Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of NDM-1-encoding P. aeruginosa in early 2023. In the present study, we present the rapid reversal of the carbapenemase-producing P. aeruginosa epidemiology from blaVIM- to blaNDM-harbouring isolates that occurred in our hospital since then. Between January 2023 and February 2024, 139 isolates tested positive for carbapenemase production with the NG-Test CARBA 5 immunochromatographic assay. Eight isolates were processed with the Hybrispot antimicrobial resistance direct flow chip molecular assay, and the first NDM-producing isolate was further analyzed through whole genome sequencing and bioinformatics analysis. Multiple resistance genes were detected by molecular techniques in accordance with the extensively drug-resistant phenotype. The isolate that was subjected to whole-genome sequencing belonged to the P. aeruginosa high-risk clone ST308, and the blaNDM was located in the chromosome in accordance with previously reported data. During the study period, NDM-producing isolates were increasingly detected, and only five months after their emergence, they overcame VIM producers. Our results indicate the potential of this new clone to spread rapidly and predominate within healthcare institutions, further restricting the already limited treatment options.
{"title":"Rapid Reversal of Carbapenemase-Producing Pseudomonas aeruginosa Epidemiology from blaVIM- to blaNDM-harbouring Isolates in a Greek Tertiary Care Hospital","authors":"Efthymia Protonotariou, Georgios Meletis, Nikoletta Vlachodimou, Andigoni Malousi, Areti Tychala, Charikleia Katsanou, Aikaterini Daviti, Paraskevi Mantzana, Lemonia Skoura","doi":"10.3390/antibiotics13080762","DOIUrl":"https://doi.org/10.3390/antibiotics13080762","url":null,"abstract":"Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of NDM-1-encoding P. aeruginosa in early 2023. In the present study, we present the rapid reversal of the carbapenemase-producing P. aeruginosa epidemiology from blaVIM- to blaNDM-harbouring isolates that occurred in our hospital since then. Between January 2023 and February 2024, 139 isolates tested positive for carbapenemase production with the NG-Test CARBA 5 immunochromatographic assay. Eight isolates were processed with the Hybrispot antimicrobial resistance direct flow chip molecular assay, and the first NDM-producing isolate was further analyzed through whole genome sequencing and bioinformatics analysis. Multiple resistance genes were detected by molecular techniques in accordance with the extensively drug-resistant phenotype. The isolate that was subjected to whole-genome sequencing belonged to the P. aeruginosa high-risk clone ST308, and the blaNDM was located in the chromosome in accordance with previously reported data. During the study period, NDM-producing isolates were increasingly detected, and only five months after their emergence, they overcame VIM producers. Our results indicate the potential of this new clone to spread rapidly and predominate within healthcare institutions, further restricting the already limited treatment options.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.3390/antibiotics13080759
Biel Garcias, Mayra Alejandra Flores, Mercedes Fernández, William Monteith, Ben Pascoe, Samuel K. Sheppard, Marga Martín, Martí Cortey, Laila Darwich
Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.
{"title":"Global Variation in Escherichia coli mcr-1 Genes and Plasmids from Animal and Human Genomes Following Colistin Usage Restrictions in Livestock","authors":"Biel Garcias, Mayra Alejandra Flores, Mercedes Fernández, William Monteith, Ben Pascoe, Samuel K. Sheppard, Marga Martín, Martí Cortey, Laila Darwich","doi":"10.3390/antibiotics13080759","DOIUrl":"https://doi.org/10.3390/antibiotics13080759","url":null,"abstract":"Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.3390/antibiotics13080760
Ignasi Sacanella, Erika Esteve-Pitarch, Jessica Guevara-Chaux, Julen Berrueta, Alejandro García-Martínez, Josep Gómez, Cecilia Casarino, Florencia Alés, Laura Canadell, Ignacio Martín-Loeches, Santiago Grau, Francisco Javier Candel, María Bodí, Alejandro Rodríguez
Background: Liposomal amphotericin B (L-AmB) has become the mainstay of treatment for severe invasive fungal infections. However, the potential for renal toxicity must be considered. Aims: To evaluate the incidence of acute kidney injury (AKI) in critically ill patients receiving L-AmB for more than 48 h. Methods: Retrospective, observational, single-center study. Clinical, demographic and laboratory variables were obtained automatically from the electronic medical record. AKI incidence was analyzed in the entire population and in patients with a “low” or “high” risk of AKI based on their creatinine levels at the outset of the study. Factors associated with the development of AKI were studied using random forest models. Results: Finally, 67 patients with a median age of 61 (53–71) years, 67% male, a median SOFA of 4 (3–6.5) and a crude mortality of 34.3% were included. No variations in serum creatinine were observed during the observation period, except for a decrease in the high-risk subgroup. A total of 26.8% (total population), 25% (low risk) and 13% (high risk) of patients developed AKI. Norepinephrine, the SOFA score, furosemide (general model), potassium, C-reactive protein and procalcitonin (low-risk subgroup) were the variables identified by the random forest models as important contributing factors to the development of AKI other than L-AmB administration. Conclusions: The development of AKI is multifactorial and the administration of L-AmB appears to be safe in this group of patients.
