Antibiotic Group Research Articles

Polyanionic Receptors for Carboxylates in Water

AbstractReceptors for carboxylate anions have many possible biomedical applications, including mimicry of the vancomycin group of antibiotics. However, binding carboxylates in water, the biological solvent, is highly challenging due to the hydrophilicity of these polar anions. Here we report, for the first time, the recognition of simple carboxylates such as acetate and formate in water by synthetic receptors with charge‐neutral binding sites. The receptors are solubilised by polyanionic side‐chains which, remarkably, do not preclude anion binding. The tricyclic structures feature two identical binding sites linked by polyaromatic bridges, capable of folding into closed, twisted conformations. This folding is hypothesised to preorganise the structures for anion recognition, mimicking the process which generates many protein binding sites. The architecture is suitable for elaboration into enclosed structures with potential for selective recognition of biologically relevant carboxylates.

Microbial exposure at birth and the development of behavioral temperament during the first three years of childhood.

We investigated cross-sectional and longitudinal associations between neonate microbial exposure and emerging behavioral temperament measures at the ages of 1, 2, and 3 years. Infants and mothers (n = 335) were extracted from the Kuopio Birth Cohort Study. Temperament was assessed using the Infant Behavioral and Early Childhood Behavioral Questionnaires. Microbial samples were collected from oral cavity at birth and the bacterial profiles were assessed using 16S rRNA gene sequencing. Microbial diversity was characterized using alpha and beta diversity metrics. Analyses were performed for the most abundant genera. The sample was analyzed as a whole, as well as divided into subgroups representing no antibiotic use during birth (n = 198) and those with antibiotic use during birth (n = 137). No significant associations were observed between microbial profiles and behavioral measures after Bonferroni corrections. Nevertheless, our pre-correction results indicated an association between increased behavioral temperament surgency in the first year and beta diversity (high abundance of Bacteroides, Faecalibacterium and Blautia, low abundance of Lactobacillus) in the antibiotic use group. Additionally, pre-corrections, a high relative abundance of Staphylococcus was associated with increased surgency through years 1, 2, and 3 in the no antibiotics group, prompting consideration into a possible link between antibiotic use and emerging behavioral temperament.

Source apportionment and ecological risk assessment of antibiotics in Dafeng River Basin using PMF and Monte-Carlo simulation.

Antibiotics, prevalent in aquatic ecosystems, pose a grave threat to human health and the ecological well-being. This paper performed a case study on Dafeng River Basin in southern China. Specifically, techniques including positive matrix factorization (PFM) and Monte-Carlo simulation were employed to comprehensively investigate the spatial variations, possible sources, and ecological risks of antibiotics in four groups: sulfonamides (SAs), macrolides (MLs), quinolones (QNs), and tetracyclines (TCs). The major findings were as follows: first, 43 and 39 antibiotics were detected in the surface water and sediments of the basin, respectively, where the respective total content were ND-490.08ng/L and ND-144.34μg/kg, and the QNs and TCs were the two dominating groups. Second, the highest antibiotic content in surface water (441.43ng/L) was observed in the midstream area, whereas the highest concentration in sediments (68.41μg/kg) was found in the upstream region. Third, the investigation identified five sources of antibiotics discharged to surface water: domestic sewage, agricultural drainage, livestock discharge, sewage treatment plants, and aquaculture; three sources were detected for antibiotics in sediments: aquaculture, sewage treatment plants, and livestock discharge. Fourth, QNs had a significantly higher ecological risk than the other three groups of antibiotics, and livestock discharge (31.4% contribution) and aquaculture (23.4% contribution) were the main sources of risks of antibiotic contamination in Dafeng River Basin. This study is expected to provide some reference for control and risk management of antibiotic pollution in Dafeng River Basin.

Suspected Cases of Chlamydia-Induced Fertility Problems in Sows: What Is the Approach of Austrian Practitioners?

Although it is generally accepted that Chlamydia spp. can induce fertility problems in sows, many questions concerning diagnostic, therapeutic, and prophylactic approaches remain unanswered. The aim of this study was to gather information about how swine practitioners deal with these knowledge gaps. Austrian swine practitioners were anonymously asked for their assessment of chlamydiosis using the Lime Survey program. PCR tests are used for molecular chlamydia detection from abortion material (64.3%), vaginal swabs (40.5%), and the genital tract (postmortem slaughterhouse samples) (9.5%). Treatment mainly includes tetracyclines (95.2%), occasionally macrolides (2.4%) or other (not mentioned) antibiotic groups (7.1%). Treatment periods vary greatly, from 5 to 10 days (23.8%), from 11 to 15 days (47.6%), from 16 to 21 days (11.9%), and >21 days (9.5%). Prophylactic measures include hygiene improvement, rodent control, and herd treatments with tetracyclines. Serological methods are perceived as inadequate, and there is a general need for better guidance on interpreting results. Knowledge about the increased incidence of tetracycline-resistant Chlamydia suis strains is limited. Weighing up economic interests, feasibility, and animal welfare plays an important role. Further research to improve diagnosis and prevention of chlamydia-related fertility diseases in sows is urgently needed.

