Gram-Negative Bacilli Blood Stream Infection in Patients with Severe Burns: Microbiological and Clinical Evidence from a 9-Year Cohort.

Bloodstream infection is one of the most important and increasing complications in patients with severe burns. Most of the species affecting this population are Gram-negative bacilli that exhibit antimicrobial resistance. We conducted this study to determine the antimicrobial susceptibility profile and resistance mechanisms of these bacterial infections and their clinical associations on morbidity and mortality. We analyzed a retrospective cohort of burn patients. All patients included in this study had monobacterial blood stream infections during their hospital stay. We performed phenotypic and genotypic tests to determine the antimicrobial resistance mechanism and profile of each strain. Univariate and multivariate logistic regression analysis was performed between variables. We found 109 patients with monobacterial bacteremia. Pseudomonas spp. (50.7%), A. baumannii (46.4%), and Klebsiella spp. (13.8%) were the most common causative microorganisms. The Pseudomonas spp. isolates showed resistance to imipenem (81.5%), mainly by class A and class B carbapenemases. The A. baumannii isolates conferred resistance to imipenem (56.2%), mainly by class D carbapenemases. One quarter of Klebsiella spp. showed resistance to 3rd generation cephalosporins. We also observed that a total body surface area greater than 40% and three or more different types of invasive procedures might be related to increased mortality. Multidrug resistance is highly present. The extent of the burned area and a high number of different types of invasive procedures had an impact in decreasing survivorship in burn patients with bacteremia.

Towards an update on the antimicrobial use in Adult Care Units in Brazil: insights from multi-hospital prevalence study.

Introduction. Efforts to understand the burden of antibiotic use in low- and middle-income countries such as Brazil are essential for developing strategies that are effective and appropriate in the context of endemic multidrug-resistant organisms.Aim. This study aims to determine antimicrobial-prescribing practices among patients hospitalized in intensive care units (ICUs) for adults in Brazil.Methodology. A 1-day point prevalence multicentre survey was conducted in 58 adult ICUs across the five regions of Brazil. The institutions were categorized according to their type and size. Detailed antimicrobial prescription data were prospectively provided to all patients hospitalized on the day of data collection.Results. A total of 620 patients were included in the study, of whom 63.9% were receiving at least one antimicrobial. Of these, 34.6% were treated for an infection, but only 39.9% of the cases were based on microbiological criteria. Empirical treatment was applied to 72.3% of the patients. Significant differences in antibiotic usage were observed across the different hospitals included in the study. Overall, treatment was most commonly directed towards pneumonia (51.8%) and bloodstream infections (29.6%). Glycopeptides (19.4%) and carbapenems (18.5%) were the most prescribed in teaching hospitals, while in non-teaching hospitals, carbapenems (17.8%) and broad-spectrum cephalosporins (16.8%) were most frequently used.Conclusion. Our study reveals alarming data on antibiotic use in adult ICUs in Brazil, with high frequencies of severe healthcare-associated infections acquired in these units, where patients are frequently subjected to empirical treatment.

[Allergic contact dermatitis due to Furacin®]. / Allergic contact dermatitis due to Furacin®.

BACKGROUND: Allergic sensitization to topical antimicrobial treatments is a well-known problem. Furacin® is one of the most widely used in our environment. It contains 0.2% nitrofurazone and polyethylene glycol (PEG) as a vehicle. CASE REPORT: 57-year-old male with no history of interest. He presented skin rash, blisters, and serous exudate 2-3 days after starting treatment with Furacin® (applied to an infected skin wound). Epicutaneous tests were performed with a true test battery, nitrofurantoin 1% in petrolatum, PEG15000 and 4000 1% in petrolatum, pure PEG 400, PEG monomethyl ether 350 1% in water. Positive result at 96 hours for nitrofurantoin. CONCLUSION: Nitrofurazone is widely used as a topical antibiotic because of its bactericidal spectrum. It (including its excipients) should be considered in case of adverse reactions after application.