{"title":"A Real-World Data Observational Analysis of the Impact of Liposomal Amphotericin B on Renal Function Using Machine Learning in Critically Ill Patients","authors":"Ignasi Sacanella, Erika Esteve-Pitarch, Jessica Guevara-Chaux, Julen Berrueta, Alejandro García-Martínez, Josep Gómez, Cecilia Casarino, Florencia Alés, Laura Canadell, Ignacio Martín-Loeches, Santiago Grau, Francisco Javier Candel, María Bodí, Alejandro Rodríguez","doi":"10.3390/antibiotics13080760","DOIUrl":"https://doi.org/10.3390/antibiotics13080760","url":null,"abstract":"Background: Liposomal amphotericin B (L-AmB) has become the mainstay of treatment for severe invasive fungal infections. However, the potential for renal toxicity must be considered. Aims: To evaluate the incidence of acute kidney injury (AKI) in critically ill patients receiving L-AmB for more than 48 h. Methods: Retrospective, observational, single-center study. Clinical, demographic and laboratory variables were obtained automatically from the electronic medical record. AKI incidence was analyzed in the entire population and in patients with a “low” or “high” risk of AKI based on their creatinine levels at the outset of the study. Factors associated with the development of AKI were studied using random forest models. Results: Finally, 67 patients with a median age of 61 (53–71) years, 67% male, a median SOFA of 4 (3–6.5) and a crude mortality of 34.3% were included. No variations in serum creatinine were observed during the observation period, except for a decrease in the high-risk subgroup. A total of 26.8% (total population), 25% (low risk) and 13% (high risk) of patients developed AKI. Norepinephrine, the SOFA score, furosemide (general model), potassium, C-reactive protein and procalcitonin (low-risk subgroup) were the variables identified by the random forest models as important contributing factors to the development of AKI other than L-AmB administration. Conclusions: The development of AKI is multifactorial and the administration of L-AmB appears to be safe in this group of patients.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"136 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.3390/antibiotics13080761
Mélanie Denizon, Eva Hong, Aude Terrade, Muhamed-Kheir Taha, Ala-Eddine Deghmane
Infections due to Haemophilus influnezae require prompt treatment using beta-lactam antibiotics. We used a collection of 81 isolates obtained between 1940 and 2001 from several countries. Whole genome sequencing showed the high heterogeneity of these isolates but allowed us to track the acquisition of beta-lactamase, which was first detected in 1980. Modifications of the ftsI gene encoding the penicillin-binding protein 3, PBP3, also involved in resistance to beta-lactams, appeared in 1991. These modifications (G490E, A502V, R517H, and N526K) were associated with resistance to amoxicillin that was not relieved by a beta-lactamase inhibitor (clavulanic acid), but the isolates retained susceptibility to third-generation cephalosporins (3GC). The modeling of the PBP3 structure suggested that these modifications may reduce the accessibility to the PBP3 active site. Other modifications appeared in 1998 and were associated with resistance to 3GC (S357N, M377I, S385T, and L389F). Modeling of the PBP3 structure suggested that they lie near the S379xN motif of the active site of PBP3. Overall resistance to amoxicillin was detected among 25 isolates (30.8%) of this collection. Resistance to sulfonamides was predicted by a genomic approach from the sequences of the folP gene (encoding the dihydropteroate synthase) due to difficulties in interpreting phenotypic anti-microbial testing and found in 13 isolates (16.0%). Our data suggest a slower spread of resistance to sulfonamides, which may be used for the treatment of H. influnezae infections. Genomic analysis may help in the prediction of antibiotic resistance, inform structure–function analysis, and guide the optimal use of antibiotics.
