Study estimates 522,000 excess US deaths during pandemic

An analysis of US mortality data shows all-cause mortality rose 23% in 2020, researchers reported today in JAMA.

To assess excess deaths during the pandemic, researchers from Virginia Commonwealth University School of Medicine examined provisional data from the National Center for Health Statistics and the US Census on observed deaths from COVID-19 and non-COVID causes in 49 states and the District of Columbia from Mar 1, 2020, through Jan 2, 2021. They then compared the numbers to a model that used US mortality data from 2014 through 2019 to predict expected deaths in 2020. They also looked at regional death patterns.

The analysis found that the US experienced 2,801,439 deaths from Mar 1, 2020 through Jan 2, 2021, 22.9% more than expected, representing 522,368 excess deaths. The excess death rate was higher among Black populations (208.4 deaths per 100,000) than among White or Hispanic populations (157.0 and 139.8 deaths per 100,000, respectively). The percentage of excess deaths among Black individuals exceeded their share of the US population (12.5%).

Excess deaths surged in four patterns, with New England and the Northeast seeing a surge in the spring, the Southeast and Southwest in the summer and early winter, the Plains, Rocky Mountain, and far West regions primarily in early winter, and the Great Lakes, bimodally, in the spring and early winter.

Deaths attributed to COVID-19 accounted for 72.4% of excess deaths. The analysis also revealed an increase in weekly deaths from non-COVID causes, including heart disease, Alzheimer disease/dementia, and diabetes. Those increases occurred mainly during COVID-19 surges, and the study authors suggest they could reflect either immediate or delayed mortality from undocumented COVID-19 infection or secondary impacts of the pandemic, such as delayed care or behavioral health crises.

In an accompanying editorial, Alan Garber, MD, PhD, of Harvard University says the analysis highlights not only the toll of the COVID-19 pandemic but also what happens when nations fail to anticipate and plan for infectious disease outbreaks.

"Despite the scientific, medical, and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars," he writes. "No nation should squander this opportunity to do what it takes to prepare for the next one."
Apr 2 JAMA research letter
Apr 2 JAMA editorial

Home oxygen care linked with low COVID-19 hospital readmission

Hospitalized patients with COVID-19 pneumonia who were discharged with home oxygen equipment after being clinically stable had an 8.5% readmission rate, which led to a 1.3% rate of in-hospital deaths, according to a study yesterday in JAMA Network Open. None died in ambulatory care.

The researchers followed up with 621 clinically stable adults discharged with home oxygen from Mar 20 to Aug 19, 2020, for a median of 26 days. All patients had been hospitalized in California for COVID-19 pneumonia and had received a median of 2.0 liters of oxygen per minute while in the hospital. Upon discharge, they received home oxygen equipment, educational resources, and at least one follow-up phone call within 12 to 18 hours.

Thirty-day readmission rate was 8.5%, well below the US all-cause rate for patients with Medicaid (13.7%), which insured 76% of study participants, and consistent with those privately insured (8.6%). The 1.3% mortality rate was comparable to overall in-hospital mortality for COVID-19 pneumonia patients who did not have a home oxygen regimen.

Median patient age was 51 years, most (65.1%) were male, and 84% spoke Spanish. The most commonly reported preexisting health conditions were diabetes (37.8%), high blood pressure (34.1%), and obesity (18.4%).

The authors conclude that home oxygen "may be considered part of a strategy to ensure right care, right place, and right time for patients with COVID-19 pneumonia, and to preserve acute care access during the pandemic."
Apr 1 JAMA Netw Open study

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

ReAct report lays out challenges, solutions for antibiotic access

Originally published by CIDRAP News Apr 1

A new report from antibiotic research and development (R&D) advocacy group ReAct outlines the challenges and solutions for creating a new model that will deliver sustainable access to antibiotics for all countries.

Arguing that governments around the world have so far failed to respond with either the scale or the urgency required to address rising antibiotic resistance, the decreasing effectiveness of current antibiotics, and the weak pipeline of new antibiotics, the report lays out five key challenges that governments must solve to achieve sustainable access to affordable, effective antibiotics. The model outlined considers how the entire chain of stakeholders in antibiotic development, from pharmaceutical companies to investors to governments, should work together.

The five challenges identified are setting research priorities that address the most significant and unmet global health needs; overcoming the scientific barriers in the early discovery and research phases for new antibiotics; financing late-stage clinical R&D without relying on price and sales revenues of the end-products; ensuring sustainable, environmentally appropriate production, quality, procurement, and registration of novel antibiotics; and ensuring sustainable, equitable access to new antibiotics in all countries in a manner that guarantees safe and responsible use.

Among the recommendations to address these challenges are establishment of a global entity for early-stage R&D, increasing public funding of early-stage research, fully delinking the cost of antibiotic R&D from the expectation of sales revenues, and adopting national legislation that sets antibiotic production standards.