ANTECEDENTES: La sensibilización o alergia a medicamentos antimicrobianos tópicos es un problema conocido. Furacin® representa uno de los fármacos más prescritos en nuestro medio; sus principios activos son: nitrofurazona al 0.2% y polietilenglicol (PEG) como vehículo. REPORTE DE CASO: Paciente masculino de 57 años, sin antecedentes de interés para el padecimiento actual, que inició con erupción cutánea, ampollas y exudado seroso 2 a 3 días después de aplicar Furacin® en una herida cutánea infectada. Se llevaron a cabo pruebas epicutáneas con batería true test, nitrofurantoína al 1% en vaselina, PEG 15000 y 4000 al 1% en vaselina, PEG 400 puro, y PEG monometil éter 350 al 1% en agua, con resultado positivo para nitrofurantoina luego de 96 horas. CONCLUSIÓN: La nitrofurazona se indica ampliamente como antibiótico tópico, debido a su espectro bactericida; no obstante, debe considerarse (incluidos sus excipientes) en pacientes que manifiestan reacciones adversas después de su aplicación.

Molecular Docking and Antibacterial Activity of Campesterol Derivatives Against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa multiresistant strains.

This work describes the evaluation the potentiating activity of antibiotics by campesterol (1) and its derivatives (2-11) against multiresistant strains of Staphylococcusaureus 10, Escherichia coli 06 and Pseudomonas aeruginosa 24 employing the microdilution test. When subjected to the in vitro potentiating activity bioassay, all compounds showed a potentiating effect associated with norfloxacin against E. coli and P. aeruginosa with a reduction in the MIC of the antibiotic of up to 75%. These compounds also reduced the MIC of gentamicin by 37% to 87% in S. aureus and E. coli. Additionally, molecular docking studies were conducted to gain a deeper understanding of the interactions between the appropriate proteins and the most effective compounds (2, 4, 9, and 10 against E. coli; 1, 2, 3, 5, 8, and 9 against S. aureus), including antibiotics. This paper registers for the first time the in vitro and in silico studies on the action of compounds 1-11 in antibiotic potentiation.

Structural insights and antimicrobial synergy of a proto-galectin from the marine sponge Aiolochroia crassa.

In this study, we isolated a novel lectin from the marine sponge Aiolochroia crassa, named AcrL. The lectin showed a preference for glycans containing sialic acid terminal residues, as indicated by the strongest inhibition with fetuin and bovine submaxillary mucin. Primary structure determination by mass spectrometry revealed that AcrL is a galectin with conserved amino acid residues typically involved in carbohydrate binding. Structural modeling indicated that AcrL adopts a typical galectin ß-sandwich motif, featuring two anti-parallel ß-sheets with five strands each. Docking calculations revealed a carbohydrate-binding site composed of a main site, capable of hosting galactopyranosides, and an extended site, facilitating the binding of complex carbohydrates. AcrL inhibited significant biofilm formation against Staphylococcus aureus, S. epidermidis, and Escherichia coli with concentrations ranging from 500 to 15.6 µg.mL-1 for S. aureus, 7.8 µg.mL-1 for S. epidermidis, and 500 µg.mL-1 for E. coli. Furthermore, when combined with different antibiotics, AcrL potentiated their effect against pathogenic bacteria. The antimicrobial mechanism of AcrL was investigated using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The analysis indicates that AcrL induces damage to the bacterial membrane. These findings underscore the discovery of a novel galectin in a basal organism and the comprehensive biochemical characterization conducted in this research, highlighting the potential of AcrL as a novel antibacterial agent and emphasizing its importance in combating bacterial infections.

Chemical Profile, Antioxidant and Antimicrobial Activity of Marine Sponge Species Combined with Multivariate Statistical Analyses: Desmapsamma anchorata, Dysidea etheria and Echinodictyum dendroides.

Marine sponges are sources of bioactive compounds, sparking pharmacological interest. This study aimed to evaluate the chemical profile, antioxidant, and antibacterial activities of the species Desmapsamma anchorata, Dysidea etheria, and Echinodictyum dendroides. The chemical profile was characterized by the identification and quantification of polyphenols. Antioxidant activity was assessed using different methods. Antibacterial and modulatory activities were evaluated through microdilution against pathogenic strains. The polyphenols were found in low abundance in the extracts. In the antioxidant assays, the EACDa and EMDa extracts exhibited better inhibitory results. In the antibacterial evaluation, extracts presented MIC ≥ 1024 µg mL-1. The modulation of the extracts in combination with antibiotics showed significant effects against the multiresistant bacterium Pseudomonas aeruginosa. This study contributes to the deepening of chemical and biological knowledge of sponge species, indicating that their extracts can act as good modulators of bacterial resistance to aminoglycoside antibiotics, warranting further investigation into their mechanisms of action.

