ASP Scan (Weekly) for Nov 01, 2019

NICU quality improvement
Antibiotic data comparisons
Expert opinion on resistant TB
ICU antibiotic stewardship
Sepsis diagnostics funding
UTI antibiotics in nursing homes
GARDP antibiotic-development goal
CARB-X funding for novel drugs
UK vet antibiotic sales
XDR-TB drug maker chosen
Resistant Klebsiella in Germany
New pneumonia antibiotic OK'd

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

NICU quality improvement steps tied to CDC compliance, fewer antibiotics

Neonatal intensive care units (NICUs) participating in a quality improvement (QI) collaborative increased adherence to the US Centers for Disease Control and Prevention (CDC) core elements of antibiotic stewardship dramatically and cut antibiotic use by a third, according to a study today in Pediatrics.

US scientists, including CDC researchers, analyzed data from 146 NICUs across the country who participated in a multidisciplinary initiative called Choosing Antibiotics Wisely, an Internet-based national QI collaborative consisting of interactive Web sessions, four point-prevalence audits, and expert coaching designed to help teams test and implement the CDC core elements of antibiotic stewardship. The seven CDC core elements encompass varying aspects of stewardship, such as leadership, accountability, and education. The audits tracked unit-level adherence to the core elements and antibiotic use.

Of the 146 NICUs, 122 (83.6%) participated in both study years—2016 and 2017—and 85 (69.7%) of the centers participated in all four audits.

The investigators found that the percentage of NICUs implementing the CDC core elements increased in each of the seven domains (leadership, 15.4%–68.8%; accountability, 54.5%–95%; drug expertise, 61.5%–85.1%; actions, 21.7%–72.3%; tracking, 14.7%–78%; reporting, 6.3%–17.7%; education, 32.9%–87.2%; P < .005 for all measures). And the median rate of antibiotic use decreased from 16.7% to 12.1% (P for trend < .0013), a 34% decline.

The authors conclude, "As in many collaborative QI initiatives, not all of the teams were able to achieve all of the goals (including the fact that only 9.9% of NICUs met all the CDC core elements), leaving further opportunities for improvement."
Nov 1 Pediatrics abstract


Drop in antimicrobial use seen with VA comparative data visualization tool

A study today in Clinical Infectious Diseases involving eight geographically dispersed Veterans Affairs (VA) medical centers finds that use of comparative data visualization tools by antibiotic stewards in a pilot implementation project was associated with significant reductions in overall antimicrobial and anti-pseudomonal use compared with uninvolved facilities.

In the pilot program, antibiotic stewards from the eight hospitals used the visualization tools, which consisted of an interactive web-based antimicrobial dashboard and, later, a standardized antimicrobial usage report updated at user-selected intervals. Following tool implementation, stewards participated in monthly learning collaboratives. VA researchers then compared outcomes at the eight facilities compared with other VA hospitals nationwide.

They determined that intervention sites demonstrated a 2.1% decrease (95% confidence interval [CI], -5.7% to 1.6%) in total antimicrobial use, versus a 2.5% increase (95% CI, 0.8% to 4.1%) in non-intervention sites (absolute difference, 4.6 percentage points; P = 0.025). Anti-pseudomonal antimicrobial use decreased 3.4% (95% CI, -8.2% to 1.7%) at intervention sites, versus a 3.4% increase (95% CI, 0.8% to 6.5%) at non-intervention sites (absolute difference, 7.0 percentage points; P = 0.018). Antimicrobial use against methicillin-resistant Staphylococcus aureus declined 11.3% (95% CI, -16.0% to -6.3%) at intervention sites, versus a 6.6% drop (95% CI, -9.1% to -3.9%) at non-intervention sites (absolute difference, 4.7 percentage points; P = 0.092).

The authors conclude, "While we cannot directly attribute the decreases in antimicrobial use to stewards' use of the antimicrobial graphic tools, we hypothesize that the overall implementation strategy and follow-up served to activate stewards to pursue interventions that focused on the particular needs of their facilities."

In a commentary on the study in the same issue, Payal Patel, MD, MPH, with the University of Michigan, said, "Large collaboratives and healthcare systems can outline a common antimicrobial stewardship target, but tailored interventions to arrive at that goal will help complement the needs and strengths of individual facilities."
Nov 1 Clin Infect Dis study
Nov 1 Clin Infect Dis commentary


WHO Europe issues expert opinion on drug-resistant TB in kids, teens

The World Health Organization's (WHO's) European office released an evidence-based expert opinion on managing drug-resistant tuberculosis (DR-TB) in children and adolescents, recommending the use of bedaquiline if necessary in those 6 years and older.

