ASP Scan (Weekly) for Apr 07, 2017

KFC cuts antibiotics
MRSA incidence in the US
Potential MDR-TB drugs
Resistant bacteria in river water
Staph aureus bacteremia
Stewardship in Israel
Hospital stewardship barriers
States' FSMA, drug resistance funds
MCR-1 in France
Russia and resistance research

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

KFC says its chicken will be free of medically important antibiotics

Kentucky Fried Chicken (KFC) has become the latest fast food chain to announce it will stop selling chicken raised with medically important antibiotics.

KFC, a subsidiary of Yum! Brands, says that by the end of 2018, all chicken bought by its 4,200 restaurants will be free of antibiotics that are also used in human medicine.

"We're constantly working to meet the changing preferences of our customers, while ensuring we deliver on the value they expect from KFC. Offering chicken raised without medically important antibiotics is the next step in that journey," Kevin Hochman, president and chief concept officer for KFC US, said in a company press release.

McDonald's made a similar pledge in 2015, and as of August 2016 said it had completed its commitment to phase out chicken raised with medically important antibiotics from its menu. Wendy's, Chik-fil-A, and Restaurant Brands International (owner of Burger King and Tim Hortons) have also committed to antibiotic-free chicken, with Chik-fil-A pledging that its chicken will be free of all antibiotics.

But Lena Brook, a food policy advocate with the Natural Resources Defense Council (NRDC), says KFC's policy will have an even wider impact on chicken production in the United States, since the company doesn't buy all the chickens in any given flock.

"This commitment from the nation's most iconic fast food chicken chain will have a major impact on the way the birds are raised in the U.S. and in the fight against the growing epidemic of drug-resistant infections," Brook said in an NRDC press release.

According to estimates, about 70% of all medically important antibiotics sold in the United States are used in poultry and livestock production. Public health officials are concerned that the widespread use of medically important antibiotics in food-producing animals is contributing to antibiotic resistance.
Apr 7 KFC press release
Apr 7 NRDC press release


Study finds wide variation in US estimates of MRSA incidence

A review of epidemiologic studies on the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States has found a wide variation in estimates and no firm evidence of significant decline, researchers report today in Antimicrobial Resistance and Infection Control.

The researchers reviewed five reports on MRSA incidence with data acquisition periods that ended on or before 2011. The reports—which came from the Emerging Infection Program (EIP), the Surveillance Network (TSN), the University Healthcare Consortium (UHC), the National Healthcare Safety Network (NHSN), and the Veterans Administration (VA) Healthcare Systems—measured different types of MRSA infections, different patient populations (including patients in military facilities, patients in acute care settings, pediatric patients, and patients in the general population), and used different data gathering methodologies. The differences made direct comparisons difficult.

Some of the reports indicated significant declines in MRSA incidence. An EIP study showed a 54.2% decrease in hospital-onset invasive MRSA at hospitals in nine diverse metropolitan areas, while a VA study showed a 43% decrease in hospital-onset MRSA bacteremia at military healthcare facilities. But another EIP study found a decrease in invasive MRSA among pediatric patients of only 2.6%, and a TSN study reported a stable rate of MRSA-related hospitalizations for pneumonia and bloodstream infections. A UHC study, meanwhile, found that MRSA infections doubled at 420 academic medical centers.

The authors say the lack of uniformity of MRSA reporting is hindering the United States' ability to formulate control strategies and shows the need for a comprehensive tracking system for MRSA and other multidrug-resistant organisms. "Without this, the difficulty achieving the 2020 MRSA reduction goal of 50% will be hindered," they write.
Apr 7 Antimicrob Resist Infect Control study


Researchers discover new class of potential drugs against resistant TB

Scientists at Rutgers University have discovered a new class of potential anti-tuberculosis (TB) drugs that kill rifampin-resistant and multidrug-resistant (MDR) Mycobacterium tuberculosis,the bacterium that causes TB, according to a study yesterday in Molecular Cell.

The researchers mapped the three-dimensional (crystal) structure of Mtb RNA polymerase (Mtb RNAP), the M tuberculosis enzyme inhibited by rifampin, a first-line TB drug and a cornerstone of treatment for decades. They also detailed the three-dimensional structure of Mtb RNAP as it binds to rifampin to help uncover what alterations in the binding site produce rifampin resistance.

In the study, the scientists report the discovery and properties of new compounds unrelated to rifampin—Na-aroyl-N-aryl-phenylalaninamides (AAPs) —that potently and selectively inhibit Mtb RNAP and kill TB bacteria. They also detailed the structures of Mtb RNAP bound to an AAP and Mtb RNAP bound to both an AAP and rifampin. These structures show that AAPs inhibit Mtb RNAP through a binding site that does not overlap the rifampin binding site and thus can inhibit rifampin-resistant Mtb RNAP and kill rifampin-resistant TB bacteria.

The results further show that AAPs, when co-administered with rifampin, produce an additive effect and can suppress resistance. Taken together, the results show that AAPs are promising compounds for TB drug development, according to a Rutgers news release.