Antibiotic resistant bacteria and antibiotic resistance genes as contaminants of emerging concern: Occurrences, impacts, mitigations and future guidelines.

Antibiotic resistance, driven by the proliferation of antibiotic resistance genes (ARGs) and antibiotic resistance bacteria (ARBs), has emerged as a pressing global health concern. Antimicrobial resistance is exacerbated by the widespread use of antibiotics in agriculture, aquaculture, and human medicine, leading to their accumulation in various environmental compartments such as soil, water, and sediments. The presence of ARGs in the environment, particularly in municipal water, animal husbandry, and hospital environments, poses significant risks to human health, as they can be transferred to potential human pathogens. Current remediation strategies, including the use of pyroligneous acid, coagulants, advanced oxidation, and bioelectrochemical systems, have shown promising results in reducing ARGs and ARBs from soil and water. However, these methods come with their own set of challenges, such as the need for elevated base levels in UV-activated persulfate and the long residence period required for photocatalysts. The future of combating antibiotic resistance lies in the development of standardized monitoring techniques, global collaboration, and the exploration of innovative remediation methods. Emphasis on combination therapies, advanced oxidation processes, and monitoring horizontal gene transfer can pave the way for a comprehensive approach to mitigate the spread of antibiotic resistance in the environment.

Microbiological Quality of Coconut Water Sold in the Grande Vitória Region, Brazil, and Phenogenotypic Antimicrobial Resistance of Associated Enterobacteria.

This study aimed to evaluate the microbiological quality of coconut water sold from street carts equipped with cooling coils or refrigerated at bakeries in the Grande Vitória Region, Brazil. Additionally, it assessed the phenotypic and genotypic antimicrobial resistance profiles of isolated enterobacteria. The results indicated that coconut water sold at street carts had lower microbiological quality compared to refrigerated samples, as evidenced by significantly higher counts of mesophilic microorganisms. Using MALDI-TOF, the following opportunistic pathogens were identified: Citrobacter freundii, Enterobacter bugandensis, E. kobei, E. roggenkampii, Klebsiella pneumoniae, and Kluyvera ascorbata. Three isolates-E. bugandensis, K. pneumoniae, and K. ascorbata-were classified as multidrug-resistant (MDR). Widespread resistance to ß-lactams and cephalosporins was detected, and some isolates were resistant to quinolones, nitrofurans, and phosphonic acids. The gene blaCTX-M-2 was detected in C. freundii, E. bugandensis, E. kobei, and K. ascorbata. However, genes blaNDM, blaKPC, blaCMY-1, and blaCMY-2 were not detected in any isolate. The findings underscore the need to enhance good manufacturing practices in this sector to control the spread of antimicrobial resistance (AMR). To our knowledge, this is the first study documenting the presence of potentially pathogenic enterobacteria in coconut water samples and their associated phenotypic and genotypic AMR profiles.

Discovery of Arylpiperazines with Broad-Spectrum Antimicrobial Activity and Favorable Pharmacokinetic Profiles.

Microorganisms can induce diseases with significant clinical implications for human health. Multidrug-resistant microorganisms have been on the rise worldwide over the past few decades, and no new antibiotics have been introduced to the market in a considerable amount of time. Such situation highlights the urgency of discovering new antimicrobial drugs to address this pressing issue. Therefore, the objective of this study was to identify bioactive compounds against 15 species of bacteria and 5 species of fungi of clinical relevance through in vitro screening of 58 synthetic compounds from four chemical classes of our internal library of synthetic compounds. Our findings highlight arylpiperazines 18, 20, 26, 27, and 29, and the aminothiazole 50, as potent broad-spectrum antimicrobials (MICs = 12.5 - 15.6 mg.mL-1) against clinically relevant bacteria and fungi. Additionally, these compounds displayed low cytotoxicity against various host cells and a favorable in vitro pharmacokinetic profile for oral administration. Indeed, all six showed adequate lipophilicity, high gastrointestinal permeability, metabolic stability in human and mouse liver microsomes, and satisfactory aqueous solubility. Thus, they emerge as promising starting points for hit-to-lead studies towards new antibacterial and antifungal agents, especially against Staphylococcus epidermidis, Staphylococcus aureus, Lactobacillus paracasei and Candida orthopsilosis.

