Platform uses metabolomic analysis to uncover novel antibiotics
A study today in Science Translational Medicine describes a new approach to determining the modes of action underlying antimicrobial compounds that could help speed the process of discovering novel antibiotics.
The platform developed by a team of European scientists involves rapid systematic metabolome profiling, a process that uses mass spectrometry to analyze and measure the changes that occur in metabolites—the small molecules produced by bacteria—upon treatment with a drug or compound. The idea is that these changes will provide clues to the underlying modes of action.
To test this strategy, the team exposed Mycobacterium smegmatis to multiple doses of 62 reference compounds with known modes of action, including currently used antibiotics and chemical stress agents, and used a computational framework to parse out predicted modes of action based on pairwise comparisons between known chemicals. They then tried this approach on 212 uncharacterized compounds from a drug discovery program by pharmaceutical company GlaxoSmithKline. This revealed 16 compounds that appeared to target unconventional cellular processes, and 6 with potentially new modes of action that exerted anti-tuberculosis effects by targeting fatty acid metabolism.
The authors of the study say the advantage of their approach for predicting modes of action in chemical screens is that it discriminates between compounds with previously known modes of action and those with new modes of action. "Knowing the MoAs [modes of action] of compounds at an early stage of drug discovery can guide the selection of the most promising leads, even in cases where the drugs do not yet exhibit strong bactericidal or bacteriostatic effects," they write.
Feb 21 Sci Transl Med study
CDC launches online antibiotic stewardship course
The US Centers for Disease Control and Prevention (CDC) yesterday launched a new online antibiotic stewardship course.
The interactive web-based activity is designed to help clinicians optimize antibiotic use to combat antibiotic resistance and improve healthcare quality and patient safety. The course will provide an overview of antibiotic resistance and explain the benefits of antibiotic stewardship across the healthcare spectrum. It will also discuss the risks and benefits of antibiotics, with a specific focus on the microbiome, adverse drug events, and Clostridium difficile infections. The first module will focus on outpatient antibiotic stewardship, and the following modules will focus on stewardship in acute care hospitals and long-term care facilities.
The CDC says the goal of the course is to help healthcare professionals deliver effective and consistent message about antibiotic use and antibiotic resistance to patients, and to provide guidance for how to apply antibiotic stewardship principles to the most common conditions that lead to inappropriate use.
Feb 20 CDC training on antibiotic stewardship
Infection diagnostic codes tied to higher rates of previous antibiotics
Chicago researchers who analyzed data on 78,094 patients found that diagnostic codes for infections are strong surrogate markers for prior antibacterial exposure, especially to broad-spectrum antibiotics, which may help identify patients who harbor multidrug-resistant bacteria.
Writing in Infection Control & Hospital Epidemiology, the investigators, from Cook County Health and Hospital System in Chicago detailed findings from 121,916 hospitalizations involving 78,094 patients in three Chicago-area hospitals.
Of the 121,916 inpatient encounters, 24% had an associated infection code, 47% of patients received an antibacterial drug, and 13% received a broad-spectrum antibacterial. Patients with infection-related ICD-9-CM codes had more than twice the rate of antibacterial use compared with those lacking such codes (relative risk [RR], 2.29) and a fivefold increased risk for broad-spectrum antibacterial use (RR, 5.52). CD-9-CM codes were also linked to a tripling of the number of antibacterial days.
The authors concluded, "Such an association can be used to enhance early identification of patients at risk of multidrug-resistant organism (MDRO) carriage at the time of admission."
Feb 20 Infect Control Hosp Epidemiol abstract