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ASP Scan (Weekly) for Jun 18, 2021

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

Outpatient antibiotic durations frequently longer than needed, study finds

Nearly 40% of outpatient antibiotic prescriptions in an integrated healthcare system in Denver were longer than necessary, researchers reported yesterday in Open Forum Infectious Diseases.

The analysis of antibiotic prescribing across the ambulatory care network of Denver Health from July 2018 to June 2019 looked at prescribing linked to visits for uncomplicated infections, including acute sinusitis, acute otitis media (AOM), community-acquired pneumonia, urinary tract infections (UTIs), and skin and soft-tissue infections (SSTIs). Antibiotics prescribed for more than 5 days were considered longer than necessary.

Of the 5,331 antibiotic prescriptions included in the analysis, the duration of therapy was longer than recommended for 39%. Prescribed durations varied significantly by ambulatory care site, sex of patient, provider type, and type of infection. Urgent care centers accounted for 52.8% of longer than recommended prescriptions, followed by family medicine clinics (29%) and internal medicine clinics (11.4%). Acute sinusitis and AOM together accounted for 43.7% of longer than recommended prescriptions, while SSTIs accounted for 33.5% and UTIs 20%.

Further analysis found that advanced care practitioners (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), urgent care centers (aOR, 1.51; 95% CI, 1.20 to 1.89), and family medicine clinics (aOR, 2.24; 95% CI, 1.76 to 2.86) were independently associated with longer than recommended durations of therapy, as were prescriptions for SSTIs (aOR, 3.82; 95% CI, 2.84 to 5.14), acute sinusitis (aOR, 4.66; 95% CI, 3.41 to 6.36), and AOM (aOR, 12.41; 95% CI, 8.68 to 17.73).

The study authors say universal adherence to the recommended 5-day duration of therapy for these uncomplicated infections would have averted 6,657 antibiotic-days over the 1-year period, or 20% of the total antibiotic-days prescribed.

“These data add to recent evidence that reducing excessive durations of therapy is an essential component of outpatient antimicrobial stewardship and highlight areas of focus that may be high yield,” they wrote.
Jun 17 Open Forum Infect Dis abstract

Phase 1 trial to begin for novel antibiotic

Qpex Biopharmaceuticals of San Diego announced yesterday that it has initiated a phase 1 clinical trial for a novel antibiotic for infections caused by drug-resistant gram-negative pathogens.

The trial will evaluate the safety, tolerability, and pharmacokinetics of QPX9003, an intravenously-administered synthetic polymyxin that has shown potent activity against target pathogens, including multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa. The drug was developed in collaboration with scientists at Monash University in Australia. 

Polymyxins are considered a last-resort class of antibiotics for difficult-to-treat, resistant infections but are known to be nephrotoxic. No new polymyxins have been approved since polymyxin B and colistin became available in the late 1950s.

“QPX9003 has shown reduced toxicity compared to the currently used polymyxin B and colistin in preclinical studies,” Jian Li, PhD, a research professor at Monash University, said in a Qpex press release. “This property, coupled with greater antimicrobial potency, is expected to translate to improved effectiveness for patients with MDR gram-negative infections.”

The research that led to the development of QPX9003 was funded by a 5-year grant from the National Institutes of Health. Qpex has also received support from the Biomedical Advanced Research and Development Authority.
Jun 17 Qpex press release


Korean study details risk factors for drug-resistant organisms in COVID patients

Originally published by CIDRAP News Jun 17

Multidrug-resistant organisms (MDROs) were isolated in more than a quarter of South Korean patients with confirmed COVID-19 pneumonia and microbial culture results, with corticosteroid use identified as a significant risk factor, researchers reported yesterday in the American Journal of Infection Control.

The researchers from Soonchunhyang University College of Medicine looked at data on patients hospitalized for COVID-19 pneumonia at 1o hospitals in South Korea from February 2020 through May 2020, analyzing microbial culture results and epidemiology and risk factors for isolation of MDROs. Of the 152 patients identified with COVID-19 pneumonia, 47 had microbial culture results.

MDROs were isolated from 28% of patients with culture data (13 of 47) and 8.6% of all patients with COVID-19 pneumonia (13 of 152). The most common MDRO isolated was Stenotrophomonas maltophilia (five isolates), followed by methicillin-resistant Staphylococcus aureus (four isolates). MDROs were most commonly isolated from sputum samples. In-hospital mortality was significantly higher in patients with MDRO isolation than those without (62% vs. 15%).

All patients with MDROs received previous antibiotics. Multivariable analysis indicated that systemic corticosteroid use after COVID-19 diagnosis (adjusted odds ratio [aOR], 15.07; 95% confidence interval [CI], 2.34 to 97.01) and long-term care facility (LTCF) stay before diagnosis of COVID-19 (aOR, 6.09; 95% CI, 1.02 to 36.49) were independent risk factors for MDRO isolation.

The study authors say that while previous LTCF stay is a well-known risk factor for MDRO colonization, the finding that corticosteroid use may promote MDRO infection has great implications, since corticosteroids have been widely used in hospitalized COVID-19 patients.