Single center experience with more than 600 drug desensitization in Colombia.

Background: Drug hypersensitivity reactions (DHRs) have a significant impact on both, patient and their treating physicians; it is considered a public health concern. The history of allergy to drugs, limits therapeutic options and will lead to the use of more expensive and potentially less effective options. Drug desensitization (DD) is considered as a procedure with a positive impact on the prognosis of the patient's disease. The objective of this study is to describe the experience with a substantial number of drugs desensitization in a fourth level center in Cali, Colombia. Methods: An observational, cross-sectional and descriptive study was conducted. Patients with DHRs who underwent a standardized institutional DD protocol, between March of 2012 and May of 2023, were included. Results: Two hundred forty-one patients were included. The median age was 47.8 years (4-88). One hundred fifty-six (64.7%) were women, including three who were pregnant. A total of 641 DDs were performed. The most frequent groups of drugs for which the desensitization was performed were monoclonal antibodies in 83 patients (34.4%), chemotherapeutic agents in 53 (21.6%), NSAIDs in 44 (18.2%), and antibiotics in 42 (17.4%). Eighty-seven patients (36.1%) experienced hypersensitivity to the culprit drug on first exposure, while 154 (63.9%) exhibited reactions during subsequent cycles. The main clinical presentation that gave rise to desensitization was anaphylaxis in 125 patients (51.8%), followed by cutaneous symptoms in 106 patients (44%). The predominant observed endophenotype was type 1 in 188 patients (78.3%), followed by mixed type in 46 patients (19.2%). Breakthrough reactions were observed in 50 patients (20.7%). Tolerance to DD was achieved in 636 of the procedures (99.2%), allowing the continuity of treatment of choice for the underlying disease. Conclusions: Most desensitized patients were women with type I reactions. Monoclonal antibodies were the most frequent culprit drugs. DD in patients with DHRs is a useful, safe and effective procedure. The administration of the implicated drug had a positive impact on the course of the disease in these patients.

The Use of Antibiotics at the End of Life: A Cross-Sectional Study.

Objective: To identify and analyze antibiotics' prescription patterns and associated factors among terminally ill patients at a hospital in southern Peru. Methodology: A cross-sectional analytical study was conducted on adult patients who died in Hospital III Daniel Alcides Carrion in Tacna, Peru, 2023. Data were collected from electronic medical records, focusing on antibiotic use during the last hospitalization. Univariate, bivariate, and multivariate analyses were performed using Poisson regression to adjust for potential confounders. Results: The study included 239 patients with an average age of 76. Antibiotics were administered to 93.72% of patients, with 42.46% lacking an identified infectious focus. Ceftriaxone, Meropenem, and Vancomycin were the most used antibiotics. A lower use of antibiotics within 72 hours prior to death was associated with hospitalizations longer than 18 days and having 2 or more comorbidities. Conclusion: The high prevalence of antibiotic use at the end of life, often without an infectious focus, suggests a need for better guidelines and education on palliative care to avoid inappropriate antibiotic prescribing. Improved communication between healthcare providers, patients, and families is essential for optimizing end-of-life care.

Efficacy of prophylactic antibiotics in the adjuvant treatment of alcohol-related liver disease (ALD): A systematic review and meta-analysisProphylactic antibiotics in ALD.

INTRODUCTION AND OBJECTIVES: This research aims to evaluate the efficacy and safety of prophylactic antibiotics in patients with alcohol-related liver disease (ALD). MATERIALS AND METHODS: We systematically searched databases including PubMed, Embase, Cochrane, and Web of Science up to October 2023. Our scope encompassed the influence of prophylactic antibiotics on all-cause mortality, infection, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), adverse events (AE), fungal infection, clostridioides difficile infection (CDI), and multidrug-resistant (MDR) bacterial infection. Additionally, total bilirubin, creatinine, platelet counts, and plasma endotoxin levels were also analyzed. RESULTS: After comprehensive selection, 10 studies with 974 participants were included for further analysis. The study demonstrated that prophylactic antibiotic therapy was associated with reductions in infection rates, HE incidence, variceal bleeding, and all-cause mortality. The treatment did not increase the incidence of AE, fungal infection, and CDI, but it did raise the MDR bacteria infection rate. The analysis revealed no significant protective effect of antibiotic prophylaxis on total bilirubin and creatinine levels. Furthermore, the administration of antibiotics led to marginal increases in platelet counts, a minor reduction in endotoxin concentrations, and a subtle enhancement in HRS; however, these changes did not reach statistical significance. CONCLUSIONS: Prophylactic antibiotic therapy was an effective and safe treatment for advanced ALD. To mitigate the risk of MDR bacterial infections, a strategy of selective intestinal decontamination could be advisable. Future investigations should prioritize varied ALD patient populations with extended follow-up periods and assorted antibiotic regimens to solidify the efficacy and safety of ALD treatments.

