ASP Scan (Weekly) for May 17, 2019

Northern Ireland AMR plan
Rapid susceptibility tests
Unnecessary abx for respiratory infections
Antibiotics in school beef
UK veterinary stewardship policy
Improper prescribing in seniors
Resistant TB testing in China
Antibiotic production partnership
MCR-1 in chickens, camels
New CARB-X funding
Grant for TB research

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Northern Ireland announces One Health AMR plan

The government of Northern Ireland yesterday announced a 5-year, One Health action plan to fight antimicrobial resistance (AMR).

The plan, developed by Northern Ireland's Department of Health and Department of Agriculture, Environment and Rural Affairs in collaboration with the United Kingdom's Food Standards Agency (FSA), aims to address the growing threat of drug-resistant pathogens by lowering the burden of infection in humans and animals, optimizing antibiotic use on farms and in human medicine, strengthening AMR surveillance, minimizing the spread of AMR in the environment, and investing in research into new therapeutics and diagnostics.

Among the specific goals laid out in the plan are a 10% reduction in the incidence of specific drug-resistant infections in people, a 50% reduction in healthcare-associated gram-negative bloodstream infections, and a 15% reduction in human antimicrobial use by 2023-2024.

"This issue affects more than just human health and healthcare. Whenever we make an environment favourable for infectious bugs, then they take advantage," Maria Jennings, FSA director in Northern Ireland, said in a press release. "This affects farming, the environment and ultimately the food we eat.  Taking a One Health approach and working with partners across government is the most effective way to address AMR."

The plan was developed in conjunction with the United Kingdom's 20-year vision and 5-year national action plan for addressing AMR, released in January. 
May 16 Northern Ireland 5-year action plan
May 16 Northern Ireland Executive press release
Jan 24 CIDRAP News story, "UK aims to cut antibiotics 15% in 5-year plan"


Rapid susceptibility test produces mixed results in German study

Introduction of a novel, rapid antimicrobial susceptibility test at a German hospital significantly reduced time for species identification (ID) and antimicrobial susceptibility testing (AST) in patients with bloodstream infections, as well as time to optimal antimicrobial therapy, researchers at University of Cologne Hospital reported yesterday in Clinical Infectious Diseases. But the test did not affect antimicrobial consumption or clinical outcomes.

In the quasi-experimental study, researchers investigated the impact of The Accelerate Pheno system (ADX), a new technology that identifies microorganisms from a positive blood culture within 90 minutes and provides phenotypic AST results within 7 hours, by analyzing three different groups of patients with a positive blood culture. One group was evaluated and treated with conventional diagnostics, a second with conventional diagnostics and antimicrobial stewardship program (ASP) intervention, and a third with ADX and ASP intervention. The goal was to see whether use of ADX leads to earlier therapeutic decision-making, decreased use of broad-spectrum antimicrobials, decreased length of hospitalization, and better clinical outcomes.

Overall, 204 patients were evaluated; 64 in the conventional diagnostics group, 68 in the conventional diagnostics plus ASP group, and 72 rapid diagnostics plus ASP group. Compared with the two groups using conventional diagnostics, the use of ADX significantly decreased time from Gram stain to ID (median: 23 vs 2.2 hours, P < 0.001) and time to AST results (median: 23 vs 7.4 hours, P < 0.001) and shortened time from Gram stain to optimal antimicrobial therapy (median: 11 vs 7 hours, p < 0.024) and to step-down antimicrobial therapy (median: 27.8 vs 12 hours, P < 0.019). But no significant differences were found in the duration of antimicrobial treatment, total antimicrobial consumption, length of hospital stay, or 7-day and 28-day in-hospital mortality.

