ASP Scan (Weekly) for Feb 01, 2019

Animal stewardship partnership
Antibiotic pipeline details
New PACCARB members
Decline in UK antibiotics
Superbug bloodstream infections in Greece
Antibiotics and malaria prevention
Promising antifungal candidate
Proposed UN AMR guidance
Proposed UN AMR guidance
Antibiotic use in nursing homes
Novel antibiotic vs C diff
Pharmacist interventions
Antibiotics for asthma attack

Public-private effort launched to boost animal antimicrobial stewardship

The Foundation for Food and Agriculture Research (FFAR) this week announced a $15 million investment in the launch of the International Consortium for Antimicrobial Stewardship in Agriculture (ICASA), a public-private partnership to advance research on antimicrobial stewardship in animal agriculture and improve animal health and welfare.

ICASA was established "to accelerate innovation and improve antibiotic stewardship by building the cross-sector partnerships critical to making advances on a broad scale," FFAR said in a news release. ICASA scientists will field-test new technologies and management practices. Ultimately, the consortium aims to publish data that improve animal health and welfare and promote responsible use of antibiotics, FFAR said.

The consortium includes three of the world's largest meat companies, along with two livestock associations that together represent more than 85,000 producers. Collectively, ICASA member organizations represent about 40% of all beef cattle sold in the United States.

ICASA members are matching FFAR's initial $7.5 million investment. ICASA projects will initially focus on animal health issues that drive antimicrobial use in beef and pork. ICASA will also support cross-species projects focused on animal health and welfare monitoring, with the aim of boosting knowledge of diseases that drive antibiotic use.

"ICASA has the potential to have extraordinary impact. The collaborative framework brings together exceptional expertise and significant resources to tackle major challenges in livestock production. Working together is critical to improving animal health and welfare and preserving the efficacy of antibiotics for both animals and people," Timothy Kurt, DVM, PhD, scientific program director at FFAR, said in the release.

FFAR, based in Washington, D.C., was established in 2014 as part of the Agriculture Act (Farm Bill).
Jan 30 FFAR news release
ICASA home page


IDSA notes antibiotic development progress, concerns for future

In an update to their 2013 antibiotic pipeline status report, experts from the Infectious Diseases Society of American (IDSA) today note that the number of new antibiotics approved by the US Food and Drug Administration (FDA) has reversed its previous decline. But they worry that, if the goal of 20 new antibiotics by 2020 (20 x '20) is achieved, it could mark the pinnacle of antibiotic development for years to come, according to their paper in Clinical Infectious Diseases.

The scientists performed an in-depth review of the literature and to identify new antibiotic drug candidates in the development pipeline, as well as FDA-approved agents since 2012.

They note that the FDA approved 7 new antibiotics in 2013 through 2017, compared with 6 in 2003 through 2007 and 2 in 2008 through 2012. Altogether, they detail 16 drugs that target gram-negative organisms and 11 that target gram-positive, lower respiratory tract, or other organisms that are in phase 2 or 3 clinical trials or approved by the FDA as of Sep 18, 2018. In addition, they note that 9 intravenous antibiotics targeting gram-negative bacteria are in early clinical development.

The authors write, "Since our 2013 pipeline status report, the number of new antibiotics annually approved for marketing in the US has reversed its previous decline, likely influenced by new financial incentives and increased regulatory flexibility."

But they add, "Although our survey demonstrates progress in development of new antibacterial drugs that target infections caused by resistant bacterial pathogens, the majority of recently approved agents have been modifications of existing chemical classes of antibiotics, rather than new chemical classes." They also point out that many drug companies are abandoning antibiotics.

The IDSA experts conclude, "Unfortunately, if 20 x '20 is achieved due to efforts embarked upon in decades past, it could mark the apex of antibiotic drug development for years to come." They advocate for increased government and industry efforts and durable solutions to regulatory and financial hurdles.
Feb 1 Clin Infect Dis report


Presidential advisory council on resistance appoints new voting members

The Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria (PACCARB) announced this week that it has appointed four new voting members to serve on the council.

