News Scan for Aug 27, 2021

News brief

COVID-19 infection tied to much higher clot risk than vaccination

The risk of blood clots is higher following COVID-19 infection than after vaccination, researchers based at Oxford University reported today in BMJ.

Earlier this year, a number of countries identified rare thrombocytopenia and thromboembolic events in people who had received adenovirus-based vaccines, which resulted in pauses to investigate and modifications in vaccination policy. Following these investigations, vaccine advisory groups said the benefits of vaccination, on the whole, still outweighed the risk.

To look for patterns with thrombocytopenia and thromboembolic events after vaccination, the researchers examined data from the health records of 29 million people in England who received their first dose of the AstraZeneca-Oxford vaccine or the Pfizer-BioNTech vaccine. The group included 19.6 million who got the AstraZeneca vaccine, 9.5 million who received Pfizer, and 1.8 million who tested positive for SARS-CoV-2.

After the first dose of the AstraZeneca vaccine, they found an increased risk of thrombocytopenia, venous thromboembolism, and other rare thrombotic events, and after the first Pfizer dose they identified an increased risk of arterial thromboembolism and ischemic stroke. However, they found that the risks of these conditions were much higher in people from the same population who were infected with SARS-CoV-2. They also wrote that the blood clot risk persisted for a longer period of time in people who were infected.

Julia Hippisley-Cox, MD, a study coauthor at the University of Oxford, said in an Oxford press release, "People should be aware of these increased risks after Covid-19 vaccination and seek medical attention promptly if they develop symptoms, but also be aware that the risks are considerably higher and over longer periods of time if they become infected with SARS-CoV-2."
Aug 27 BMJ study
Aug 27 Oxford press release

 

Kids with cancer have much higher risk of COVID-19 severity, study finds

One in five children with cancer and COVID-19, or 20%, experience severe illness compared with 1% to 6% in the general pediatric population, according to a Lancet Oncology study yesterday.

The researchers looked at 1,500 cancer or hematopoietic stem-cell transplantation patients 18 or younger hospitalized for COVID-19 from Apr 15, 2020, to Feb 1, 2021 (median age, 8 years). While most were in the Americas (56.7%), the cohort encompassed 45 countries. The most common cancer type was acute lymphoblastic leukemia or acute lymphoblastic lymphoma (49.1%) and then extracranial solid tumors (24.2%).

Of 1,319 patients who had 30-day follow-up, 67.4% were hospitalized and 3.8% died of COVID-related causes, compared with the 0.01% to 0.7% mortality rate among general pediatric COVID-19 infections. One in five (19.9%) of the cancer patients had severe or critical infections.

Severe or critical illness was associated with lower- or middle-income country status (odds ratio [OR], 5.8), upper-middle income country status (OR, 1.6), older age (15 to 18 years OR, 1.6), and intensive treatment (OR, 1.8). Severity was also linked with having an absolute lymphocyte count of 300 or fewer cells per cubic millimeter (cells/mm3; OR, 2.5) and absolute neutrophil count of 500 or fewer cells/mm3 (OR, 1.8), with the researchers noting that delaying myelosuppressive and lymphocyte-depleting therapy may be recommended during active COVID-19 infection.

About 56% of cancer therapies were modified among 1,092 patients, with lower likelihoods among patients in upper- or middle-income countries (OR, 0.5) or who had a primary diagnosis of other hematological issues (OR, 0.5). Higher likelihoods were tied to COVID-19 symptoms at presentation (OR, 1.8) or one or more comorbidities (OR, 1.6).

"As absolute lymphocyte count, absolute neutrophil count, and age are not significantly associated with treatment disruption in our models, our data suggest there might be opportunity to improve outcomes by tailoring treatment decisions to identified risk factors when provider decision making, rather than health system limitations, are driving disruptions," the researchers write.
Aug 26 Lancet Oncol study

 

Multistate Salmonella outbreaks now linked to specific Italian meats

The Centers for Disease Control and Prevention (CDC) said yesterday that two outbreaks of Salmonella involving 36 cases in 17 states that it first reported earlier this week are now linked to a specific brand of Italian meat.

