Stewardship / Resistance Scan for Oct 16, 2018

C difficile on hospital bed sheets
Colistin resistance diagnostics
Dearth of point-of-care tests
New-antibiotic distribution

Study finds standard washing doesn't remove C diff from hospital sheets

A team of researchers from the United Kingdom report that Clostridioides difficile spores can survive on hospital sheets even after being washed with high-temperature water and industrial detergents, and that those spores could be contributing to outbreaks of C difficile infection (CDI) in hospitals.

In a study published today in Infection Control and Hospital Epidemiology, researchers from De Montfort University inoculated swatches of cotton sheets with a strain of C difficile, then laundered them with uncontaminated swatches in a simulated washer extractor cycle using an industrial bleach detergent. A control wash with no detergent was also conducted. In addition, they assessed spore survival on swatches of hospital sheets that were naturally contaminated with C difficile and washed, dried, and pressed at a commercial healthcare laundry according to National Health Service standards.

The results revealed that both the simulated and in-situ laundering processes failed the microbiological standards of containing no pathogenic bacteria. Even in the simulated washer extractor cycle with detergent, some spores from the two strains of C difficile survived the process and contaminated the sterile swatches. And in the naturally contaminated sheets, the commercial laundering process only reduced the spore load by 40%. Subsequent ribotyping of C difficile isolates recovered before and after washing showed that they were indistinguishable, indicating that spores recovered after washing were present before washing and were not a result of contamination during the washing cycle.

"The surviving spores may contribute to environmental contamination when the sheets are used for bed making in the healthcare environment," the authors of the study write. "Processing infected linen in commercial washer extractor cycles could disseminate low levels of C. difficile spores and may be contributing to sporadic outbreaks of CDI."

The authors say further research is needed to establish the role that hospital bedsheets may play in CDI outbreaks, and to determine what is needed to fully remove C difficile spores from bedsheets during the laundry process.
Oct 16 Infect Control Hosp Epidemiol abstract


Two tests do well in detecting colistin-resistant Enterobacteriaceae

Two commercial tests performed well in screening for colistin-resistant Enterobacteriaceae on rectal swabs, according to a study yesterday in Antimicrobial Agents and Chemotherapy.

Investigators from Paris-Sud University evaluated the performance of Superpolymyxin medium (made by ELITechGroup) and the Chromid Colistin R plates (made by bioMerieux) to screen for colistin-resistant Enterobacteriaceae from contaminated rectal swabs. Stools were tainted with a total of 94 enterobacterial isolates (Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, and Enterobacter cloacae), including 53 colistin-resistant isolates.

Colistin is a "last resort" antibiotic used for some multidrug-resistant infections.

The sensitivity of detecting colistin-resistant Enterobacteriaceae was 86.8% (95% confidence interval [CI], 74.0% to 94.0%) using both tests, but the isolates that were not detected differed between the two media. Specificity was 97.9% (95% CI, 87.3% to 99.9%) for Superpolymyxin and 100% (95% CI, 90.4% to 100% for Chromid.

The researchers conclude that both tests "provide a useful tool to screen for colistin-resistant Enterobacteriaceae from patient samples (rectal swabs) regardless of the level and mechanism of colistin resistance."
Oct 15 Antimicrob Agents Chemother abstract


Patent filings for AMR point-of-care tests are declining, with funds lacking

Patent filings for point-of-care (POC) diagnostic tests for antimicrobial resistance have been slowly declining since reaching their peak in 2014, according to a study commissioned by the Longitude Prize, a UK program launched in 2014 to spur the development of such tests. The 14-page study was conducted by two intellectual property firms and released on Oct 14 at the World Health Summit in Berlin.

According to a blog post yesterday from Longitude Prize, which has awarded funding to 29 teams to develop POC tests to address antibiotic resistance, researchers looked at what patents are being filed and what technology is being developed, with an eye toward market implications.

Following a drop in filings in 2008 that seemed related to the global financial crisis, filings reached 118 globally in 2014. By 2015, however, the number fell to 94 patents, and researchers don't yet have a clear picture for 2016 and 2017 because of an 18-month delay in filing publication. The team notes that much of the new funding for antimicrobial resistance had targeted new antibiotics, with limited funds for new diagnostics.

Among other findings, the United States dominated the filings for patents for new tests, with 60%, followed by the United Kingdom with 8%. Japan, Australia, India, and South Africa all saw upward trends. Innovations for POC tests are led by private companies, accounting for 60% in the United States and Europe, and academic institutions were responsible for 32%.

At the same time, the percentage of patent filings related to bacterial tests have increased over the same period, while patent filings for World Health Organization priority pathogens have tailed off after an increase between 2009 and 2012, possibly because developers are focusing on more broadly applicable tests.

In addition, Longitude Prize teams say they're struggling to attract adequate funding and investment to bring the tests to market and validate them for regulatory bodies, and investors say prize expectations are too low to ensure a return on investment. "This is a warning to policy makers that initially there will be a need to ring-fence funds to make sure that new products are purchased," the Longitude Prize staff wrote in the blog post.
Oct 15 Longitude Prize blog post
Oct 12 Longitude Prize report
Dec 22, 2017, CIDRAP News story "Four groups get Longitude funds for point-of-care tests"


Market study finds new antibiotics often not widely distributed globally

Antibiotics launched since 1999 took awhile to attain fairly wide geographic dispersal and often targeted common conditions rather than antibiotic-resistant infections, according to a study today in PLoS One.

Of 25 new antibiotics reaching the market from 1999 through 2014, only 12 had registered sales in more than 10 countries. Those with the widest geographic availability had sales in more than 70 countries within 10 years, and in 30 countries within 3 years.

Just 13 (52%) of the new antibiotics had an indication for infections caused by antibiotic-resistant bacteria, with little diversity as far as the target pathogen and indication: 18 were for community-acquired respiratory tract infections, 14 for skin and skin-structure infections, and 12 for urinary tract infections (obviously, several had multiple indications). None targeted gram-negative bacteria, which are among the most troublesome.

The new antibiotics were largely produced in Japan (11 drugs) and the United States (6). Seven were launched in Japan and 12 in the US market. The antibiotics with the greatest geographic availability by 2014—ertapenem, linezolid, moxifloxacin, and tigecycline, which all reached more than 60 countries—originated from European or US companies and were launched in those regions. In general, drugs launched in Japan were less likely to be available in other nations, though antibiotics for drug-resistant infections tended to have greater geographic distribution.

The authors conclude, "Our findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization."
Oct 16 PLoS One study

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