Restriction Of Antibiotic Use Research Articles

Evaluating antibiotic occurrence, degradation, and environmental risks in poultry litter within Argentina's agricultural hub

This study explores the relationship between poultry farming's antibiotic administration practices and residual antibiotic levels in the litter before its application onto agricultural soils. Twenty-three antibiotics were performed across 19 Argentinean farms representing diverse antibiotic management practices. Analysis revealed up to 20 antibiotics from eight chemical classes in poultry litter samples, with tylosin, enrofloxacin, and salinomycin being the most relevant drugs. Farms with restricted antibiotic use in feed exhibited lower residual concentrations. A self-heating treatment was tested to reduce litter antibiotic levels. Although a 60 % reduction of antibiotics was found after treatment, prevalent compounds persisted at residual levels. Regulatory measures and comprehensive litter treatments pre-application are crucial to mitigate environmental risks. This is the first study that provides insight on the occurrence of >20 drugs in real poultry production scenarios from Latin America and demonstrates how relatively simple treatments can be readily applied to decrease the associated environmental risks.

Unveiling the emergence of multidrug-resistant pathogens in exotic pets from France: a comprehensive study (2017-2019)

Aim: This study intends to assess the occurrence of multi-drug resistant (MDR) resistant pathogens among exotic pets from France (2017-2019). Methods: Isolates were identified using MALDI-TOF-MS. Antimicrobial susceptibility testing was conducted for 21 antimicrobials and was assayed by disk diffusion methods. Statistical analyses were carried out using GraphPad Prism® (version 9.4.1.). Results: Isolates (n = 2,100) recovered from samples of 10 small mammals (n = 1,555), 23 birds (n = 287), and 18 reptiles (n = 208) species were identified as Enterobacterales (n = 634), Pseudomonadaceae (n = 176), Pasteurellacea (n = 276), Staphylococcaceae (n = 563) , Streptococcaceae (n = 259), and Enterococcaceae (n = 186). Consistent high resistance rates were observed among diverse genera and/or species to beta-lactams, tetracyclines, and macrolides. Notably, a significant prevalence of MDR bacteria was identified, with 22.8% (n = 479/2,100, P < 0.05). Furthermore, 23.5% (P < 0.05) of these MDR bacteria displayed resistance to all tested antimicrobials: E. faecalis (n = 47/49; 95.0%), E. coli (n = 19/52; 36.5%), Klebsiella spp. (n = 12/32; 37.5%), S. epidermidis (n = 7/25; 28%), Streptococcus spp. (n = 6/68; 8.8%), Enterococcus spp. (n = 6/23; 26%), Staphylococcus spp. (n = 4/51; 7.8%), Lactococcus spp. (n = 4/8; 50%), Citrobacter spp. (n = 3/7; 42.8%), Raoultella spp. (n = 2/3; 66.6%), Serratia spp. (n = 1/9; 11.1%), Pasteurella spp. (n = 1/14; 7.1%), and S. xylosus (n = 1/28; 3.5%). Conclusions: This study emphasizes exotic pets as an emergent reservoir of MDR bacteria, focusing on E. faecalis as a potential route of transmission of MDR bacteria to humans, other animal species and environment. Urgent measures, including the establishment of mandatory monitoring for antimicrobial resistance (AMR) and the enforcement of restrictive antibiotic use policies in exotic pets, should be implemented to mitigate the risk of further spread and safeguard public and animal health.

Plasmid and Cell Envelope Characterization of <i>Vibrio alginolyticus</i> Isolated from Infected Tiger Prawn,<i>Penaeus monodon</i>

It has been reported that indiscriminate use of antibacterial compounds in aquaculture has resulted in an increase in populations of antibiotic resistant strains of bacteria. In the present study, Vibrio alginolyticus isolated from infected Penaeus monodon has been found resistant to Furoxone (30 g), Ampicillin (10 g), Cloxacillin (1 g), Bacitracin (10 units), Penicillin (10 units) and Oxytetracycline (30 pg) by antibiotic sensitivity test, suggesting the restricted prophylactic use of antibiotics in shrimp aquaculture industry. As an approach towards differentiation and identification of bacterial strain, the plasmid characterization of V. alginolyticus by restriction enzyme analysis was carried out which revealed the presence of 6.3 kb and 0.8 kb DNA fragments by Hind lil and a 7. 9 kb DNA fragment by EcoRI enzymes. The cell envelope characterization of V. alginolyticus by SOS-PAGE showed the presence of 12 protein bands in the range of 29 to 112.20 kD. The preliminary information on the cell envelope characterization may help in studies relating towards development of immunostimulant against vibriosis.