“Owing to the risk of MDRO infection, corticosteroid usage should be carefully considered only for patients with indication,” they wrote.
Jun 16 Am J Infect Control study


Report finds increased use of critical class of antibiotic on UK pig farms

Originally published by CIDRAP News Jun 17

Previously unpublished data indicate use of certain medically important antibiotics more than doubled on United Kingdom pig farms from 2015 through 2019.

The data, compiled by the Agriculture and Horticulture Development Board (AHDB) and obtained under Freedom of Information laws by the Bureau of Investigative Journalism, Vet Record, and The Guardian, show that use of aminoglycosides in pigs jumped from 2.6 milligrams per kilogram of body weight in 2015 to 5.9 mg in 2019.

The news follows a report from AHDB last week showing that overall antibiotic use, along with use of highest-priority critically important antibiotics, on UK pig farms has declined significantly since 2015. Aminoglycosides are considered a critically important antibiotic by the World Health Organization.

Industry experts told the Bureau of Investigative Journalism that the increase in aminoglycoside use could be linked to the phasing out of other critically important antibiotics like colistin, and to preparations for a European Union ban on zinc oxide, which is used to treat post-weaning diarrhea in piglets. They al
so expressed concern that the ban could lead to a rise in antibiotic use on pig farms in the coming years.

“We do have great concern about losing zinc oxide because there’s a chance it will increase our antibiotic use,” a veterinarian with the Pig Health and Welfare Council told the Bureau.
Jun 17 Bureau of Investigative Journalism story
Jun 10 AHDB report


US lawmakers re-introduce the PASTEUR Act

Originally published by CIDRAP News Jun 16

US lawmakers today re-introduced a bill to reinvigorate the antibiotic development market.

Originally introduced in September 2020, the Pioneering Antimicrobial Subscriptions to End Upsurging Resistance (PASTEUR) Act would establish a subscription-style payment model for new antibiotics, under which companies that develop innovative, critically-needed antibiotics for drug-resistant infections would receive a contract from the federal government ranging from $750 million to $3 billion. In return, the drug would be made available for patients covered by federal insurance programs, and the companies would be required to support appropriate use and post-marketing studies.

The model would be fully de-linked, so companies that receive contracts would not receive income based on sales volume. The sales-based model has hindered antibiotic development because antibiotics are expensive to develop but are used for short periods of time and need to be used judiciously to maintain their effectiveness, and therefore don’t generate enough revenue for companies. Many large pharmaceutical companies have abandoned antibiotic development, while smaller companies struggle to survive.

The aim of the bipartisan legislation, which was re-introduced by Sen. Michael Bennet (D-Colo.), Sen. Todd Young (R-Ind.), Rep. Mike Doyle (D-Pa.), and Rep. Drew Ferguson (R-Ga.), is to help address the broken market for new antibiotics and ensure domestic availability when needed.

“Tens of thousands of Americans die each year from antimicrobial-resistant infections,” Rep. Doyle said in a press release. “Infectious disease experts agree that antimicrobial resistance is an urgent public health threat that requires a comprehensive, effective solution now. The PASTEUR Act will help scientists and researchers bring better antimicrobials to market, and it will help hospitals and doctors ensure these drugs are used properly.”    

Antibiotic resistance and development experts say the legislation is necessary for fixing the antibiotic pipeline and addressing the growing threat of drug-resistant infections.

“The bipartisan PASTEUR Act would establish a new avenue of federal support for the development of new antibiotics that are critically needed for patient care and public health,” the Infectious Diseases Society of America (IDSA) said in a statement. “IDSA will continue to urge Congress to advance the PASTEUR Act and the important solutions to a national health crisis that it provides.”
Jul 16 Senate press release
Jul 16 IDSA statement


WHO supports shorter regimen for drug-susceptible TB

Originally published by CIDRAP News Jun 16

The World Health Organization (WHO) said this week that, based on data from a recent phase 3 clinical trial, it will recommend a shorter treatment regimen for drug-susceptible tuberculosis (TB).

In a rapid communication intended to inform national TB programs, technical partners, and other stakeholders, the WHO said a review of Study 31 findings by members of the Guideline Development Group indicated a 4-month regimen composed of rifapentine, isoniazid, pyrazinamide, and moxifloxacin was non-inferior to the standard 6-month regimen for drug-susceptible pulmonary TB and was equally well tolerated.

The trial, which involved more than 2,500 newly-diagnosed TB patients from 13 countries, compared two 4-month regimens, one with moxifloxacin and one without, to the standard 6-month regimen. The results were published May 6 in the New England Journal of Medicine.

The 6-month regimen has been the standard for drug-susceptible TB for decades, but the TB treatment community has long sought a shorter regimen that could improve treatment adherence and reduce drug costs and adverse effects.

“The 4-month regimen, which is shorter, effective and all-oral, would be a preference for many patients and also national TB programmes, allowing faster cure and easing the burden on both patients and the healthcare system,” the WHO said, adding that the implementation and uptake of the regimen will be more feasible if the cost of rifapentine is reduced. The agency also noted that appropriate use of the regimen will need to be ensured, since moxifloxacin is usually used for treatment of drug-resistant TB.

The WHO said updated guidelines for drug-susceptible TB treatment will be released later in 2021.
Jun 14 WHO rapid communication
May 6 N Engl J Med study

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