Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.

Background: To evaluate systematically the failure rate of short versus long courses of antibiotic agents for prosthetic joint infections (PJIs). Methods: PubMed, Embase, and Cochrane Library databases were searched for controlled studies of short- and long-course antibiotic agents for joint prosthesis infections, all from the time of database creation to April 2022. Literature search, quality evaluation, and data extraction were performed independently by two researchers, and the primary outcome was the rate of surgical failure after antibiotic treatment. Stata 11.0 software was then applied for meta-analysis. Publication bias was assessed using Begg test. Heterogeneity was assessed using the I2 test, and fixed or random effects models were used accordingly. Meta-regression was used to determine the causes of heterogeneity. Results: A total of 14 articles involving 1,971 participants met the inclusion criteria, including 12 observational studies and two randomized controlled trials. Meta-analysis showed no difference between short and long courses of antibiotic agents (relative risk, 1.08; 95% confidence interval [CI], 0.89-1.32). The results of the subgroup analysis showed no differences between the failure rates of patients with PJI treated with short and long courses of antibiotic agents in studies with different study areas, different treatment modalities, and different locations of the artificial joints. Conclusions: Patients with PJIs may not require long-term or lifelong antibiotic agents after surgical treatment, and short-term (four to six weeks) antibiotic therapy is usually safe.

Antimicrobial resistance is a serious challenge to the success and sustainability of our healthcare systems. There has been increasing policy attention given to antimicrobial resistance in the last few years, and increased amounts of funding have been channeled into funding for research and development of antimicrobial agents. Nevertheless, manufacturers doubt whether there will be a market for new antimicrobial technologies sufficient to enable them to recoup their investment. Health technology assessment (HTA) has a critical role in creating confidence that if valuable technologies can be developed they will be reimbursed at a level that captures their true value. We identify 3 deficiencies of current HTA processes for appraising antimicrobial agents: a methods-centric approach rather than problem-centric approach for dealing with new challenges, a lack of tools for thinking about changing patterns of infection, and the absence of an approach to epidemiological risks. We argue that, to play their role more effectively, HTA agencies need to broaden their methodological tool kit, design and communicate their analysis to a wider set of users, and incorporate long-term policy goals, such as containing resistance, as part of their evaluation criteria alongside immediate health gains.

BACKGROUND: The aim of this review was to evaluate the efficacy and safety of antibiotic agents in children with COVID-19, as well as to introduce the present situation of antibiotics use and bacterial coinfections in COVID-19 patients.
METHODS: We searched Cochrane library, Medline, Embase, Web of Science, CBM, Wanfang Data and CNKI from their inception to March 31, 2020. In addition, we searched related studies on COVID-19 published before March 31, 2020 through Google Scholar. We evaluated the risk of bias of included studies, and synthesized the results using a qualitative synthesis.
RESULTS: Six studies met our inclusion criteria. Five studies on SARS showed an overall risk of death of 7.2% to 20.0%. One study of SARS patients who used macrolides, quinolones or beta lactamases showed that the mean duration of hospital stay was 14.2, 13.8 and 16.2 days, respectively, and their average duration of fever was 14.3, 14.0 and 16.2 days, respectively. One cohort study on MERS indicated that macrolide therapy was not associated with a significant reduction in 90-day mortality (adjusted OR 0.84, 95% CI: 0.47-1.51, P=0.56) and improvement in MERS-CoV RNA clearance (adjusted HR 0.88, 95% CI: 0.47-1.64, P=0.68). According to the findings of 33 studies, the proportion of antibiotics use ranged from 19.4% to 100.0% in children and 13.2% to 100.0% in adults, despite the lack of etiological evidence. The most commonly used antibiotics in adults were quinolones, cephalosporins and macrolides and in children meropenem and linezolid.
CONCLUSIONS: The benefits of antibiotic agents for adults with SARS or MERS were questionable in the absence of bacterial coinfections. There is no evidence to support the use of antibiotic agents for children with COVID-19 in the absence of bacterial coinfection.