Restrictive Versus Permissive Use of Broad-spectrum Antibiotics in Patients Receiving Allogeneic Stem Cell Transplantation and With Early Fever Due to Cytokine Release Syndrome: Evidence for Beneficial Microbiota Protection Without Increase in Infectious Complications.

Intestinal microbiome contributes to the pathophysiology of acute gastrointestinal (GI) graft-versus-host disease (GvHD) and loss of microbiome diversity influences the outcome of patients after allogeneic stem cell transplantation (SCT). Systemic broad-spectrum antibiotics have been identified as a major cause of early intestinal dysbiosis. In 2017, our transplant unit at the university hospital in Regensburg changed the antibiotic strategy from a permissive way with initiation of antibiotics in all patients with neutropenic fever independent of the underlying cause and risk to a restrictive use in cases with high likelihood of cytokine release syndrome (eg, after anti-thymocyte globulin [ATG] therapy). We analyzed clinical data and microbiome parameters obtained 7 days after allogeneic SCT from 188 patients with ATG therapy transplanted in 2015/2016 (permissive cohort, n = 101) and 2918/2019 (restrictive cohort, n = 87). Restrictive antibiotic treatment postponed the beginning of antibiotic administration from 1.4 ± 7.6 days prior to 1.7 ± 5.5 days after SCT (P = .01) and significantly reduced the duration of antibiotic administration by 5.8 days (P < .001) without increase in infectious complications. Furthermore, we observed beneficial effects of the restrictive strategy compared with the permissive way on microbiome diversity (urinary 3-indoxylsulfate, P = .01; Shannon and Simpson indices, P < .001) and species abundance 7 days post-transplant as well as a positive trend toward a reduced incidence of severe GI GvHD (P = .1). Our data indicate that microbiota protection can be achieved by a more careful selection of neutropenic patients qualifying for antibiotic treatment during allogeneic SCT without increased risk of infectious complications.

Restrictive Use of Empirical Antibiotics Is Associated with Improved Short Term Outcomes in Very Low Birth Weight Infants: A Single Center, Retrospective Cohort Study from China.

Antibiotics are essential for treating neonatal sepsis, but abuse or inappropriate use of antibiotics have harmful adverse effects. The inappropriate use of antibiotics has led to the significant increase in bacterial antimicrobial resistance in the neonatal intensive care unit (NICU). The aim of this study was to retrospectively analyze the changes in antibiotic usages in a NICU after the implementation of an antibiotic stewardship program and to determine the impact of this implementation on the short-term clinical outcomes of very low birth weight (VLBW) infants. The antibiotic stewardship program was initiated in the NICU in early 2015. For analysis, all eligible VLBW infants born from 1 January 2014 to 31 December 2016 were enrolled, and we classified the year 2014 as pre-stewardship, 2015 as during stewardship, and 2016 as post-stewardship. A total of 249 VLBW infants, including 96 cases in the 2014 group, 77 cases in the 2015 group, and 76 cases in the 2016 group, were included for final analysis. Empirical antibiotics were used in over 90% of VLBW infants in all three groups during their NICU stay. Over the 3-year period, the duration of an initial antibiotic course was significantly reduced. The proportion of patients receiving an initial antibiotic course for ≤3 days gradually increased (2.1% vs. 9.1% vs. 38.2%, p < 0.001), while the proportion of babies treated with an initial antibiotic course >7 days significantly decreased (95.8% vs. 79.2% vs. 39.5%, p < 0.001). The total days of antibiotic usage during the entire NICU stay also showed a significant reduction (27.0 vs. 21.0 vs. 10.0, p < 0.001). After adjusting for confounders, the reduction in antibiotic usage was associated with decreased odds of having an adverse composite short-term outcome (aOR = 5.148, 95% CI: 1.598 to 16.583, p = 0.006). To assess the continuity of antibiotic stewardship in the NICU, data from 2021 were also analyzed and compared to 2016. The median duration of an initial antibiotic course further decreased from 5.0 days in 2016 to 4.0 days in 2021 (p < 0.001). The proportion of an initial antibiotic course in which antibiotics were used for ≤3 days increased (38.2% vs. 56.7%, p = 0.022). Total antibiotic usage days during the entire NICU stay also decreased from 10.0 days in 2016 to 7.0 days in 2021 (p = 0.010). The finding of this study strongly suggests that restricting antibiotic use in VLBW infants is beneficial and can be achieved safely and effectively in China.