The new members are Paula Fedorka-Cray, PhD, MS, a professor of population health and pathobiology at North Carolina State University College of Veterinary Medicine; Christine Ginocchio, PhD, MT, vice president of global medical affairs for bioMerieux and Biofire Diagnostics; Locke Karriker, DVM, MS, professor of veterinary medicine at Iowa State University College of Veterinary Medicine; and David White, PhD, MS, associate dean for research at the University of Tennessee Institute of Agriculture. Each member was appointed to a 4-year term.

Established in 2014, PACCARB provides advice, information, and recommendations to the Assistant Secretary for Health on programs and policies that support US government activities related to antibiotic resistance. The council meets at least twice a year.
Jan 29 PACCARB announcement


UK One Health report shows declines in human, animal antibiotic use

Originally published by CIDRAP News Jan 31

The UK government today published a One Health report on antibiotic use and antibiotic resistance in animals and humans from 2013 through 2017, noting a 40% reduction of antibiotics in food-producing animals and a 9% decline in people.

Antibiotic use declined from 62 milligrams per kilogram (mg/kg) to 37 mg/kg over the study period in food animals and from 135 mg/kg to 123 mg/kg in people, for declines of 40.3% and 8.9%, respectively. In addition, the use and sales in tons of antibiotics dropped 18.5%, from 957 to 773 tons. Of those 773 tons, 491 tons were used in people and 282 tons in livestock, pets, and other animals.

Overall, 89% of highest-priority antibiotics (17 tons) were used in people. Their use increased by 8% in people and decreased by 51% in animals.

In food-producing animals, scientists detected no resistance in Escherichia coli or Salmonella isolates to colistin, and very low or no resistance to third-generation cephalosporins. There was low resistance level to fluoroquinolones for E coli and only very low resistance level for Salmonella.

In people, E coli demonstrated moderate resistance to third-generation cephalosporins and to fluoroquinolones, while E coli had low resistance and Salmonella moderate resistance to colistin.

The report is a follow-up to a 2015 UK One Health report.
Jan 31 UK report


Greek ICU study links resistant Klebsiella colonization, blood infections

Originally published by CIDRAP News Jan 31

Greek researchers report that a study of intensive care unit (ICU) patients colonized with carbapenem-resistant Klebsiella pneumoniae (CRKP) found that more than 20% developed CRKP bloodstream infections (BSIs) from their colonizing strains. The findings appear in the Journal of Medical Microbiology.

For the prospective study, which was conducted in a Greek tertiary care hospital over 39 months, researchers enrolled all adults admitted to the ICU to determine the risk factors for CRKP rectal colonization and the incidence of and risk factors for subsequent BSI. CRKP isolates from blood cultures and corresponding patient rectal specimens were screened by polymerase chain reaction (PCR) for the presence of antibiotic-resistance genes, and pulsed-field gel electrophoresis (PFGE) was conducted to investigate the clonal relatedness of the isolates. The researchers also evaluated the time from admission to colonization and BSI.

Over the study period, 226 of 498 patients (45.4%) were rectally colonized with CRKP, and 48 (21.2%) developed a CRKP BSI. The median time from admission to colonization was 8 days, and the median time from colonization to BSI was 4 days. Multivariate analysis showed that the length of ICU stay, patient/nurse ratio, and prior use of antibiotics that disturb the anaerobic flora were independent risk factors for colonization, but no specific risk factors were associated with BSIs in the colonized patients.

PCR analysis of 96 isolates (48 from blood cultures, 48 from corresponding patient rectal specimens) found that all were positive for the blaKPC2 gene and all belonged to sequence type ST-258. PFGE results showed that the BSI and rectal strains from the same patients were identical.