{"title":"A Hunt for the Resistance of Haemophilus influnezae to Beta-Lactams","authors":"Mélanie Denizon, Eva Hong, Aude Terrade, Muhamed-Kheir Taha, Ala-Eddine Deghmane","doi":"10.3390/antibiotics13080761","DOIUrl":"https://doi.org/10.3390/antibiotics13080761","url":null,"abstract":"Infections due to Haemophilus influnezae require prompt treatment using beta-lactam antibiotics. We used a collection of 81 isolates obtained between 1940 and 2001 from several countries. Whole genome sequencing showed the high heterogeneity of these isolates but allowed us to track the acquisition of beta-lactamase, which was first detected in 1980. Modifications of the ftsI gene encoding the penicillin-binding protein 3, PBP3, also involved in resistance to beta-lactams, appeared in 1991. These modifications (G490E, A502V, R517H, and N526K) were associated with resistance to amoxicillin that was not relieved by a beta-lactamase inhibitor (clavulanic acid), but the isolates retained susceptibility to third-generation cephalosporins (3GC). The modeling of the PBP3 structure suggested that these modifications may reduce the accessibility to the PBP3 active site. Other modifications appeared in 1998 and were associated with resistance to 3GC (S357N, M377I, S385T, and L389F). Modeling of the PBP3 structure suggested that they lie near the S379xN motif of the active site of PBP3. Overall resistance to amoxicillin was detected among 25 isolates (30.8%) of this collection. Resistance to sulfonamides was predicted by a genomic approach from the sequences of the folP gene (encoding the dihydropteroate synthase) due to difficulties in interpreting phenotypic anti-microbial testing and found in 13 isolates (16.0%). Our data suggest a slower spread of resistance to sulfonamides, which may be used for the treatment of H. influnezae infections. Genomic analysis may help in the prediction of antibiotic resistance, inform structure–function analysis, and guide the optimal use of antibiotics.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.3390/antibiotics13080756
Manon Launay, Edouard Ollier, Benjamin Kably, Félicien Le Louedec, Guillaume Thiery, Julien Lanoiselée, Sophie Perinel-Ragey
To rapidly achieve ceftazidime target concentrations, a 2 g loading dose (LD) is recommended before continuous infusion, but its adequacy in critically ill patients, given their unique pharmacokinetics, needs investigation. This study included patients from six ICUs in Saint-Etienne and Paris, France, who received continuous ceftazidime infusion with plasma concentration measurements. Using MONOLIX and R, a pharmacokinetic (PK) model was developed, and the literature on ICU patient PK models was reviewed. Simulations calculated the LD needed to reach a 60 mg/L target concentration and assessed ceftazidime exposure for various regimens. Among 86 patients with 223 samples, ceftazidime PK was best described by a one-compartment model with glomerular filtration rate explaining clearance variability. Typical clearance and volume of distribution were 4.45 L/h and 88 L, respectively. The literature median volume of distribution was 37.2 L. Simulations indicated that an LD higher than 2 g was needed to achieve 60 mg/L in 80% of patients, with a median LD of 4.9 g. Our model showed a 4 g LD followed by 6 g/day infusion reached effective concentrations within 1 h, while a 2 g LD caused an 18 h delay in achieving target steady state.