Best management of patients with an acute sore throat – a critical analysis of current evidence and a consensus of experts from different countries and traditions

Background There is a very large body of publications discussing the management of patients with an acute sore throat. Advocates for a restrictive antibiotic policy and advocates for a more liberal use of antibiotics emphasise different and valid arguments and to date have not been able to unite in a consensus. Contradicting guidelines based on the same body of knowledge is not logical, may cause confusion and cause unwanted variation in clinical management. Methods In multiple video meetings and email correspondence from March to November 2022 and finally in a workshop at the annual meeting for the North American Primary Care Group in November 2022, experts from different countries representing different traditions agreed on how the current evidence should be interpreted. Results This critical analysis identifies that the problem can be resolved by introducing a new triage scheme considering both the acute risk for suppurative complications and sepsis as well as the long-term risk of developing rheumatic fever. Conclusions The new triage scheme may solve the long-standing problem of advocating for a restrictive use of antibiotics while also satisfying concerns that critically ill patients might be missed with severe consequences. We acknowledge that the perspective of this problem is vastly different between high- and low-income countries. Furthermore, we discuss the new trend which allows nurses and pharmacists to independently manage these patients and the increased need for safety netting required for such management.

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial

The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. The Netherlands Organization for Health Research and Development.

Evaluation of factors associated with biosecurity, antimicrobial use and mortality in broiler farms in Northern Kerala

A survey was conducted (March 2020 to October 2020) on biosecurity practices, disease occurrence and antimicrobial usage of 77 broiler farms from five districts of Northern Kerala. Data were collected through a questionnaire and field-level disease diagnostic tests were conducted. Biosecurity status varied from farm to farm with 97.4 per cent promoted vaccination and 61.04 per cent disposed carcasses by burning. However, limitations were observed in the use of a footbath, quarantine of new stock, isolation of diseased birds and quality of water. The five most common diseases recorded were Chronic respiratory disease (48.1%), Acute Death Syndrome (27.3%), Colibacillosis (23.4%), Pullorum (18.2%) and Coccidiosis (18.2%). The commonly used antibiotics in poultry farms were Enrofloxacin (35.1%), Cephalexin (14.3%), Tylosin (11.7%) and Levofloxacin (10.4%). Some of the farmers (14.3%) were unaware of the antibiotics used in their farms, a potent risk factor for the emergence of antimicrobial resistance. About 19.49 per cent of farms restricted antibiotic use and 44.15 per cent of farms supported herbal traditional medicines as an alternative to antimicrobials.

Molecular Epidemiology of Neonatal-Associated Staphylococcus haemolyticus Reveals Endemic Outbreak.

Staphylococcus haemolyticus is a major cause of late-onset sepsis in neonates, and endemic clones are often multidrug-resistant. The bacteria can also act as a genetic reservoir for more pathogenic bacteria. Molecular epidemiology is important in understanding bacterial pathogenicity and preventing infection. To describe the molecular epidemiology of S. haemolyticus isolated from neonatal blood cultures at a Swedish neonatal intensive care unit (NICU) over 4 decades, including antibiotic resistance genes (ARGs), virulence factors, and comparison to international isolates. Isolates were whole-genome sequenced, and single nucleotide polymorphisms in the core genome were used to map the relatedness. The occurrence of previously described ARGs and virulence genes were investigated. Disc diffusion and gradient tests were used to determine phenotypic resistance. The results revealed a clonal outbreak of S. haemolyticus at this NICU during the 1990s. Multidrug resistance was present in 28 (82%) of all isolates and concomitant resistance to aminoglycoside and methicillin occurred in 27 (79%). No isolates were vancomycin resistant. Genes encoding ARGs and virulence factors occurred frequently. The isolates in the outbreak were more homogenous in their genotypic and phenotypic patterns. Genotypic and phenotypic resistance combinations were consistent. Pathogenic traits previously described in S. haemolyticus occurred frequently in the present isolates, perhaps due to the hospital selection pressure resulting in epidemiological success. The clonal outbreak revealed by this study emphasizes the importance of adhering to hygiene procedures in order to prevent future endemic outbreaks. IMPORTANCE This study investigated the relatedness of Staphylococcus haemolyticus isolated from neonatal blood and revealed a clonal outbreak in the 1990s at a Swedish neonatal intensive care unit. The outbreak clone has earlier been isolated in Japan and Norway. Virulence and antibiotic resistance genes previously associated with clinical S. haemolyticus were frequently occuring in the present study as well. The majority of the isolates were multidrug-resistant. These traits should be considered important for S. haemolyticus epidemiological success and are probably caused by the hospital selection pressure. Thus, this study emphasizes the importance of restrictive antibiotic use and following the hygiene procedures, to prevent further antibiotic resistance spread and future endemic outbreaks.

