Stewardship / Resistance Scan for Jun 18, 2021

News brief

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

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News Scan for Jun 18, 2021

News brief

CDC looking into TB outbreak in spinal surgery patients

The Centers for Disease Control and Prevention (CDC) said this week that it's investigating a cluster of tuberculosis (TB) infections in patients who've recently undergone spinal surgery that used a single lot of a bone repair product.

The CDC said patients who underwent spinal fusions or fracture repairs using FiberCel products from a single lot (#NMDS210011) are likely to have been exposed to Mycobacterium tuberculosis. The agency is recommending that all patients who received this product lot obtain TB treatment, even if they are asymptomatic.

The manufacturer sent a voluntary recall notice for the product on Jun 2, and as of Jun 10, all unused products in the lot have been sequestered.

The CDC said it is working with the Food and Drug Administration and with health department, hospitals, and surgical centers in the affected states to prevent further patient harm.
Jun 14 CDC notice

 

2020 excess deaths in Switzerland were mostly older people

In 2020, Switzerland's all-cause mortality saw a standardized mortality rate 8.8% higher than in 2019, with statistical significance only for men older than 70 and women older than 75, according to a study yesterday in PLOS One. Standardized mortality rates adjust for changes in the population, such as age and sex composition.

The researchers used official death data and found that 2020 had excess deaths in both crude and standardized mortality rates (8.8%). Prior to 2020, crude rates had looked relatively constant since 1980, and standardized mortality rates had decreased by a factor of about 2.5, they note.

The data also showed that men had a higher increase in mortality rates than women (10.6% vs 7.2%), but statistical significance occurred only for men over 70 years and women over 75. From 2020 to 2019, a 0.7% decrease in life expectancy was found, with men losing 9.7 months and women losing 5.3 months.

"There was an excess mortality in Switzerland in 2020, linked to the COVID-19 pandemic. However, as this excess only concerned the elderly, the resulting loss of life expectancy was restricted to a few months, bringing the mortality level back to 2015," the researchers conclude.

Overall, the country's 6.8 million population has experienced more than 650,000 COVID-19 cases and 10,500 deaths since the pandemic began, with about 7,400 of those deaths in 2020.
Jun 17 PLOS One study

 

Convalescent plasma linked with survival of COVID blood cancer patients

Convalescent blood plasma treatment was associated with a reduced risk of 30-day, all-cause mortality in hospitalized COVID-19 patients with blood cancers, according to a JAMA Oncology study yesterday.

The retrospective cohort consisted of 966 COVID-19 patients admitted to US hospitals between Mar 17, 2020, and Jan 21, 2021. All had blood cancers, with the most common type being lymphoid cancers, and 143 (14.8%) received plasma from COVID-19 survivors.

Plasma recipients were more likely to be treated with corticosteroids, tocilizumab, and/or remdesivir and less likely to be treated with hydroxychloroquine. Overall, a little over half were men (55.8%), and the mean age was 65 (all were adults).

Of the 845 patients who had absolute lymphocyte counts, 57.9% had lymphopenia, which increased to 79.1% among those who received anti-CD20 monoclonal antibodies.

During the 30-day follow-up, 223 people died of COVID-19, comprising 13.3% of the convalescent plasma group and 24.8% of the control group. The researchers found an adjusted hazard ratio (aHR) of 0.60 for convalescent plasma patients (95% confidence interval [CI], 0.37 to 0.97), which remained significant after propensity score matching (aHR, 0.52; 95% CI, 0.29 to 0.92). Among 338 patients in the intensive care unit (ICU) and 227 who needed mechanical ventilation, propensity-matched mortality risk was still lower in plasma recipients (aHRs, 0.40 and 0.32, respectively).

Convalescent plasma recipients were more likely to need higher levels of care (53.1% needed ICU admission and 31.5% required mechanical ventilatory support), and in propensity score matches, bleeding (11.2% vs 4.2%), sepsis (40.6% vs 22.4%), pulmonary complications (69.2% vs 46.2%), and congestive heart failure (7% vs less than 3.5%) were more common. The study did not note convalescent plasma antibody levels or regimen.

"Notably, despite superior survival in the convalescent plasma group, there were considerably more sepsis and respiratory complications in this group. This finding likely reflects a higher severity of SARS-CoV-2 infection rather than complications from the treatment, although this possibility cannot be entirely excluded," the researchers write.
Jun 17 JAMA Oncol study

 

Seven countries report more vaccine-derived polio cases

Seven countries—Afghanistan and six African nations—reported more polio cases this week, all involving circulating vaccine-derived poliovirus type 2 (cVDPV2), according to the latest update from the Global Polio Eradication Initiative (GPEI).

Afghanistan's latest case is from Ghanzi in the southeastern part of the country, putting its total for the year at 41.

In Africa, Burkina Faso reported two more cVDPV2 cases, one each from Dori and Banfora, which are counted in its 2020 total, which is now 65. Benin reported one case, which involves a patient from Couffo, marking the country's second case of the year.

The Democratic Republic of Congo reported one case from Sud-Ubangi province, lifting its 2021 total to eight. Ethiopia reported six new cases, four from Oromiya and one each from Tigray and the Southern Nations, Nationalities, and Peoples region, the first cases reported for 2021. In 2020, the country identified 26 cases.

Elsewhere in Africa, Niger reported one more case in Zinder, which is counted with the country's 2020 total now standing at 10. And finally, Senegal reported five cases from five different areas, bringing its 2021 total to nine.
Jun 17 GPEI update

 

Global flu stays low, mainly influenza B

In its latest update, which looked at data collected through the middle of May, the World Health Organization (WHO) said Northern Hemisphere flu activity remained below baseline, though influenza B detections involving the Victoria lineage increased slightly, especially in China.

In the Southern Hemisphere, flu remained at interseasonal levels. Elsewhere, a few detections were reported in parts of western and middle Africa and in India.

Globally, of the few respiratory samples that tested positive for flu in the middle of May, influenza B was dominant at 91%, mostly all involving the Victoria lineage. Of subtyped influenza viruses, 55% were H1N1 and 45% were H3N2.

The WHO urged people to interpret the flu surveillance trends with caution, given that COVID-19 priorities have influenced healthcare routines and public health measures may be playing a role in reducing flu transmission.
Jun 7 WHO global flu update

ASP Scan (Weekly) for Jun 18, 2021

News brief

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 also 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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