Chinese Herbal Medicines as Natural Alternative Products to Antibiotics in Weaned Piglets through Intestinal Microbiota Regulation.

During the growth process of weaned piglets, digestive problems such as gastrointestinal disorders and diarrhea are common. Farmers usually use antibiotics to help piglets grow smoothly. However, the overuse of antibiotics can lead to antibiotic resistance issues. Therefore, this study chose to use plant extracts as feed additives to explore their potential as alternatives to antibiotics. Additionally, Tilmicosin was used as the antibiotic because it is widely used in treating respiratory infections in piglets. Since traditional Chinese medicine often uses natural products, we selected Guizhi Li-Zhong (GLZ) extract as an alternative to antibiotics. The experiment involved 126 piglets, each 4 weeks old, which were randomly assigned to one of four groups: the sham group (basal diet without supplements, 10.3 ± 0.4 kg, n = 31), the low-dose GLZ group (basal diet with 0.05% GLZ, 10.9 ± 0.4 kg, n = 32), the regular-dose GLZ group (basal diet with 0.2% GLZ, 10.6 ± 0.4 kg, n = 32), and the regular-dose Tilmicosin antibiotic group (basal diet with 0.2% Tilmicosin, 10.2 ± 0.3 kg, n = 31). We recorded and compared the survival rate, growth rate, feed conversion ratio, and diarrhea incidence among four groups of weaned piglets from the 4th to the 10th weeks of age. Then, we examined the oxidative stress, inflammation, and apoptosis in small intestine tissue (jejunum and ileum) through immunohistochemistry and Western blot and compared the gut microbiota in large intestine tissue (colon and rectum) through a next-generation sequencing (NGS) analysis. Our results showed that weaned piglets supplemented with 0.05% and 0.2% GLZ had better survival rates, growth rates (p < 0.01), and feed conversion ratios (p < 0.01) compared to those receiving sham treatment. Even weaned piglets supplemented with 0.2% GLZ performed better than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). Furthermore, the incidence of diarrhea and small intestine injury (indicated by oxidative stress-, inflammation-, and apoptosis-related proteins) in piglets supplemented with 0.05% and 0.2% GLZ was lower than in piglets receiving sham treatment (p < 0.05). Even piglets supplemented with 0.2% GLZ had less injury than those supplemented with 0.2% Tilmicosin antibiotics (p < 0.05). The NGS results further showed that GLZ treatment significantly improved beneficial bacteria in weaned piglets (p < 0.05), while antibiotic treatment reduced beneficial bacteria (p < 0.05). In summary, we recommend adding GLZ to the feed as an alternative to antibiotics. This not only effectively reduces intestinal damage but also improves the gut microbiota, thereby promoting the growth of weaning piglets.

Effects of monoglyceride blend on systemic and intestinal immune responses, and gut health of weaned pigs experimentally infected with a pathogenic Escherichia coli

BackgroundMonoglycerides have emerged as a promising alternative to conventional practices due to their biological activities, including antimicrobial properties. However, few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance, immune response, and gut health using a disease challenge model. Therefore, this study aimed to investigate the effects of dietary monoglycerides of short- and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18.ResultsPigs supplemented with high-dose zinc oxide (ZNO) had greater (P < 0.05) growth performance than other treatments, but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period. Pigs in ZNO and antibiotic groups had lower (P < 0.05) severity of diarrhea than control, but the severity of diarrhea was not different between antibiotic and monoglycerides groups. Pigs fed with monoglycerides or ZNO had lower (P < 0.05) serum haptoglobin on d 2 or 5 post-inoculation than control. Pigs in ZNO had greater (P < 0.05) goblet cell numbers per villus, villus area and height, and villus height:crypt depth ratio (VH:CD) in duodenum on d 5 post-inoculation than pigs in other treatments. Pigs supplemented with monoglycerides, ZNO, or antibiotics had reduced (P < 0.05) ileal crypt depth compared with control on d 5 post-inoculation, contributing to the increase (P = 0.06) in VH:CD. Consistently, pigs in ZNO expressed the lowest (P < 0.05) TNFa, IL6, IL10, IL12, IL1A, IL1B, and PTGS2 in ileal mucosa on d 5 post-inoculation, and no difference was observed in the expression of those genes between ZNO and monoglycerides. Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control, particularly on carbohydrate and amino acid metabolism, while limited impacts on serum metabolites were observed in monoglycerides group when compared with control.ConclusionsThe results suggest that supplementation of monoglyceride blend may enhance disease resistance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation, although the effectiveness may not be comparable to high-dose zinc oxide.