Outpatient Antibiotic Use and Costs in Adults: A Nationwide Register-Based Study in Finland 2008-2019.

The objective of this study was to describe the prevalence of outpatient use and costs for systemic antibacterials by age and sex among adults in Finland from 2008-2019. Data from the Finnish statistical database Kelasto, containing information concerning all reimbursed medicines for 18+-year-olds during 2008-2019, were analyzed. In addition to the decreased (26%) use of systemic antibiotics, decreased use was observed in all antibiotic categories, notably including several wide-spectrum antibiotics. The use of quinolones decreased by 49% and of tetracyclines by 39%. The 10 most frequently used antibiotics covered 89% of all adult antibiotic prescriptions. Antibiotic use also decreased in every age group during the study period. Although the overall yearly costs of outpatient antibiotics during the 10-year study period decreased from EUR 36.4 million to EUR 30.7 million, the cost per prescription increased slightly. In conclusion, according to the findings of this study, concerning adults and the results of our previous study concerning children and adolescents (2008-2016), there has been a decreasing trend of outpatient antibacterial use among the whole Finnish outpatient population over the duration of nearly one decade. However, during the same time period, there has been a specific increasing trend for the Gram-negative AMR threat regarding E. coli resistance. Therefore, based on our important findings in Finland, methods other than the restriction of antibiotic use, such as new anti-infective innovations, including antibacterials, are needed as soon as possible to tackle this major global health threat-a silent pandemic.

Clinical and Antimicrobial profile of Acinetobacter Species at a Tertiary Care Teaching Hospital

Acinetobacter infection with multidrug resistant strains is an emerging infection of global concern as it leads to serious disease. They are also important pathogens causing hospital acquired infections. Information on the prevalence, spectrum of illness and antibiotic sensitivity pattern of Acinetobacter is important for appropriate management of patients. We aimed to determine the prevalence of Acinetobacter species and evaluate the clinical profile and antibiotic sensitivity pattern of Acinetobacter species from various clinical samples. From October 2018 to September 2019, various clinical samples received in the microbiology laboratory were studied from the electronic records and the data on the isolation of Acinetobacter from these samples and its antibiotic sensitivity pattern was collected and analysed. The clinical data was also collected to determine the clinical spectrum. The prevalence of Acinetobacter species from various clinical samples was found to be 8.9%. Isolates were more common in general wards than in ICUs. The Acinetobacter infections occurred significantly in male patients (65.7%) than in female patients (34.3%), with male: female ratio of 1.9:1. The most common infection caused by Acinetobacter species was Wound infection (54.36%) followed by Respiratory tract infection (34.27%). Multidrug resistance was seen in 75 % of the isolates. Significant prevalence of multidrug resistant Acinetobacter infections was noted in our study. The findings emphasize the need for strict hospital infection control practices and the restricted use of antibiotics to prevent the occurrence of these infections.

Antimicrobial use and resistance in food-producing animals-How can we protect the efficacy of antibiotics for reproductive diseases?