"In conclusion, the use of ADX significantly reduced time to ID and AST as well as time to optimal antimicrobial therapy but did not affect clinical outcome parameters," the authors of the study write. "It remains to be determined if a larger study in a high resistance setting or in a setting with 24/7 microbiology service or with less active ASP involvement can show lower mortality rates and antimicrobial consumption when rapid susceptibilities are provided."
May 16 Clin Infect Dis abstract


Study: Antibiotics for respiratory infections common in cancer patients

In another study yesterday in Clinical Infectious Diseases, researchers with Fred Hutchinson Cancer Research Center found that nearly one-third of hematology-oncology patients were prescribed antibiotics for a respiratory tract infection. But viral causes were identified in 75% of patients tested, and viral testing was associated with reduced prescribing.

The retrospective study looked at the electronic medical records of patients who presented for care at Seattle Cancer Care Alliance and had received a diagnosis for acute upper respiratory tract infection (URI) or acute bronchitis from October 2015 through September 2016. The researchers obtained antibiotic prescribing, viral testing, and other clinical data from the first clinical encounter for the URI through day 14 to characterize antibiotic prescribing patterns, use of respiratory viral diagnostic tests, and clinical outcomes associated with URI in an immunocompromised population.

Of the 251 patients included in the final analysis, 81 (32%) were prescribed an antibiotic for URI symptoms, with 52 (64%) receiving prescriptions on day 0, 11 (14%) on days 1-2, and 18 (22%) on days 3-14. Viral testing was performed in 113 patients (45%), and at least one virus was detected in 85 (75%). Antibiotic prescribing and viral testing varied substantially by clinical service.

On univariate analysis, sputum production or chest congestion were associated with higher risk of antibiotic prescribing (relative risk [RR], 2.3; 95% confidence interval [CI], 1.4 to 3.8, P < 0.001), while viral testing on day 0 was associated with lower risk of antibiotic prescribing (RR=0.4, 95% CI 0.2 to 0.8, P = 0.01), though collinearity between viral testing and clinical service limited the ability to separate these effects on prescribing. Antibiotic prescribing was not associated with subsequent URI-related healthcare visits (P = 0.89).

The authors of the study conclude, "These findings highlight the need for further research to explore the role and cost-effectiveness of molecular respiratory viral testing in limiting unnecessary antibiotic use among hematology-oncology patients."
May 16 Clin Infect Dis abstract


School procurement policy calls for beef raised on fewer antibiotics

Originally published by CIDRAP News May 16

Using a first-of-its-kind procurement policy aimed at combating antibiotic resistance, four school districts in upstate New York today awarded contracts to Slate Foods, a beef supplier that buys cattle from farms that have agreed to use practices that reduce the use of on-farm antibiotics.

The procurement policy, which was developed by four Tompkins County school districts in conjunction with the Center for Agricultural Development and Entrepreneurship (CADE) and the Cornell Cooperative Extension, specifies that vendors that bid on the school districts' beef contracts must source the beef from farmers who employ on-farm management practices that lower the risk of infection in animals. In addition, those farmers must only use antibiotics in individual animals that are sick or at high-risk of infection.

The policy is a response to concerns about routine, blanket use of antibiotics in cattle to prevent infection, a practice that is widely seen as contributing to antibiotic resistance. CADE believes the policy, if it's adopted by other school districts, could be a tool to incentivize farmers to adopt more stringent antibiotic stewardship measures than are currently required by the US Department of Agriculture and the Food and Drug Administration.

"We'd like to see school districts throughout New York State—and potentially across the nation—replicate the same food buying policy," CADE executive director Phoebe Schreiner said in a press release. "It will not only have important public health implications for our communities, it will also reward beef producers who use improved antibiotic practices. For those who don't, it offers a carrot to move in that direction."
May 16 CADE beef procurement policy 


British veterinarian group updates policy on antimicrobials in food-animals

Originally published by CIDRAP News May 15

The British Veterinary Association (BVA) has issued an updated policy position on responsible antimicrobial use in food-producing animals.

