Stewardship / Resistance Scan for Nov 10, 2020

News brief

CARB-X supports bacteriophage therapy for recurrent urinary infections

CARB-X announced today that it is awarding up to $2.05 million to Locus Biosciences of Morrisville, North Carolina, to develop a CRISPR-Cas3-enhaced bacteriophage for treating recurring urinary tract infections caused by Klebsiella pneumoniae.

The money from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) will help fund the development of LBP-KP01, a cocktail of bacteriophages that specifically target K pneumoniae bacteria and are engineered with a CRISPR-Cas3 construct that targets the K pneumoniae genome. The company says the dual phage-CRISPR mechanism makes LBP-KP01 more effective at killing K pneumoniae cells, even in strains that are antibiotic resistant, than corresponding bacteriophages.

"This approach has the potential to kill with laser-sharp precision the bacteria causing an infection without causing damage to other cells," CARB-X research and development director Erin Duffy, PhD, said in a press release. "If successful, this could transform the treatment of these serious life-threatening infections and save lives."

Locus will be eligible for an additional $10.5 million from CARB-X if certain project milestones are met.

Since its launch in 2016, CARB-X has awarded $257 million to fund early development of 72 new treatments or diagnostics for drug-resistant infections.
Nov 10 CARB-X press release

NICU study finds high rate of nonsusceptibility in E coli infections

A study of infants in neonatal intensive care units (NICUs) with Escherichia coli infections found a substantial rate of nonsusceptibility to commonly administered antibiotics, researchers reported yesterday in JAMA Pediatrics.

In the study, a team led by researchers at Children's Hospital of Philadelphia assessed patterns of antibiotic susceptibility in E coli among infants admitted to NICUs at 69 hospitals. E coli is a leading cause of serious infections among infants in NICUs, including early- and late-onset sepsis, and reports of resistance to commonly used antibiotics have been emerging in recent years. But there neonatal-specific antibiotic susceptibility data for E coli in the United States are scarce.

Using data from the Premier Health Database, the researchers identified infants admitted to US NICUs from 2009 through 2017, then assessed microbiologic data on E coli isolated from infant blood, urine, and cerebrospinal fluid. The primary outcome was changes in annual antibiotic susceptibility over the study period. A total of 721 infants with at least one episode of E coli infection and available antibiotic susceptibility results were analyzed.

Nearly all isolates were tested against ampicillin (720) and gentamicin (718), the two antibiotics most commonly administered to newborns as empiric therapy. No significant changes were observed over time in the overall annual proportions of antibiotic nonsusceptibility to ampicillin, with a mean of 66.8% of isolates showing nonsusceptibility and an estimated yearly change of −0.28% (95% confidence interval [CI], −1.75% to 1.18%).

The proportion of isolates nonsusceptible to aminoglycosides (gentamicin) was 16.8%, with an estimated yearly change of −0.85% (95% CI, −1.93% to 0.23%), and 5% of isolates were nonsusceptible to the extended-spectrum beta-lactamase phenotype, with an estimated yearly change of 0.46% (95% CI, −0.18% to 1.11%). No isolates with nonsusceptibility to carbapenems were identified.

Among 218 infants with early-onset infection, 22 (10.1%) had isolates with nonsusceptibility to both ampicillin and gentamicin.

"Our findings emphasize the importance of ongoing surveillance of neonatal antibiotic susceptibility patterns to inform empirical antibiotic therapies for newborn infants," the authors of the study wrote.
Nov 9 JAMA Pediatr abstract

Focus groups identify major themes shaping antibiotic perceptions

A series of focus groups held with adult patients and parents across the United States identified four major themes in attitudes toward antibiotic use and risks, researchers reported yesterday in Open Forum Infectious Diseases.