"Epidemiologic data show that Fratelli Beretta brand prepackaged Uncured Antipasto trays may be contaminated with Salmonella and may be making people sick," the CDC said in an update. "Of the 25 people with information, 22 (88%) reported eating a variety of Italian-Style meats. Among 15 people who remembered the specific product or had shopper card records showing a purchase, 14 had Fratelli Beretta brand prepackaged Uncured Antipasto trays."

The agency reported no new cases since it first warned about the outbreak on Aug 24. As of Aug 25, the outbreak includes at least 13 people infected with Salmonella Infantis and 23 with Salmonella Typhimurium, but the true number of sick people is likely much higher than the 36 total confirmed infections. The CDC has combined the two outbreaks into one investigation.

Illness-onset dates range from May 9 to Jul 27, and California (7), Arizona (5), and Illinois (4) have reported the most cases. Twelve people have been hospitalized, but no deaths are reported.

Although no food recall has yet been announced, the CDC update says, "CDC is advising people not to eat Fratelli Beretta brand prepackaged Uncured Antipasto trays with 'best by' dates on or before February 11, 2022. This does not include Italian-style meats sliced at a deli. The investigation is ongoing to determine if additional products are linked to illness."
Aug 26 CDC update and news release
Aug 24 related
CIDRAP News scan

Stewardship / Resistance Scan for Aug 27, 2021

News brief

Study indicates stewardship helped reduce pediatric vancomycin use

A quality improvement (QI) program combining clinician education, clear and concise recommendations, and decision support was associated with a safe reduction in vancomycin use in a pediatric intensive care unit (PICU), researchers reported today in Pediatrics.

To reduce unnecessary vancomycin use in PICU patients with suspected community-acquired infections (CAIs), a multidisciplinary team at Nationwide Children's Hospital in Columbus, Ohio, developed consensus indications for empirical vancomycin use based on epidemiologic risk factors for methicillin-resistant Staphylococcus aureus (MRSA). While vancomycin is the antibiotic of choice for MRSA infections, not all patients have the same risk factors, and exposure to vancomycin can increase the risk for developing resistant bacteria.

Starting in May 2018, the indications were posted on PICU workstations, education on empiric vancomycin use was provided for medical residents, and antibiotic order sets were modified. To determine the impact of the intervention, the researchers measured the percentage of patients with suspected CAIs who received empiric vancomycin within 48 hours of admission to the PICU from May 2017 to July 2019.

A total of 1,620 PICU patients with suspected CAIs were identified during the study period. The percentage of patients who received empirical vancomycin fell from 73% during the baseline (May 2017 to April 2018) to 45% post-intervention, a 38% relative reduction. During the same period, overall vancomycin use in the PICU fell from an average of 343 to 218 days of therapy per 1,000 patient-days, or a 36% reduction. No patient not prescribed empiric vancomycin later required the addition of vancomycin or other MRSA-targeted antibiotics.

The study authors say that while they can't prove causality, the QI program was the only new intervention targeting vancomycin use in the PICU during the study period.

"A multidisciplinary QI approach with consensus empirical vancomycin indications successfully and safely reduced vancomycin use in our large academic center PICU," they write. "Validating the consensus indications in our own, local population and obtaining buy-in from front-line, critical care providers were essential to successful implementation of the indications and subsequent decreased vancomycin use."
Aug 27 Pediatrics abstract

 

UK survey looks at awareness of, and attitudes toward, drug resistance

A new survey conducted in the United Kingdom suggests some public confusion over the terms "antibiotic resistance" and "antimicrobial resistance."

The survey, by the UK Food Standards Agency (FSA) and including 2,555 residents aged 16 to 75, found that only about a fourth of respondents (26%) had heard of "antimicrobial resistance," while only 11% had heard of the "AMR" acronym. But much higher proportions were familiar with antibiotic resistance and "superbugs," with more than two thirds of respondents (69% and 70%, respectively) having heard those terms. More than half of respondents (57%) did not understand the difference between antibiotic resistance and antimicrobial resistance, while 14% said they had not heard of any of the terms.