Antibiotic prescribing patterns in pediatric patients using the WHO access, watch, reserve (AWaRe) classification at a quaternary hospital in Nampula, Mozambique.

Antibiotics are often prescribed inappropriately, either when they are not needed or with an unnecessarily broad spectrum of activity. This is a serious problem that can lead to the development of antimicrobial resistance (AMR). This study was conducted to assess the antibiotic prescribing pattern in pediatric patients hospitalized at a quaternary hospital in Nampula, Mozambique, using the WHO indicators and Framework as a reference. A retrospective study was conducted using secondary data obtained from medical records. The study population consisted of children aged 0-10 years who were hospitalized in a quaternary-level hospital ward in Nampula, Mozambique. The pattern of antibiotic prescriptions was assessed using indicators and the WHO classification of antibiotics into AWaRe categories. Descriptive statistics were applied. A total of 464 antibiotics were prescribed during the study. The age groups of 1-3 years and 28 days-12 months were prescribed more antibiotics. The most common antibiotics were ceftriaxone and crystallized penicillin, which were frequently prescribed for patients suffering from bronchopneumonia, gastroenteritis, and malaria. 74.8% of the antibiotics prescribed belonged to the Access group, while 23.7% belonged to the Watch group. There were no prescriptions of antibiotics from the Reserve group. The average number of antibiotics per prescription was 1.51 (SD ± 0.725). The percentage of antibiotic prescribing was 97.5%, with 96.20% by injection. All antibiotics prescribed were on the essential medicines list and prescribed by generic name. These results are concerning and highlight the urgency of strengthening antimicrobial optimization measures, as well as implementing the AWaRe framework in antibiotic prescribing as an essential strategy to combat AMR.

Antibiotics stimulates the development of persistent cells in biofilms of Candida albicans bloodstream isolates.

Candida albicans invasive candidiasis is considered a global health problem. In such cases, biofilm formation on implanted devices represents a therapeutic challenge and the presence of metabolically inactive persistent cells (PCs) in these communities increases their tolerance to fungicidal drugs. This study investigated the influence of amoxicillin, AMX; cefepime, CEF; gentamicin, GEN; amikacin, AMK; vancomycin, VAN; and ciprofloxacin, CIP; on the production of PCs in biofilms of C. albicans bloodstream isolates. 48 h-mature biofilms (n = 6) grown in RPMI-1640 supplemented with antibiotics were treated with 100 µg ml-1 amphotericin B and then evaluated for PCs. Biofilms grown in the presence of antibiotics produced more PCs, up to 10×, when exposed to AMX and CIP; 5 × to CEF; and 6 × to GEN and VAN. The results indicate that antibiotics can modulate PC production in C. albicans biofilms. This scenario may have clinical repercussions in immunocompromised patients under broad-spectrum antibiotic therapy.

Biofilms are microbial communities tolerant to antifungals. Our research showed that antibiotics stimulate the formation of persistent cells within Candida albicans biofilms. These are dormant, metabolically silent cells that resist to therapy and can be related to metastatic and recalcitrant infections.

Social wasp-associated Tsukamurella sp. strains showed promising biosynthetic and bioactive potential for discovery of novel compounds.