Novel β-lactam antibiotics versus other antibiotics for treatment of complicated urinary tract infections: a systematic review and meta-analysis.

Novel β-lactam antibiotics as well as other kinds of antibiotics have been used to treat complicated urinary tract infections (cUTIs); however, their efficacy and safety remain controversial. We conducted a systematic review with meta-analysis to explore the efficacy and safety of novel β-lactam antibiotics versus other antibiotics against cUTIs. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched systematically from inception through 15 March 2024 for clinical trials comparing novel β-lactam antibiotics with other antibiotics for treatment of cUTIs. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of clinical response, microbiologic response, adverse effects (AEs), serious adverse effects (SAEs). The quality of evidence was evaluated with the Cochrane Risk of Bias assessment tool. The review was registered in INPLASY (INPLASY202440054). Ten randomized controlled trials involving 5, 925 patients met our inclusion criteria. Our meta-analysis revealed that there was no significant difference in overall clinical response (RR = 1.02), AEs (RR = 1.07), SAEs (RR = 1.20) between novel β-lactam antibiotics groups and other antibiotics groups. However, a significant difference was found in a subgroup of clinical cure rates at the end of treatment between novel β-lactam antibiotics groups and carbapenems groups, with low heterogeneity (RR = 1.02). A significant difference was observed in microbiologic response (RR = 1.11). Subgroup analysis revealed a significant difference in microbiologic response between novel BBL/BLS groups and carbapenems groups (RR = 1.13, I2 = 21%, P = 0.005). Differences was observed between novel BBL/BLS groups and piperacillin/tazobactam sodium groups (RR = 1.21, I2 = 70%, P = 0.02). Similar results were obtained from subgroup analysis of the difference in microbiologic response between novel β-lactam antibiotics groups and ertapenem groups (RR = 0.92, I2 = 0, P = 0.01). Novel β-lactam antibiotics had similar overall clinical cure, AEs, SAE, to other antibiotics in the treatment of cUTIs. However, novel β-lactam antibiotics demonstrated superior clinical cure rates compared to carbapenems in a subgroup analysis, and exhibited better microbiologic response than other antibiotics.

Secretion of the human parathyroid hormone through a microcin type I secretion system in Escherichia coli

BackgroundGram negative bacteria possess different secretion systems to export proteins to the extracellular medium. The simplest one, type I secretion system (T1SS), forms a channel across the cell envelope to export proteins in a single step. Peptides secreted by the T1SSs comprise a group of antibiotics, called class II microcins, which carry an amino terminal secretion domain that is processed concomitantly with export. Mature microcins range in size from 60 to 90 amino acids and differ in their sequences. Microcin T1SSs show a high versatility in relation to the peptides they are able to secrete, being mainly limited by the length of the substrates. Different bioactive peptides unrelated to bacteriocins could be secreted by microcin V (MccV) T1SS, while retaining their biological activity.ResultsIn this work heterologous secretion of two variants of human parathyroid hormone (PTH) by MccV T1SS was evaluated. PTH is a bioactive peptide of 84 amino acids (PTH84), which is involved in the maintenance of bone homeostasis. Currently, a drug corresponding to the active fraction of the hormone, which resides in its first 34 amino acids (PTH34), is commercially produced as a recombinant peptide in Escherichia coli. However, research continues to improve this recombinant production. Here, gene fusions encoding hybrid peptides composed of the MccV secretion domain attached to each hormone variant were constructed and expressed in the presence of microcin T1SS in E. coli cells. Both PTH peptides (PTH34 and PTH84) were recovered from the culture supernatants and could be confirmed to lack the MccV secretion domain, i.e. microcin T1SS efficiently recognised, processed and secreted both PTH variants. Furthermore, the secreted peptides were stable in the extracellular medium unlike their unprocessed counterparts present in the intracellular space.ConclusionThe successful secretion of PTH variants using MccV T1SS could be considered as a new alternative for their production, since they would be recovered directly from the extracellular space without additional sequences. Furthermore, it would be a new example revealing the potential of microcin type I secretion systems to be conceived as a novel strategy for the production of recombinant peptides in E. coli.

