Experts identify priority research areas for effective stewardship

A workgroup on behavioral approaches to antibiotic stewardship has identified research priority areas for optimizing effective implementation of antibiotic stewardship programs (ASPs) in hospital settings. The findings were published yesterday in Clinical Microbiology and Infection.

The workgroup, which included experts in antibiotic stewardship, implementation science, and social sciences, met on two separate occasions in 2017 to identify broad areas for future research using a structured consensus method. Because antibiotic stewardship requires complex behavioral change at both individual and organizational levels, the ultimate aim is to identify the behavior change techniques that are most effective for implementing ASPs in high-income countries that have publicly funded healthcare systems.

Following their discussions, the group combined overlapping ideas into 10 research priority areas, listed below in ranked order:

Comprehensively identifying barriers and facilitators to implementing ASPs and clinical recommendations intended to optimize antibiotic prescribing Identifying actors and actions of ASPs and clinical teams Synthesizing available evidence to support future research and planning for ASPs Specifying the activities in current ASPs with the purpose of defining a "control group" for comparison with new initiatives Defining a balanced set of measures to evaluate the effects of interventions focused on reducing unnecessary antibiotics Conducting robust evaluations of ASPs with built-in process evaluations and fidelity assessments Defining and designing ASPs Establishing the evidence base for impact of ASPs on resistance Investigating the role and impact of government and policy contexts on ASPs Understanding what matters to patients in ASPs in hospitals

The authors say the list should be assessed and revised every 2 years, and that the same methodology could be applied to propose research priority areas in low- and middle-income countries.

Sep 6 Clin Microbiol Infect abstract

Studies find probiotics lacking for restoring gut microbiome

Though probiotics are touted as balancing the gut bacteria and doing everything from repairing damage from antibiotics to preventing disease, they appear to offer little benefit but might prove efficacious if tailored to individual patients, according to two small studies involving both people and mice published yesterday in Cell.

In the first human trial, Israeli researchers addressed the effect of probiotics taken after antibiotic treatment. The researchers administered wide-spectrum antibiotics to 21 human volunteers, who then underwent an upper endoscopy and colonoscopy to observe the changes to both the gut and its microbiome. Then the volunteers were randomly assigned to one of three groups: (1) "watch and wait," (2) administration of an 11-strain probiotic preparation over 4 weeks, and (3) treatment with autologous (their own) fecal microbiome transplant (aFMT).

The investigators found that probiotics could easily colonize the human gut after the antibiotics had cleared. To the team's surprise, however, the probiotics' gut colonization prevented both the host gut's gene expression and their microbiome from returning to normal pre-antibiotic configurations for months afterward. In contrast, aFMT resulted in the native gut microbiome recolonizing and the gut gene expression profile returning to normal within days.

"These results reveal a new and potentially alarming adverse side effect of probiotic use with antibiotics that might even bring long-term consequences," said lead researcher Eran Elinav, MD, PhD, of the Weizmann Institute of Science, in a press release. "In contrast, personalized treatment—replenishing the gut with one's own microbes—was associated with a full reversal of the drugs' effects."

In the second human study, the researchers recruited 25 volunteers who underwent upper endoscopy and colonoscopy to assess their baseline microbiome in different gut regions. Fifteen of those volunteers were then divided into two groups, one of which received an 11-strain probiotic preparation while the others got placebo pills. Three weeks into the 4-week treatment, all participants underwent a second upper endoscopy and colonoscopy to assess their response to the probiotics or placebo, and they were then followed for an additional 2 months.

The researchers discovered that gut colonization with probiotics was highly individual but fell into two groups: "persisters," whose guts hosted the probiotic microbes, and "resisters," who expelled them. The team found they could predict whether a person would be a persister or resister just by examining their baseline microbiome and host gene expression profile.

"Our results suggest that probiotics should not be universally given to the public as a 'one size fits all' supplement," Elinav said. "Instead, they could be tailored to each individual and their particular needs."

Results were similar in the mouse studies.

Sep 6 Cell study 1

Sep 6 Cell study 2

Sep 6 Weizmann Institute of Science news release

In related news, the US Food and Drug Administration (FDA) yesterday posted draft guidance on probiotics.

"The draft guidance, when finalized, will advise firms that manufacturer, market, or distribute dietary supplements of FDA's intent to exercise enforcement discretion if a firm wishes to specify the amount of a live microbial in colony forming units (CFUs) in addition to the currently required unit of measure (milligrams) in the Supplement Facts label," the agency said.

Sep 6 Fed Register FDA guidance

Study ties pharmacist intervention to longer survival with MRSA vanco

Japanese scientists have found that pharmacist intervention in vancomycin (VCM) treatment for patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with longer survival, according to data published yesterday in PLoS One.

The single-center retrospective cohort study involved 77 patients. The researchers assessed death within 30 days of the start of VCM therapy, positive blood culture 7 days after the start of therapy, change from VCM to another anti-MRSA antibiotic, and the development of toxicity in the kidneys—all of which indicated failure of VCM therapy. They compared pharmacist intervention with no intervention.

Among seven parameters that they assessed, only pharmacist intervention was associated with prolonged survival time, with a hazard ratio of 0.26.

The authors conclude, "To our knowledge, this is the first study to evaluate the failure of VCM treatment based on the composite endpoint. Pharmacist intervention through the initial VCM dose planning could maintain a balance between the efficacy and safety of VCM treatment and might avoid treatment failure for patients with MRSA bacteremia. Further investigations with large sample sizes are required to confirm our findings."

Sep 4 J Antimicrob Chemother abstract