Dr Masoud Dara, the coordinator of communicable diseases with WHO Europe, said in a news release yesterday, "In public health terms, this is an important step towards addressing a future reservoir of DR-TB that could prolong the epidemic. From a human perspective, these are children robbed of significant parts of their childhood by a severe disease."

In addition to the bedaquiline advice, the expert opinion, published as a commentary in The Lancet Child & Adolescent Health, also recommends delamanid, another fairly new DR-TB drug, for children 3 years old and older.

WHO Europe estimates that 2,000 children under age 15 in the WHO European Region who have TB remain undiagnosed each year, and the figure is likely higher in older teens. Of those infected, the agency said, 14% have "especially dangerous and hard-to-treat forms of TB," which raises the risk that those who are undiagnosed with DR-TB will unknowingly spread the disease.

The agency said in the release that the guidance "will act as a cornerstone of WHO/Europe's efforts to end TB for everyone including children and adolescents."
Oct 31 WHO Europe news release
Oct 29 Lancet Child Adolesc Health commentary


ICU stewardship program tied to drop in antibiotics, bloodstream infection

Originally published by CIDRAP News Oct 31

An interrupted time series analysis conducted in two Italian intensive care units (ICUs) demonstrated a substantial reduction in antibiotic consumption and bloodstream infections (BSIs) caused by multidrug-resistant (MDR) gram-negative bacteria after the teaching hospital instituted an antimicrobial stewardship (AMS) program, with no change in mortality or length of stay, according to a study yesterday in Clinical Microbiology and Infection.

The analysis spanned January 2017 through 2018 to assess the effects of prospective audit and feedback in the ICUs. Primary outcomes were differences in antibiotic consumption and the incidence of BSIs caused by MDR organisms, while secondary outcomes included mortality rate, mean length of stay, and antibiotic expense.

During the study, hospital staff performed 231 audits that evaluated 693 antibiotic prescriptions. The AMS program was tied to a global reduction in antibiotic consumption, with an overall drop of 324.8 daily defined doses (DDD) per 100 patient-days (PD; P = 0.04), particularly in the use of fluoroquinolone (-63.5 DDD/100 PD, P < 0.001). The authors noted non-significant declines of carbapenems and third- and fourth-generation cephalosporins.

In addition, they noted a drop of 5.8 events of BSI/100 PD (P = 0.026) and in BSI caused by gram-negative MDR bacteria (-2.96 events/100 PD, P = 0.043). The researchers observed no change in hospital mortality or length of stay.
Oct 30 Clin Microbiol Infect abstract


BARDA funds development of rapid sepsis test, digital diagnostic tool

Originally published by CIDRAP News Oct 31

The Biomedical Advanced Research and Development Authority (BARDA) announced that it will provide Cytovale of San Francisco an initial $3.4 million, with an option for an additional $4.17 million, to advance development of the company's sepsis test, which may be able to diagnose the blood infection in less than 10 minutes.

"We need faster diagnostics to reduce the health burden of sepsis in our country and save lives," said BARDA Director Rick Bright, PhD. "Like so many threats, speed of diagnosis is critical to improving outcomes for sepsis patients. Through this and other projects, our Solving Sepsis program continues to focus on catalyzing technology to address sepsis."

According to the CDC, sepsis kills about 270,000 Americans annually. Sepsis occurs during a faulty immune response to an infection, and can cause tissue damage, organ failure, and even death.

Earlier this week, BARDA also announced it will provide Beckman Coulter Diagnostics, of Brea, California, with an initial $1.25 million, with an option for an additional $6.5 million, to develop a machine-learning algorithm-based diagnostic for sepsis.

According to Beckman Coulter, the digital diagnostic tool combines clinical data from laboratory tests and patient data from electronic health records to create a predictive machine-learning algorithm expected to more accurately detect sepsis in clinical settings.

Both Cytovale's and Beckman Coulter's projects are part of BARDA DRIVe's Solving Sepsis program, which aims to reduce the incidence, morbidity, mortality, and cost associated with sepsis. BARDA operates under the US Department of Health and Human Services's Office of the Assistant Secretary for Preparedness and Response.
Oct 29 BARDA press releases 


Study notes UTI antibiotic prescribing problems in Aussie nursing homes

Originally published by CIDRAP News Oct 31

An antimicrobial prescribing survey of Australian nursing homes found that antibiotics for urinary tract infection (UTIs) often didn't follow guidelines, researchers reported yesterday in the American Journal of Infection Control.

The analysis is based on data from the country's Aged Care National Antimicrobial Prescribing Survey, which has been collecting data since 2015. For the study, the team looked at 2016 and 2017 survey data, comparing antibiotic prescribing for UTIs with national guidelines. The study included 662 antibiotic prescriptions from 247 nursing homes.