Positive impact of early-probiotic administration on performance parameters, intestinal health and microbiota populations in broiler chickens

Minimizing the utilization of antibiotics in animal production is crucial to prevent the emergence of antimicrobial resistances. Thus, research on alternatives is needed to maintain productivity, sustainability, and animal health. To gain a comprehensive understanding of probiotics' modes of action on performance, intestinal microbiota, and gut health in poultry, 3 probiotic strains (Enterococcus faecalis CV1028 [EntF], Bacteroides fragilis GP1764 [BacF], and Ligilactobacillus salivarius CTC2197 [LacS]) were tested in 2 in vivo trials. Trial 1 comprised of a negative control group fed basal diet (BD) and 3 treatment groups that received BD with EntF, BacF and LacS. Trial 2 included a negative control group, a positive control group with Zinc-Bacitracin as antibiotic growth promoter (AGP), and 2 groups treated with a blend of probiotics (EntF+BacF+LacS) during 0 to 10 or 0 to 35 d, respectively. Wheat-soybean-rye based diets without exogenous enzymes were used as a challenge model to induce intestinal mild- or moderate-inflammatory process in the gut. In Trial 1, individually administered probiotics improved FCR at 8 d compared to Control, but these positive effects were lost in the following growing periods probably due to the high grade of challenging diet and a too low dose of probiotics. In Trial 2, both Probiotic treatments, administered only 10 or 35 d, significantly improved FCR to the same extent as of the Antibiotic group at the end of the trial. Although the performance between antibiotic and probiotic mixture showed similar values, microbiota analysis revealed different microbial composition at 7 d, but not at 21 d. This suggests that modes of action of the AGP and the tested probiotic blend differ on their effects on microbiome, and that the changes observed during the first days' posthatch are relevant on performance at the end of the study. Therefore, the probiotics administration only during the first 10 d posthatch was proven sufficient to induce similar performance improvements to those observed in birds fed antibiotic growth promoters throughout the whole experimental trial.

Evaluation of Risk Factors Associated with Selected Elements in Veterinary Active Pharmaceutical Ingredients Using ICP-MS.

One of the major concerns for animal health is the pollution of food and medicines given to animals by non-essential and toxic elements, which also poses a risk to human health via the food chain. The essential (Ca, Cr, Mn, Fe, Co, and Ni) and non-essential elements (Li, Ti, V, Ga, Ag, Cd, In, Ba, Bi, Th, and U) were monitored using inductively coupled plasma mass spectrometry (ICP-MS) in veterinary active pharmaceutical ingredients (V APIs). Samples were divided into four groups including antibiotic (14 samples), anthelmintic (7 samples), anticoccidial (5 samples), and externally used (5 samples). The results of the antibiotic group had the highest concentrations of most elements. The concentrations of the targeted elements were below the permissible limits as recommended by the United States Pharmacopeia (USP). The target hazard quotient (THQ) and the total target hazard quotient (TTHQ) were applied to evaluate the animal health risk associated with the exposure of the target elements in V API samples; the results showed that elements do not pose any risk to animals in all samples as indicated by THQ values less than 1. Validation parameters performed in this study showed good accuracy and validity of the ICP-MS analysis method, with good linearity (R2 ˃ 0.990), and the relative standard deviations (%RSD) were < 4% for all target elements. Analysis of variance (ANOVA-one way) was used to compare the means of veterinary drug groups for all targeted elements. The results showed that all elements have p-values < 0.05 except 52Cr and 54Fe.

Visual Endoscopic Retrograde Appendicitis Therapy versus Antibiotic Therapy for Treatment of Uncomplicated Acute Appendicitis.

Visual endoscopic retrograde appendicitis therapy (V-ERAT) involves a Single-use Video Scope, allowing real-time visualization of the appendiceal lumen during the procedure to treat uncomplicated acute appendicitis (AA). This study aims to compare V-ERAT to antibiotic therapy in treating uncomplicated AA. This multicenter, retrospective cohort study was conducted at nine hospitals in China from August 2021 to July 2023. Propensity score matching was performed to minimize selection bias. A total of 692 uncomplicated AA patients were included, with 188 undergoing V-ERAT and 504 receiving antibiotic therapy. The primary outcome was treatment success rate. The secondary outcomes included recurrent appendicitis rate, the appendectomy rate during the initial hospitalization, length of initial hospitalization, time to disease recurrence, and overall adverse events. The treatment success rate did not differ between the V-ERAT and antibiotic groups (93.6%; 95% confidence interval [CI] 89.1% to 96.7% vs. 90.5%; 95% CI, 87.6% to 92.9%) ( P = 0.225). However, V-ERAT demonstrated a significantly lower risk of appendicitis recurrence compared to antibiotic therapy during the follow-up (log-rank P < 0.001), with a hazard ratio of 0.14 (95% CI 0.07-0.29, P < 0.001). V-ERAT was associated with a lower appendectomy rate during the initial hospitalization (4.3%; 95% CI, 1.9% to 8.2% vs. 9.5%; 95% CI, 7.1 to 12.4%) (P = 0.027), a shorter length of initial hospitalization (3 [IQR, 3-4] vs. 4 [IQR, 4-6] days, P < 0.001), and a longer time to recurrence (269 [IQR, 210-318] vs. 70 [IQR, 21-103] days, P < 0.001). The overall adverse event rates did not differ between the two groups (log-rank P = 0.064). V-ERAT appears to be a safe and effective alternative to antibiotic therapy in treating uncomplicated AA, significantly reducing the risk of appendicitis recurrence.

