Restriction Of Antibiotic Use Research Articles

Gb3 trisaccharide-bearing exosomes as a novel neutralizer for Shiga toxin type 1

Shiga toxin types 1 (Stx1) and 2 (Stx2), produced by Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae, are key virulence factors responsible for severe foodborne diseases, such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). The receptors for Stxs are Gb3 and P1 glycotope, which contain the Galα1→4Galβ epitope and are synthesized by human α1,4-galactosyltransferase (A4galt). Stx-related infections pose a global public health challenge, owing to the limited therapeutic options due to the restricted use of antibiotics. Therefore, there is an urgent need to develop novel therapeutic strategies. This study proposes an innovative strategy utilizing exosomes derived from CHO-Lec2 cells, which were modified with Functional-Spacer-Lipid (FSL) conjugates bearing the Gb3 carbohydrate epitope (exo-Gb3-FSL). Flow cytometry analysis confirmed the presence of Galα1→4Galβ disaccharides on exo-Gb3-FSL constructs, enabling them to bind Stx1. Moreover, using CHO-Lec2 cells verified the ability of exo-Gb3-FSL agents to bind Stx1 and protect these cells from Stx1-mediated cytotoxicity. For Stx1-treated CHO-Lec2 cells, increased cell survival was observed when using 25 μM exo-Gb3-FSL constructs, compared to control cells. These findings highlight the potential of exosome-based anti-Stx1 agents as promising alternatives to conventional therapies. This innovative strategy may provide novel directions for studies on Stx1 neutralization, offering a valuable strategy for the treatment of Stx-related diseases.

Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?

BackgroundThe current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. MethodsA cohort study of patients managed for malaria in a non-endemic setting (2005–2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2–10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. ResultsAmong 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). ConclusionsSeverity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.

The Impact of the Antimicrobial Stewardship Program on Antibiotic Use, Resistance Patterns, and Cost in Madinat Zayed Hospital

Antimicrobial resistance and excessive antibiotic usage are a growing public health concern. Antimicrobial Stewardship Programs (ASPs) aim to optimize antibiotic use and curb resistance. This retro-respective study evaluated the impact of an ASP at Madinat Zayed Hospital, Abu Dhabi (January 2021-December 2022). It analyzed electronic health records to assess the ASP's impact on antibiotic consumption, resistance patterns, and economic outcomes. Patients from intensive care units, medical wards, and outpatient settings were included, though patients admitted to obstetrics/gynaecology, paediatrics, neonatal intensive care, and surgical wards were excluded. The primary objective of this study was to report on the ASP experience and measure the prescribing appropriateness percentage of empirical antibiotic therapy along with the de-escalation of broad-spectrum antimicrobials, after ASP implementation at Madinat Zayed Hospital in Al Dhafra Region, United Arab Emirates. The secondary objectives were to reflect on the rate of Multidrug-Resistant Organisms (MDROs), total utilization using defined daily dose, and the total direct cost of antibiotics. Descriptive analysis, proportions, mean values, and percentage changes were employed for data analysis. The ASP achieved high compliance rates with restricted antibiotics (>90%) and approved guidelines (inpatient 97-100%, outpatient 93-98%). Antibiotic de-escalation rates were also high (>80%). Significant reductions in use were observed for cefixime (91.3%), levofloxacin (46.3%), and several others. Notably, cefepime use increased (1137.5%). Direct antibiotic expenditure decreased by 2% (saving Dhs2.6 million), and resistance decreased in some bacteria. However, a concerning rise in ceftazidime resistance against Pseudomonas aeruginosa was identified. This study concluded that the implementation of a new Antimicrobial Stewardship Program at Madinat Zayed Hospital demonstrated effectiveness in promoting responsible antibiotic use. The program achieved high compliance with restricted antibiotic use and approved guidelines, leading to significant reductions in overall antibiotic consumption. Keywords: Antimicrobial, resistance, Multidrug-Resistant Organisms, de-escalation, consumption

Decision-making on systemic antibiotics in the management of periodontitis: A retrospective comparison of two concepts.