For all prophylactic antibiotics for UTIs, 51.8% were prescribed for longer than 6 months, which doesn't follow guidelines.

Most (71.6%) of the antibiotics that doctors prescribed were for cystitis. Cefalexin was most frequently prescribed for the condition, but only 10.4% aligned with recommendations. Prescribing extra daily doses of the drug occurred in 63.2% of the prescriptions.

Researchers said the longer duration findings suggest that many nursing home residents aren't reviewed and tested without antibiotic prophylaxis as often as they should be; however, they note that the study couldn't assess the clinical appropriateness of starting prophylactic therapy, a topic that would be worthy of more detailed study.

They said the reasons for prescribing extra doses of cefalexin for cystitis is unclear, but factors may include that clinicians often prescribe it for other indications, including skin and soft-tissue infections, they may be confused about the higher number of doses recommended for pyelonephritis and lower number recommended for cystitis, or they may believe extra doses are needed for nursing home residents.

Researchers concluded that antimicrobial stewardship activities that target UTI prophylaxis for longer than 6 months and excessive use of cefalexin for cystitis could significantly reduce unnecessary antibiotic prescribing in Australian nursing home residents.
Oct 30 Am J Infect Control abstract


GARDP launches '5 by 25' antibiotic delivery plan

Originally published by CIDRAP News Oct 30

The Global Antibiotic Research and Development Partnership (GARDP) unveiled a new strategy to deliver five new treatments by 2025 to address the burden of antibiotic-resistant infections in populations disproportionally affected by drug-resistance.

The plan, released at the World Health Summit earlier this week, lays out GARDP's commitment to developing new and improved antibiotics for serious and potentially life-threatening infections in hospitalized adults, neonatal sepsis and pediatric infections, sexually transmitted infections, and infections caused by WHO priority pathogens. The nonprofit organization says it will achieve this goal by working with public and private sector partners and focusing on treatments in late-stage clinical development. The plan also ensures responsible and sustainable access to these treatments.

GARDP, which to date has formed more than 50 partnerships in 20 countries, is asking governments, philanthropic groups, and other global organizations to contribute €500 million ($557 million US) to the effort.

"WHO is one of the co-founders supporting GARDP in building a pipeline of innovative treatments to address antibiotic resistant infections and make these treatments available to all," WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said in a GARDP press release. "I call on governments, foundations and other donors to engage and help GARDP in achieving its aim to develop five new treatments by 2025."
Oct 28 GARDP press release
Oct 28 GARDP 5x25 strategy


CARB-X announces funding for new drugs targeting Staph aureus

Originally published by CIDRAP News Oct 29

CARB-X announced today funding of up to $4.98 million for BioVersys's new small-molecule drugs targeting Staphylococcus aureus bacteria, including methicillin-resistant S aureus. The drugs could be used as a stand-alone to treat uncomplicated skin and skin-structure infections, as well as in combination with other antibiotics for more severe infections.

According to CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), BioVersys's candidate biologicals are a new type of drug that acts not as a direct antibiotic—instead, the small molecules are able to disarm Staphylococcus aureus bacteria of virulence factors. BioVersys will receive $3.94 million in non-dilutive funding for the drugs, the BV200 series molecules, with a possibility of up to $4.98 million if certain milestones are met.

"Drug-resistant bacteria represent one of the greatest threats to public health globally. New approaches, like the BioVersys' project, are urgently needed to help save lives and to curb the spread of drug-resistant bacteria," said Kevin Outterson, executive director of CARB-X, in a press release. "This project is in early stages of development but if successful and approved for use in patients."

Since its inception in 2016, CARB-X has announced 49 awards exceeding $155 million, to develop antibacterial products. Through 2021, CARB-X plans to invest $500 million into the research and development of novel antibacterial products.
Oct 29 CARB-X 
press release


UK veterinary antibiotic sales cut in half since 2014, report shows

Originally published by CIDRAP News Oct 29

A report today from the United Kingdom's Veterinary Medicines Directorate highlights the steep reductions in antibiotic use by UK livestock producers in recent years.

The 2018 UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS) shows a 53% reduction in overall sales of antibiotics for food-producing animals since 2014 (measured in milligrams per kilogram), along with a 68% reduction in highest-priority critically important antibiotics (HP-CIAs). Data on antibiotic usage (the amount of antibiotics purchased, prescribed, and/or administered per sector) show significant reductions among pigs, chickens, turkeys, ducks, and dairy cows.