To better understand how adult patients and parents view antibiotic risks, and how they incorporate those risks into their antibiotic use decision-making, researchers from the Centers for Disease Control and Prevention (CDC) and Emory University School of Medicine conducted 12 focus groups in states with the highest antibiotic prescribing rates in March 2017. Topics included perceptions of antibiotics, expectations for antibiotics, reaction to not receiving antibiotics when desired, knowledge and perception of antibiotic risks, and response to antibiotic message testing. Fifteen parents and 16 adult patients participated.

The first major theme identified was that participants understood that antibiotics weren't necessary for all infections, such as those caused by viruses, but were confused about when they were needed, and that emotion often influenced their desire for antibiotics. In addition, they believed that antibiotics were needed if symptoms were severe or prolonged, regardless of their clinical syndrome. Second, participants had a limited understanding of antibiotic risks. Antibiotic resistance was seen as the primary risk, but understanding of resistance varied, and it was viewed as a distant harm, while immediate adverse events, like side effects, were seen as uncommon.

The third theme identified was that participants, when weighing the risks and benefits of antibiotics, prioritized the potential benefits and instant gratification, often overestimating the benefits. The fourth theme was a willingness to defer to clinicians' decisions about antibiotics, especially if the clinician is a good communicator who provides guidance and suggestions for alternative treatments.

The authors say the information gleaned from the focus groups has been used to inform the CDC's Be Antibiotics Aware educational campaign.

"Previous public health messaging has emphasized antibiotic resistance as the main risk of antibiotic overuse; however, our findings show that this message is unlikely to reduce patient demand for antibiotics," the authors wrote. "Instead, health messaging should focus on educating patients about both the frequency and potential severity of antibiotic adverse events."
Nov 9 Open Forum Infect Dis abstract

News Scan for Nov 10, 2020

News brief

Study finds 46% of high-risk adults endangered by workplace exposure

A study yesterday found that employment-related exposure to SARS-CoV-2, the virus that causes COVID-19, endangers workers and their household members.

The JAMA Internal Medicine study used pre-pandemic household survey data and the Centers for Disease Control and Prevention (CDC) COVID-19 risk factors to estimate the number of adults at increased risk of severe COVID-19 who hold essential jobs and are unable to work at home (WAH), or who live in households with such workers.

CDC risk factors for severe disease include obesity, age 65 or older, or any of the following: diabetes, emphysema or chronic pulmonary disease, cancer, or coronary heart disease. The CDC also employs broader guidelines that include possible indicators of increased risk such as current smoking, treated asthma, or treated high blood pressure.

Of the 157.3 million workers studied, 112.4 million (71.5%) were essential, and, of these, only 31.2 million could WAH. Among all adults, 49.7% (123.2 million of 248.0 million) were at increased risk of severe COVID-19 using the main CDC guidelines (61.0% using the broader CDC guidelines).

Among 112.4 million essential workers, 41.0% (46.1 million) and 54.4% (61.1 million) met the main and broader CDC increased-risk guidelines, respectively. In the group of increased-risk adults, 27.7% (34.1 million) held essential jobs and could not WAH.

"Incorporating other household members, 46.1% (56.7 million) increased-risk adults either lived with or were themselves essential employees who could not WAH. Using the broader CDC definition increased this total to 74.3 million," the study authors wrote.

"Policy makers seeking to make efficient and equitable decisions about reopening the economy and about vaccine distribution should consider the health risks not only of workers, but also of those with whom they live," they concluded.
Nov 9 JAMA Intern Med study

US researchers: 18% of COVID-19 survivors have psychiatric disorders

Survivors of COVID-19 appear to be at increased risk for mental health disorders, including anxiety, depression, and insomnia, and a psychiatric diagnosis might be an independent risk factor for the disease.

A Lancet Psychiatry study yesterday involved analysis of electronic health record (EHR) data from 69.8 million patients in 54 US healthcare organizations from Jan 20 to Aug 1. The authors found an 18.1% overall incidence of psychiatric diagnosis among 62,354 COVID-19 patients (95% confidence interval [CI], 17.6% to 18.6%) in the 14 to 90 days after COVID-19 diagnosis.

