FDA addresses accuracy concerns with rapid COVID-19 test

The US Food and Drug Administration (FDA) says it's working with Abbott Laboratories to address potential false-negative results provided by the company's rapid coronavirus test.

In a news release yesterday, the FDA said it's evaluating the information about inaccurate results reported for the Abbott ID NOW COVID-19 assay, which can provide results within 5 to 13 minutes. A preprint study published earlier this week found that the test missed between 33% and 48% of positive coronavirus samples at a New York City hospital. The FDA has also received 15 reports of adverse event related to false-negative test results.

"We will continue to study the data available and are working with the company to create additional mechanisms for studying the test. This test can still be used and can correctly identify many positive cases in minutes. Negative results may need to be confirmed with a high-sensitivity authorized molecular test," said Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA's Center for Devices and Radiological Health.

Abbott, in a company press release, said the results of the study conducted at New York University Langone Tisch Hospital are not consistent with other studies, and could reflect the test being used in ways it was not designed to be used. While the study evaluated some test results using nasopharyngeal samples transported in viral transport media, the company says the test is meant to be used with dry nasal swabs obtained at the point of care.

The FDA issued an Emergency Use Authorization for the Abbott ID NOW test on Mar 27, and since then it has been shipped to all 50 states. The system is also used by the White House to test staff members.

The FDA said it will continue to monitor interim data. Abbott has agreed to conduct post-market studies that will include at least 150 patients in a variety of clinical settings.
May 14 FDA press release
May 14 Abbott Laboratories press release

Stay-at-home order in Iowa may have slowed COVID-19 spread

A study today in JAMA Network Open looks at COVID-19 cases in border counties in Iowa, which never issued a stay-at-home order, and Illinois, which did so on Mar 21. The authors say the evidence indicates that a stay-at-home order in Iowa would have eliminated as many as 217 excess cases in the state within a month.

The cross-sectional study compared daily changes in COVID-19 cases per 10,000 residents in 8 Iowa counties bordering Illinois, to those in the 7 Illinois counties bordering Iowa before and after Illinois issued a stay-at-home order. The total population (based on 2019 census estimates) in the Iowa border counties was 462,445, compared with 272,385 in the Illinois border counties.

The authors noted that, from Mar 15 to Mar 21, when the stay-at-home order became effective in Illinoi), the average daily cases per 10,000 residents was 0.024 in the Iowa counties and 0.026 in the Illinois counties.

Within 10, 20, and 30 days after the enactment of the stay-at home order in Illinois, however, the difference in cases was −0.51 per 10 000 residents on day 10, −1.15 per 10,000 residents on day 20, and −4.71 per 10,000 residents on day 30, reflecting the decrease per population in Illinois compared with Iowa.

"The estimates indicate excess cases in the border Iowa counties by as many as 217 after 1 month without a stay-at-home order," the authors wrote. "This estimate of excess cases represents 30.4% of the 716 total cases in those Iowa counties by that date."

Iowa was one of only five US states to never issues a stay-at-home order, though school, restaurants, and several non-essential businesses were ordered to close in March and April. Iowa's governor countered that these closures were comparable to stay-at-home orders in neighboring states.
May 15 JAMA Netw Open study

Distancing measures have big impact on COVID-19 spread, study finds

States and cities that imposed distancing measures, such as stay-at-home orders, had a big impact on the growth rate and spread of COVID-19, according to a modeling study from a team led by University of Kentucky scientists. The group published its findings yesterday in Health Affairs.

Using an event-study design, the investigators examined the impact of the measures among US counties from Mar 1 to Apr 27. For growth rate, the impact of the measures increased over time, reducing the daily growth rate by 5.4 percentage points after 1 to 5 days to 9.1 percentage points after 16 to 20 days.

The group predicted that COVID-19 spread would have been 10 times greater—meaning 10 million more cases—by Apr 27 without shelter-in-place orders. Without other measures such as event bans, school closures, and closures of other venues such as restaurants and gyms, COVID-19 spread would have been 35 times greater, potentially resulting in 35 million more cases.

The authors concluded that their findings outline the threat of exponential spread if interventions aren't in place and provide information for reopening planning.
May 14 Health Aff abstract

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

Study shows rising use of second-, third-line antibiotics in Indian hospitals

Originally published by CIDRAP News May 14

Use of second- and third-line antibiotics and fixed-dose combinations (FDCs) of antibiotics increased over a 10-year period at two Indian hospitals, a team of Swedish researchers reported yesterday in BMC Infectious Diseases.

In the study, researchers from Karolinska Insitutet looked at antibiotic prescribing practices at a teaching hospital and a non-teaching hospital in Madhya Pradesh, a large state in central India. The hospitals were selected because they were representative of most healthcare facilities in low- and middle-income countries, where the infectious disease burden is often high and antibiotic resistance is a common cause of mortality in patients with infectious disease.

Antibiotic prescription data were analyzed using the World Health Organization (WHO) classification system, which categorizes antibiotics under the Access, Watch, and Reserve labels based on the risk of antibiotic resistance. Access antibiotics are first-choice antibiotics that should be widely available, while Watch antibiotics are drugs that should be used only for specific indications, and Reserve antibiotics should be used only when other antibiotics don't work. FDCs, which are not recommended because they have been shown to drive resistance, consist of at least two antibiotics, often from different classes.

