ASP Scan (Weekly) for Sep 07, 2018

Priority areas for ASP research
Ineffective probiotics
Pharmacist intervention for MRSA
Drug resistance and death certificates
Preventive antibiotics for COPD
MDR bacteria in pets
Maryland antibiotic regulations

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:

  1. Comprehensively identifying barriers and facilitators to implementing ASPs and clinical recommendations intended to optimize antibiotic prescribing
  2. Identifying actors and actions of ASPs and clinical teams
  3. Synthesizing available evidence to support future research and planning for ASPs
  4. Specifying the activities in current ASPs with the purpose of defining a "control group" for comparison with new initiatives
  5. Defining a balanced set of measures to evaluate the effects of interventions focused on reducing unnecessary antibiotics
  6. Conducting robust evaluations of ASPs with built-in process evaluations and fidelity assessments
  7. Defining and designing ASPs
  8. Establishing the evidence base for impact of ASPs on resistance
  9. Investigating the role and impact of government and policy contexts on ASPs
  10. 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


England's top medical officer wants deaths from drug resistance recorded

Originally published by CIDRAP News Sep 6

England's chief medical officer is calling for antibiotic-resistant infections to be recorded on death certificates, according to reports in the British press.

The Guardian reports that Dame Sally Davies told British members of parliament on the Health and Social Care Select Committee on Tuesday that recording deaths from drug-resistant infections would raise public awareness of antibiotic resistance.

"I would really love death certificates to collect when people die of infections and if resistance has been involved, because that would really wake people up to the deaths as they happen," Davies said.

Davies said England's National Health Service (NHS) rarely tells families when a loved one has died of a resistant infection, because doing so would make it look like the service is failing patients.

Davies, a leading voice on the dangers of antibiotic resistance, also warned that unless more effective measures were introduced to contain the spread of drug-resistant infections, advanced medical procedures and organ transplants will be threatened. "There will be a lot of suffering, and modern medicine will be lost," she said.
Sep 4 Guardian story


Meta-analysis finds preventive antibiotics effective for COPD but at a cost

Originally published by CIDRAP News Sep 5

A meta-analysis of 12 randomized controlled trials has determined that prophylactic (preventive) antibiotics appear to be effective in preventing chronic obstructive pulmonary disease (COPD) exacerbations and improving quality of life in stable patients who have moderate to severe disease, but also appear to raise antibiotic resistance rates.

Writing in the Journal of Antimicrobial Chemotherapy yesterday, Dutch experts said the 12 studies they analyzed involved 3,683 COPD patients. The researchers found that prophylactic antibiotics reduced the frequency of exacerbations by 26% (range, 8% to 40%) and the number of patients who had at least one exacerbation by 18% (range, 10% to 26%).

Erythromycin and azithromycin appeared to be the most effective antibiotics, with the number needed to treat ranging from four to seven. Quality of life was also significantly improved by prophylactic antibiotics, the authors found, and the time to first exacerbation was prolonged in six studies, with one conflicting result.

The benefits appear to come at a cost, however, as antibiotic-resistant isolates were more than quadruple in patients who received the prophylactic regimens compared with those who didn't.

The authors conclude, "The choice of prophylactic antibiotics should be analysed and considered case by case, especially for long and continuous use."
Sep 4 J Antimicrob Chemother abstract


Singapore study finds multidrug-resistant bacteria in sick pets

Originally published by CIDRAP News Sep 4

An analysis of diagnostic reports from a veterinary clinic in Singapore suggests sick companion pets could be a reservoir for multidrug-resistant bacteria, according to a letter published in Antimicrobial Resistance and Infection Control.

Researchers from Singapore's Environmental Health Institute analyzed 186 diagnostic reports from a single, community-based companion animal practice from 2014 to 2016. The reports included antibiotic susceptibility results from bacteria isolated from sick dogs and cats after initial treatment was ineffective. Bacterial specimens were collected from wounds/abscesses, ear swabs, urine, and skin and nasal swabs.

Resistance to multiple antibiotics and was observed in the samples, with 45% (162 of 359 bacterial isolates) showing multidrug resistance (i.e. resistance to at least 3 antibiotic classes) and 40% (144/359) displaying resistance to one to two antibiotic classes. Extended-spectrum beta-lactamase (ESBL)-producing organisms were found in 18% (66/359) of the isolates. Resistance to broad-spectrum antibiotics was also observed in individual species, including methicillin resistance in Staphylococcus pseudintermedius (the most frequently detected bacteria) and Staphylococcus aureus, fluoroquinolone resistance in Escherichia coli, and carbapenem resistance in Klebsiella pneumoniae.

The authors write, "The detection of these clinically relevant bacteria suggests that sick pets, as they live in close proximity with their owners, may play a role in the transmission of AMR [antimicrobial resistance] between animal and human sources. Conversely, pet owners may also play a role in this transmission."

They suggest a more extensive study on the epidemiology of AMR bacteria carried by sick pets is necessary to better understand the extent of distribution, the direction, and risk factors for transmission.
Aug 31 Antimicrob Resist Infect Control study


Advocates press Maryland governor on livestock antibiotic regulations

Originally published by CIDRAP News Sep 4

A coalition of health and environmental advocacy groups today delivered a letter urging Maryland governor Larry Hogan to revise regulations for legislation aimed at curbing antibiotic use in livestock, according to a press release from Maryland PIRG (Public Interest Research Group).

The Keep Antibiotics Effective Act, passed by the Maryland legislature in 2017 without a signature from the governor, eliminates the routine use of antibiotics in animals that aren't sick. But supporters of the legislation have argued that draft regulations released recently by the Maryland Department of Agriculture contain significant loopholes and fail to carry out the legislature's intent. The public comment period for the draft regulations ends today.

"We must act now to preserve these life-saving drugs for future generations," Maryland PIRG director Emily Scarr said in the press release. "Governor Hogan should strengthen the Department of Agriculture's proposed regulations to ensure antibiotics are reserved for when they are needed most: for sickness and surgery."

The letter was signed by more than a dozen groups, including Maryland Sierra Club, the Society of Infectious Disease Pharmacists, and the Maryland Nurses Association.
Sep 4 Maryland PIRG press release 

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