Prolonged SARS-CoV-2 shedding may be tied to in-hospital delirium, death by 6 months

Indications of persistent SARS-CoV-2 shedding in hospitalized COVID-19 patients is tied to a higher risk of in-hospital delirium and death by 6 months, according to a study published this week in GeroScience.

A team led by Northwestern University researchers retrospectively evaluated potential viral shedding in 2,518 COVID-19 patients hospitalized in Illinois from Mar 5 to Aug 9, 2020. A total of 959 patients were tested for SARS-CoV-2 using polymerase chain reaction (PCR) at least once 14 or more days after their initial positive test, 405 (42.2%) of whom were still shedding virus. Average age of patients who underwent repeat testing was 59.4 years. Findings of PCR-positivity could be due to the presence of live virus or ongoing excretion of viral debris that results in a positive PCR result in the absence of live virus.

Signs of prolonged viral shedding were linked to male sex, higher body mass index, diabetes, chronic kidney disease, and corticosteroid treatment during initial COVID-19 hospitalization. After adjustment for factors such as severity of respiratory dysfunction, shedding remained linked to in-hospital delirium (odds ratio [OR], 2.45) and death by 6 months (OR, 2.43). Of persistent shedders, 56% experienced delirium.

Relative to nonshedding patients, shedders were more often men (53.8% vs 47.1%) and had more repeat tests (median, 4 vs 3), but nonshedders were tested for a longer time (median, 131.5 vs 64.0 days after the initial positive result).

The last positive PCR test in persistent shedders was obtained at a median of 34.6 days after initial testing, but 49 (12.1%) still tested positive 90 or more days later. A total of 111 (27.4%) had a positive repeat test after a negative repeat test at a median of 53.4 days after their initial test. One patient was still shedding SARS-CoV-2 at 269 days.

"Many studies, even pre-dating the COVID-19 pandemic, suggest that patients who are delirious during hospitalization are more likely to have long-term cognitive issues and may experience accelerated cognitive decline with aging," senior author Eric Liotta, MD, said in a Northwestern Medicine press release. "As such, patients with persistent viral shedding may warrant closer surveillance and monitoring for development of complications following COVID-19."
May 11 GeroScience study
May 11 Northwestern Medicine press release

Omicron COVID-19 variant tied to croup in children

Boston Children's researchers have found evidence that the COVID-19 Omicron variant is more likely to cause croup in children that previous SARS-CoV-2 iterations, according to a study today in Pediatrics.

The investigators noted that, from Mar 1, 2020, to Jan 15, 2022, 75 children were diagnosed as having COVID-19–associated croup at Boston Children's Hospital. Of those, 61 (81%) were diagnosed during the Omicron period. One child tested positive for rhinovirus in addition to SARS-CoV-2.

Children with croup have a swollen larynx and trachea, often accompanied by a barking-type cough and difficulty breathing.

Nine of the 75 children (12%) were hospitalized (7 during Omicron; 2 pre-Omicron), and they spent a median of 1.7 days in the hospital. Four of them required intensive care. The rest were treated in the emergency department.

All but two patients were treated with dexamethasone. Hospitalized patients received a median of six dexamethasone and eight racemic epinephrine doses.

The study authors wrote that the data present "compelling evidence" that Omicron causes croup. The variant's tendency to affect the upper airway may help explain the connection, they added. They concluded, "Further research is needed to characterize the underlying mechanisms of COVID-19-associated croup, differences in clinical features from other viral etiologies, and appropriate management strategies."
May 13 Pediatrics study

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

Team effort linked to significant C diff reductions at community hospital

Originally published by CIDRAP News May 12

A quality-improvement program led by an interprofessional team was associated with significant and sustained reductions in hospital-onset Clostridioides difficile infection (HO-CDI) at a community hospital, researchers reported today in the American Journal of Infection Control.

The program, implemented at a 410-bed community hospital in the southeastern United States from 2015 to 2020, was led by a team that included nurses, a physician champion, a hospital epidemiologist, an infection preventionist, a clinical microbiologist, and an antimicrobial stewardship pharmacist.