The ongoing emergence of antibiotic resistance jeopardizes efficacy of antibiotics in curing animals from bacterial infections that threaten their health, welfare and productivity. This review gives an overview of antimicrobial use data in food-producing animals, a discussion on how antimicrobials are used for some infections in the reproductive system in cattle, the horse and pig in Europe where there are differences in treatment practices including options to refine the use of antibiotics, and finally, a presentation of the antibiotic resistance for some bacteria collected from the reproductive system. It is shown that there are differences in applied treatment regimens for, as well as prevention of, several reproductive diseases in Europe. Some of the treatments are not evidence-based, which should be considered by clinicians and other stakeholders. It is concluded that a more refined and restrictive use of antibiotics could be achieved by adhering to evidence-based guidelines by national and international expertise including the scientific literature when available. This may call for a re-think among the animal health stakeholders regarding the use of antibiotics and may demand new skill-sets in the animal health sphere.

Outcomes of Restricted versus Liberal Post-Operative Antibiotic Use in Patients Undergoing Appendectomy: A DOOR/RADAR Post Hoc Analysis of the EAST Appendicitis MUSTANG Study

Background: There is no consensus on the duration of antibiotic use after appendectomy. We hypothesized that restricted antibiotic use is associated with better clinical outcomes. Patients and Methods: We performed a post hoc analysis of the Eastern Association for the Surgery of Trauma (EAST) Multicenter Study of the Treatment of Appendicitis in America-Acute, Perforated, and Gangrenous (MUSTANG) study using the desirability of outcome ranking/response adjusted for duration of antibiotic risk (DOOR/RADAR) framework. Three separate datasets were analyzed based on restricted versus liberal post-operative antibiotic groups: simple appendicitis (no vs. yes); complicated appendicitis, only four days (≤24 hours vs. 4 days); and complicated appendicitis, four or more days (≤24 hours vs. ≥4 days). Patients were assigned to one of seven mutually exclusive DOOR categories RADAR ranked within each category. DOOR/RADAR score pairwise comparisons were performed between all patients. Each patient was assigned either 1, 0, or -1 if they had better, same, or worse outcomes than the other patient in the pair, respectively. The sum of these numbers (cumulative comparison score) was calculated for each patient and the group medians of individual sums were compared by Wilcoxon rank sum. Results: For simple appendicitis, the restricted group had higher median sums than the liberal group (552 [552,552] vs. -1,353 [-1,353, -1,353], p < 0.001). For both complicated appendicitis analyses, the restricted group had higher median sums than the liberal: only 4 (196 [23,196] vs. -121 [-121, -121], p < 0.02) and 4 or more (660 [484,660] vs -169 [-444,181], p < 0.001). Conclusions: Restricted post-operative antibiotic use in patients after appendectomy is a dominant strategy when considering treatment effectiveness and antibiotic exposure.

Usage pattern of chemicals, biologicals and veterinary medicinal products in Indian aquaculture

AbstractThe use of chemicals, biologicals and veterinary medicinal products (VMPs) helps in healthy and sustainable fish production. Information on the use of these products is essential for assessing farming practices, potential human health and environmental risks. A questionnaire‐based nationwide survey covering aquaculture farms (n = 2936) producing carps, tilapia, pangasius and rainbow trout in freshwater and shrimp in brackishwater estimated the use of 52 different types of inputs which included disinfectants (597 g t−1), probiotics (2.28 kg t−1), environmental modifiers (22.82 kg t−1), nutritional supplements (1.96 kg t−1), natural anti‐infective agents (293 g t−1), herbicide and piscicides (844 g t−1), antibiotics (2 mg PCU−1), antifungal (4 mg PCU−1), and antiparasitic (14 mg PCU−1) agents. The bulk of these inputs was used for soil and water quality improvement and had low environmental and human safety concerns. The multivariate analysis revealed significant variation in the frequency and quantity of compounds use among farm groups. Redundancy analysis revealed a significant association between the number of products used and stocking density. The survey also showed a considerable influence of education and farming experience on the usage pattern of aquaculture inputs. Results of the study indicated greater reliance of farmers on the use of disinfectants for biosecurity, nutritional supplements for enhanced growth and environmental modifiers for maintaining soil and water quality in culture systems. Though there was no use of restricted antibiotics and antiparasitic agents, the development and implementation of standard regulatory guidelines are essential for safe and effective use of inputs for sustainable aquaculture.

Early initiation of broad-spectrum antibiotics in premature infants.