{"title":"Loading Dose of Ceftazidime Needs to Be Increased in Critically Ill Patients: A Retrospective Study to Evaluate Recommended Loading Dose with Pharmacokinetic Modelling","authors":"Manon Launay, Edouard Ollier, Benjamin Kably, Félicien Le Louedec, Guillaume Thiery, Julien Lanoiselée, Sophie Perinel-Ragey","doi":"10.3390/antibiotics13080756","DOIUrl":"https://doi.org/10.3390/antibiotics13080756","url":null,"abstract":"To rapidly achieve ceftazidime target concentrations, a 2 g loading dose (LD) is recommended before continuous infusion, but its adequacy in critically ill patients, given their unique pharmacokinetics, needs investigation. This study included patients from six ICUs in Saint-Etienne and Paris, France, who received continuous ceftazidime infusion with plasma concentration measurements. Using MONOLIX and R, a pharmacokinetic (PK) model was developed, and the literature on ICU patient PK models was reviewed. Simulations calculated the LD needed to reach a 60 mg/L target concentration and assessed ceftazidime exposure for various regimens. Among 86 patients with 223 samples, ceftazidime PK was best described by a one-compartment model with glomerular filtration rate explaining clearance variability. Typical clearance and volume of distribution were 4.45 L/h and 88 L, respectively. The literature median volume of distribution was 37.2 L. Simulations indicated that an LD higher than 2 g was needed to achieve 60 mg/L in 80% of patients, with a median LD of 4.9 g. Our model showed a 4 g LD followed by 6 g/day infusion reached effective concentrations within 1 h, while a 2 g LD caused an 18 h delay in achieving target steady state.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.3390/antibiotics13080758
Arif Iftikhar Khan, Shahzad Nazir, Muhammad Nadeem ul Haque, Rukesh Maharjan, Farooq-Ahmad Khan, Hamza Olleik, Elise Courvoisier-Dezord, Marc Maresca, Farzana Shaheen
Antimicrobial peptides (AMPs) are a promising class of therapeutic alternatives with broad-spectrum activity against resistant pathogens. Small AMPs like temporin-SHa (1) and its first-generation analog [G10a]-SHa (2) possess notable efficacy against Gram-positive and Gram-negative bacteria. In an effort to further improve this antimicrobial activity, second-generation analogs of 1 were synthesised by replacing the natural glycine residue at position-10 of the parent molecule with atypical amino acids, such as D-Phenylalanine, D-Tyrosine and (2-Naphthyl)-D-alanine, to study the effect of hydrophobicity on antimicrobial efficacy. The resultant analogs (3–6) emerged as broad-spectrum antibacterial agents. Notably, the [G10K]-SHa analog (4), having a lysine substitution, demonstrated a 4-fold increase in activity against Gram-negative (Enterobacter cloacae DSM 30054) and Gram-positive (Enterococcus faecalis DSM 2570) bacteria relative to the parent peptide (1). Among all analogs, [G10f]-SHa peptide (3), featuring a D-Phe substitution, showed the most potent anticancer activity against lung cancer (A549), skin cancer (MNT-1), prostate cancer (PC-3), pancreatic cancer (MiaPaCa-2) and breast cancer (MCF-7) cells, achieving an IC50 value in the range of 3.6–6.8 µM; however, it was also found to be cytotoxic against normal cell lines as compared to [G10K]-SHa (4). Peptide 4 also possessed good anticancer activity but was found to be less cytotoxic against normal cell lines as compared to 1 and 3. These findings underscore the potential of second-generation temporin-SHa analogs, especially analog 4, as promising leads to develop new broad-spectrum antibacterial and anticancer agents.
