ASP Scan (Weekly) for Mar 23, 2018

Contact precautions and resistance
Antimicrobial use on farms
CARB-X funds antibiotic candidate
Resistance surveillance in poor nations
MDR-TB treatment outcomes
New stewardship e-book
Sepsis, diagnostics technology
Resistant TB in Europe
Appropriate C diff testing
Fast sepsis detection

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

Study finds contact precautions did not reduce drug-resistant infections

A 9-year single-center study by Columbia University scientists published yesterday in Infection Control & Hospital Epidemiology found that decreases in multidrug-resistant organisms (MDROs) were likely not due to implementing universal contact precautions (UCPs).

The researchers analyzed data from a clinical research database from 2006 through 2014 and compared monthly MDRO rates before and after UCP implementation. They compared three intensive care units that implemented UCP with three that did not.

They determined that MDRO rates overall decreased over time, but they found no significant decrease in the trend during the UCP period compared with the baseline period for any of the three UCP units. They also found no significant difference between UCP units (6.6% decrease in MDRO rates per year) and non-UCP units (6.0% decrease per year).

The authors concluded, "The results of this 9-year study suggest that decreases in MDROs, including multidrug-resistant gram-negative bacilli, were more likely due to hospital-wide improvements in infection prevention during this period and that UCP had no detectable additional impact."
Mar 22 Infect Control Hosp Epidemiol study


Group publishes guidance for monitoring farm-level antimicrobial use

The veterinary antimicrobial stewardship network AACTING this week released experience-based guidelines detailing best practices on setting up systems for antimicrobial use (AMU) data collection, analysis, benchmarking, and reporting at the farm level.

AACTING, which is a "network on quantification of veterinary antimicrobial usage at herd level and analysis, communication and benchmarking to improve responsible usage," said in the guidance, "At the national level, data on the sales of veterinary antimicrobial products have been shown to be important for guiding and supporting general policy making decisions."

The authors add, "Monitoring antimicrobial use at farm or prescriber level, however, is much more targeted than at the national level, as it offers the ability to pinpoint 'non-prudent' or excessive AMU and can help guide farm-specific preventive or corrective actions. The information arising from farm-level AMU monitoring is critical for driving antimicrobial stewardship, i.e. the establishment and implementation of measures aimed at combatting AMR by promoting responsible AMU practices."

The guidelines not only provide support for designing or fine-tuning farm-level AMU monitoring systems, they can help sync farm-level data within and among countries, the report says.
Mar 21 AACTING guidelines
AACTING website


CARB-X funds potential antibiotic against CRE superbugs

Originally published by CIDRAP News Mar 22

In a first for a Japanese company, CARB-X, a public-private collaboration that supports companies to combat antimicrobial resistance, has awarded Shionogi, of Osaka, $4.7 million to support the development of a novel beta-lactam antibiotic with potent activity against the worrisome superbugs that produce carbapenemase, including BL/BLI-resistant carbapenem-resistant Enterobacteriaceae (CRE), CARB-X said in a news release today.

Under the award, Shionogi can receive an additional $2.4 million if it meets certain project milestones, according to CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator).

"We are very excited to welcome the first Japanese company into the Powered by CARB-X portfolio, strengthening the global fight against drug-resistant bacteria," said Kevin Outterson, JD, executive director of CARB-X. "The world urgently needs innovative approaches, like the Shionogi project, to protect us from drug-resistant bacteria."

CRE bacteria represent a significant and increasing public health threat globally, are difficult to treat because of their high levels of antibiotic resistance, and are associated with high death rates.

Since the beginning of 2017, CARB-X has announced awards projects totaling $73.9 million, plus an additional $89.0 million if project milestones are met, to accelerate the development of antibiotics, diagnostics, and other products. The new award increases CARB-X's reach to seven countries.
Mar 22 CARB-X news release


Study: Gene sequencing possible to find resistance in low-income nations

Originally published by CIDRAP News Mar 22

Genetic sequencing can be a valuable tool for the surveillance of antibiotic resistance in low-income countries, according to a study today led by World Health Organization experts published in The Lancet Infectious Diseases.

The investigators conducted population-level surveys in hospitals and clinics in Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine to evaluate the use of genetic sequencing to estimate resistance of Mycobacterium tuberculosis isolates to several common antibiotics. They analyzed isolates from 7,094 tuberculosis (TB) patients.

Overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% for the rpoB gene (rifampicin resistance), 86% for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% for pncA (pyrazinamide resistance), 85% for gyrA and gyrB combined (ofloxacin resistance), and 88% for gyrA and gyrB combined (moxifloxacin resistance).