In the face of escalating antibiotic resistance, the quest for novel antimicrobial compounds is critical. Actinobacteria is known for producing a substantial fraction of bioactive molecules from microorganisms, nonetheless there is the challenge of metabolic redundancy in bioprospecting. New sources of natural products are needed to overcome these current challenges. Our present work proposes an unexplored potential of Neotropical social wasp-associated microbes as reservoirs of novel bioactive compounds. Using social wasp-associated Tsukamurella sp. strains 8F and 8J, we aimed to determine their biosynthetic potential for producing novel antibiotics and evaluated phylogenetic and genomic traits related to environmental and ecological factors that might be associated with promising bioactivity and evolutionary specialization. These strains were isolated from the cuticle of social wasps and subjected to comprehensive genome sequencing. Our genome mining efforts, employing antiSMASH and ARTS, highlight the presence of BGCs with minimal similarity to known compounds, suggesting the novelty of the molecules they may produce. Previous, bioactivity assays of these strains against bacterial species which harbor known human pathogens, revealed inhibitory potential. Further, our study focuses into the phylogenetic and functional landscape of the Tsukamurella genus, employing a throughout phylogenetic analysis that situates strains 8F and 8J within a distinct evolutionary pathway, matching with the environmental and ecological context of the strains reported for this genus. Our findings emphasize the importance of bioprospecting in uncharted biological territories, such as insect-associated microbes as reservoirs of novel bioactive compounds. As such, we posit that Tsukamurella sp. strains 8F and 8J represent promising candidates for the development of new antimicrobials.

The Efficacy of Topical or Systemic Antibiotics as Adjuvants to Non-Surgical Periodontal Treatment in Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Periodontitis and diabetes mellitus (DM) exhibit a bidirectional relationship and are globally significant systemic chronic conditions. The utilization of antibiotics alongside non-surgical periodontal treatment (NSPT) has been a subject of investigation in numerous clinical studies involving human subjects. Thus, the objective of this systematic review is to address the following question: "What is the efficacy of scaling and root planing (SRP) associated with antimicrobials in patients with type 2 DM and periodontitis?". Methods: A systematic review of the literature was conducted encompassing databases such as MEDLINE/PubMed, Scopus, and Web of Science up to July 2024. Additionally, alerts were configured to capture studies published from the initial search until manuscript submission. Randomized clinical trials assessing clinical periodontal parameters in DM patients undergoing SRP and receiving either topical or systemic antibiotics were compared against a control group (SRP only). Two investigators independently screened articles, extracted data, and evaluated their quality. The selection process, study characteristics, risk of bias, impact of antibiotics on clinical parameters, and certainty of evidence were elucidated in both textual and tabular formats. Meta-analysis was performed separately with forest plots generated for treatment modalities, period of evaluation, and type of antibiotics used. Results: Following the analysis of abstracts and full articles, a total of 30 randomized clinical trials were incorporated into this review, comprising 9 studies on the association of topical antibiotics and 21 studies on systemic antibiotic administration. The principal periodontal parameters assessed included probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BoP). Conclusions: Analysis of the results led to the conclusion that adjunctive periodontal treatment with either topical or systemic antibiotics confers subtle clinical benefits. Nevertheless, owing to the heightened emergence of resistant bacteria and potential side effects, the use of antibiotic therapy in periodontal treatment should be judiciously administered.

The Vehicle of Administration and Prandial State May Reduce the Spectrum of Oral Broad-Spectrum Antibiotics (Oxytetracycline, Fosfomycin and Amoxicillin) Administered to Piglets: A Pharmacokinetic/Pharmacodynamic Approach.

The objective of this study was to assess the impact of the vehicle of administration and the prandial state of post weaning piglets on the indices of therapeutic efficacy for different broad-spectrum antibiotic/pathogen combinations. Pharmacokinetic data were retrieved from previous studies, in which we orally administered oxytetracycline (OTC), fosfomycin (FOS), or amoxicillin (AMX) according to the following treatments: dissolved in soft water to fasted or non-fasted piglets, dissolved in hard water to fasted or non-fasted piglets, and mixed with feed. Minimum inhibitory concentration (MIC) values for susceptible strains of bacteria causing swine diseases were obtained from the database of European Committee on Antimicrobial Susceptibility Testing (EUCAST) for each antibiotic. Pharmacokinetic/pharmacodynamic (PK/PD) indices of therapeutic efficacy-drug exposure over the dosing interval (fAUC/MIC) for OTC and FOS; time that free drug concentration remains above MIC (%fT>MIC) for AMX-were calculated for each antibiotic/pathogen combination under each treatment. After all OTC and in-feed FOS and AMX treatments, the indices of therapeutic efficacy were below the target value for all the study microorganisms. When FOS or AMX were delivered dissolved in soft or hard water, the indices were above the target value over which therapeutic efficacy would be expected for Escherichia coli treated with FOS and, Glaesserella parasuis, Pasteurella multocida, and Actinobacillus pleuropneumoniae treated with AMX. The prandial state of piglets showed no influence on the indices of therapeutic efficacy. Pharmacokinetic profiles of broad-spectrum antibiotics, specifically the ability to achieve target concentrations, may be largely reduced due to drug interactions with components present in feed or water resulting in a discrepancy with PK/PD principles of prudent and responsible use of antibiotics.