Neonatal sepsis remains one of the main reasons for mortality among premature infants, and the early initiation of empirical broad-spectrum antibiotics could increase the risk of complications, including late-onset sepsis. This study aimed to investigate the complications related to the use of empirical broad-spectrum antibiotics in the first week of life. A retrospective study of 365 neonates with gestational age ≤32 weeks and birth weight <1500 g who survived and had no confirmed sepsis in the first week of life from July 2015 to June 2018 was performed in a large tertiary Neonatal Intensive Care Unit. The primary outcome of this study was the incidence of a composite outcome consisting of late-onset sepsis, necrotizing enterocolitis, and mortality. The secondary outcomes were the incidences of late-onset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and infant mortality. Of the 365 premature infants, 75 (20.5%) received broad-spectrum antibiotics. Multivariate regression analysis revealed that administration of broad-spectrum antibiotics in infants was independently associated with adverse outcomes. The composite outcome (late-onset sepsis, necrotizing enterocolitis, and death) had an odds ratio of 3.03 with 95% confidence interval of 1.41-6.49. Administration of empirical broad-spectrum antibiotics in the first week of life is associated with severe adverse outcomes. Thus, the restricted use of broad-spectrum antibiotics in the first week of life is recommended.

The Role of Nutraceuticals and Phytonutrients in Chickens' Gastrointestinal Diseases.

Simple SummaryThe use of nutraceuticals and phytonutrients in poultry nutrition has been extensively explored over the past decade. The interest in these substances is linked to the search for natural compounds that can be effectively used to prevent and treat some of the main diseases of the chicken. The serious problem of antibiotic resistance and the consequent legislative constraints on their use required the search for alternatives. The purpose of this review is to describe the current status of the effects of some substances, such as probiotics and prebiotics, organic acids, vitamins and phytogenic feed additives, focusing specifically on studies concerning the prevention and treatment of four main gastrointestinal diseases in chicken: salmonellosis, necrotic enteritis (caused by Clostridium perfringens), campylobacteriosis, and coccidiosis. A brief description of these diseases and the effects of the main bioactive principles of the nutraceutical or phytonutrient groups will be provided. Although there are conflicting results, some works show very promising effects, with a reduction in the bacterial or protozoan load following treatment. Further studies are needed to verify the real effectiveness of these compounds and make them applicable in the field.In poultry, severe gastrointestinal diseases are caused by bacteria and coccidia, with important economic losses in the poultry industry and requirement of treatments which, for years, were based on the use of antibiotics and chemotherapies. Furthermore, Salmonella spp., Clostridium perfringens, and Campylobacter jejuni can cause serious foodborne diseases in people, resulting from consumption of poultry meat, eggs, and derived products. With the spread of antibiotic resistance, which affects both animals and humans, the restriction of antibiotic use in livestock production and the identification of a list of “critically important antimicrobials” became necessary. For this reason, researchers focused on natural compounds and effective alternatives to prevent gastrointestinal disease in poultry. This review summarizes the results of several studies published in the last decade, describing the use of different nutraceutical or phytonutrients in poultry industry. The results of the use of these products are not always encouraging. While some of the alternatives have proven to be very promising, further studies will be needed to verify the efficacy and practical applicability of other compounds.

Lowbury Lecture 2021: tales of the unexpected in antibiotic resistance

Since the 1990s few new antibiotics have become available; during the same period the appearance and spread of bacteria no longer susceptible to first- and second-line antibiotics has accelerated; indeed some bacterial infections have become untreatable with existing antibiotics. Control of antibiotic resistance is multifactorial, and includes restrictive antibiotic use and good infection control. This lecture addresses three aspects of antibiotic resistance, with reference to the Netherlands, that illustrate the complexity of antibiotic resistance epidemiology. Initially selective decontamination of the digestive tract (SDD) was not adopted in the Netherlands because of concern about antibiotic resistance. However, three trials showed that SDD regimens, including four days of systemic cephalosporins, gave better clinical outcomes with no effect on antibiotic-resistant bacteria. Many predictions have been made about the impact of infections with antibiotic-resistant bacteria on human health. However, the situation is complex, because the risk factors for infection with multidrug-resistant bacteria are also risk factors for poor clinical outcome. A study in eight Dutch hospitals estimated the mortality attributable to antibiotic resistance as close to zero. Concern about the emergence of resistance in Staphylococcus aureus has limited the universal use of mupirocin to prevent surgical site infections. However, the risk may have been overstated, and universal decolonization with mupirocin and chlorhexidine has now become standard of care in patients undergoing cardiothoracic or orthopaedic surgery in many Dutch hospitals. Prophylactic antibiotics can improve patient outcomes with acceptable risks of promoting resistance.