MICROBIOME: The trials and errors of developing an experimental model to study the impact of maternal gut microbiome disruption on perinatal asphyxia.

Maternal gut microbiome impairment has garnered attention for its potential role in influencing neurodevelopmental outcomes in offspring, especially in situations that increase brain vulnerability such as perinatal asphyxia (PA). Maternal microbiome and fetal brain interplay emerge as a critical link between maternal health and offspring neurodevelopment. This study aims to generate a model to assess the impact of maternal dysbiosis triggered by gestational antibiotic administration and PA on offspring neurodevelopment. Wistar rats were subjected to antibiotics in drinking water from the 11th gestational day until birth. On the 6th postnatal day, pups were subjected to PA/normoxia, resulting in four experimental groups: control-normoxia, antibiotics-normoxia, control-asphyxia, and antibiotics-asphyxia. Early-life behavioral tests were conducted between postnatal days 7 and 9. The initial antimicrobial cocktail (ampicillin, vancomycin, neomycin, clindamycin, amphotericin-B) led to an increased number of miscarriages, poor weight gain during pregnancy, reduced offspring weight, and changes in the maternal gut microbiome compared to control. Offspring presented impaired neurodevelopmental reflexes in both PA and antibiotic groups and increased hippocampal neuroinflammation. Due to these detrimental effects, a more pregnancy-safe antibiotic cocktail was used for a second experiment (ampicillin, vancomycin, neomycin, meropenem). This resulted in no miscarriages or pregnancy-weight loss but was still linked to gut microbiome disruption. PA impaired neurodevelopmental reflexes and increased neuroinflammation, effects amplified by antibiotic administration. These preliminary findings reveal the cumulative potential of maternal dysbiosis and PA on neurodevelopment impairment, emphasizing caution in gestational antimicrobial use. Further investigations should include offspring long-term follow-up and maternal behavior and integrate probiotics to counteract antibiotic effects. This study investigates the impact of maternal gut microbiome disruptions caused by gestational antibiotic treatment and low oxygen exposure shortly after birth on the development of the rats' babies. We found that both antibiotic exposure and reduced oxygen levels led to changes in early behavior and increased inflammation of the nervous tissue in the baby rats. Although using a different, potentially safer antibiotic combination reduced pregnancy complications, it still changed the bacteria in the mother's gut and worsened early behavior. These findings show that antibiotics during pregnancy can affect the developing brain of baby rats and careful consideration should be used before prescribing them. Future research will explore longer-term effects and potential medicines.

Could the Adoptive Transfer of Memory Lymphocytes be an Alternative Treatment for Acinetobacter baumannii Infections?

We evaluated the efficacy of the adoptive transfer of memory B, CD4+, and CD8+ T lymphocytes compared with sulbactam and tigecycline in an experimental murine pneumonia model by two multidrug-resistant Acinetobacter baumannii strains, colistin-susceptible AbCS01 and colistin-resistant AbCR17. Pharmacodynamically optimized antimicrobial dosages were administered for 72 h, and intravenous administration of 2 × 106 of each of the memory cells in a single dose 30 min post-infection. Bacterial lung and blood counts and mortality rates were analyzed. Results showed that a single dose of memory B or CD4+ T cells was as effective as sulbactam in terms of bacterial clearance from the lungs and blood compared with the untreated mice or the tigecycline-treated mice inoculated with the AbCS01 strain. In the pneumonia model by AbCR17, a single dose of memory B or CD4+ T cells also reduced the bacterial load in the lungs compared with both antibiotic groups and was more efficacious than tigecycline in terms of blood clearance. Regarding survival, the adoptive transfer of memory B or CD4+ T cells was as effective as three days of sulbactam treatment for both strains. These data suggest that adoptive memory cell transfer could be a new effective treatment of multidrug-resistant A. baumannii infections.