To retrospectively compare two approaches for the adjunctive use of systemic antibiotics in non-surgical periodontal therapy: one based on the detection of Aggregatibacter actinomycetemcomitans (Aa) and the other on age and severity of periodontitis (Age & PPD). We also assessed the additional benefit of antibiotics in reducing the need for further surgical therapy in each group. Patients of the Department of Periodontology, Goethe University Frankfurt, Germany, were screened for microbiological testing between 2008 and 2018. Patients were categorized by their microbiological result (Aa+/-) and demographic/clinical data (Age & PPD+/-). Agreement on antibiotic indication was tested. The clinical evaluation focussed on teeth with probing pocket depths (PPDs) ≥ 6 mm. Analysis of 425 patients revealed 30% categorized as Age & PPD+ and 34% as Aa+. Sixty-three percent had consistent antibiotic recommendations (phi coefficient 0.14, p = .004). Patients in the Age & PPD+ group receiving antibiotics showed the most substantial reduction in the number of teeth with PPD ≥ 6 mm after non-surgical periodontal therapy. Both strategies resulted in a significant clinical improvement compared with those without antibiotic treatment and restricted antibiotic use similarly, but targeted different patient groups. Younger individuals with severe periodontitis benefited most from antibiotics, reducing the need for additional surgeries. The study was registered in an international trial register (German Clinical Trial Register number DRKS00028768, registration date 27 April 2022, https://drks.de/search/en/trial/DRKS00028768).

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.

Antimicrobial Consumption and Resistance of Restricted Antibiotics in a Level III Government Hospital.

The objectives of the study were to determine the antibiotic consumption of restricted antibiotics and to correlate this with resistance rate. A retrospective review of pharmacy dispensing records was conducted in the adult internal medicine wards of a tertiary level teaching hospital in the Philippines between March 2019 to February 2020. Antibiotic consumption was determined using Defined Daily Dose (DDD) per 1000 patient-days (PD). Correlations between antibiotic consumption and antibiotic resistance of restricted antibiotics were done. Outcomes were compared between Ward 1 (with the presence of a unit-dose pharmacist) and Ward 3 (without a unit-dose pharmacist). Both wards showed decreasing trends of piperacillin-tazobactam consumption and increasing trends of ceftazidime consumption from quarter 1 to quarter 4. It was observed that levofloxacin was the most prescribed fluoroquinolone with the highest consumption recorded from March to May 2019 in Ward 3 of 350.2 DDD/1000 PD as compared with ciprofloxacin which has the highest consumption (23.3 DDD/1000 PD) during the period June to August 2019 in Ward 1. Antibiotic resistance of Acinetobacter baumannii against ciprofloxacin, levofloxacin, and piperacillin-tazobactam were statistically significantly different between the wards. In Ward 1, ciprofloxacin consumption was strongly positively correlated with Escherichia coli resistance (r = 0.90). In Ward 3, a significantly moderately positive association was observed for ceftazidime consumption and A. baumannii resistance (r = 0.61), positive correlation between piperacillin-tazobactam and E. coli resistance (r = 0.65), and a strong positive correlation in Ward 3 between levofloxacin and Pseudomonas aeruginosa resistance (r = 0.71). The restriction and pre-authorization strategy of the AMS program has greatly contributed to the decrease in the consumption of almost all restricted antibiotics. This strategy has been helpful in minimizing unnecessary antibiotic use associated with inappropriate drug therapy. The success of the AMS program has been based on the collective efforts of the AMS team with the implementation of hospital policies, such as the AMS program, across the different sites in the hospital in order to achieve optimum patient health outcomes. It was noted that the resistance rates of A. baumannii against ciprofloxacin, levofloxacin, and piperacillin-tazobactam were higher in Ward 3 compared to Ward 1 which makes infections very difficult to treat which may result to prolonged hospital stay, increased health-care costs and increased mortality rate. This study has supported the involvement of pharmacists in the AMS team by conducting auditing activities that promote safe compliance of restricted antibiotic use among patients. Pharmacists can greatly participate on either prospective or retrospective review of antibiotic utilization and analyze trends of antibiotic consumption data to provide feedback to prescribing physicians on prescribing patterns and possible correlation with occurrence of antibiotic resistance.

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.