The team and program were created in response to HO-CDI rates at the hospital that were continuously above the national benchmark set by the Centers for Disease Control and Prevention. Interventions to reduce HO-CDI rates included diagnostic stewardship (a C difficile testing algorithm named the "diarrhea decision tree"), enhanced environmental cleaning, antimicrobial stewardship, and education and accountability.

Prior to implementation of the program the HO-CDI incidence rate at the hospital was 12.91 per 10,000 patient-days. After the first year of implementation, HO-CDI incidence fell to 4.72/10,000 patient-days, a 63% reduction. After three years, HO-CDI incidence fell to 2.8/10,000 patient-days, a 77% reduction from the baseline. The standardized infection ratio saw a sustained decrease, falling from 1.11 in 2015 to 0.43 in 2020—below the national benchmark of 0.51.  

The intervention also resulted in increased C difficile testing for appropriate patients within the first 3 days of hospital admission and decreased use of fluoroquinolones.

"Our project showed that interprofessional collaboration and continuous improvement can profoundly impact HO-CDI incidence, and sustain reductions over years," Cherith Walter, MSN, RN, first author on the study, said in a press release from the Association for Professionals in Infection Control (APIC), which publishes the journal. "We hope our findings will help other healthcare teams struggling with this incredibly challenging healthcare-associated infection to improve patient safety and reduce associated costs."
May 12 Am J Infect Control abstract
May 12 APIC press release

Study suggests link between diet and antibiotic resistance in gut bacteria

Originally published by CIDRAP News May 11

A study published yesterday in mBio suggests a diverse, high-fiber diet is associated with fewer antibiotic-resistance genes (ARGs) in gut bacteria.

In the study, researchers from the US Department of Agriculture-Agriculture Research Service (USDA-ARS) used shotgun metagenomic sequencing to analyze stool samples from 290 healthy adults participating in the USDA Nutritional Phenotyping Study. The analysis revealed a large diversity, both in abundance and composition, of ARGs, with people having a high ARG abundance generally having a higher diversity of resistance mechanisms.

Aminoglycoside resistance was the most common mechanism of resistance within the cohort, followed by resistance to macrolide-lincosamide-streptogramin and tetracyclines.

Examining the participants' diet using a food frequency survey and 24-hour dietary recalls, the researchers found that participants who consumed more fiber, fewer animal proteins, and more diverse foods had lower total abundances of ARGs, while participants with less diverse diets had the highest levels of ARGs. Machine learning analysis showed a strong association between more diverse diets with higher amounts of soluble fiber and low ARG levels. Those with the lowest levels of ARGs in their gut microbiome also had a greater abundance of strict anaerobic microbes, especially from the family Clostridiaceae.

"Surprisingly, the most important predictor of low levels of ARG, even more than fiber, was the diversity of the diet," senior study author Danielle Lemay, PhD, of the USDA-ARS Western Human Nutrition Research Center, said in an agency press release. "This suggests that we may want to eat from diverse sources of foods that tend to be higher in soluble fiber for maximum benefit."

Lemay added that while further research is needed, the findings suggest dietary interventions could play a role in reducing antibiotic resistance.
May 10 mBio study
May 10 USDA-ARS press release

High antimicrobial use observed in NYC hospitals in first pandemic year

Originally published by CIDRAP News May 10

A study of three hospitals in New York City found that antimicrobial use in COVID-19 patients during the first year of the pandemic far exceeded the incidence of coinfections, researchers reported today in Antimicrobial Stewardship & Healthcare Epidemiology.

The study, conducted at three tertiary-care hospitals, found that, among 7,209 patients (median age, 65 years) admitted with a confirmed COVID-19 infection from Jan 1, 2020, to Feb 1, 2021, 663 (9.2%) had a positive culture from the respiratory tract or blood sometime during their initial hospitalization. Positive respiratory cultures were found in 449 patients (6.2%), and blood culture positivity occurred in 334 (4.6%). Staphylococcus aureus was among the most common pathogens isolated from both blood and respiratory cultures.