Nearly 1 in 17 COVID-19 patients (5.8%) were diagnosed as having anxiety, depression, or insomnia for the first time, and COVID-19 diagnosis doubled the odds of a mental health diagnosis in the subsequent 14 to 90 days (hazard ratio [HR], 2.1; 95% CI, 1.8 to 2.5; P < 0.0001). The risk of mental health diagnosis was higher than that of influenza, bone fracture, and other common health events, underscoring the need for enhanced psychiatric follow-up care for COVID-19 patients.

The researchers also found that a preexisting psychiatric diagnosis was associated with a 65% higher risk of COVID-19 diagnosis (relative risk 1.65; 95% CI, 1.59 to 1.71; P < 0.0001), a finding that aligns with previous studies showing increased risk of pneumonia among patients with psychiatric disorders. The authors note that psychiatric patients have higher rates of comorbidities and tend to live in social conditions that result in high exposure.

In a commentary in the same journal, Robert Yolken, MD, of Johns Hopkins School of Medicine in Baltimore, points out that EHR data do not typically capture housing density, family size, employment and immigration status, geographic location, and contact information, which are key factors in COVID-19 risk that spotlight the need for cohort studies.

Michael Bloomfield, PhD, of University College London, said in a BBC story on the study that the link between COVID-19 and psychiatric disorders was probably due to "a combination of the psychological stressors associated with this particular pandemic and the physical effects of the illness." Neither Yolken nor Bloomfield was involved in the study.
Nov 9 Lancet Psychiatry study
Nov 9 Lancet Psychiatry commentary
Nov 9 BBC article

Preemie tests negative after drinking COVID-19–infected breast milk

A preterm baby girl delivered via emergency cesarean delivery at 32 weeks remained healthy despite drinking SARS-CoV-2–infected breast milk from her mother, a case report today in Pediatrics notes.

The infant was born at 1.6 kilograms (3 pounds, 9 ounces). During her first 3 days of life, she was largely on noninvasive mechanical ventilation and given donor human or expressed breast milk. The mother occasionally visited the neonatal intensive care unit (NICU) wearing a facemask and gown.

After the mother was discharged on day 3 of the infant's life, she developed a sore throat and fever and was no longer able to visit the NICU. A family member brought fresh breast milk to the hospital, which the infant consumed on days 3 and 6 of life.

The mother returned to the hospital for a follow-up on day 9 of the infant's life and tested positive for SARS-CoV-2. The breast milk she had brought with her—which had already been given to the infant—tested positive the next day, as did a batch that was pumped on day 9 for research purposes. The viral load in both samples is unclear, but threshold cycles indicate it was low.

The infant had no COVID-19 symptoms, had a normal chest radiograph and blood gas analysis, and had negative nasopharyngeal and stool swabs on days 8, 10, and 18 of life. On day 25, she tested negative for immunoglobulin G and immunoglobulin M antibodies.

Until day 32 of life when the infant was discharged, she consumed human donor breast milk. By then, the mother had tested negative for SARS-CoV-2 twice via nasopharyngeal swabs, and so she took up breastfeeding again.

Researchers don't yet know if SARS-CoV-2 can be transmitted via breast milk to infants. Recently in Germany, one of two mothers with SARS-CoV-2 in her breast milk had a child test positive for COVID-19, but the transmission mode is unclear.
Nov 10 Pediatrics study

H5N1 avian flu infects young child in Laos; first global case in 18 months

Laos has reported an H5N1 avian flu case in a child, the first human case anywhere in the world since Nepal reported an infection in May 2019, according to a Taiwanese health ministry statement translated and posted by Avian Flu Diary (AFD), an infectious disease news blog.

The patient is a 1-year-old girl whose symptoms began on Oct 13. She is from Sarawan province in the southern part of the country.

Prior to Nepal's case, no H5N1 cases had been reported since 2017. The new case from Laos brings the global total since 2003 to 862 cases, 455 of them fatal.
Nov 10 AFD post
May 2, 2019, CIDRAP News scan on H5N1 case in Nepal