Intestinal Microbiome Profiles in Broiler Chickens Raised with Different Probiotic Strains.

The composition of the intestinal microbiota can influence the metabolism and overall functioning of avian organisms. Therefore, the objective of this study was to evaluate the effect of three different probiotics and an antibiotic on the microbiomes of 1.400 male Cobb® broiler raised for 42 days. The experiment was conducted with the following treatments: positive control diet (basal diet + antibiotic); negative control diet (basal diet without antibiotic and without probiotic); basal diet + Normal Avian Gut Flora (NAGF); basal diet + multiple colonizing strain probiotics (MCSPs); and basal diet + non-colonizing single strain probiotics (NCSSPs). The antibiotic (enramycin-antibiotic growth promoter) and probiotics were administered orally during all experiment (1 to 42 days), mixed with broiler feed. To determine the composition of the microbiota, five samples of ileal digesta were collected from 42-day-old chickens of each experimental group. The alpha and beta diversity of the ileal microbiota showed differences between the groups. MCSPs presented greater richness and uniformity compared to the positive control, negative control, and NCSSPs treatments, while the negative control exhibited greater homogeneity among samples than NCSSPs. MCSPs also showed a higher abundance of the genus Enterococcus. There were differences between the groups for low-abundance taxa (<0.5%), with NAGF showing higher levels of Delftia, Brevibacterium, and Bulleidia. In contrast, NCSSPs had a higher abundance of Ochrobactrum, Rhodoplanes, and Nitrospira. It was concluded that the treatments analyzed in this study induced modulations in the ileal microbiota of the chickens examined.

Validation of Lyophilized Human Fecal Microbiota for the Treatment of Clostridioides difficile Infection: A Pilot Study with Pharmacoeconomic Analysis of a Middle-Income Country-Promicrobioma Project.

BACKGROUND: Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost-benefit analysis in the treatment of recurrent or refractory CDI. METHODS: The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost-benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole. RESULTS: The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil. CONCLUSIONS: The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI.

Effects of sulfamethazine and tetracycline at molecular, cellular and tissue levels in Eisenia fetida earthworms.

Soil contamination by antibiotics is a global issue of great concern that contributes to the rise of bacterial antibiotic resistance and can have toxic effects on non-target organisms. This study evaluated the variations of molecular, cellular, and histological parameters in Eisenia fetida earthworms exposed to sulfamethazine (SMZ) and tetracycline (TC), two antibiotics commonly found in agricultural soils. The earthworms were exposed for 14 days to a series of concentrations (0, 10, 100, and 1000 mg/kg) of both antibiotics. SMZ and TC did not affect the survival of E. fetida, however, other effects at different levels of biological complexity were detected. The two highest concentrations of SMZ reduced the viability of coelomocytes. At the highest TC concentration, there was a noticeable decline in cell viability, acetylcholinesterase activity (neurotoxicity), and the relative presence of mucopolysaccharides in the epidermis (mucous production). Glutathione S-transferase activity decreased in all TC treatments and at the highest SMZ concentration. However, levels of malondialdehyde and protein carbonyls did not change, suggesting an absence of oxidative stress. Tetracycline was neurotoxic to E. fetida and changed the integrity of the epidermis. Both antibiotics altered the intestinal microbiota of E. fetida, leading to a reduction in the relative abundance of bacteria from the phyla Proteobacteria and Bacteroidetes, while causing an increase in the phylum Actinobacteroidota. All observed changes indicate that both SMZ and TC can disrupt the earthworms' immune system and gut microbiome, while fostering the growth of bacteria that harbour antibiotic resistance genes. Finally, both antibiotics exerted additional metabolic and physiological effects that increased the vulnerability of E. fetida to pathogens.