Study of Some Resistance Genes of Salmonella from Asymptomatic Patients in Baghdad Government

Aim The current study aimed to isolate and diagnose Salmonella typhi bacteria from people with typhoid fever and their role in pathogenicity and to determine the antimicrobial susceptibility and virulence-associated genes. Methodology In all, 110 human stool samples from Iraqi patients were collected between November 2022 and the end of April 2023. The colony morphology method was used to identify the isolates. The antimicrobial susceptibility test was conducted using the disc diffusion method and the VITEK-2 Compact system. Results The antibiotic sensitivity test was conducted, as the current study showed that all isolates were 100% resistant to Ampicillin (AM) and Pincillin (P) of the β-lactams group, and Cefotaxime (CTX) of the Cephalosporines. The resistance was 93.7% for amoxicillin-clavulanic acid,while the resistance was weak or non-existent for the group of Carbapenem antibiotics, which was 9.37% for imipenem (IPM) and non-existent for meropenem (MEM), meaning that the bacteria are fully sensitive. The re-sults also showed that the resistance to some antibiotics of the Tetracycline group was low compared to the Cephalosporine group and the β-lactams group. In Tetracycline (TE), it was 15.6%, and Doxycycline antibody was 21.8%. Aztreonam (ATM), which belongs to the Monobactams group, showed a high resistance of 96.8%, as well as high resistance also appeared by 93.7% to Ciprofloxacin (CIP) and 56.1% to Chloramphenicol (C), while the resistance was low by 18.7% to Levofloxacin (LEV). Conclusion Serotype typhi was the most common serotype of Salmonella enteric that caused enteric fever during the course of the study.The majority of the Salmonella isolates exhibited an intermediate level of sensitivity to ciprofloxacin, indicating a heightened resistance to the drug used in the treatment of enteric fever.

Modification of gut and airway microbiota on ozone-induced airway inflammation

Ground-level ozone (O3) has been shown to induce airway inflammation, the underlying mechanisms remain unclear. The aim of this study was to determine whether gut and airway microbiota dysbiosis, and airway metabolic alterations were associated with O3-induced airway inflammation. Thirty-six 8-week-old male C57BL/6 N mice were divided into 2 groups: sterile water group and broad-spectrum antibiotics group (Abx). Each group was further divided into two subgroups, filtered air group (Air) and O3 group (O3), with 9 mice in each subgroup. Mice in the Air and O3 groups were exposed to filtered air or 1 ppm O3, 4 h/d for 5 consecutive days, respectively. Mice in Abx + Air and Abx + O3 groups were exposed to filtered air or O3, respectively, after drinking broad-spectrum Abx. 24 h after the final O3 exposure, mouse feces and bronchoalveolar lavage fluids (BALF) were collected and subjected to measurements of airway oxidative stress and inflammation biomarkers, 16S rRNA sequencing and metabolite profiling. Hematoxylin-eosin staining of lung tissues was applied to examine the pathological changes of lung tissue. The results showed that O3 exposure resulted in airway oxidative stress and inflammation, as well as gut and airway microbiota dysbiosis, and airway metabolism alteration. Abx pre-treatment markedly changed gut and airway microbiota and promoted O3-induced metabolic disorder and airway inflammation. Spearman correlation analyses indicated that inter-related gut and airway microbiota dysbiosis and airway metabolic disorder were associated with O3-induced airway inflammation. Together, inhaled O3 causes airway inflammation, which may implicate gut and airway microbiota dysbiosis and airway metabolic alterations.

“Antimicrobial utilization in a paediatric intensive care unit in India: A step towards strengthening antimicrobial stewardship practices"

Antimicrobials are frequently used in critically ill children admitted to the Paediatric Intensive Care Unit (PICU). The antimicrobial use data from Indian PICUs is limited using standard metrics such as Days of therapy (DOT). This study aimed to determine the baseline trend of antimicrobial use in PICU of a tertiary care teaching hospital of Raipur district of Chhattisgarh, India using standard metrics with the goal of developing facility-wide antibiotic policy and strengthening the antimicrobial stewardship activities. This active surveillance was conducted over a period of 18 months, from November 1, 2019, to March 21, 2021, in patients aged one month to 14 years who were admitted for ≥ 48 hours to the PICU at a tertiary care teaching hospital of Raipur District. Data on patient characteristics, antimicrobial indications, antimicrobial prescription information, and clinical outcomes were collected using pre-designed data abstraction forms. The descriptive statistic was used to represent the results. The antimicrobial consumption was analyzed according to the WHO AWaRe Class (Access, Watch, and Reserve groups) of antibiotics. The antimicrobial consumption was expressed as DOT/1000 patient-days (PD). A total of 216 patients were surveyed during the study period. The average number of antimicrobials prescribed per hospitalisation was 2.60 (range: 1–12), with 97.22% administered via parenteral route. Overall, DOT/1000-PD was 1318. The consumption of Watch Group antimicrobials was highest with 949 DOT/1000-PD, followed by Access (215) and Reserve Group (154), respectively. Ceftriaxone (208 DOT/1000 PD) was the most commonly prescribed antimicrobial agent, followed by Vancomycin (201), Meropenem (175), Piperacillin-Tazobactam (122) and Colistin (91). The patients who were escalated (28.24%) from empirical antimicrobial therapy had longer median PICU stay (8 days) compared those who were de-escalated (23.6%). Targeted therapy was given in 10.2% patients. The overall mortality rate was 14.35% and was higher (29.3%) in patients in whom empirical therapy was escalated compared to those who were de-escalated or continued. The study established a benchmark for antimicrobials use in the PICU and highlighted priority areas for antimicrobial stewardship intervention to enhance de-escalation rates, enhance targeted therapy, and reduce the overuse of antimicrobials especially belonging to the reserve group.