A commentary in the same issue points out, "Studies on the real-time use of genomics in clinical settings have found whole genome sequencing-based DST [drug susceptibility testing] to be accurate, faster, and cheaper than phenotypic DST."

The commentator, Grant Hill-Cawthorne, MB BChir, PhD, from the University of Sydney, adds, "By showing that population-based surveillance in low-income settings is a reality, Zignol and colleagues have advanced our understanding of how genetic DST can be implemented in real-life scenarios." He also notes that the researchers in the new study still relied on a culture step, which is a common bottleneck in many healthcare systems, but in the coming years new technologies may help circumvent that step.
Mar 22 Lancet Infect Dis study
Mar 22 Lancet Infect Dis commentary


Alcohol misuse, HIV tied to worse outcomes with multidrug-resistant TB

Originally published by CIDRAP News Mar 22

Alcohol misuse and an HIV diagnosis were both tied to unsuccessful treatment outcomes for multidrug-resistant and extensively drug-resistant TB, according to a meta-analysis published yesterday in Scientific Reports.

The researchers included 48 studies that involved a cumulative 18,257 participants in their review. They found that the pooled relative risk (RR) of treatment failure unsuccessful outcome was higher in people living with HIV (RR, 1.41; 95% confidence interval [CI], 1.15-1.73) and in people with alcohol misuse (RR, 1.45;95% CI, 1.21-1.74). Outcomes were similar in people who had diabetes or in those who smoked.

The authors conclude, "Further research is required to understand the role of comorbidities in driving unsuccessful treatment outcomes."
Mar 21 Sci Rep study


New e-book provides global primer on antimicrobial stewardship

Originally published by CIDRAP News Mar 21

The British Society for Antimicrobial Chemotherapy (BSAC) today released a free e-book on global antimicrobial stewardship.

Antimicrobial Stewardship: From Principles to Practice, published in collaboration with the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the ESCMID Study Group for Antimicrobial Stewardship, provides an overview of antimicrobial resistance and the challenges it poses in healthcare settings around the world, a synopsis of antibiotic use and misuse, and examples of antimicrobial stewardship in various settings. In addition, it provides tools for setting up stewardship programs, resources to apply stewardship principles to a wide range of populations and clinical/care settings, and guidance on how to make the most of existing stewardship programs.

The multimedia e-book also contains links to case studies, videos, presentations, and other resources that illustrate good stewardship practices.

"We hope this book has something to offer everyone practicing in this area," editor-in-chief and BSAC President Dilip Nathwani, OBE, writes in the preface. "It aims to support health care professionals, or teams, or policy makers interested in learning about bringing the principles of stewardship to the bedside.
Mar 21 BSAC e-book (download link)


BARDA to tackle development of diagnostics, sepsis countermeasures

Originally published by CIDRAP News Mar 21

The US Biomedical Advanced Research and Development Authority (BARDA) is launching a new initiative to accelerate the development of innovative medical countermeasures against natural and man-made threats, with sepsis and pre-exposure, pre-symptomatic diagnostics as its initial targets.

In an email to colleagues, BARDA's Tyler Merkeley said the Division for Research, Innovation and Ventures (DRIVe) will "accelerate the research, development, and availability of transformative countermeasures to protect Americans from natural and international health security threats." Those threats include biological, chemical, radiological, and nuclear agents, as well as emerging infectious diseases

While sepsis and pre-exposure, pre-symptomatic diagnostics will be the initial targeted areas, the email said DRIVe will tackle additional challenges in coming years. DRIVe is looking to recruit staff over the next 60 days to support launch of the initiative.
BARDA website


TB incidence falling in Europe, but drug-resistant cases rising

Originally published by CIDRAP News Mar 20

A new surveillance report from the European Centre for Disease Prevention and Control (ECDC) shows that the TB incidence rate in Europe is declining by an average of 4.3% a year, the fastest decline in the world compared with other regions. But officials warn that it's not falling fast enough to achieve the World Health Organization (WHO) goal of TB elimination in Europe by 2050.

The report, based on data from 2016, shows that 58,994 cases of TB were reported in 30 European Union/European Economic Area countries in 2016, with decreasing notification rates observed in most countries. Of all notified TB cases in 2016, 70.4% were newly diagnosed and 71% were confirmed by culture, smear, or nucleic amplification test; 33% of all TB cases were of foreign origin, mostly in low-incidence countries.