{"title":"Synthesis of Second-Generation Analogs of Temporin-SHa Peptide Having Broad-Spectrum Antibacterial and Anticancer Effects","authors":"Arif Iftikhar Khan, Shahzad Nazir, Muhammad Nadeem ul Haque, Rukesh Maharjan, Farooq-Ahmad Khan, Hamza Olleik, Elise Courvoisier-Dezord, Marc Maresca, Farzana Shaheen","doi":"10.3390/antibiotics13080758","DOIUrl":"https://doi.org/10.3390/antibiotics13080758","url":null,"abstract":"Antimicrobial peptides (AMPs) are a promising class of therapeutic alternatives with broad-spectrum activity against resistant pathogens. Small AMPs like temporin-SHa (1) and its first-generation analog [G10a]-SHa (2) possess notable efficacy against Gram-positive and Gram-negative bacteria. In an effort to further improve this antimicrobial activity, second-generation analogs of 1 were synthesised by replacing the natural glycine residue at position-10 of the parent molecule with atypical amino acids, such as D-Phenylalanine, D-Tyrosine and (2-Naphthyl)-D-alanine, to study the effect of hydrophobicity on antimicrobial efficacy. The resultant analogs (3–6) emerged as broad-spectrum antibacterial agents. Notably, the [G10K]-SHa analog (4), having a lysine substitution, demonstrated a 4-fold increase in activity against Gram-negative (Enterobacter cloacae DSM 30054) and Gram-positive (Enterococcus faecalis DSM 2570) bacteria relative to the parent peptide (1). Among all analogs, [G10f]-SHa peptide (3), featuring a D-Phe substitution, showed the most potent anticancer activity against lung cancer (A549), skin cancer (MNT-1), prostate cancer (PC-3), pancreatic cancer (MiaPaCa-2) and breast cancer (MCF-7) cells, achieving an IC50 value in the range of 3.6–6.8 µM; however, it was also found to be cytotoxic against normal cell lines as compared to [G10K]-SHa (4). Peptide 4 also possessed good anticancer activity but was found to be less cytotoxic against normal cell lines as compared to 1 and 3. These findings underscore the potential of second-generation temporin-SHa analogs, especially analog 4, as promising leads to develop new broad-spectrum antibacterial and anticancer agents.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.3390/antibiotics13080757
Mohamed I. Hassan, Naela Abdel-Monem, Ayman Moawed Khalifah, Saber S. Hassan, Hossam Shahba, Ahmad R. Alhimaidi, In Ho Kim, Hossam M. El-Tahan
The current study was designed to assess the impact of L-carnitine (LC) supplementation in the drinking water of growing Alexandria-line rabbits on performance and physiological parameters. Two hundred eighty-eight 35-day-old rabbits were divided into four groups of twenty-four replicates each (seventy-two rabbits/treatment). The treatment groups were a control group without LC and three groups receiving 0.5, 1, and 1.5 g/L LC in the drinking water intermittently. The results showed that the group receiving 0.5 g LC/L exhibited significant improvements in final body weight, body weight gain, feed conversion ratio, and performance index compared to the other groups. The feed intake remained unaffected except for the 1.5 g LC/L group, which had significantly decreased intake. Hematological parameters improved in all supplemented groups. Compared with those in the control group, the 0.5 g LC/L group showed significant increases in serum total protein and high-density lipoprotein, along with decreased cholesterol and low-density lipoprotein. Compared to other supplemented groups, this group also demonstrated superior carcass traits (carcass, dressing, giblets, and percentage of nonedible parts). In conclusion, intermittent supplementation of LC in the drinking water, particularly at 0.5 g/L twice a week, positively influenced the productivity, hematology, serum lipid profile, and carcass traits of Alexandria-line growing rabbits at 84 days of age.
{"title":"Effect of Adding the Antimicrobial L-Carnitine to Growing Rabbits’ Drinking Water on Growth Efficiency, Hematological, Biochemical, and Carcass Aspects","authors":"Mohamed I. Hassan, Naela Abdel-Monem, Ayman Moawed Khalifah, Saber S. Hassan, Hossam Shahba, Ahmad R. Alhimaidi, In Ho Kim, Hossam M. El-Tahan","doi":"10.3390/antibiotics13080757","DOIUrl":"https://doi.org/10.3390/antibiotics13080757","url":null,"abstract":"The current study was designed to assess the impact of L-carnitine (LC) supplementation in the drinking water of growing Alexandria-line rabbits on performance and physiological parameters. Two hundred eighty-eight 35-day-old rabbits were divided into four groups of twenty-four replicates each (seventy-two rabbits/treatment). The treatment groups were a control group without LC and three groups receiving 0.5, 1, and 1.5 g/L LC in the drinking water intermittently. The results showed that the group receiving 0.5 g LC/L exhibited significant improvements in final body weight, body weight gain, feed conversion ratio, and performance index compared to the other groups. The feed intake remained unaffected except for the 1.5 g LC/L group, which had significantly decreased intake. Hematological parameters improved in all supplemented groups. Compared with those in the control group, the 0.5 g LC/L group showed significant increases in serum total protein and high-density lipoprotein, along with decreased cholesterol and low-density lipoprotein. Compared to other supplemented groups, this group also demonstrated superior carcass traits (carcass, dressing, giblets, and percentage of nonedible parts). In conclusion, intermittent supplementation of LC in the drinking water, particularly at 0.5 g/L twice a week, positively influenced the productivity, hematology, serum lipid profile, and carcass traits of Alexandria-line growing rabbits at 84 days of age.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944212","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}
Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1–2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.