The authors of the study conclude, "A direct correlation between colonization and the progression to BSI was demonstrated. The early detection of asymptomatic CRKP carriers in conjunction with rigorous control measures (contact precautions, hand hygiene, and patient cohorting) and the appropriate management of antibiotic therapy are crucial to prevent the spread of CRKP stains in ICUs."
Jan 28 J Med Microbiol abstract


Study shows some benefits for adding antibiotics to malaria prevention

Originally published by CIDRAP News Jan 31

Adding azithromycin to monthly seasonal malaria chemoprevention in children in Burkina Faso and Mali didn't decrease the incidence of death or hospital admission, but it did lower rates of certain infections, researchers from the London School of Hygiene and Tropical Medicine and their partners in Africa reported yesterday in the New England Journal of Medicine.

The team explored the potential benefits of adding azithromycin to malaria prevention treatment as a way of maximizing the delivery of other health interventions after recent studies showed mass azithromycin administration had some success at lowering childhood mortality and trachoma in sub-Saharan African children.

In July 2014, the researchers randomized children ages 3 to 59 months by household to receive either azithromycin or placebo with sulfadoxine-pyrimethamine plus amodiaquine for seasonal malaria prevention. The drugs were given in four 3-day cycles for three successive seasons. Of 19,578 children, 9,735 received the added azithromycin and 9,843 received placebo.

The researchers didn't see any difference in incidence of death or hospitalization not linked to trauma or surgery, but azithromycin treatment lowered the incidence of gastrointestinal infection, upper-respiratory tract infection, and nonmalarial febrile illness by 15%, 15%, and 21%, respectively. Malaria parasitemia and adverse events were similar among the two groups.
Jan 30 N Engl J Med abstract
Aug 14, 2018, CIDRAP News story "Study: Mass antibiotic use limits but doesn't banish trachoma"


Antifungal candidate shows positive early results in phase 3 trial

Originally published by CIDRAP News Jan 31

Biotechnology company Scynexis released positive interim results yesterday from an ongoing phase 3 study evaluating the novel antifungal ibrexafungerp in patients with difficult-to-treat fungal infections.

An interim efficacy analysis of the first 20 patients treated in the FURI study, which is evaluating oral ibrexafungerp in adults with documented invasive and/or severe mucocutaneous fungal disease that has been intolerant or refractory to standard-of-care treatment, showed clinical benefits in 17 out 20 patients, with 11 patients achieving a complete or partial response and 6 a stable disease response. The drug was also well tolerated.

The company, which is based in Jersey City, N.J., says the results demonstrate the drug's ability to treat fungal infections in vulnerable patients who've failed other therapies.

"The positive results of this interim analysis reassure us of oral ibrexafungerp's clinical benefits in this difficult-to-treat patient population, warranting continued enrollment in the FURI study," Scynexis chief medical officer David Angulo, MD, said in a statement.

Ibrexafungerp is currently in development for treatment of fungal infections cause by Apergillus and Candida species, including Candida auris, and has demonstrated in vivo and in vitro activity against multidrug-resistant pathogens. The drug has been granted qualified infectious disease product (QIDP) and Fast Track designations from the US Food and Drug Administration for treatment of invasive candidiasis, invasive aspergillosis, and vulvovaginal candidiasis.
Jan 30 Scynexis press release


UN committee publishes AMR recommendations, seeks input

Originally published by CIDRAP News Jan 30

An ad hoc expert panel convened by the UN secretary-general in March 2017 yesterday published guidelines on antimicrobial resistance (AMR) and is seeking public input, the World Health Organization (WHO) announced.

The Interagency Coordination Group (IACG) on Antimicrobial Resistance has a mandate "to provide practical guidance for approaches needed to ensure sustained effective global action to address antimicrobial resistance," the WHO said. "The terms of reference for the IACG include to promote, plan and facilitate collaborative action, to align activities so gaps are closed, and resources are optimally utilized, to explore the feasibility of developing global goals and targets related to antimicrobial resistance." The report and IACG's recommendations will be submitted to the UN secretary-general in April.