"Today it is almost thirty-four years since the last class of antibiotics was discovered. The world cannot afford another 30 years of stalemate," ReAct founder Otto Cars, MD, PhD, a professor of infectious diseases at Sweden's Uppsala University, writes in the introduction to the report. "New ways forward must be explored and seen as an opportunity to create a system that by design serves the health needs of us all—rich and poor."
Mar 30 ReAct report

Study finds high use of topical antimicrobials in Australian nursing homes

Originally published by CIDRAP News Apr 1

A national point-prevalence survey found that topical antimicrobials are frequently prescribed in Australian nursing homes, researchers reported yesterday in the American Journal of Infection Control.

To evaluate patterns of topical antimicrobial prescribing at Australian residential aged care facilities (RACFs), a team led by researchers from the University of Melbourne extracted all data submitted by RACFs in 2018 and 2019 to the National Antimicrobial Prescribing Survey. Data included the antimicrobial selection, start date, frequency, route of administration, therapy type, and indication. Antimicrobials were classified as topical if applied to skin or mucous membranes and included drops for eyes, nose, and ears.

The results showed that 4,277 of 52,431 residents at 629 RACFs were prescribed one or more antimicrobial, for a prevalence of 8.1% (95% confidence interval [CI], 7.9% to 8.4%). Of those residents, 1,500 were prescribed a topical antimicrobial (2.9%; 95% CI, 2.7% to 3.0%). Of all prescribed antimicrobials, 33% (1,614 of 4,899) were for topical application, mainly antifungals and antibacterials. The most frequently prescribed topical antifungals were clotrimazole (85.3%) and miconazole (9.1%), and the most frequently prescribed antibacterials were chloramphenicol (64.1%) and mupirocin (21.8%). 

Tinea (38.3%) and conjunctivitis (23.8%) were the two most common indications. Topical antimicrobials were sometimes prescribed for pro re nata (as-needed) administration (38.8%) and for more than 6 months (11.3%). The review or stop date was not always documented (38.7%).

The study authors note that widespread use of mupirocin has been known to cause increased resistance rates in Staphylococcus aureus and that the widespread use of clotrimazole (86.4%) and chloramphenicol (95.1%) for tinea and conjunctivitis, respectively, is questionable. Based on their findings, they have recommended the implementation of some simple antimicrobial stewardship (AMS) practices at RACFs to improve prescribing of topical antimicrobials.

"It is recommended that those RACFs who need to develop or revise AMS policies and practices to improve topical antimicrobial use, do so using a multidisciplinary team based approach," they wrote. "Significant benefits in engaging all staff responsible for prescribing, dispensing and administration of antimicrobials is improved communication and coordination of care."
Mar 31 Am J Infect Control abstract

CARB-X to fund development of gonorrhea vaccine

Originally published by CIDRAP News Mar 30

CARB-X announced today that it is awarding the Jenner Institute at Oxford University up to $2 million to develop a novel gonorrhea vaccine.

The funding will support optimization work and scale-up of Jenner's vaccine candidate, dmGC_0817560 NOMV, which is in early development. The hope is that the vaccine will induce protective immunity against gonorrhea that will prevent individuals from developing the disease and will also interrupt the spread of antibiotic-resistant gonorrhea.

The World Health Organization (WHO) estimates that roughly 78 million people a year are infected with gonorrhea, and only one class of antibiotics remains effective in treating the disease. An estimated 550,000 gonorrhea infections in the United States and United Kingdom involve drug-resistant gonorrhea strains.

The Jenner Institute will be eligible for an additional $5.3 million from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) if certain project milestones are reached.

"Vaccines are powerful tools in the prevention of bacterial infections," CARB-X Chief of Research and Development Erin Duffy, PhD, said in a CARB-X press release. "Jenner's vaccine project is an exciting approach which, if successful, could prevent the disease, and significantly curb the spread of resistant bacteria across the globe."

Since its launch in 2016, CARB-X has announced 82 awards and committed more than $305 million to early development of new antibiotics, vaccines, therapeutics, and rapid diagnostic tests targeting antibiotic-resistant bacteria.
Mar 30 CARB-X press release

Trial suggests shorter antibiotic course for hospitalized pneumonia

Originally published by CIDRAP News Mar 29

The results of a randomized clinical trial conducted in France indicate that 3 days of beta-lactam therapy is non-inferior to 8 days of treatment in patients hospitalized with community-acquired pneumonia who meet clinical stability criteria after 3 days, French investigators reported last week in The Lancet Infectious Diseases.

The Pneumonia Short Treatment (PTC) trial was conducted in 16 hospitals in France and involved non-immunocompromised adult patients admitted to the hospital with moderately severe community-acquired pneumonia who met prespecified clinical criteria after 3 days of treatment with beta-lactam therapy. The trial participants were randomly assigned to receive either 5 days of additional beta-lactam therapy (oral amoxicillin plus clavulanate) or 5 days of placebo, with participants, clinicians, and study staff blinded to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, with a non-inferiority margin of 10 percentage points.