与保守目标相比，积极的药代动力学（PK）/药效学（PD）目标显示出更好的微生物根除率和更低的耐药菌株产生倾向。我们研究了在因脓毒症急性肾损伤（AKI）而接受持续肾脏替代治疗（CRRT）的患者中，使用每 8 小时输注 1 克、持续 3 小时的美罗培南方案，从疗效和安全性的角度来看，美罗培南的血药浓度（包括积极的 PK/PD）是否可以接受。积极的 PK/PD 目标被定义为游离浓度（%fT）> 4 × 最小抑菌浓度（MIC）的时间百分比，毒性阈值被定义为谷浓度>45 mg/L，并评估了每个 MIC 的达标百分比。MIC 为 0.5 mg/L 的病原体的 100% fT > 4 × MIC 为 89%，MIC 为 2 mg/L 的病原体的 100% fT > 4 × MIC 为 56%。美罗培南的平均稳态谷浓度为 11.9 ± 9.0 mg/L，最大稳态谷浓度为 29.2 mg/L。使用贝叶斯估算法进行的模拟显示，在MIC为2 mg/L的情况下，通过3 g/24小时连续输注给药实现100% fT > 4 × MIC的概率为100%。我们发现，对于因脓毒性AKI接受CRRT治疗的患者来说，在MIC为0.5 mg/L的情况下，采用每8小时输注1 g、持续3小时的美罗培南方案可实现积极的PK/PD。此外，该方案达到毒性范围的风险较低。此外，如果 MIC 为 1-2 mg/L，模拟结果表明，在不增加每日剂量的情况下，以 3 克/24 小时的剂量持续输注可实现积极的 PK/PD。
{"title":"Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI","authors":"Shinya Chihara, Tomoyuki Ishigo, Satoshi Kazuma, Kana Matsumoto, Kunihiko Morita, Yoshiki Masuda","doi":"10.3390/antibiotics13080755","DOIUrl":"https://doi.org/10.3390/antibiotics13080755","url":null,"abstract":"Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1–2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-11DOI: 10.3390/antibiotics13080754
Clemens Kittinger, Johannes Stadler, Klaus Dieter Kühn
(1) Background: There is an ongoing discussion on the elution efficacy of antibiotic-impregnated cements. Our experiments were intended to clarify if there are differences in the antibiotic elution of HPLC compared with inhibition zone testing using eluates or PMMA discs. (2) Materials and Methods: Two cement brands with different concentrations of the active ingredient were tested in antimicrobial Kirby–Bauer (disc diffusion) assays. Cement platelets were directly applied on the agar plates and their zone of inhibition was measured. In parallel, the platelets were incubated in phosphate buffered saline (PBS) and at distinct points of time transferred into new buffer. At these time points, 50 µL of the bone cement eluates was used for zone of inhibition testing. Standard gentamicin sulfate solutions served as a control in the same test setup. To verify the microbiological investigations, the antibiotic content of the eluates was also measured via high-performance liquid chromatography (HPLC). (3) Results: The experiments with cement eluates showed better differentiable results than the direct application of the cement discs. The results were also comparable to investigations with HPLC and gentamicin sulfate standard solutions. (4) Conclusions: The results of elution rates are influenced by the test system and the period of observation chosen. The microbial test systems reflect the results of HPLC to the same degree and give evidence of the efficacy of the antibiotics. The HPLC tests on eluates were more suitable in representing differences in release characteristics.
