Stewardship / Resistance Scan for Feb 21, 2018

News brief

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

News Scan for Feb 21, 2018

News brief

New MERS cases reported as hospital outbreak confirmed

Saudi Arabia's Ministry of Health (MOH) reported two new MERS cases yesterday, and the World Health Organization (WHO) confirmed that a small healthcare-associated outbreak occurred in Hafar Al-Batin in January.

Two 66-year-old Saudi men, one from Riyadh and the other from Taif, have been diagnosed as having MERS-CoV (Middle East respiratory syndrome coronavirus). The man from Riyadh is in stable condition and the source of his illness is listed as "primary," meaning it's unlikely he contracted the virus from another person. The Taif man is in critical condition, and the MOH said he had direct contact with camels, a known risk factor for MERS-CoV.

Saudi Arabia has now confirmed 1,798 MERS cases since 2012, including 731 deaths. Seven people are still being treated for their infections, the MOH said.

The WHO also released its monthly situation update on MERS, noting Saudi Arabia reported 25 cases, including 8 deaths, in January. They also confirmed a small hospital outbreak in Hafar Al-Batin, which involved one patient and three asymptomatic healthcare workers.

Globally since 2012, there have been 2,160 cases of MERS, including 773 deaths. The case fatality rate for the virus is 35.8%.
Feb 20 Saudi MOH report
Feb 20 WHO report

Trump backs off on Kennedy's anti-vaccine review

Robert F. Kennedy Jr., tapped by President Donald Trump to investigate whether vaccines cause autism, said he hasn't heard from the White House in months, according to a report today in the UK newspaper The Guardian.

A year ago, Trump and Kennedy met weeks after Trump became president, and Kennedy was tasked with leading a review of the possible connection between childhood immunizations and autism. Trump had spoken at some anti-vaccine events as a presidential candidate, and tweeted about the connection between childhood immunizations and the rise in autism.

Now, Kennedy said he hasn't heard from the White House for the last 6 months, and said President Trump is "going in a different direction," on vaccines. The review has never been formerly supported by the White House, Kennedy told the Guardian.

In 2005, Kennedy wrote an article for Rolling Stone magazine suggesting thimerosal, a preservative used in vaccines until 2001, led to autism. The article was later retracted.

The American Academy of Pediatrics and the Centers for Disease Control and Prevention both maintain that childhood vaccines are safe, effective, and in no way cause autism.
Feb 21 Guardian story

Vaccine protects non-human primates against Ebola and Marburg viruses

A new prophylactic vaccine was immunogenic and effective against multiple filoviruses, including Ebola and Marburg, in monkeys, according to a study yesterday in PLoS One.

The vaccine, which expresses glycoproteins from Ebola virus (EBOV), Sudan virus (SUDV), Tai Forest virus (TAFV) and Marburg virus (MARV), is being investigated as a universal filovirus vaccine. Unlike ring vaccines, which have been used during filovirus outbreaks, a single-prophylactic vaccine could be introduced in childhood and offer life-long protection.

To test the vaccine, a team of international researchers immunized macaques with a multivalent vaccine comprising adenovirus serotypes 26 and 35 (Ad26 and Ad35) and modified vaccinia virus Ankara. The animals were then challenged with EBOV, MARV, and SUDV. The vaccine protected the monkeys from EBOV and MARV fully and SUDV partially.

"A multivalent filovirus vaccine would be optimal for prophylactic administration, for example, of populations who are deemed to be at risk of geographical or occupational exposure, and also for aid workers and other professionals who may be called into filovirus endemic regions," the authors concluded. "The results from our studies, combined with clinical data, indicate that a prophylactic multivalent filovirus vaccine is a realistic goal."
Feb 20 PLoS One study