The report is divided into five main areas, each with its own recommendations: (1) accelerate progress in countries, (2) innovate to secure the future, (3) collaborate for more effective action, (4) invest for a sustainable response, and (5) strengthen accountability and global governance.

The deadline for submitting feedback is Feb 19, and an email address is provided in the WHO announcement.
Jan 29 WHO announcement


ECDC launches survey of healthcare workers and antibiotics

Originally published by CIDRAP News Jan 30

Earlier this week, Public Health England (PHE) and the European Centre for Disease Prevention and Control (ECDC) launched a Europe-wide survey to gauge health worker perceptions about antibiotic use and antibiotic resistance.

"ECDC and PHE are aiming for a return of at least 10,000 responses with representation from healthcare workers, including doctors, nurses, pharmacists and hospital managers, as well as clinical scientists, physiotherapists, nursing assistants, dental/pharmacy technicians, public health teams and health students," ECDC said in a news release yesterday.

The online survey takes 5 to 10 minutes to complete and is open until Feb 14.

ECDC said the results will be used to guide communication aimed at healthcare workers and to see what, if any, gaps exist in the current education around antibiotic use.
Jan 29 ECDC press release


Study: Half of UK residents long-term care residents receive antibiotics

Originally published by CIDRAP News Jan 30

Half of all residents in long-term care (LTC) facilities received at least one antibiotic in the previous year, according to a retrospective cohort study from the United Kingdom published yesterday in the Journal of Antimicrobial Chemotherapy.

To conduct the study, researchers extracted from a national pharmacy chain database antibiotic prescriptions written for LTC residents from November 2016 to October 2017. In total they analyzed 544,796 antibiotic prescriptions dispensed for 167,002 residents in England, Northern Ireland, Scotland, and Wales.

During the study period, 56.6% of LTC residents in Northern Ireland, 53.2% in Scotland, 48.5% in England, and 45.0% in Wales received at least one antibiotic prescription. Amoxicillin, trimethoprim, nitrofurantoin, and flucloxacillin accounted for 66.4% of all antibiotic prescribing. LTC residents were frequently rates for respiratory infections, urinary tract infections, and skin infections.

"Half of the residents (52.1%) were dispensed one antibiotic drug over the 12 month period, a quarter (27.5%) were dispensed two different antibiotics, 12.9% were dispensed three, and 5.1% were dispensed four (the remaining 2.4% were dispensed between 5 and 10 different antibiotics)," the study authors wrote.

This was the largest study to examine antibiotic prescribing among LTC residents in the UK, and the authors said the information can help both clinicians and pharmacists support antibiotic stewardship efforts.
Jan 29 J Antimicrob Chemother study


Novel antibiotic cadazolid underperforms in two phase 3 C difficile trials

Originally published by CIDRAP News Jan 30

Cadazolid, a novel quinoxolidinone antibiotic developed by Actelion Pharmaceuticals, was safe and well tolerated but was shown inferior to vancomycin for the clinical cure of Clostridioidis difficile infection (CDI) in one of two identical phase 3 trials, making its future uncertain, an international team reported yesterday in The Lancet Infectious Diseases.

The study highlights the results of IMPACT 1 and IMPACT 2, two identically designed multicenter, double-blind, placebo-controlled, randomized trials. IMPACT 1 was conducted in Australia, Brazil, Canada, France, Germany, Italy, the Netherlands, Peru, Poland, Romania, Spain, and the United States. IMPACT 2 was done in Argentina, Belgium, Brazil, Canada, Chile, Croatia, Czech Republic, Greece, Hungary, Israel, Romania, Slovakia, South Korea, the United Kingdom, and the United States. Adults with mild to severe CDI were randomized 1:1 to either the same daily dosage of oral cadazolid or oral vancomycin, with a placebo disguised as the other drug.