Citing a need for a collaborative One Health approach to the issue of antimicrobial resistance, the updated policy proposes 15 overarching recommendations for veterinarians, farmers, and policy makers on antimicrobial stewardship in food-animal production. It recommends that veterinarians carefully consider their use of antimicrobials in food animals, pay attention to the risk of resistance, and restrict the use of critically important antibiotics (as defined by the European Medicines Agency) to last-resort scenarios, while also urging that critically important antimicrobials be kept as a treatment option, in the interest of animal welfare.

The updated policy also calls for prioritizing development of effective diagnostic tools for animal illness, including rapid diagnostic tests; government incentives to improve husbandry and biosecurity measures on farms; farm assurance schemes that require commitment to responsible antimicrobial use; empowering farmers to work with vets to ensure the responsible use of antimicrobial on farms; and collaboration between government, veterinarians, and farmers on rational targets for reducing antimicrobial usage.

In addition, the policy reiterates that veterinarians should be guided by the BVA's seven principles on responsible antimicrobial use, which include avoiding inappropriate use and working with farmers to avoid the need for antimicrobials.

"Antimicrobial resistance is a shared problem that must be addressed by medical, veterinary, and environmental professionals collaboratively and not subject to a culture of blame," BVA president Simon Doherty said in a press release. "BVA is committed to providing continued leadership on the issue."

Doherty noted that ongoing efforts by veterinarians, farmers, and industry have already contributed to a 40% reduction in the sales of antibiotics for use in food-producing animals in the United Kingdom over the past 5 years. 
May 10 BVA policy position 
May 10 BVA press release


Inappropriate prescribing linked to adverse outcomes for seniors

Originally published by CIDRAP News May 15

A new study in the Annals of Family Medicine highlights the increased risks associated with inappropriate antibiotic prescribing in older primary care patients.

In the systematic review and meta-analysis, researchers in Singapore looked at more than 2,800 articles to find studies relating to "older persons," "primary care," and "inappropriate prescribing." After reviewing the articles, the researchers included eight studies with a total of 77,624 participants in the final analysis, pooling the adverse outcomes of potentially inappropriate prescribing (PIP) reported in the literature.

The results of the meta-analysis showed that while PIP did not affect mortality (risk ratio [RR], 0.98; 95% confidence interval [CI], 0.93 to 1.05), it was associated with increased risk of emergency room visits (RR, 1.63; 95% CI, 1.32 to 2.00), adverse drug events (RR, 1.34; 95% CI, 1.09 to 1.66), functional decline (RR, 1.53; 95% CI, 1.08 to 2.18), hospitalizations (RR, 1.25; 95% CI, 1.09 to 1.44), and health-related quality of life (standardized mean difference – 0.26; 95% CI, – 0.36 to – 0.16).

"This study demonstrated the associations between PIP and a wide range of adverse outcomes and highlighted the relevance of PIP among older persons in primary care," the authors of the study write, adding that the findings warrant further research into PIP interventions in primary care.

A previous systematic review found that one in five older patients attending primary care receive a potentially inappropriate antibiotic.
May/June Ann Fam Med study


Expanded resistance testing tied to more diagnoses of resistant TB

Originally published by CIDRAP News May 15

Chinese and Dutch researchers report today in Emerging Infectious Diseases that expanding rapid testing for drug-resistance in tuberculosis (TB) patients in two provinces was associated with a tripling of the number of patients diagnosed as having rifampin-resistant TB.

In the before-and-after study, researchers evaluated the introduction of rapid resistance testing of sputum samples by line-probe assay (LPA) for all patients given a primary diagnosis of smear-positive TB (rather than just those suspected of having rifampin-resistant TB) in two prefectures in eastern and middle China. They also evaluated LPA-based testing of cultures in smear-negative patients.

The study was part of an effort by the Chinese Ministry of Health, supported by the Bill and Melinda Gates Foundation, to expand access to diagnosis and treatment of rifampin-resistant TB. A total of 13,069 cases of rifampin-resistant TB were reported in China in 2017, but because only 14% of Chinese TB patients were tested for drug resistance, the vast majority of rifampin-resistant cases go undetected.