The survey also found that public concern about antimicrobial resistance from people overusing antibiotics has declined slightly, falling from 71% in a 2019 survey to 65%. Almost two fifths of respondents (39%) said overuse of antibiotics by doctors and patients was the biggest contributor to the increase in infections caused by antibiotic-resistant bacteria, while 15% cited antibiotic use in farming as the biggest contributor, and 7% cited poor personal hygiene.

Concern about antimicrobial resistance in the food chain was lower, at 58%, but up from 55% in 2019. Respondents were less concerned about the risk of antimicrobial resistance from food imported from the European Union (51%) or produced in the United Kingdom (48%) than they were about food imported from countries outside the European Union (58%).

The authors of the survey note that international research has found similar low levels of familiarity surrounding antimicrobial resistance.
Aug 26 FSA survey

ASP Scan (Weekly) for Aug 27, 2021

News brief

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

Study indicates stewardship helped reduce pediatric vancomycin use

A quality improvement (QI) program combining clinician education, clear and concise recommendations, and decision support was associated with a safe reduction in vancomycin use in a pediatric intensive care unit (PICU), researchers reported today in Pediatrics.

To reduce unnecessary vancomycin use in PICU patients with suspected community-acquired infections (CAIs), a multidisciplinary team at Nationwide Children's Hospital in Columbus, Ohio, developed consensus indications for empirical vancomycin use based on epidemiologic risk factors for methicillin-resistant Staphylococcus aureus (MRSA). While vancomycin is the antibiotic of choice for MRSA infections, not all patients have the same risk factors, and exposure to vancomycin can increase the risk for developing resistant bacteria.

Starting in May 2018, the indications were posted on PICU workstations, education on empiric vancomycin use was provided for medical residents, and antibiotic order sets were modified. To determine the impact of the intervention, the researchers measured the percentage of patients with suspected CAIs who received empiric vancomycin within 48 hours of admission to the PICU from May 2017 to July 2019.

A total of 1,620 PICU patients with suspected CAIs were identified during the study period. The percentage of patients who received empirical vancomycin fell from 73% during the baseline (May 2017 to April 2018) to 45% post-intervention, a 38% relative reduction. During the same period, overall vancomycin use in the PICU fell from an average of 343 to 218 days of therapy per 1,000 patient-days, or a 36% reduction. No patient not prescribed empiric vancomycin later required the addition of vancomycin or other MRSA-targeted antibiotics.

The study authors say that while they can't prove causality, the QI program was the only new intervention targeting vancomycin use in the PICU during the study period.

"A multidisciplinary QI approach with consensus empirical vancomycin indications successfully and safely reduced vancomycin use in our large academic center PICU," they write. "Validating the consensus indications in our own, local population and obtaining buy-in from front-line, critical care providers were essential to successful implementation of the indications and subsequent decreased vancomycin use."
Aug 27 Pediatrics abstract

 

UK survey looks at awareness of, and attitudes toward, drug resistance

A new survey conducted in the United Kingdom suggests some public confusion over the terms "antibiotic resistance" and "antimicrobial resistance."

The survey, by the UK Food Standards Agency (FSA) and including 2,555 residents aged 16 to 75, found that only about a fourth of respondents (26%) had heard of "antimicrobial resistance," while only 11% had heard of the "AMR" acronym. But much higher proportions were familiar with antibiotic resistance and "superbugs," with more than two thirds of respondents (69% and 70%, respectively) having heard those terms. More than half of respondents (57%) did not understand the difference between antibiotic resistance and antimicrobial resistance, while 14% said they had not heard of any of the terms.

The survey also found that public concern about antimicrobial resistance from people overusing antibiotics has declined slightly, falling from 71% in a 2019 survey to 65%. Almost two fifths of respondents (39%) said overuse of antibiotics by doctors and patients was the biggest contributor to the increase in infections caused by antibiotic-resistant bacteria, while 15% cited antibiotic use in farming as the biggest contributor, and 7% cited poor personal hygiene.

