News Scan for May 11, 2020

News brief

Phase 2 study: Triple-drug COVID-19 therapy better than 2-drug regimen

A phase 2 trial has shown that a 2-week course of triple antiviral therapy with interferon beta-1b plus lopinavir-ritonavir and ribavirin is safe and better at shortening COVID-19 viral shedding than lopinavir-ritonavir alone in patients with mild to moderate illness if started within 7 days of symptom onset.

The prospective study, published late last week in The Lancet, involved 127 adult COVID-19 patients (mean age, 52 years) admitted to six Hong Kong hospitals from Feb 10 to Mar 20. Eighty-six patients were randomly assigned to receive 2 weeks of the triple-drug combination every 12 hours plus as many as three doses of injectable interferon beta-1b every other day, while 41 received lopinavir-ritonavir alone every 12 hours.

The researchers detected no live virus on nose-throat swabs within, on average, 7 days of starting the triple-drug combination, 5 days faster than with lopinavir-ritonavir alone (hazard ratio, 4.37; 95% confidence interval, 1.86 to 10.24; P = 0.0010). The combination treatment also halved the mean time to complete symptom relief (4 versus 8 days) and Sequential Organ Failure Assessment score of 0 (3 versus 8 days) and shortened the mean hospital stay from 14.5 to 9 days.

While patients who received the combination therapy within 7 days of symptom onset did better than those in the control group, there was no difference in outcomes when they were treated 7 or more days after symptoms began. The authors said that the results suggest that the triple combination may minimize the risk of antiviral resistance and decrease risks to healthcare workers by reducing the duration and quantity of viral shedding.

"Despite these encouraging findings, we must confirm in larger phase 3 trials that interferon beta-1b alone or in combination with other drugs is effective in patients with more severe illness (in whom the virus has had more time to replicate)," said lead author Kwok-Yung Yuen, MD, from the University of Hong Kong, in a Lancet news release.
May 8 Lancet study and news release


Chinese study shows COVID-19 RNA shed for up to 49 days

A new study published in Emerging Infectious Diseases shows that genetic material of SARS-CoV-2—the virus that causes COVID-19—was detected in body fluids from COVID-19 patients for up to 49 days.

The study was conducted in 49 patients from Guangdong, China, and assessed the presence of viral RNA in throat swabs, nasopharyngeal swabs, sputum samples, and feces specimens. Forty-three of the patients had mild cases of COVID-19, while 6 had severe cases. Researchers obtained specimens every 3 days for 4 weeks.

The authors found persistent shedding of virus RNA in both nasopharyngeal swab and feces samples.

"The estimated time until loss of virus RNA detection ranged from 45.6 days for nasopharyngeal swab samples to 46.3 days for feces samples in mild cases and from 48.9 days for nasopharyngeal swab samples to 49.4 days for feces samples in severe cases, which was longer than those of SARS-CoV and MERS-CoV," the authors wrote, referring to the coronaviruses that cause SARS and MERS, respectively.

The findings are consistent with published case reports, the authors concluded. They said their findings should inform diagnostic testing for COVID-19 and prevention measures.
May 8 Emerg Infect Dis


H9N2 avian flu infects girl in China

China has reported one more illness from H9N2 avian flu, involving a 5-year-old girl from Hunan province, according to the monthly zoonotic flu report from the World Health Organization (WHO).

Her symptoms began on Apr 20, and she had a mild illness but was hospitalized and isolated on Apr 24. She was released from the hospital on Apr 30. An investigation revealed that the girl had been exposed to slaughtered poultry that were brought home from a live-bird market.

China had reported another similar case in early April, in a 3-year-old girl from Zhuhai in Guangdong province, who also had a mild illness and had contact with poultry. Both patients recovered. Their illnesses were found through flulike illness surveillance, and no other cases were found among their contacts.

The country has now reported 31 human H9N2 cases since 2015. The WHO said H9N2 is enzootic in Asian poultry and has been increasingly reported in Africa.
May 8 WHO monthly zoonotic flu update
Apr 8 CIDRAP News scan "China reports H9N2 avian flu in Guangdong province"


H5N6 and H5N1 avian flu strike poultry in Vietnam

Vietnam has reported more highly pathogenic H5N6 and H5N1 avian flu outbreaks in poultry, according to new notifications from the World Organization for Animal Health (OIE).

The country reported two new H5N6 outbreaks, one in Ninh Binh province and the other in Ha Noi province, both in the north, part of sporadic outbreak activity since early February. The outbreak in Ninh Binh began on Apr 14, and the event in Ha Noi started on May 6. Taken together, the virus killed 1,500 of 21,138 birds, and the rest were culled to curb the spread of the virus.

Also, the country reported three more H5N1 outbreaks in three provinces: Can Tho, Dong Thap, and Vinh Long, all involving village poultry in southern Vietnam. The outbreak began between Apr 16 and Apr 27, killing 2,160 of 3,070 susceptible birds. The remaining poultry were destroyed as part of the outbreak response. Vietnam's last H5N1 outbreak occurred in the middle of February.
May 10 OIE report on H5N6 in Vietnam
May 10 OIE report on H5N1 in Vietnam

Stewardship / Resistance Scan for May 11, 2020

News brief

Nursing home intervention associated with fewer antibiotics for UTIs

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

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

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

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