Data on antibiotic resistance in food-producing animals is also encouraging, showing further reductions and less resistance among indicator Escherichia coli bacteria from poultry examined at slaughter. In addition, a high percentage of Salmonella isolates (76% of 4,414) from pigs, turkeys, chickens, cattle, and sheep were susceptible to all antibiotics tested, with data showing an increase in susceptibility since 2016.

Writing in a foreword to the report, Peter Borriello, PhD, chief executive officer of the Veterinary Medicines Directorate, calls the antibiotic sales reductions "a remarkable achievement" and says future UK-VARSS reports will include data on companion animal antibiotic sales data, more detailed analysis of susceptibility in a range of animal pathogens, and data on vaccine uptake.  
Oct 29 UK-VARSS 2018 report


TB Alliance picks Indian firm to manufacture, commercialize pretomanid

Originally published by CIDRAP News Oct 28

Nonprofit drug developer TB Alliance announced today that it will partner with an Indian company to manufacture and commercialize pretomanid for treating extensively drug-resistant tuberculosis (XDR-TB).

TB Alliance is granting Macleods Pharmaceuticals Limited of Mumbai a non-exclusive license to manufacture pretomanid, which was approved by the US Food and Drug Administration (FDA) in August as part of a three-drug, 6-month regimen for treatment of patients who have XDR-TB. The all-oral regimen, known as BPaL (bedaquiline, pretomanid, and linezolid), is significantly shorter than current treatment regimens for XDR-TB, which last 18 to 24 months.

"TB Alliance is committed to ensuring an affordable, sustainable and competitive market for all our new TB products," Mel Spigelman, MD, president and CEO of TB Alliance, said in a press release. "We are proud to partner with Macleods, which has a strong record of delivering high-quality, affordable tuberculosis medicines."

Pending approval from other regulatory agencies, Macleods will make pretomanid available in about 140 countries and territories. 
Oct 28 TB Alliance press release


Germany reports outbreak of carbapenem-resistant Klebsiella

Originally published by CIDRAP News Oct 28

At least 17 patients at three German hospitals and a rehabilitation clinic have been infected with carbapenemase-producing (with resistance genes NDM-1 and OXA-48) and colistin-resistant Klebsiella pneumoniae ST307, according to a risk assessment today from the European Centre for Disease Prevention and Control (ECDC).

The outbreak is taking place in Mecklenburg-West Pomerania in northeast Germany. As of Oct 21, 6 of the 17 patients presented with clinical symptoms, while 11 were identified as carriers, the ECDC said.

"This is the first reported outbreak in Germany of K. pneumoniae that produce both NDM-1 and OXA-48 while also involving the emerging clone ST307," the ECDC said. The outbreak strain is closely related to the same carbapenemases detected earlier this year in Finland from a patient previously hospitalized in Russia, but there is no epidemiologic link between the Finnish case and the outbreak in Germany. 

The ECDC said the risk to individuals outside healthcare settings is low, but the strain shows markers of increased virulence. Officials warned that not all European countries have effective screening systems in place for carbapenemase-producing Enterobacteriaceae, adding that German hospitals have put in place enhanced control measures. 
Oct 28 ECDC risk assessment


FDA approves Baxdela for community-acquired pneumonia

Originally published by CIDRAP News Oct 28

The FDA has approved the supplemental New Drug Application (sNDA) for Baxdela (delafloxicin) for the treatment of community-acquired bacterial pneumonia (CABP), drug maker Melinta Therapeutics, Inc., announced last week, but its launch for that indication will be delayed.

FDA approval was based on the results of a phase 3 clinical trial that found that intravenous (IV)-to-oral Baxdela was noninferior to IV-to-oral moxifloxacin in early clinical response at 96 hours after initiation of therapy (88.9% vs 89%) and success at test of cure visit (90.5% vs 89.7%). Data also showed that Baxdela successfully eradicated key pathogens at rates comparable to moxifloxacin, and it was well-tolerated by study participants.

Baxdela was initially approved by the FDA in 2017 for use in patients with acute bacterial skin and skin-structure infections.

But Melinta, of Morristown, New Jersey, also said the commercial launch of Baxdela for CABP will be delayed because of the company's financial troubles. 

"As previously disclosed, we are closely managing our liquidity position and continue to evaluate our potential strategic and other alternatives," interim CEO Jennifer Sanfilippo, JD, said in a press release. "As such, while we believe that Baxdela will play a significant role in the treatment of this potentially life-threatening illness, we are delaying the commercial launch of CABP until we have greater insight into our ability to secure additional sources of liquidity."
Oct 24 Melinta press release

Newsletter Sign-up

Get CIDRAP news and other free newsletters.

Sign up now»


Unrestricted financial support provided by

Bentson Foundation Gilead 
Grant support for ASP provided by


  Become an underwriter»