Concern about antimicrobial resistance in the food chain was lower, at 58%, but up from 55% in 2019. Respondents were less concerned about the risk of antimicrobial resistance from food imported from the European Union (51%) or produced in the United Kingdom (48%) than they were about food imported from countries outside the European Union (58%).

The authors of the survey note that international research has found similar low levels of familiarity surrounding antimicrobial resistance.
Aug 26 FSA survey

 

Procalcitonin testing may reduce antibiotics for COVID pneumonia

Originally published by CIDRAP News Aug 23

Early use of a procalcitonin-guided algorithm in non-critically ill patients hospitalized with COVID-19 pneumonia reduced antimicrobial use with no adverse effects, researchers reported last week in JAC-Antimicrobial Resistance.

In a retrospective, single-site cohort study, researchers from the United Kingdom compared outcomes in two groups of patients who had confirmed or suspected COVID-19 pneumonia and were receiving antimicrobial therapy. One group had levels of procalcitonin—a biomarker for bacterial infection—measured within 72 hours of receiving antimicrobials; the other had no procalcitonin testing. The algorithm advised that procalcitonin levels of 0.25 nanograms per liter or lower were negatively predictive of a bacterial co-infection, and that antimicrobial therapy could be stopped.

The primary outcomes were duration of antimicrobial exposure and per-patient antimicrobial consumption. Secondary measures included a composite outcome of death, admission to the intensive care unit, and hospital readmission.

A total of 259 patients were included in the final analysis, 117 of whom had procalcitonin levels measured (45.2%). The patients in the procalcitonin group had lower antimicrobial exposure (mean duration, 4.4 vs 5.5 days) and consumption (mean, (6.8 vs 8.4 defined daily doses) than those who did not have procalcitonin levels measured. There were no differences in the composite safety outcome in both the unadjusted and adjusted analyses. 

"We found a moderate reduction in antimicrobial duration and consumption in patients where procalcitonin was measured within 72 h of starting antimicrobials, with no differences in adverse outcomes or length of stay," the authors wrote. "Our results suggest that it is safe to use a procalcitonin-based protocol in the antimicrobial decision-making process."

The authors add that the impact of higher or lower procalcitonin thresholds should be further investigated in larger prospective studies.
Aug 20 JAC-Antimicrob Resist study

 

Report highlights need, market potential for new antibiotics

Originally published by CIDRAP News Aug 23

A new report from the Global Antimicrobial Resistance Research and Development (AMR R&D) Hub highlights how the financial challenges of the antibiotic market will continue to hamper the development of technologies considered critical to address rising drug resistance.

To further understand how the current market for AMR-related health technologies will impact development of therapeutics and diagnostics, the Global AMR R&D Hub initiated a study to determine the priority targets and the greatest patient need for new AMR technologies over the next 20 years. The study concluded that cases of multidrug-resistant bloodstream infection (MDR BSI) will rise to 5.5 million by 2040, cases of MDR pneumonia will rise to 2.8 million, and that two new antibiotics will be needed to effectively treat these infections.

But under current market conditions, if these two antibiotics were approved in 2025, they would generate less than $200 million in sales revenue ($184 million for BSI and $127 million for pneumonia) at their market peak in 2036.

"These estimates are broadly in line with similar estimates previously carried out and confirm a now solid body of evidence—from studies and anecdotally—that antibiotic markets are unattractive investments for private companies and investors, both in absolute terms and relative to other therapeutic areas," the report states. "This situation, combined with the long development time of new drugs, signals that action is warranted increasingly urgently."

In addition, the forecast indicates a worsening access gap, in which many patients in low- and middle-income countries—where the need for new therapeutics is growing most rapidly—won't have access to these antibiotics.

The study also estimated that sales revenues for the two priority diagnostic tests identified were similarly modest, around $400 million by 2040.

In light of the findings, the report recommends national-level reform of antibiotic pricing and reimbursement, along with additional pull incentives to make antibiotic development more attractive to pharmaceutical companies and private investors. 
Aug 19 Global AMR R&D Hub report

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