Stimulating Transcription in Antibiotic-Tolerant Escherichia coli Sensitizes It to Fluoroquinolone and Nonfluoroquinolone Topoisomerase Inhibitors.

Antibiotic tolerant bacteria and persistent cells that remain alive after a course of antibiotic treatment can foster the chronicity of infections and the development of antibiotic resistance. Elucidating how bacteria overcome antibiotic action and devising strategies to bolster a new drug's activity can allow us to preserve our antibiotic arsenal. Here, we investigate strategies to potentiate the activities of topoisomerase inhibitors against nongrowing Escherichia coli that are often recalcitrant to existing antibiotics. We focus on sensitizing bacteria to the fluoroquinolone (FQ) levofloxacin (Levo) and to the spiropyrimidinetrione zoliflodacin (Zoli)-the first antibiotic in its class of compounds in clinical development. We found that metabolic stimulation either alone or in combination with inhibiting the AcrAB-TolC efflux pump sensitized stationary-phase E. coli to Levo and Zoli. We demonstrate that the added metabolites increased proton motive force generation and ATP production in stationary-phase cultures without restarting growth. Instead, the stimulated bacteria increased transcription and translation, which rendered the populations more susceptible to topoisomerase inhibitors. Our findings illuminate potential vulnerabilities of antibiotic-tolerant bacteria that can be leveraged to sensitize them to new and existing classes of topoisomerase inhibitors. These approaches enable us to stay one step ahead of adaptive bacteria and safeguard the efficacy of our existing antibiotics.

COVID-19: Safe Guidelines for Breast Imaging During the Pandemic.

During the COVID-19 pandemic, breast imaging must be performed using safe practices. Balancing the need to avoid delays in the diagnosis of breast cancer while avoiding infection requires careful attention to personal protective equipment and physical distancing and vigilance to maintain these practices. The Canadian Society of Breast Imaging/Canadian Association of Radiologists guideline for breast imaging during COVID-19 is provided based on priority according to risk of breast cancer and impact of delaying treatment. A review of the best practices is presented that allow breast imaging during COVID-19 to maximize protection of patients, technologists, residents, fellows, and radiologists and minimize spread of the infection. The collateral damage of delaying diagnosis of breast cancer due to COVID-19 should be avoided when possible.

Local diagnostic reference levels for typical radiographic procedures.

PURPOSE: To establish local diagnostic reference levels (DRL) for typical radiographic examinations in a fully digital imaging institution. METHODS: The initial survey included 6 standard radiographic projections performed in 19 computed radiography (CR) and digital radiography (DR) rooms. Because of the expected difference in the performance, the local reference levels were analysed separately for those 2 modalities. Data of 226 average size adult patients were included in the analysis. Entrance surface dose (ESD) was calculated from the recorded radiographic techniques and tube radiation output measurements. After observing wide variations in the results of the patient survey, the examinations were repeated by using anthropomorphic phantoms. Initial efforts to understand the reasons for dose variations were focused on CR chest, abdomen, pelvis, and lumbar spine examinations. RESULTS: The average size patient doses for similar examinations were lower in the DR rooms than in the CR rooms by factors that ranged from 1.2 to 3, with the exception of the chest examination. Standardization of the CR exposure index value allowed us to decrease ESD by 21%-30%. Detector sensitivity had an insignificant effect (2%) on ESD; proper collimation lowered the dose by 17%. However, the major effect, up to 46% difference, was found because of antiscatter grids cutoff. CONCLUSION: Modality specific local diagnostic reference levels for standard examinations have been established in a large digital imaging department with hybrid modalities. Typically the local reference values were lower than those recommended in Safety Code 35, except for CR chests. Factors that affect the dose variations have been investigated and determined.