No abstract

Antimicrobial resistance among enteric organisms in food animals varied among countries, particularly for older antimicrobials, but clinical resistance to essential compounds used to treat disease in humans was generally zero or low. In the absence of clinical resistance to newer compounds in E. coli and Salmonella, the apparent decreased susceptibility should be monitored carefully.

Resistance patterns varied widely depending on bacterial species, antibiotics, hosts and region. Resistance varied among countries, particularly for older antimicrobials, but clinical resistance to newer antibiotics used to treat foodborne disease in humans was generally very low. In the absence of resistance to newer compounds in E. coli and Salmonella, the apparent decreased susceptibility should be monitored.

Background In patients with atopic dermatitis (AD), Staphylococcus aureus frequently colonizes lesions and is hypothesized to be linked to disease severity and progression. Treatments that reduce S. aureus colonization without significantly affecting the skin commensal microbiota are needed. Methods and findings In this study, we tested ATx201 (niclosamide), a small molecule, on its efficacy to reduce S. aureus and propensity to evolve resistance in vitro. Various cutaneous formulations were then tested in a superficial skin infection model. Finally, a Phase 2 randomized, double‐blind and placebo‐controlled trial was performed to investigate the impact of ATx201 OINTMENT 2% on S. aureus colonization and skin microbiome composition in patients with mild‐to‐severe AD (EudraCT:2016‐003501‐33). ATx201 has a narrow minimal inhibitory concentration distribution (.125–.5 μg/ml) consistent with its mode of action – targeting the proton motive force effectively stopping cell growth. In murine models, ATx201 can effectively treat superficial skin infections of methicillin‐resistant S. aureus. In a Phase 2 trial in patients with mild‐to‐severe AD (N = 36), twice‐daily treatment with ATx201 OINTMENT 2% effectively reduces S. aureus colonization in quantitative colony forming unit (CFU) analysis (primary endpoint: 94.4% active vs. 38.9% vehicle success rate, p = .0016) and increases the Shannon diversity of the skin microbiome at day 7 significantly compared to vehicle. Conclusion These results suggest that ATx201 could become a new treatment modality as a decolonizing agent.

Objectives To describe the susceptibility of Escherichia coli to medically important antibiotics, collected over four periods (2004–2006, 2008–2009, 2013–2014, 2017–2018), from food-producing animals at slaughter. Methods Intestinal contents from cattle, pigs and broilers were randomly sampled (5–6 countries/host; ≥4 abattoirs/country; one sample/animal/farm) for isolation of Escherichia coli; antimicrobial susceptibilities were centrally determined by CLSI agar dilution. Clinical breakpoints (CLSI) and epidemiological cut-off values (EUCAST) were applied for data interpretation. Results In total, 10 613 E. coli strains were recovered. In broilers, resistance percentages were the lowest (P ≤ 0.01) in the latest time period. A significant decrease in MDR over time was also observed for broilers and a tendency for a decrease for pigs. Resistance to meropenem and tigecycline was absent, and resistance to azithromycin was 0.2%–2.0%. Also, low resistance to third-generation cephalosporins (1.1%–7.4%) was detected in broilers. Resistance to colistin varied between 0.1%–4.8%. E. coli from broilers showed high resistance to ciprofloxacin (7.3%–23.3%), whereas for cattle and pigs this was 0.2%–2.5%. Low/moderate resistance to chloramphenicol (9.3%–21.3%) and gentamicin (0.9%–7.0%) was observed in pigs and broilers. The highest resistance was noted for ampicillin (32.7%–65.3%), tetracycline (41.3%–67.5%), trimethoprim (32.0%–35.7%) and trimethoprim/sulfamethoxazole (27.5%–49.7%) from pigs and broilers, with marked country differences. MDR peaked in pigs and broilers with 24 and 26 phenotypes, with 21.9%–26.2% and 18.7%–34.1% resistance, respectively. Conclusions In this pan-EU survey antibiotic susceptibility of commensal E. coli varied largely between antibiotics, animal species and countries. Resistance to critically important antibiotics for human medicine was absent or low, except for ciprofloxacin in broilers and ampicillin in pigs and broilers.