ASP Scan (Weekly) for Aug 10, 2018

Cost of antibiotic resistance
Antibiotic resistance in Australia
New antibiotic for pneumonia, skin infections
Ventilator-associated pneumonia risk factors
Autism and early antibiotic exposure
Stewardship standouts
AMR innovation competition
Phased stewardship strategy
Antibiotic use in the Amazon

Researchers estimate $2.9 billion in US resistance costs for 5 key pathogens

In a study yesterday in Antimicrobial Resistance & Infection Control, scientists estimate that the annual economic cost of five common antimicrobial-resistant (AMR) pathogens to be $0.5 billion in Thailand and $2.9 billion in the United States.

United Kingdom, Thai, and Vietnamese researchers assessed correlations between human antibiotic use and subsequent resistance, the economic cost of AMR for five key pathogens, and consumption data for antibiotic classes driving resistance in the organisms. They analyzed costs for Staphylococcus aureusEscherichia coli, Klebsiella pneumoniaeAcinetobacter baumannii, and Pseudomonas aeruginosa, using resistance rates of 0.37, 0.27, 0.35, 0.45, and 0.52, respectively.

The scientists determined that the cost of AMR associated with the consumption of one standard unit (SU) of antibiotics ranged from $0.1 for macrolides to $0.7 for quinolones, cephalosporins and broad-spectrum penicillins in Thailand. Using US data, the cost of AMR per SU of antibiotic consumed ranged from $0.1 for carbapenems to $0.6 for quinolones, cephalosporins, and broad-spectrum penicillins.

The total annual economic cost of AMR in these five pathogens was $0.5 billion and $2.9 billion in Thailand and the United States, respectively.

The authors conclude, "The economic costs of AMR per antibiotic consumed were considerable, often exceeding their purchase cost. . . . Notwithstanding their limitations, use of these estimates in economic evaluations can make better-informed policy recommendations regarding interventions that affect antimicrobial consumption and those aimed specifically at reducing the burden of AMR."
Aug 9 Antimicrob Resist Infect Control study


Australian report highlights drug-resistant gonorrhea, CPE infections

Originally published by CIDRAP News Aug 9

Neisseria gonorrhea and carbapenamase-producing Enterobacteriaceae (CPE) remain the most commonly reported organisms with resistance to critical antibiotics in Australia, according to a report yesterday by the Australian Commission on Safety and Quality in Health Care (the Commission).

The 6-month report from the National Alert System for Critical Antimicrobial Resistance (CARAlert), covering October 2017 through March 2018, found that, of 653 strains of bacteria with some type of critical antimicrobial resistance detected, azithromycin non-susceptible N gonorrhea (46.6%) were the most frequently reported, followed by CPE (36.9%), either alone or in combination with ribosomal methyltransferases (2.1%). CPE were the most frequently detected drug-resistant organisms reported in hospital patients.

"The finding that CPE remains prevalent in Australian hospitals is concerning," John Turnidge, MBBS, FRACP, senior medical advisor for the Commission's antibiotic use and resistance surveillance system, said in a press release. "This group of bacteria has the ability to cause common infections, has limited treatment options, and can have a death rate as high as 50% for blood stream infections."

While the number of azithromycin non-susceptible N gonorrhea isolates fell by 26% from the previous reporting period, the number of CPE isolates rose by 20%, from 213 to 255. A 266% increase in multidrug-resistant Shigella species was also observed.

The report also highlights two detected N gonorrhea infections that were resistant to both ceftriaxone and azithromycin, and five additional strains with high-level azithromycin resistance. Australian health officials are concerned about the potential for an outbreak of these extensively drug-resistant strains.
July 2018 CARAlert summary report 
Aug 8 Commission press release


FDA committee urges approval of antibiotic for pneumonia, skin infections

Originally published by CIDRAP News Aug 9

The Antimicrobials Drug Advisory Committee of the US Food and Drug Administration (FDA) yesterday voted in favor of approving intravenous (IV) and oral omadacycline for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP).

Omadacycline is a modernized tetracycline designed to overcome tetracycline resistance and has demonstrated activity against gram-positive and gram-negative bacterial strains. The drug was granted Qualified Infectious Disease Product Designation and Fast Track status by the FDA for the target indications of ABSSSI, CABP, and urinary tract infections.

The committee's decision was based in part on data from three completed phase 3 trials, in which IV and oral formulations of omadacycline met all FDA-designated primary and secondary outcomes for treating ABSSSI and CABP, and was generally safe and well-tolerated. Nearly 2,000 patients received the drug in those trials.