"The structure of Mtb RNAP has been the 'Holy Grail' for TB drug discovery targeting Mtb RNAP," said lead author Richard Ebright, PhD, in the release.

"AAPs represent an entirely new class of Mtb RNAP inhibitors and are, without question, the most promising Mtb RNAP inhibitors for anti-TB drug development since rifampin," Ebright said. "We are very actively pursuing AAPs. We have synthesized and evaluated more than 600 novel AAPs and have identified AAPs with high potencies and favorable intravenous and oral pharmacokinetics." 
Apr 6 Mol Cell study
Apr 6 Rutgers news release


Spanish researchers find carbapenem-resistant bacteria in urban river

Originally published by CIDRAP News Apr 6

A Spanish study yesterday in PLoS One noted the presence of carbapenemase-producing Enterobacteriaceae (CPE) in a river ecosystem in the Barcelona metro area, the latest in a string of environmental detections of "superbugs."

Researchers collected 11 sediment and 12 water samples from the Sant Joan Despi station of the Llobregat River in Catalunya. The river receives wastewater treatment and industrial effluents along its course in the Barcelona area, but the impact of animal fecal contaminants is very low, according to the study authors.

The scientists identified eight CPE isolates of different species: Escherichia coliEnterobacter cloacaeKlebsiella pneumoniaeKlebsiella oxytoca, and Raoultella ornithinolytica. Drug-resistance enzyme included 6 KPC-2 types, 2 VIM-1, and 1 IMI-2, but no OXA-48-type. One additional strain was positive for both KPC-2 and VIM-1 enzymes.

The authors conclude, "These findings support the high dissemination potential of the carbapanemase-encoding genes and reinforce the idea that the environment is another reservoir that may play an important role in the capture, selection and dissemination of carbapenem resistance genes."
Apr 5 PLoS One study


Automated intervention aids treatment of Staph aureus bacteremia

Originally published by CIDRAP News Apr 5

An automated, pharmacist-driven intervention significantly improved adherence to quality of care standards in patients with Staphylococcus aureus bacteremia (SAB), according to a small study yesterday in Clinical Infectious Diseases.

In the retrospective, single-center experimental study conducted at The Ohio State University Wexler Medical Center, researchers set out to investigate the impact on SAB patients of an automated patient scoring tool integrated into the electronic medical record. When the tool detects S aureus DNA in the blood, it triggers an alert in the medical record that prompts hospital pharmacists to make standardized recommendations (based on the hospital's evidence-based practice guidelines) to promote adherence to SAB quality-of-care measures and encourage ID consultation.

The primary outcome of the study, which compared a 3-month pre-intervention period with a 3-month intervention period, was overall compliance with adherence to four individual quality-of-care components (infectious disease [ID] consult, repeat blood cultures, echocardiogram, and initiation of SAB-targeted antimicrobial treatment). Secondary outcomes were also analyzed.

Overall, 84 patients were included in the study (45 in the pre-intervention and 39 in the intervention group). As a whole, all four quality-of-care components were more frequently adhered to in the intervention group, with the incidence of ID consult increasing by 20% in the intervention group. In addition, all 39 patients in the intervention group had SAB-targeted antimicrobial therapy initiated, compared with 84.4% in the pre-intervention group. There were no significant differences in the number of patients from the two groups who received echocardiograms and repeat blood cultures.

In addition, there were no differences between the two groups in duration of bacteremia, length of stay, infection-related length of stay, or readmission. All-cause mortality, however, was six times higher in the pre-intervention group.

The authors of the study say the findings suggest the intervention could become an integral part of SAB treatment and an element of expanded hospital antibiotic stewardship programs.
Apr 4 Clin Infect Dis abstract 


Israeli stewardship programs lead to reduced antibiotic use in hospitals

Originally published by CIDRAP News Apr 4

A nationwide antibiotic stewardship program (ASP) in Israel led to a reduction in antibiotic use in acute and long-term care hospitals, according to research presented at the spring conference of the Society for Healthcare Epidemiology of America (SHEA).

The program, implemented in 2012 by the Israel Ministry of Health (MOH), required all general and post-acute care hospitals, along with the ambulatory care sector of the country's health maintenance organizations (HMOs), to establish ASP committees, develop treatment guidelines and methods to control prescribing, and report antibiotic consumption annually to MOH. Institutions used computerized databases to report all systemic antibiotics dispensed to patients.

The investigators calculated antibiotic consumption as defined daily doses (DDD) per 100 patient-days for the hospitals and DDD per 1,000 insured patients per day for the HMOs. In general hospitals, comparisons were reported for intensive care units (ICUs), internal medicine, and general surgery wards

Looking at dispensing data from 2012 through 2015, the investigators observed a decline in antibiotic use of 3.7 DDD/100 patient-days, with use declining by 7% in ICUs, by 11% in general surgery wards, and by 8% in internal medicine. In post-acute care hospitals, there was a decline of 3.4 DDD/100 patient-days—a 32% reduction in antibiotic use. But in the HMO outpatient settings, the data showed only a 4% decline in antibiotic use (0.3 DDD/1000 insured patients per day).