The researchers analyzed prescribing data on a total of 3,766 patients with infections—2,504 in the non-teaching hospital and 1,262 in the teaching hospital—and 92% and 98%, respectively, received antibiotics. Sixty-one percent of total prescriptions in the teaching hospital and 40% in the non-teaching hospital were for the Access category of antibiotics, while Watch category antibiotics comprised 29% and 40% of total prescriptions in the teaching and non-teaching hospital, respectively. Prescribing of FDCs of antibiotics was significantly higher in the non-teaching hospital (18%) than in the teaching hospital (8%, P < 0.05).

From 2008 through 2017, prescribing of all categories of antibiotics and FDCs increased significantly in the non-teaching hospital. Although overall antibiotic prescribing at the teaching hospital did not change significantly, prescribing of Watch and Reserve antibiotics increased, as did FDCs. Total antibiotic prescribing among patients with pneumonia, peritonitis, and cellulitis increased in both hospitals.

The authors say the establishment of antibiotic stewardship programs based in the WHO classification system, along with the implementation of routine diagnostics, could improve antibiotic prescribing.
May 13 BMC Infect Dis study

Board game helps improve AMR knowledge, Saudi study find

Originally published by CIDRAP News May 14

The results of a study conducted in Saudi Arabia suggest that the use of a board game can significantly increase knowledge of antimicrobial resistance (AMR), with better retention than a conventional lecture, researchers reported yesterday in BMC Public Health.

Using a single-blinded parallel-group randomized controlled design, researchers from the College of Dentistry at Umm-Al Qura University randomized 93 volunteers into two groups. Participants in the study group received information about AMR by playing a board game involving dice and flash cards with questions and information. The control group received the same information but by a conventional lecture. Participants filled out questionnaires to test their knowledge at three different time points: (T1) before the intervention, (T2) immediately after the intervention, and (T3) 1 month after the intervention for follow-up to evaluate their retention of the information.

The results showed significant improvements (P < 0.05) in knowledge scores for T2 and T3 in comparison to the T1 baseline scores in both groups. The knowledge scores also relapsed significantly from T2 to T3 in both groups, but the reduction of total knowledge scores from T2 to T3 was significantly greater in the control group than in the study group (P = 0.002), and the improvements in total knowledge scores from T1 to T3 were significantly higher in the study group than in the control group (P < 0.001). The overall mean knowledge score at T3 was also higher in the study group than the control group.

"Gamification using board games seems to be a promising tool for promotional efforts to improve public health knowledge about AMR in relation to dental treatment, as well as other oral health care topics," the authors wrote. "A board game is easy and affordable for use in middle and low socioeconomic communities, and this game provided good levels of retention of information about AMR. Nevertheless, further studies are needed to generalize this study's results."
May 13 BMC Public Health study

Paper addresses liability concerns for antibiotic stewardship programs

Originally published by CIDRAP News May 13

A white paper published today in Infection Control and Hospital Epidemiology calls on antibiotic stewardship programs (ASPs) to take steps to address the potential legal implications of stewardship activities.

The paper, written by a team of legal and antibiotic stewardship experts, aims to address some of the concerns that ASPs, which are now required in most US hospitals, have about liability to patients they neither see nor examine. Although there is no legal precedent addressing liability and standards of care, and there have been no specific lawsuits filed involving ASPs, the question is whether ASPs put hospital staff at risk of litigation if they make errors that lead to patient harm. Using the results of a survey of healthcare professionals and analysis of case law, the experts provide an outline of the legal issues and strategies to address those issues.

Among the issues covered in the paper are the principles of medical liability in the context of ASPs, the existing regulatory landscape and whether it insulates ASPs from liability, documentation of ASP recommendations, clinical training of ASP personnel, the use of clinical practice guidelines, and what happens when treating teams do not accept ASP recommendations, or when ASP recommendations are incorrect.

To address these issues, the authors conclude that ASPs should work with hospital administration, treating teams, pharmacists, and other stakeholders to develop: (1) protocols to communicate and resolve differences with treating teams or other stakeholder, (2) documentation to provide the basis of recommendations as well as preserve the record of ASP involvement, and (3) standards for credentialing ASP team members based on experience or formal training.

"Regardless of specific circumstances, considering the best practices for program structure, interventions, and documentation is essential not only for risk mitigation, but also to optimize the quality of antibiotic prescribing and patient care," they write.
May 13 Infect Control Hosp Epidemiol abstract

Nursing home intervention associated with fewer antibiotics for UTIs

Originally published by CIDRAP News May 11

A low-intensity, multifaceted stewardship intervention implemented at nursing homes was associated with improved antibiotic prescribing for urinary tract infections (UTIs), US researchers reported today in JAMA Internal Medicine.