Enhanced release of volatile halocarbons of microalgae in response to antibiotic-induced stress: Based on laboratory and ship-field experiments

This study investigated the impacts of sulfamethazine (SMZ) and oxytetracycline (OTC) antibiotics on the marine microalgae Nitzschia closterium and its release of volatile halocarbons (VHCs), which contribute to ozone depletion and climate change. High concentrations of SMZ and OTC suppressed cell density, reduced chlorophyll a content, and hindered Fv/Fm elevation in N. closterium, indicating its growth was inhibited. The exposure of N. closterium to antibiotics led to increased reactive oxygen species (ROS), reduced soluble protein content, and heightened catalase (CAT) activity, indicative of increased oxidative stress. This stress increased the release of three VHCs (CHBrCl2, CHBr2Cl, and CHBr3). Ship-borne experiments showed that high phytoplankton biomass was linked to high VHC release. Notably, the production and release of VHCs were significantly higher in the high-concentration antibiotic group (100 μg/L) than the low-concentration group (0.1 μg/L). These findings suggested that antibiotics induce excess ROS in algal cells, stimulating VHC production and release.

Dried Chlorella powder supplementation: Impact on broiler chicken growth, health, and intestinal microflora

The use of dried Chlorella as an immune and growth stimulant to enhance nonspecific host defense mechanisms or as an antimicrobial to inhibit bacterial growth has been reported. This study aimed to assess the effects of dried Chlorella powder (DCP) supplementation on the growth, health, and intestinal microflora of commercial broiler chicks, comparing a diet containing DCP with an antibiotic-based diet. A total of 120 pieces day-old Cobb 500 broiler chicks were reared at Sher-e-Bangla Agricultural University Poultry Farm, Dhaka, and randomly divided into four experimental groups of three replicates each, with 10 chicks per replication. One group was fed a control diet, while the remaining three groups were fed diets with 0.5% and 1.0% DCP, and antibiotics, respectively. Results indicated significant (P&lt;0.05) improvements in body weight and dressing percentage with DCP inclusion compared to control-fed broilers. A linear increase in body weight was observed with higher DCP levels, with birds on the 1% DCP diet achieving superior body weights (1665.13±8.82) compared to the control and antibiotic groups. Feed Conversion Ratio (FCR) and feed consumption were also significantly (P&lt;0.05) improved, with the best FCR at 1% DCP (1.37±0.01) and the highest FCR in the control group (1.45±0.00). The highest feed consumption was noted in the control group. No significant (P&gt;0.05) differences were observed in the relative weight of spleen and bursa among the groups. DCP had no significant (P&gt;0.05) effects on liver, gizzard, intestine, and heart weights. Hematological studies revealed no significant (P&gt;0.05) differences, except for Hemoglobin and Red Blood Cells (RBC), which were significantly (P&lt;0.05) increased by DCP compared to control and antibiotic groups. DCP supplementation significantly (P&lt;0.05) reduced E. coli and Salmonella sp. counts while increasing Lactobacillus sp. counts. Additionally, treatments with DCP significantly (P&lt;0.05) boosted Newcastle disease (ND) titre levels compared to the control group. The study showed that DCP can be effectively replaced antibiotics in broiler diets, enhancing growth, health, and immune response, thereby promoting sustainable and safer poultry production practices.

Effects of a Combined Chinese Herbal Medicine on Growth Performance, Intestinal Barrier Function, Immune Response, and Cecal Microflora in Broilers Infected with Salmonella enteritidis.