"Omadacycline has the potential to help address the urgent and growing need for new antibiotics to treat serious community-acquired infections," Michael F. Bigham, chairman and CEO of Paratek Pharmaceuticals, of Boston, said in a company press release. "With once-daily dosing and bioequivalent IV and oral formulations, omadacycline may help facilitate early discharge from the hospital or, in other cases, allow for safe and effective treatment in the outpatient setting."

The FDA is expected to make a final decision on the drug in October.
Aug 8 Paratek Pharmaceuticals press release


ESBL gut colonization seen as risk factors for drug-resistant pneumonia

Originally published by CIDRAP News Aug 9

French researchers report a significant relationship between colonization of the digestive tract with extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBLE) and subsequent ventilator-associated pneumonia (VAP) related to ESBLE, according to a study yesterday in PLoS One.

In the retrospective study, conducted from 2008 through 2011 at the University Hospital of Lille in France, researchers examined the risk factors for ESBLE-related VAP among patients in the intensive care unit. Because the spread of ESBLE infections has led to an increase in the use of carbapenems, the team wanted to determine how to better identify at-risk patients, in order to reduce the spectrum of initial antibiotic treatment. They also looked at the impact of ESBLE on the outcomes of VAP patients.

Among 410 patients with confirmed VAP, 43 (10.5%) had ESBLE VAP, 76 (19%) had polymicrobial VAP, and 189 (46%) had VAP related to multidrug-resistant bacteria. Among the patients with ESBLE VAP, 79% were previously identified as ESBLE carriers. Multivariate analysis identified prior ESBLE colonization of the digestive tract as the only independent risk factor for ESBLE VAP (odds ratio, 23; P < 0.001). While the positive prediction value of ESBLE digestive colonization was low (43.6%), the negative prediction value was excellent in predicting ESBLE VAP (97.3%).

Analysis of outcomes showed no significant differences between patients with ESBLE VAP and those with VAP caused by other bacteria in duration of mechanical ventilation (28 vs. 23 days), length of ICU stays (31 vs. 29 days), or mortality (55.8% vs. 50%).

Although the authors caution that further prospective studies are need to confirm the results, they write, "Our results suggest that patients without ESBLE colonization should probably not receive carbapenems as part of their initial empirical treatment to cover ESBLE. Such a strategy of restricting the use of carbapenems would be helpful to prevent subsequent resistance."
Aug 8 PLoS One study


Canadian study finds no link between autism, early antibiotic exposure

Originally published by CIDRAP News Aug 9

A new study in the International Journal of Epidemiology has found no clinically significant association between early life antibiotics exposure and the risk of autism spectrum disorders (ASD).

To test the hypothesis that early life changes to gut microbiota composition—potentially induced by antibiotic exposure—may impair the gut-brain axis and increase the risk of ASD, researchers at the University of Manitoba conducted a population-based cohort study that included all births identified in the Manitoba Health Insurance Registry from April 1998 through March 2016. Early exposure to antibiotics was defined as having filled one or more antibiotic prescriptions during the first year of life, and the main outcome during follow-up was ASD diagnosis.

Of the 214,834 subjects in the cohort, 94,024 (43.8%) filled an antibiotic prescription during the first year of life, and 2,965 children received an ASD diagnosis. After adjusting for covariates, antibiotic exposure was found to be associated with a slightly reduced risk of ASD (adjusted hazard ratio [HR], 0.91), but the researchers concluded that this observed association was not clinically meaningful. Secondary analyses showed no association between ASD and the number of treatment courses or cumulative duration of antibiotic exposure.

In an analysis based on a sibling-controlled design, conducted to address possible confounding due to environmental, genetic, and other familial or social factors, early life antibiotic exposure was not associated with ASD (adjusted HR, 1.03).
Aug 7 Int J Epidemiol abstract                     


IDSA names hospital stewardship standouts

Originally published by CIDRAP News Aug 7

The Infectious Diseases Society of America (IDSA) yesterday awarded its Antimicrobial Stewardship Centers of Excellence designation to 25 US hospitals.

The program, created in 2017, recognizes hospitals that have established stewardship programs that are led by infectious diseases (ID) physicians and ID-trained pharmacists and have achieved standards established by the Centers for Disease Control and Prevention. It places emphasis on a hospital's ability to implement stewardship protocols using its electronic health record system and to provide continuing stewardship education to its medical staff.

"The Centers of Excellence program recognizes institutions that share our commitment by establishing antimicrobial stewardship programs that foster optimal therapies that protect patients from dangerous antimicrobial resistant infections while safeguarding our vulnerable drug supply. IDSA is proud to partner with each of these institutions in turning the tide against antimicrobial resistance," IDSA President Paul Auwaerter, MD, MBA, said in a news release.