Analyzing data on 5,222 pulmonary TB patients in the 12-month baseline period and 4,364 in the 12-month intervention period, the researchers found that the number of smear-positive patients with rifampin-resistant TB rose from 30 in the baseline period to 97 in the intervention period, while the number of smear-negative patients with rifampin-resistant TB rose from 0 to 13, reflecting a low proportion of positive cultures. Of the 110 patients give a diagnosis of rifampin-resistant TB during the intervention period, 94 (85.5%) started second-line drug treatment, compared with 20 of 33 (60.6%) during the baseline period.

The authors of the study note that even though the intervention increased the number of patients receiving second-line treatment, 14% of patients with rifampin-resistant TB did not start second-line treatment, and treatment success remained low (50%). "This finding clearly calls for improvement of linkage into care and retention in treatment," they write.
May 15 Emerg Infect Dis study


Civica and Xellia partner to ease antibiotic shortages

Originally published by CIDRAP News May 15

Civica Rx, a nonprofit group formed in 2018 to reduce chronic shortages of generic drugs in the United States, today announced that it and Danish company Xellia Pharmaceuticals have signed an agreement for Xellia to make essential antibiotics—including vancomycin and daptomycin—for its member health systems. It added that shortages of the two drugs are affecting patient care in hospitals across the country.

In a news release, Civica said today marks its first generic drug production announcement since it was formed to tackle chronic drug shortages. It said it will partner with suppliers to deliver 14 essential generic drugs this year.

Xellia is expanding its manufacturing and sales capacity in the United States and produces its own active pharmaceutical ingredients and injectable drugs for serious and often life-threatening bacterial and fungal infections, Civica said. It said Xellia will make medications for Civica under Xellia's abbreviated new drug application and Civica labeling and new drug code.

Martin VanTrieste, president and chief executive office of Civica, thanked Xellia for its efforts to ease shortages, including those to treat infections caused by resistant bacteria. "By helping to stabilize the supply of Vancomycin and Daptomycin, we will have a direct impact on patient safety and public health by providing consistent access to antibiotics that are important treatment options in the management of difficult-to-treat and life-threatening infections," he added.

Vancomycin is an intravenous (IV) antibiotic used to treat serious infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA) that are resistant to certain other medications. Daptomycin, also administered as an IV antibiotic, is used to treat complicated skin and skin-structure infections caused by susceptible gram-positive bacteria, including MRSA. Clinicians also use it to treat bloodstream infections and infective endocarditis caused by MRSA and methicillin-susceptible S aureus.
May 15 Civica press release


MCR-1 resistance genes found in Vietnamese chickens, Tunisian camels

Originally published by CIDRAP News May 15

Two new studies to assess the presence of the resistance gene MCR-1 in food animals found high levels in chicken farms from Vietnam and that the gene is present in both tourist and meat-producing camels in Tunisia.

Both studies were published yesterday in the Journal of Global Antimicrobial Resistance. MCR-1 confers resistance to the last-resort antibiotic colistin.

In the study on chickens, researchers from Canada and Senegal examined isolates from chicken feces from Canada (Quebec), Senegal, and Vietnam for Escherichia coli resistance to colistin and for MCR-1 and MCR-2 genes in extended-spectrum beta-lactamase (ESBL)- or AmpC-producing E coli. They also looked at susceptibility patterns of the colistin-resistant E coli isolates to other clinically important antimicrobials. They tested 327 possible ESBL/AmpC-producing E coli isolates.