"The reporting requirement and annual feedback provided by the MOH have led to a reduction in use in acute and long-term care hospitals nationwide, but little effect as yet in the outpatient setting," the authors concluded.
SHEA spring 2017 conference 


Report notes distrust in guidelines, other barriers to stewardship

Originally published by CIDRAP News Apr 4

Pulmonary physicians and nurses cite various obstacles to promoting antimicrobial stewardship, including doctors' distrust of clinical guidelines for pulmonary infections, according to a small study yesterday in the American Journal of Infection Control.

Australian researchers conducted semi-structured interviews with 28 pulmonary physicians and nurses from two hospitals. They identified both clinical and social barriers.

The clinical barriers were differentiating pneumonia from chronic obstructive pulmonary disease (challenges often lead to overtreatment), differentiating viral from bacterial infections, and differentiating colonization from infection, which could lead to either under- or overprescribing.

Social barriers included perceptions of antibiotic resistance as not an immediate threat, a mistrust of antibiotic guidelines, and hospital hierarchies, which were said to have a significant influence on prescribing practices.

The authors said hospitals must understand these dynamics in order to implement effective antibiotic stewardship programs.
Apr 3 Am J Infect Control study


States need $100M for FSMA, $47M for antibiotic resistance, group says

Originally published by CIDRAP News Apr 4

State agencies need about $100 million for implementing the Food Safety Modernization Act (FSMA) and $47 million for antimicrobial resistance efforts, among other public health spending initiatives, according to a letter to Congress yesterday from the National Association of State Departments of Agriculture (NASDA).

NASDA, in the appropriations request for fiscal year 2018, asked for $40 million a year for produce safety, $40 million a year for disease prevention in human food, and $20 million a year disease prevention in animal food as part of FSMA steps.

"NASDA requests the committee to continue to increase funding for the state implementation activities that are required by FSMA," the letter states. "While FDA [the Food and Drug Administraion] is charged with writing the rules, significant implementation and enforcement activities under FSMA are the primary responsibilities of state agencies."

The group also advocates for $63 million for state food safety and inspection services.

"NASDA strongly supports the continuation of the National Antimicrobial Resistance Monitoring System (NARMS) presently funded at $10.8 million," the letter says, while thanking Congress for increasing NARMS funding for meat testing by $3 million in previous years. The group also called for $36 million for the National Action Plan for Combating Antibiotic Resistant Bacteria (CARB).

Other requests affecting infectious disease funding include at least $195 million for animal and plant health inspections, fully funding the National Animal Health Monitoring System (NAHMS) for antibiotic research, and $15 million for the National Animal Health Laboratory Network (NAHLN), an early warning system for emerging and foreign animal diseases.
Apr 3 NASDA letter


MCR-1 identified in French surgical patient

Originally published by CIDRAP News Apr 4

French investigators yesterday confirmed the colistin-resistance MCR-1 gene in a Klebsiella pneumoniae isolate in a man who had been hospitalized for fungal meningitis, according to a report yesterday in Emerging Infectious Diseases.

MCR-1 was first identified in China in November 2015 in Escherichia coli samples from pigs, pork products, humans. It has since been detected in more than 30 countries and is especially worrisome because it resides on small gene segments called plasmids that can transfer among different pathogens.

The newly reported patient is a 38-year-old man who had chronic granulomatous disease that was diagnosed when he was a baby. Since then, he has had several minor and major diseases and conditions that required treatment with antimicrobial drugs—but he was never prescribed colistin, a drug of last resort for resistant infections.

In April 2016 he was hospitalized for removal of a thyroid abscess, which harbored Aspergillus fumigatus. During the course of his treatment he received multiple antifungals and antibiotics.

MCR-1 was confirmed at a national lab, and the K pneumoniae isolate also harbored seven other resistance genes. The authors say the source of MCR-1 remains unknown, and screening of 39 contacts revealed no further MCR-1 samples.
Apr 3 Emerg Infect Dis report 


Russia funds FAO effort to address AMR in food, on farms

Originally published by CIDRAP News Apr 3

Russia is investing about $3.25 million in an effort led by the United Nations Food and Agriculture Organization (FAO) to promote food safety and prevent the spread of antimicrobial resistance (AMR) in food and on farms, the FAO said in a press release today.

The FAO project in Armenia, Belarus, Kazakhstan, Kyrgyzstan, and Tajikistan will assist national officials in combating resistance threats. The bulk of the funding will support steps on three broad fronts:

  • Strengthening the regulatory and legal frameworks that underpin national efforts to address AMR in agriculture and food chains, including developing national response plans
  • Building the capacity of national surveillance systems to monitor and test for AMR in food systems
  • Raising awareness among farmers, animal health and human health professionals, food safety authorities, and other constituents regarding AMR risks and how to manage them

FAO Deputy Director-General Maria Helena Semedo commended Russia for its support. "AMR is intimately connected to health, medical care, safe food production systems, and the environment," she said. "Leaving AMR unchecked would leave a dim vision of the future."
Apr 3 FAO news release

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