This study investigated the effects of CCHM in drinking water on broilers infected with Salmonella enteritidis. One-day-old male Cobb 500 broilers (n = 300) were randomly assigned to five groups: a control (NC) group, a Salmonella enteritidis challenge (SE) group, an antibiotic (AB) group, a low dose of CCHM (CL) group, and a high dose of CCHM (CH) group. Each group had six replicate cages with ten broilers per cage. The broilers in the NC and SE groups were given normal drinking water. From days 12 to 18, the AB group received water treated with ciprofloxacin lactate injection (1 mL/L), while the CL and CH groups received water containing CCHM at doses of 5 mL/L and 10 mL/L, respectively. Broilers in all groups except the NC group were orally given Salmonella enteritidis daily from days 9 to 11. The experimental period was 28 days. The results showed that, compared with the SE group, the CL and CH groups showed improved growth performance; increased immune organ indices, expressions of ileal occludin and ZO-1 proteins, jejunal and ileal villus heights (except at day 19), and cecal Lactobacillus counts on days 19 and 28 (p < 0.05); and decreased jejunal and ileal lesion scores, ileal interleukin 1β (IL-1β) (except at day 19), interferon-γ (IFN-γ), interleukin 6 (IL-6) (except at day 19), secretory immunoglobulin A (slgA) and tumor necrosis factor α (TNF-α) (except at day 19) levels, serum D-lactic acid and diamine oxidase (DAO) (except at day 19) contents, jejunal and ileal crypt depths (except at day 19), and cecal Salmonella and Escherichia coli counts on days 19 and 28 (p < 0.05). On day 28, except for the levels of ileal interleukin 10 (IL-10), TNF-α, slgA, and serum D-lactic acid content, there were no differences among the NC, AB, and CL groups (p > 0.05). In conclusion, drinking water supplemented with CCHM alleviated the intestinal damage caused by Salmonella enteritidis infection and improved growth performance and cecal microbiota in broilers. The optimal addition rate of CCHM was 5 mL/L.

515 Effects of Bacillus licheniformis HG76 on barrier function and inflammation in the intestinal epithelia cells and gut health of weaned piglets under enterotoxigenic Escherichia coli F4 infection

Abstract Enterotoxigenic Escherichia coli (ETEC) F4 secretes enterotoxins and invades the small intestine, which damages the gut barrier function and stimulates the immune reactions characterized by inflammation. In the current study, the effects of B. licheniformis HG76 on gut health were evaluated with ETEC F4-induced IPEC-J2 cells and weaned piglets. The B. licheniformis HG76 was isolated from cecal contents of Rhode Island Red laying hens raised without using antibiotics. The results from the in vitro study showed that the ETEC F4 infection significantly induced IPEC-J2 cell death, and this effect was significantly attenuated by B. licheniformis HG76 treatment (P &amp;lt; 0.05). The gene expressions of zona occludens (ZO1) and tumor necrosis factor (TNF)-α were significantly increased during ETEC F4 infection with B. licheniformis HG76 treatment (P &amp;lt; 0.05). Meanwhile, the ETEC F4 infection significantly increased the mRNA abundance of toll-like receptors (TLR2, TLR4, and TLR5) (P &amp;lt; 0.05), but the B. licheniformis HG76 treatment alleviated this increase. For the in vivo study, 28 weaned piglets susceptible to ETEC F4 at 28 d of age were individually allotted to four experimental groups: NNC: unchallenged control group; NC: challenged control group; PC: antibiotic group (80 mg·kg-1 of avilamycin); and HG76: Bacillus group (1.0 × 109 CFU kg-1 diet of B. licheniformis HG76). The in vivo results showed during the post-challenge phase, ETEC F4 infection decreased average daily gain (ADG) and increased the severity of diarrhea at 44 h post-inoculum (hpi), respectively, in the NC group compared with the NNC group (P &amp;lt; 0.05). In addition, the infection decreased the villus height (VH) in the duodenum of pigs from the NC, PC and HG76 groups compared with the NNC group. The VH of jejunum and ileum in the pigs from the HG76 group were higher than other groups (P &amp;lt; 0.05). There was an increase (P &amp;lt; 0.05) of crypt depth (CD) in the jejunum and ileum of pigs from the HG76 group compared with those from the NNC group. The pigs in the NNC group had the greatest duodenal VH:CD ratio, but the least ileal VH:CD ratio among all the treatment groups. The Vmax value of sucrase in the HG76 group was greater than the NNC group (P &amp;lt; 0.05). When compared with the NC group, the relative mRNA abundance of interleukin 6 (IL6) was increased in the PC group (P &amp;lt; 0.05). In summary, these results suggest that B. licheniformis HG76 can protect the intestinal cells from ETEC F4 infection by inhibiting inflammation and maintaining barrier integrity, and the supplementation of B. licheniformis HG76 can improve the gut development and increase the digestive enzyme activity of ETEC F4 challenged piglets.