MDR TB was reported for 3.7% of 36,071 cases, and extensively drug-resistant TB was reported for 20.1% of 984 MDR-TB cases tested for second-line drug susceptibility. Diagnosis of MDR-TB patients increased from 33% in 2011 to 73% in 2016, and treatment success for cases with drug resistance rose from 46% in 2013 to 55% in 2016.

From 2007 through 2016, TB incidence in the WHO European region, which includes 52 countries, fell from 47 to 32 cases per 100,000 population, and the TB mortality rate dropped from 6.5 deaths to 2.8 deaths per 100,00 population. Overall 26,000 TB deaths occurred in the region in 2016.

"It is not enough to 'walk' towards ending TB, as this way we would arrive too late for too many people," Zsuzsanna Jakab, PhD, WHO Regional Director for Europe, said in an ECDC press release. "We need to revamp political commitment at all levels to achieve tangible and immediate results that change and save the lives of all those people suffering from TB today and ensure a TB-free world for our children tomorrow."

Europe accounted for 3% of the 10.4 million global TB cases estimated by the WHO in 2016.  
Mar 19 ECDC 2018 TB surveillance and monitoring report 
Mar 19 ECDC press release


Electronic tool helps reduce inappropriate C difficile testing

Originally published by CIDRAP News Mar 20

New research from the University of California Irvine School Medicine indicates an electronic tool for enforcing clinically appropriate Clostridium difficile infection (CDI) testing significantly reduced inappropriate testing and rates of hospital-onset CDI.

In a research brief published yesterday in Infection Control and Hospital Epidemiology, the researchers describe a pre- and post-intervention cohort study to evaluate the impact of an automated, real-time computer physician order entry (CPOE) alert on CDI testing in adults hospitalized at a 417-bed academic hospital from April 2015 through June 2017. The CPOE alert was developed to enforce appropriate use of polymerase chain reaction–based testing, which cannot distinguish between C difficile colonization and active colitis and can result in unnecessary antibiotic treatment.

CPOE verification involves five criteria for ordering CDI testing: (1) diarrhea, (2) no alternate cause for diarrhea, (3) no laxative use within 24 hours, (4) no previous CDI test result within 7 days, and (5) age 1 year or older. Any contraindication to testing results in a "hard stop" that prompts prescribers to either exit the order or submit the name of an approving infectious diseases or gastrointestinal physician to override hospital protocol.

The results of the study showed that CDI testing in the hospital-onset period decreased 46%, from 155 tests per 10,000 patient-days pre-intervention (April 2015 through March 2016) to 84 tests per 10,000 patient-days post-intervention (June 2016 through June 2017). Testing while on laxatives decreased 69%, from 77 per 10,000 patient days to 24, and the number of CDI tests reordered within 7 days also decreased 71%, from 28 per 10,000 patient days to 8. Hospital-onset CDI rates decreased 59%, from 17 cases per 10,000 patient days to 7 cases.

"As data showing the harms of overtesting and overtreatment for CDI emerge, CPOE strategies can be an effective training tool to improve use and stewardship of diagnostic tests," the authors write.
Mar 19 Infect Control Hosp Epidemiol research brief


New assay diagnoses sepsis from a drop of blood

Originally published by CIDRAP News Mar 20

Scientists with Massachusetts General Hospital report that a test that can quickly detect sepsis from a single drop of blood showed high sensitivity and specificity in a small observational study.

In a study published yesterday in Nature Biomedical Engineering, the researchers describe the microfluidic assay, which uses a droplet of diluted blood to measure the spontaneous motility of neutrophils in the presence of plasma. Neutrophils are a type of white blood cell that lead the immune system's response to infection, and neutrophil dysfunction has long been thought to play a role in septic responses.

Previous research has shown that a sepsis-specific spontaneous motility signature displayed by neutrophils isolated from blood enabled the prediction of sepsis in patients with major burns. The researchers hypothesized that measuring neutrophil movement using whole-blood samples could amplify these behavioral changes and enable much quicker differentiation of patients with sepsis from those without.

The scientists measured the performance of the assay in two independent cohorts of critically ill patients suspected of having sepsis. Using data from a first cohort, they developed a sepsis score that segregated patients with sepsis from those without sepsis. They then validated the sepsis score in a double-blind, prospective case-control study. For the 42 patients across the two cohorts, the assay identified sepsis patients with 97% sensitivity and 98% specificity.

The authors of the study say the assay, which requires minimal handling and can be performed in less than 7 hours, will need to be validated in larger and more diverse cohorts of patients. But they suggest it could be a dramatic improvement over current diagnostic tests.
Mar 19 Nat Biomed Eng study

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