The intervention focused on antibiotic use in cases of uncomplicated and unlikely cystitis (inflammation of the bladder), which are significant drivers of inappropriate antibiotic prescribing in nursing homes. Specific interventions included a 1-hour introductory webinar, pocket-sized educational cards, web-based coaching sessions, routine audit-and-feedback regarding UTI rates, and educational clinical vignettes addressing the diagnosis and treatment of uncomplicated cystitis.

Twenty-five nursing homes were involved in the study, with 12 randomized to receive the intervention from May 1, 2017, to Apr 30, 2018, and 13 receiving standard care. The primary outcome was antibiotic treatment for unlikely cystitis, and secondary outcomes included overall antibiotic use for any UTI, rates of Clostridioides difficile infection (CDI), and rates of all-cause hospitalization and death.

The study period included 512,408 intervention facility resident-days and 443,912 control-facility resident days. Analysis of the results found that the incidence of antimicrobial use for unlikely cystitis was 27% less in the intervention facilities compared with control facilities (adjusted incident rate ratio [AIRR], 0.73; 95% confidence interval [CI], 0.59 to 0.91; P = .004), and overall antibiotic use for any type of UTI was 17% lower in the intervention facilities than in the control facilities (AIRR, 0.83; 95% CI, 0.70 to 0.99; P = .04).

The rate of CDI remained stable in the intervention group but increased in the control facilities, resulting in a baseline-adjusted reduction in the intervention group of 65% (AIRR, 0.35; 95% CI, 0.19 to 0.64; P < .001). In addition, there was no statistically significant difference in all-cause hospitalizations (AIRR, 0.95; 95% CI, 0.75 to 1.19; P = .63) or all-cause deaths (AIRR, 0.92; 95% CI, 0.73 to 1.16; P = .48) between the two groups.

"Nursing homes face many challenges in addressing antimicrobial stewardship," the authors wrote. "Pragmatic approaches to antimicrobial stewardship are thus important in such a setting. Our findings suggest that facilities can successfully improve antibiotic use and outcomes with such tools and an approach with a low level of onsite engagement."
May 11 JAMA Internal Med abstract

CARB-X to fund rapid diagnostic and antibiotic susceptibility test

Originally published by CIDRAP News May 11

CARB-X announced today an award of more than $6 million to Day Zero Diagnostics, of Boston, to develop a rapid diagnostic and antibiotic susceptibility test for bacterial infections that combines whole-genome sequencing and machine learning.

The $6.2 million in initial funding will support the development of a diagnostic system that extracts and sequences DNA from a patient sample, then analyzes the genomic data to identify the pathogen and determine its antibiotic susceptibility profile within hours. Traditional methods of identifying bacterial pathogens and their antibiotic susceptibility take 2 to 3 days to produce results. The system is designed to simultaneously test a broad range of bacteria and their antibiotic susceptibility.

"This is the first whole-genome sequencing and machine learning technology in the CARB-X portfolio, and an exciting new diagnostic approach," Erin Duffy, PhD, chief of research and development at CARB-X, said in a press release. "New technologies, like the diagnostic under development by Day Zero, if successful, could transform the way the way physicians diagnose and treat drug-resistant infections, and save lives."

Day Zero will be eligible for an additional $18.7 million from CARB-X if the project meets certain development milestones.

The project is the 60th to be funded by CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) since it was established in 2016. The public-private partnership has awarded more than $220 million to support preclinical development of new antibiotics, diagnostics, and alternative therapies for antibiotic-resistant infections.
May 11 CARB-X press release

Review finds use of acid suppressors linked to recurrent C difficile

Originally published by CIDRAP News May 11

Use of acid-suppressing medication (ASM) during hospitalization for CDI was associated with a 64% increase in recurrent CDI, according to a systematic review and meta-analysis published in Clinical Infectious Diseases.

A literature search with no limitations on date and a primary focus on the risk of CDI recurrence in patients using any ASM—primarily histamine-2 receptor antagonists and proton pump inhibitors (PPIs)—identified nine studies involving 5,668 patients. Of these patients, 3,027 (53.4%) were on ASM, and 1,003 (17.7%) developed recurrent CDI. Meta-analysis of the studies demonstrated that patients on ASM were 64% more likely to develop recurrent CDI compared with patients not using ASM (odds ratio [OR], 1.64; 95% CI, 1.13 to 2.38; P = 0.009), while patients using PPIs had an 84% increased risk of recurrent CDI compared with patients on ASM (OR, 1.84; 95% CI, 1.18 to 2.85; P = 0.007).

The authors say the findings are limited by the heterogeneity of the studies, which defined CDI recurrence and ASM exposure in different ways, and add that additional research is needed to confirm the findings and understand the mechanism by which ASM increases the risk of recurrent CDI. But they suggest a reassessment of ASM is needed, and that clinicians should consider discontinuing use of these medications during treatment whenever possible, since ASMs are frequently overprescribed.

"During CDI treatment clinicians should carefully review the indication for ASM and if no clear indication is evident, ASM should be discontinued," they wrote. "Given the high risk of recurrence of CDI and the significant morbidity, mortality, and cost burden associated with CDI recurrence, this modifiable risk factor cannot be neglected."
May 9 Clin Infect Dis abstract