International Journal of Antimicrobial Agents最新文献

Antimicrobial resistance (AMR) poses a global threat to the health of humans, animals and plants, as well as the environment. In recent years, attention has increasingly focused on the role of antimicrobials as growth promoter (AGPs) in livestock. While the mechanism of action of AGPs is still poorly understood, mounting evidence suggests a link between AGP use and AMR. Consequently, several countries and regions have restricted/banned AGP use in livestock. However, such efforts encounter political, financial, social, and cultural challenges. This systematic review aims to investigate the impact of AGP use on AMR in food-producing animals and focused on the emergence of phenotypic resistance in Escherichia coli isolated from livestock exposed to AGPs. Overall, 7,000 studies were screened at title, abstract and full text; from these, 10 were deemed eligible for inclusion in this review. Among the 10 selected studies, seven noted significant increase of AMR associated with AGP use. Significantly increased resistance levels to Highest Priority Critically Important Antimicrobials for human health such as ceftiofur, cefotaxime, ciprofloxacin, and nalidixic acid were observed among other antimicrobials. However, the studies revealed high risk of bias underscoring the need for further research. This review provides a deeper understanding of the consequences of AGP use and occurrence of AMR. It highlights the need for implementing efficient surveillance systems and fostering research into suitable alternatives to AGPs. A shift to sustainable husbandry practices including responsible AMU while safeguarding animal health, productivity and farmers' livelihoods are essential for successful policy implementation.

Fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) requires careful selection of stool donors to avoid transmitting pathogens. Dientamoeba fragilis detection remains an exclusion criterion based on its uncertain pathogenicity. The aim of this study was to assess D. fragilis interhuman transmission by FMT and its impact on the clinical success of rCDI. A retrospective study was conducted in rCDI patients from the COSMIC cohort undergoing FMT to investigate the potential transfer of D. fragilis from donor to recipient. The impact of FMT involving D. fragilis was also evaluated on the clinical outcomes of rCDI and adverse effects. This protist was found to be present in 15 out of 86 healthy donors screened (18.7%) who voluntarily took part in an FMT program. Examination of D. fragilis presence in stool samples from 17 patients both before and after FMT with D. fragilis-positive donations revealed no evidence of interhuman transmission through this process. Analysis of clinical outcomes and adverse events in 124 rCDI patients who underwent FMT (with 45 receiving D. fragilis-positive donations) showed no significant differences in success rates between patients receiving positive or negative D. fragilis transplants, 95.5% and 93.6%, respectively. No significant variances were observed in other side effects analyzed. These findings underscore the safety of using fecal transplant from D. fragilis positive donors in the FMT process. D. fragilis should be removed from the donor screening, which will represent a major improvement in the donor selection process from financial and practical standpoints.

Objective: We aimed to evaluate the susceptibility of various clinical methicillin-resistant Staphylococcus aureus (MRSA) lineages to omadacycline and investigate the mechanisms underlying omadacycline resistance.

Methods: Omadacycline MICs for all MRSA isolates were determined via broth dilution. Representative clinical MRSA isolates of ST59, ST5 and ST9 were exposed to increasing concentrations of omadacycline. Mutants developing omadacycline resistance were isolated, sequenced, and compared using breseq. Molecular cloning was employed to elucidate the mechanisms of omadacycline resistance.

Results: Omadacycline MICs against MRSA ranged from 0.06 to 8 mg/L, with MIC₅₀ and MIC₉₀ values at 0.25 and 4 mg/L, respectively, and an overall resistance rate of 13%. All CC59 isolates were susceptible to omadacycline. Resistant isolates were mainly concentrated in HA-MRSA clones CC5. All 47 isolates with MICs ≥4 mg/L harbored tet(M) and the rpsJ K57M mutation. Cloning experiments demonstrated that both tet(M) and mutated rpsJ reduced susceptibility to omadacycline. The rpsJ gene was a common target in different MRSA lineages for decreased omadacycline susceptibility. Continuous exposure to omadacycline induced novel mutations in rpsJ (H56Y in ST9; H56R, K57M in ST59; and K57M, H56Y in ST5), which cloning experiments confirmed could variably reduce omadacycline susceptibility. Furthermore, mutated mepA also contributed to reduced omadacycline susceptibility.

Conclusion: Susceptibility to omadacycline varied among different MRSA lineages, while some CC5 isolates exhibiting the resistance phenotype. The rpsJ gene serves as a general target for the evolution of omadacycline resistance and plays an important role in the refinement of future tetracycline derivatives.