None of the 108 isolates from 7 farms in Canada were resistant to colistin or had the MCR-1 or MCR-2 gene. Of samples from 15 farms in Senegal, the researchers found a low prevalence (2.2% of 93 samples) of colistin resistance, with no MCR-1 or MCR-2. However, the 126 samples from 2 of 4 farms in Vietnam had a higher prevalence (8.7%) of colistin resistance, and the team found MCR-1 genes in 85% of 13 colistin-resistant isolates. Also, all of the colistin-resistant samples showed evidence of multidrug resistance.

The team concluded that the coexistence of MCR-1 and ESBL/AmpC genes and very high levels of multidrug resistance in all colistin-resistant E coli isolates from the chicken farms in Vietnam is a major concern.

In the camel study, a research team from Tunisia and France set out to examine the role of camels as reservoirs of resistant genes by analyzing fecal swabs collected from 232 camels—from tourist-riding attractions and meat-producing facilities—in Tunisia from April 2016 to July 2018. They found E coli in 70.3% of the samples and Klebsiella pneumoniae in 6.9%. One K pneumoniae and one E coli from a tourist farm had the blaCTX-M-15 gene on an IncY plasmid, and two E coli samples from a camel butchery had the blaCTX-M-15gene on an IncIl plasmid and co-location of blaCTX-M-1 and MCR-1 genes on an INcHI2 plasmid.

The authors note that the study documents ESBL-producing Enterobacteriaceae in Tunisian camels, from both the tourist and meat-producing sectors, and the first detection of MCR-1 in a meat-producing camel. "Though not alarming, this context needs specific attention to avoid that camels become a bigger reservoir of multidrug-resistant Enterobacteriaceae," they wrote.
May 14 J Glob Antimicrob Resist abstract on chickens
May 14 J Glob Antimicrob Resist abstract on camel


CARB-X to fund development of new antibiotic for MDR Acinetobacter

Originally published by CIDRAP News May 14

CARB-X announced today that it will award Swiss biopharmaceutical company Debiopharm International up to $2.1 million in funding for the development of a new class of antibiotics to treat hospital-acquired pneumonia caused by multidrug-resistant Acinetobacter baumannii.

The money will support work on Debio1454, an antibiotic that inhibits bacterial fatty acid biosynthesis in A baumannii, which has been designated as a priority pathogen by the World Health Organization. Disrupting this mechanism can weaken bacterial cell membranes and the cell wall and ultimately lead to cell death.

"Debiopharm's Debio 1454 project represents an exciting new class of antibiotics, that if successful and approved for use in patients, could save lives and be a huge step forward in the global fight against drug resistance," CARB-X executive director Kevin Outterson, JD, said in a press release.

Debiopharm, of Lausanne, Switzerland, could receive an additional $1.6 million if additional project milestones are met. It's the second grant the company has received from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator).
May 14 CARB-X press release


NIAID awards $28 million grant to develop shorter TB, MDR-TB drugs

Originally published by CIDRAP News May 13

The National Institute of Allergy and Infectious Diseases (NIAID) has awarded TB Alliance and four research institutions a grant to develop novel drugs to shorten treatment for TB, including multidrug-resistant (MDR) forms of the disease.

The 5-year Center for Excellence in Translational Research (CETR) grant, totaling up to $28.4 million by 2024, will support development of two new compounds that modulate protein synthesis and waste disposal in drug-sensitive TB and MDR-TB. TB Alliance suggests that drugs based on these compounds, in combination and with other novel medications, could reduce treatment time for all forms of TB to less than 2 months.

The current treatment regimen for drug-sensitive TB typically lasts 6 months, while MDR-TB treatment lasts from 9 months to 24 months.

The research is being carried out with the University of Chicago at Illinois, Harvard University, Johns Hopkins University, and Research Triangle Institute.

"Expanding the global portfolio of new TB drug candidates, from which we can assemble tomorrow's shorter and simpler cures, is crucial in the fight against TB," TB Alliance CEO and president Mel Spigelman, MD, said in a press release. "We are excited to advance this work with our partners and grateful for NIAID's support."
May 9 TB Alliance press release

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