From December 2013 to February 2018, 310 eligible patients were assigned to receive placebo (157) or beta-lactam treatment (153). Seven patients withdrew consent before treatment started. In the intention-to-treat analysis (ITT), cure at day 15 occurred in 117 of 152 patients (77%) in the placebo group and 1o2 of 151 (68%) in the beta-lactam group (between-group difference, 9.42 percentage points; 95% confidence interval [CI], -0.38 to 20.04), indicating non-inferiority.

Results of the per protocol analysis also indicated non-inferiority, with 113 of 145 placebo patients (78%) and 100 of 146 in the beta-lactam group (68%) cured at day 15 (between-group difference, 9.44 percentage points; 95% CI, -0.15 to 20.34). Incidence of adverse events was similar in the placebo group (11%) and the beta-lactam group (19%). By day 30, 3 patients (2%) in the placebo group and 2 (1%) in the beta-lactam group died.

"These data support the concept that antibiotic therapy can be safely discontinued in patients who have moderately severe community-acquired pneumonia who have early clinical response to therapy, which could allow an important reduction in antibiotic exposure among patients being treated in hospital for community-acquired pneumonia," the authors wrote.
Mar 25 Lancet Infect Dis abstract

Report highlights R&D, access gap for pediatric drugs

Originally published by CIDRAP News Mar 29

A new report from the Access to Medicine Foundation finds significant gaps in treatments aimed specifically at children under 12, highlighted by a lack of access to a child-friendly Clostridioides difficile treatment and a dearth of drugs that address diarrheal diseases in infants in low- and middle-income countries (LMICs).

According to the report, among the five treatments that could be "game-changers" for children in LMICs is an oral suspension of fidaxomicin for C difficile-associated diarrhea in children over 6 months of age. The treatment, developed by MSD and Astellas Pharma Europe, was approved by the US Food and Drug Administration in 2o20 but does not show any evidence of an access plan that would help ensure it is accessible and affordable in all the markets where it's needed.

The report shows that of the 1,073 pharmaceutical research and development (R&D) projects assessed, less than 7% (69) target children under the age of 12 and are focused mainly on lower respiratory infections, cancer, HIV/AIDS. Only five projects target neonatal sepsis, and the pipeline for certain diarrheal infections such as Escherichia coli and cholera is completely empty, despite being identified as a priority R&D target by the WHO.

The authors of the report suggest that stakeholders can address these gaps by simplifying regulatory procedures for pediatric drugs, establishing targeted economic incentives to encourage pediatric R&D, integrating access plans into the R&D process, and increasing funding for innovative approaches to expanding access to pediatric drugs in LMICs.

"For the millions of children waiting in line for medicines that are taken for granted in high-income countries, it is not enough that a few projects are in development," the report states. "It is not enough that a few more mechanisms are in place to ensure some of these projects will reach children who need them. It is time to close the gaping disparities in access that persist."
Mar 25 Access to Medicine Foundation report

Spanish stewardship intervention linked to reduced carbapenem use

Originally published by CIDRAP News Mar 29

A multifaceted antimicrobial stewardship program (ASP) was associated with reduced carbapenem use and decreased incidence of carbapenem-resistant Acinetobacter baumannii, according to a study last week in the Journal of Antimicrobial Chemotherapy.

The quasi-experimental time-series study involved seven hospitals in Andalusia, Spain, with carbapenem use above the region's average. A team of Spanish researchers looked at carbapenem use and identification of carbapenem-resistant gram-negative bacilli (CR-GNB) from January 2014 through September 2018, comparing the 11 quarters prior to the introduction of the ASP with the 8 quarters after.

The ASP intervention had four components addressing carbapenem prescribing, with the core activity being educational interviews between stewardship teams and prescribing physicians after they prescribed carbapenems. During the intervention period, 6,046 interviews on antibiotic prescriptions were carried out, and 1,747 involved carbapenem prescriptions.

The use of carbapenems decreased throughout the study period (average quarterly percentage change [AQPC], -1.5%), with a level change of -8.170 observed following the start of the intervention. The total number of educational interviews per hospital was correlated with a decrease in carbapenem use. While the overall incidence density (ID) of CR-GNB remained stable during the study period (AQPC, -0.4%), the ID of CR-A baumannii decreased (AQPC, -3.5%). CR-GNB, CR-A baumannii, and CR-Pseudomonas aeruginosa IDs per hospital correlated with the local consumption of carbapenems.

The study authors note that the reduced consumption of carbapenems was achieved without adopting restrictive measures, using educational interventions only, and despite a shortage of piperacillin/tazobactam, which increased carbapenem use in the third quarter of 2017.
Mar 26 J Antimicrob Chemother abstract