Among this year's recipients are Cleveland Clinic (Cleveland), Tufts Medical Center (Boston), Rush University Medical Center (Chicago), Rose Medical Center (Denver), and UCLA Health (Los Angeles).
Aug 6 IDSA news release


Competition seeks innovative AMR solutions for low-resource settings

Originally published by CIDRAP News Aug 7

A new online competition looking for innovative and creative solutions to address antimicrobial resistance (AMR) in low-resource healthcare settings has launched, with the goal of implementing the solutions in various countries around the world.

Innovate4AMR is seeking to engage student teams to design novel strategies that could help current or future healthcare professionals tackle the underuse, overuse, and misuse of antibiotics that occur in many low-resource settings. The proposed solutions should be catered to the existing AMR landscape in a given geographic area, be financially sustainable, and have the potential for real-world adoption and lasting impact.

The competition is sponsored by ReAct—Action on Antibiotic Resistance, the Innovation + Design Enabling Access (IDEA) Initiative at Johns Hopkins Bloomberg School of Public Health, and the International Federation of Medical Students' Associations.

"We hope to engage and enlist the next generation of leaders in developing innovative, scalable approaches to address the challenge of conserving existing antibiotics. Those in the healthcare sector have a particularly crucial role to play in finding new solutions," Anthony So, MD, MPA, director of the ReAct Strategic Policy Program and the IDEA Initiative, said in a press release.

Proposals are due Sep 17, and winners will be announced Oct 5. Finalist teams will attend a capacity building workshop in Geneva during World Antibiotic Awareness Week (Nov 12-18).
Aug 3 Innovate4AMR press release


Study shows benefits of phased approach for implementing stewardship

Originally published by CIDRAP News Aug 6

Researchers with a large community hospital system report that a phased approach for implementation of antibiotic stewardship programs was associated with significant clinical and financial benefits.

The study, published in the American Journal of Infection Control, describes the efforts of the Hospital Corporation of America (HCA) to implement a stewardship initiative in its network of 178 community hospitals in 20 states. The HCA Antimicrobial Management Program (AMP) was implemented in four phases—preparatory work, foundational work, clinical care optimization, and stewardship refinement—with individual facilities needing to meet goals before moving to the next phase. Surveys were distributed to the hospitals in 2010 (pre-implementation), 2015 (mid-implementation), and 2017 (post-implementation) to assess progress.  

The results or the surveys showed that stewardship activities improved in most areas of the HCA AMP initiative in 2015, with substantial improvement by 2017. Among the highlights were the increase in established stewardship programs at individual hospitals, from 82% in 2010 to 88% in 2015 and 96% in 2017. In addition, programs with physician champions increased from 73% in 2010 to 94% in 2017, prospective audit and feedback programs increased from 58% in 2010 to 83% in 2017, and tracking of antibiotic use metrics rose from 54% in 2010 to 100% in 2017. Total antibiotic cost per adjusted patient day fell by 40% from the 2010 baseline.

The authors conclude that these improvements have helped build momentum for the larger goals of better patient outcomes, reduced morbidity and mortality, prevention or slowing of the emergence of antimicrobial resistance, and reduced healthcare expenditures.
Aug 3 Am J Infect Control study


Researchers find inappropriate antimicrobial use in remote Amazon region

Originally published by CIDRAP News Aug 6

A new study in PLoS One suggests that inappropriate antibiotic use is occurring in even the remotest places.

A team of Brazilian and Spanish researchers conducted the population-based cross-sectional study among riverside dwellers in the Amazon Basin. The riverside dwellers live in isolated communities with a poor health infrastructure and limited access to urban areas. The study looked specifically at the population of the Coari municipality, located in Amazonas state in the central Amazon region, with the researchers interviewing and collecting information on antimicrobial use among 492 riverside dwellers.

The investigators found that 346 of those surveyed (70.3%) had taken at least one medication in the previous month, and 74 (21.4% of those taking a medication, 15.0% of the entire study population) used an antimicrobial. In addition, 49 of the patients taking an antimicrobial (66.2%) obtained it without a prescription, and 32.5% of the antimicrobials consumed were for a non-infectious or non-bacterial disease. Respondents reported that antimicrobials such as amoxicillin, ampicillin, and tetracycline were consumed for symptoms such as "gut inflammation," "pain," and "flu."

The researchers say the findings highlight the need for specific public health policies in the region regarding the appropriate use of antimicrobials. 
Aug 3 PLoS One study

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