%, 42%, and 71% of strains demonstrated ESBL production, hemolytic activity, and weak biofilm production, respectively. Continuous monitoring and characterization of UPEC strains are essential to track the spread of the most resistant and virulent phylogenetic groups over time, facilitating rapid therapeutic decisions to treat infections and prevent the emergence of new resistant organisms, helping choose the most effective antibiotics and reducing treatment failure.</p>","PeriodicalId":54246,"journal":{"name":"Antibiotics-Basel","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094206","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}