{"title":"Evaluation of Gentamicin Release of PMMA Cements Using Different Methods: HPLC, Elution and Inhibition Zone Testing","authors":"Clemens Kittinger, Johannes Stadler, Klaus Dieter Kühn","doi":"10.3390/antibiotics13080754","DOIUrl":"https://doi.org/10.3390/antibiotics13080754","url":null,"abstract":"(1) Background: There is an ongoing discussion on the elution efficacy of antibiotic-impregnated cements. Our experiments were intended to clarify if there are differences in the antibiotic elution of HPLC compared with inhibition zone testing using eluates or PMMA discs. (2) Materials and Methods: Two cement brands with different concentrations of the active ingredient were tested in antimicrobial Kirby–Bauer (disc diffusion) assays. Cement platelets were directly applied on the agar plates and their zone of inhibition was measured. In parallel, the platelets were incubated in phosphate buffered saline (PBS) and at distinct points of time transferred into new buffer. At these time points, 50 µL of the bone cement eluates was used for zone of inhibition testing. Standard gentamicin sulfate solutions served as a control in the same test setup. To verify the microbiological investigations, the antibiotic content of the eluates was also measured via high-performance liquid chromatography (HPLC). (3) Results: The experiments with cement eluates showed better differentiable results than the direct application of the cement discs. The results were also comparable to investigations with HPLC and gentamicin sulfate standard solutions. (4) Conclusions: The results of elution rates are influenced by the test system and the period of observation chosen. The microbial test systems reflect the results of HPLC to the same degree and give evidence of the efficacy of the antibiotics. The HPLC tests on eluates were more suitable in representing differences in release characteristics.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-10DOI: 10.3390/antibiotics13080753
Alejandro Fenollar-Penadés, Pablo Catalá-Gregori, Vicente Tallá-Ferrer, María Ángeles Castillo, Miguel García-Ferrús, Ana Jiménez-Belenguer
The food chain acts as an entry point for antibiotic resistance to reach humans and environment. Because of the importance of the poultry sector, we investigated the prevalence and evolution of antibiotic resistance in Escherichia coli isolates from a series of 14,500 breeding hens and their farm environment during the rearing period. Samples included meconium from one-day-old breeders and fecal samples and boot swabs from the breeding sheds of pullets and adult hens. All E. coli isolates from one-day-old chicks, 77% from feces and 61% from boot swabs, were resistant to at least one antibiotic. Cefotaxime and multi-drug resistance in fecal isolates decreased during the rearing period from 41.2% and 80.8% in one-day-old chicks to 3.8% and 33.8% in adults. All genes studied were detected in E. coli from feces and boot swabs, the most common being blaTEM (75%), blaSHV (72%), and qnrB (67%). blaCMY-2 was detected in 100% of one-day-old breeders. The combination of at least one cephalosporin and one quinolone resistance gene was detected in 68.7% of fecal and boot swab isolates. Our results highlight the need to monitor the prevalence of antibiotic resistance on farms and to take appropriate measures to reduce the risk to public and environmental health.
{"title":"Evolution of the Antibiotic Resistance Levels, Multi-Resistance Patterns, and Presence of Antibiotic Resistance Genes in E. coli Isolates from the Feces of Breeding Hens during the Rearing Period","authors":"Alejandro Fenollar-Penadés, Pablo Catalá-Gregori, Vicente Tallá-Ferrer, María Ángeles Castillo, Miguel García-Ferrús, Ana Jiménez-Belenguer","doi":"10.3390/antibiotics13080753","DOIUrl":"https://doi.org/10.3390/antibiotics13080753","url":null,"abstract":"The food chain acts as an entry point for antibiotic resistance to reach humans and environment. Because of the importance of the poultry sector, we investigated the prevalence and evolution of antibiotic resistance in Escherichia coli isolates from a series of 14,500 breeding hens and their farm environment during the rearing period. Samples included meconium from one-day-old breeders and fecal samples and boot swabs from the breeding sheds of pullets and adult hens. All E. coli isolates from one-day-old chicks, 77% from feces and 61% from boot swabs, were resistant to at least one antibiotic. Cefotaxime and multi-drug resistance in fecal isolates decreased during the rearing period from 41.2% and 80.8% in one-day-old chicks to 3.8% and 33.8% in adults. All genes studied were detected in E. coli from feces and boot swabs, the most common being blaTEM (75%), blaSHV (72%), and qnrB (67%). blaCMY-2 was detected in 100% of one-day-old breeders. The combination of at least one cephalosporin and one quinolone resistance gene was detected in 68.7% of fecal and boot swab isolates. Our results highlight the need to monitor the prevalence of antibiotic resistance on farms and to take appropriate measures to reduce the risk to public and environmental health.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944217","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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