In the intention-to-treat arm of the study, cure rates for cadazolid were 84% in IMPACT 1 and 81% in IMPACT 2, versus 85% and 86% for vancomycin, respectively. In the per-protocol patients, cure rates were 88% and 87% for cadazolid, respectively, and 92% for vancomycin in both IMPACT 1 and 2. That means the data revealed non-inferiority for cadazolid in IMPACT 1 but not in IMPACT 2. Safety and tolerability was the same for both antibiotics in both trials.

The authors concluded, "Further commercial development of cadazolid for C difficile infection is unlikely." The study was funded by Actelion.

In an accompanying commentary, Benoit Guery, MD, PhD, with the University of Lausanne in Switzerland, wrote, "IMPACT 1 and 2 do not provide a strong basis for the implementation of cadazolid in treatment of C difficile infection, but they do underline the need for strong and uniform definitions and the development of new tools to assess the response to treatment."
Jan 29 Lancet Infect Dis study
Jan 29
 Lancet Infect Dis commentary


Pooled data show pharmacists' input helpful in stewardship programs

Originally published by CIDRAP News Jan 29

A meta-analysis of 15 studies published yesterday in the Journal of Antimicrobial Chemotherapy concluded that antimicrobial stewardship programs (ASPs) involving pharmacists are effective in decreasing antibiotic prescribing and increasing guideline-adherent antibiotic prescribing by general practitioners (GPs).

For the study, Australian experts searched multiple databases for studies published up to February 2018 that met their inclusion criteria and included 15 studies that involved 18 randomized and non-randomized trials of ASPs involving pharmacists as interventionists to GPs.

Overall, researchers noted a 14% reduction in the antibiotic prescribing rate (APR) (odds ratio [OR], 0.86) and a doubling in the antibiotic prescribing adherence rate (APAR) (OR, 1.96) at 6 months median intervention follow-up. High-quality randomized trials showed an 8% decrease in APR and a 2.6-times increase in APAR. When pharmacists and GPs teamed up, ASPs were tied to a 7% lower APR and an increased APAR (OR, 1.72). Interventions involving pharmacist–infectious disease professional teams also decreased the APR (OR, 0.81) and increased the APAR (OR, 2.36).

The meta-analysis authors also noted that GP education plus prescribing feedback and group meetings were effective in both outcomes, whereas GP education, academic detailing, and workshop training were effective in APAR outcome. They add, "However, substantial heterogeneity was demonstrated."
Jan 28 J Antimicrob Chemother study


Study: No antibiotic benefits for hospital asthma exacerbation

Originally published by CIDRAP News Jan 29

Antibiotic therapy for patients hospitalized for asthma exacerbation isn't associated with better outcomes and shouldn't be routinely used in adults for that purpose, a research team based at the University of Massachusetts Medical School reported yesterday in JAMA Internal Medicine.

Though professional groups discourage empiric use of antibiotics for treating asthma exacerbation, use of the drugs is still high in the United States and other countries, they note. To see if adding them improves outcomes in hospitalized patients who also received corticosteroids, they looked at outcomes in a cohort of 19,811 patients hospitalized with asthma at 542 US acute care hospitals from January 2015 through December 2016 who received corticosteroids. Of the group, 8,788 (44%) got antibiotics in their first 2 days of hospitalization.

Compared with those who didn't get antibiotics, the group who got the drugs had significantly longer hospital stays, higher hospitalization costs, similar treatment failure rates, and higher risk of antibiotic-related diarrhea.

The team wrote that asthma exacerbation is an important cause of hospitalization and that decreasing inappropriate antibiotic use in that population fits well with the US Centers for Disease Control and Prevention's national strategy for combating antibiotic-resistant bacteria. They also emphasized that the short-term antibiotic treatment lacks effectiveness evidence and may be harmful and that more research is needed on strategies to curb antibiotic use in patients hospitalized for asthma exacerbation.
Jan 28 JAMA Intern Med abstract

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