A Study on Prescribing Pattern, Indications and Rationality of Restricted Antibiotic Use in a Tertiary Care Hospital

Background: Antibiotic stewardship aims to optimise restricted antibiotic use and thereby prevent the emergence of antibiotic resistance and improve treatment outcome. Resistance to conventional antimicrobial’s is a major reason why restricted antibiotics are prescribed. Aim: To assess the prescribing pattern of restricted antibiotics, the indications for which restricted antibiotics were prescribed, the drug related problems associated and the sensitivity pattern of the isolated organisms. Results: Out of 340 patients included in the study, majority of patients was in the age group of 58-67(60.06 ±14.90) in both genders. There was a male (64.12%) dominance observed in the study populace and the minimum and maximum age observed was 18 and 93 years respectively. Most commonly prescribed antibiotic was Piperacillin tazobactum (31%) followed by Linezolid (16.06%). Empirically the most prescribed antibiotic was Piperacillin tazobactum (27.37%) while in definitive therapy it was Cefepime tazobactum (10.63%). The most common indication for which restricted antibiotics prescribed were for respiratory tract infection (n=116), followed by infection prophylaxis (n=114). Mean days of restricted antibiotic therapy was found to be 8.85 days ± 8.11. The maximum duration of antibiotic treatment was 62 days and minimum was 1 day. In 47% of cases IV to oral conversion was possible. When analysed retrospectively, in majority of the patients the duration of restricted antibiotic treatment was inappropriate (69.71%) while the inappropriateness in frequency and dose were 7.05% and 3.23% respectively. The total number of cultures collected were 292 in that 120 cultures were urine and found growth in 50.83%, followed by 84 cultures in sputum which accounted for 67.85% growth. The most common organism isolated was Klebsiella pneumoniae 39.73% cases followed by Pseudomonas aeruginosa 17.46% and Acinetobacter baumannii15.41. There was clinical cure in 91.47% of cases. Conclusion: When analysed retrospectively majority of the restricted antibiotics showed inappropriateness. This higher amount of inappropriateness could have been avoided to a certain extent, by the timely interventions of a clinical pharmacist. By implementing an effective antimicrobial stewardship program we could improve the rational use of restricted antibiotics and thereby prevent the future resistance and improve clinical outcome.

A Clinico-Microbiological Study of Β-Lactamase Producing Klebsiella Pneumoniae Among Neonates From Neonatal Intensive Care Unit At Tertiary Care Hospital, Ujjain

Abstract: Infection caused by drug resistance Klebsiella pneumoniae is very common now days in community as well as nosocomial environment. K.pneumoniae is second most common pathogen in neonatal septicemia. Our aim to detect drug resistance K.pneumoniae by production of β-lactamase enzymes such as extended spectrum β-lactamase (ESBL), AmpC β-lactamase, metalo β-lactamase (MBL) and carbapenemase in neonatal septicemia. A total 13 isolates of K.pneumoniae detected from neonates admitted in tertiary care centre during study period from February 2015 to July 2016. We analyzed risk factors in K. pneumoniae infection among neonates on the basis of prolong rupture of membrane, preterm birth, onset of septicemia etc. Antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion methods. β-lactamase enzymes includes, Extended spectrum β-lactamase(ESBL), AmpC β-lactamase, metalo β-lactamase (MBL)and carbapenemase were detected by phenotypic methods using standard guidelines. Distribution of MDR, XDR and PDR detected according to antimicrobial resistance pattern as per guideline. Among 13 K.pneumoniae isolate, antimicrobial resistance profile was studied. Isolates were 100% resistant to third generation cephalosporin and least resistant to imipenem 54%. MDR K.pneumoniae were 23 %, XDR were 77% and no PDR isolated. ESBL production seen in 23.1%, AmpC in 7.7 %, MBL in 00 % and Carbapenemase in 46.1 %. The study indicates that drug resistance higher in NICU of our institute. It requires strict implementation of infection control guidelines in NICU by safe hygiene practices, restricted use of broad spectrum antibiotics as empirical therapy and also formulation of uniform antibiotic policy for such patients based on the current trend of antibiotic resistance.