Despite the low incidence of coinfections, antimicrobials were administered to 5,056 patients, or  70.1%, with a median of 6 antimicrobial days per patient. Third-generation cephalosporins the most frequently used antimicrobial agent (3,311 patients, 45.9%), followed by azithromycin (3,130 patients, 43.4%). A higher proportion of patients received antimicrobials in the first wave of the pandemic compared with the later period (82.4% vs 52%). Infection-free survival decreased over the course of hospitalization.

"With the COVID-19 pandemic continuing to significantly affect various parts of the world, resource utilization and overuse of antimicrobials warrant continued focus," the study authors wrote. "Our data, obtained through the period of peak COVID-19 activity in New York City, may be used to guide the process of diagnostic decision making, optimizing resource utilization, and antimicrobial stewardship."
May 10 Antimicrob Steward Healthc Epidemiol study

Australian coalition to address antibiotic resistance in food, agribusiness

Originally published by CIDRAP News May 9

A coalition of 70 organizations in Australia is joining forces to combat antimicrobial resistance (AMR) in the food and agribusiness industries.

Announced last week, the Cooperative Research Centre for Solving Antimicrobial Resistance in Agribusiness, Food, and Environments (CRC SAAFE) will bring together partners from water, organic waste, aquaculture, horticulture, viticulture, animal feed, and livestock sectors to develop shared solutions to monitor, manage, and mitigate the spread of AMR.

The effort will focus on the emergence and spread of resistant pathogens on farms, in feed and food production systems, and in waste processing. Partner organizations will work on developing solutions such as vaccines, water treatment technologies, and new animal feed and supplements.

"Antimicrobial resistance makes our food supply less safe," CRC SAAFE CEO and University of South Australia professor Erica Donner, PhD, said in a university press release. "Internationally, there are many cases of multidrug resistant bacterial strains causing serious disease being spread via food. CRC SAAFE will help Australian industries stay on top of this risk, ensuring we remain a top producer of premium food and beverage products."

CRC SAAFE will receive $34.5 million Australian Dollars from the Australian government, and partner organizations will contribute an additional $115 million.
May 6 University of South Australia press release

Clinical decision support boosts stewardship at community hospital

Originally published by CIDRAP News May 9

Implementation of a clinical decision support system (CDSS) in a tele-antimicrobial stewardship program (TASP) at a community hospital was associated with reduced antibiotic use, higher use of oral antibiotics, and faster time to therapy, researchers reported today in Open Forum Infectious Diseases.

In the study, researchers from the University of Pittsburgh conducted an interrupted time series analysis to assess differences in antibiotic use before and after the CDSS was implemented at a 146-bed community hospital in Pennsylvania. In July 2018, infectious disease (ID) consult services at the hospital were transitioned to remote telemedicine utilizing ID physicians from the University of Pittsburgh Division of Infectious Diseases. The CDSS, which provides real-time alerts to ASP members on bug-drug mismatches, positive cultures, de-escalation opportunities, and other scenarios of interest, was implemented in February 2020 to address the challenges of not having an ID specialist on site.

Implementation of the CDSS into the TASP was associated with an immediate 11% reduction in antibiotic use. Prior to CDSS implementation, antibiotic use was trending downward by 0.25% per month, and continued to trend down after CDSS implementation by 0.24% per month. In addition, the frequency of conversion from intravenous (IV) to select oral (PO) agents increased from 38% to 57% in the 6 months after implementation compared with the 6 months prior, and median time to optimal therapy (TTOT) was one day faster (2.9 day pre-CDSS vs 1.9 days post-CDSS).

On average, pharmacists documented 2.2-fold more interventions per month (198 vs 90) and patients received 1.03 fewer days of antibiotics per admission post-CDSS.

"Implementation of a CDSS into an established, integrated TASP at a community hospital allowed for increased involvement and transfer of knowledge from remote ID experts, resulting in decreased total antimicrobial usage, increased rates of IV to PO conversion, improved TTOT, decreased antimicrobial exposure, and improved workflow efficiency," the study authors wrote. "Implementation of the CDSS addressed several challenges in our TASP, while minimizing the need for additional staffing support."
May 9 Open Forum Infect Dis abstract