Longitudinal Analysis of Gut Bacteriome, Mycobiome, Virome and Metabolome in Allogeneic Stem Cell Transplantation Reveals Susceptibility for Acute Graft-Versus-Host Disease

The intestinal microbiome directly effects outcomes in patients undergoing allogeneic stem cell transplantation (ASCT) (Peled et al., N Engl J Med, 2020). Recent developments in microbiome research allow us to look beyond bacterial communities at the composition of the intestinal mycobiome and virome. However, only few studies have addressed these fungal (Zhang et al., Nat Commun, 2021; Legoff et al., Nat Med, 2017) and viral communities (Van Der Velden et al., Biol Blood Marrow Transplant, 2013) in the ASCT setting.Loss of bacterial diversity and domination of single taxa was linked to increased incidence of graft-versus-host-disease (aGvHD) and mortality. However, the functional consequences of intestinal dysbiosis remain poorly understood. Recently, microbial-derived metabolites such as short-chain fatty acids (SCFAs), indoles and secondary bile acids (BA) have been proposed to explain how microbiota exert effects on epithelial and immune responses and shown to protect from GVHD in animal models.To assemble a complete picture of the phylogenetic and metabolic changes which occur as patients undergo ASCT we designed a multiomics approach and identified patterns in bacteriome, mycobiome, virome and metabolome dynamics in relation to clinical factors and GvHD.353 stool samples from 80 patients undergoing ASCT were obtained at two different transplantation centers (Munich and Regensburg) at defined timepoints before and after transplantation. Changes in metabolite composition were evaluated via mass spectrometry using a targeted metabolomic profiling approach, accompanied by bacterial 16S rDNA-, fungal 18S-ITS- and deep virome sequencing. Results were linked among each other and with clinical metadata such as GvHD, response to steroids, antimicrobial therapy and mortality.Longitudinal profiling of ASCT patients revealed a significant loss of bacterial, fungal and viral diversity following ASCT. At both centers, the effect was most pronounced in the early post-transplant period. Patients that developed GI-GVHD had the lowest diversity scores (Panel 1). GVHD patient samples were dominated by Enteroccocus and Candida, and loss of Caudovirales species, indicative of deep dysbiosis effecting all intestinal communities.ASCT had a strong impact on microbiome function and their ability to produce metabolites. We assayed each sample for production of metabolites with reported protective effects: SCFAs (acetate, butyrate and propionate), indoles (indole-3-carboxylaldehyde, ICA) and BAs (deoxycholic and lithocholic acid). When admitted to the transplantation unit (timepoint “conditioning”) most patients had rich metabolite expression profiles. In the early post-transplant period, metabolite levels became progressively more depleted. GVHD patients displayed a nearly complete loss of metabolites (Panel 2a). Importantly, levels of the metabolite ICA at early timepoints could predict the occurrence of GVHD, leading us to consider prophylactic administration in future studies.We performed beta diversity analysis to identify clinical factors that had the highest impact on microbial communities. As expected, we noted that administration of broad-spectrum antibiotics had a profound impact of bacteria, fungi and viruses; but also had a significant negative effect on metabolites levels.Lastly, we report on a case of successful treatment of severe GI-GVHD with fecal microbiota transplant. Response to treatment was characterized by the recipient adopting the FMT donor's rich metabolite expression profile (Panel 2b) .To our knowledge, this is the first multicenter study that combines bacteriome, mycobiome, virome and metabolome analyses a longitudinal fashion in matched patient cohorts. Our results are consistent with previous findings that there are major alterations in gut microbiome and metabolite composition after ASCT. We expand upon those findings by characterizing the time course of phylogenetic alterations and their functional consequences. Those alterations play an important role in GvHD pathogenesis and might serve as potential biomarkers to identify patients at high risk for developing lethal GvHD early on. Our results highlight two strategies for targeted microbiome-based interventions: (1) preventing loss of microbial communities by restrictive use of antibiotics and (2) prophylactic administration of metabolite cocktails. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.