Phase 2 data support bedaquiline-delamanid combo for resistant TB

The results of a National Institutes of Health-funded phase 2 study indicate the new tuberculosis (TB) drugs delamanid and bedaquiline, when combined, have only a modest effect on the electrical activity of the heart, US, South African, and Peruvian researchers reported last week in the Lancet Infectious Diseases.

In the phase 2 randomized controlled trial, patients in South Africa and Peru with multidrug-resistant or rifampicin-resistant TB were randomized 1:1:1 to receive bedaquiline, delamanid, or both for 24 weeks. The two new drugs are considered critical components of a shorter, less toxic regimen for multidrug-resistant and rifampicin-resistant TB, but the cardiac and microbiologic safety of combining the two has not been well-established.

Both drugs are known to cause modest QTc prolongation, which can lead to an irregular heartbeat and increase the risk of sudden cardiac arrest, but the combined effect on QTc-related cardiac risk is unknown.

A total of 84 participants were enrolled in the trial from August 2016 through July 2018, with 28 in each treatment group and patients with higher-than-normal QTc values excluded. The primary endpoint was mean QTc change from baseline, as measured by electrocardiogram.

The mean change in QTc from baseline was 12.3 milliseconds (ms) in the bedaquiline group (95% confidence interval [CI], 7.8 to 16.7), 8.6 ms in the delamanid group (95% CI, 4.0 to 13.1), and 20.7 ms in the combined group (95% CI, 16.1 to 25.3). There were no grade 3 or 4 (life-threatening) QTc prolongation events, and the maximum QTc increase seen was similar for bedaquiline plus delamanid versus bedaquiline alone.

"These results are reassuring and provide evidence of the safety of concurrent bedaquiline and delamanid use in patients with multidrug-resistant or rifampicin-resistant tuberculosis," the authors wrote.

In addition, exploratory analysis found high rates of 8-week culture conversion in all groups, with early and sustained culture results seen in the combined treatment group. The authors said this is an encouraging sign that the combined treatment is effective but noted that the finding needs to be confirmed in larger clinical trials.
Feb 12 Lancet Infect Dis abstract


Multistate Listeria outbreak linked with Hispanic-style cheese

A Listeria monocytogenes outbreak has hospitalized seven people in four states, the Centers for Disease Control and Prevention (CDC) said on Feb 12.

CDC investigators have traced the outbreak to Hispanic fresh- and soft-style cheeses, including queso fresco, queso blanco, and queso panela and are working to identify a singular brand or cheese type.

The affected states are Maryland (4 cases), Connecticut (1), New York (1), and Virginia (1), and whole-genomic sequencing has shown that the strains are closely related. The date of first symptoms extend from Oct 20, 2020, to Jan 22, 2021.

Patient ages range from 45 to 75, with a median age of 61. Of the four people the CDC has been able to interview, three said they ate at least one type of Hispanic-style fresh or soft cheese in the month before they got sick. No deaths have been reported.

Listeria symptoms include headache, stiff neck, confusion, loss of balance, convulsions, fever, and muscle aches. Symptoms start 1 to 4 weeks after eating the affected food, but onset could be the same day or at least 70 days later. The CDC recommends people only eat cheeses that have been made with pasteurized milk. Those at higher risk for Listeria, such as pregnant women, those 65 years or older, or those with compromised immune systems, should avoid the food group as a whole for now.

A 2018 CDC study reported that Listeria outbreaks associated with soft cheeses have risen in recent decades, with an 88% hospitalization rate and 17 deaths (9.4%) among 180 illnesses.
Feb 12 CDC outbreak notice


Neurologic problems noted in children with hemolytic uremic syndrome

Pediatric patients who develop hemolytic uremic syndrome (HUS)—a rare kidney failure that follows an Escherichia coli infection—are at risk for severe acute neurologic symptoms (ANS), according to a study based on almost 4,000 US patients. The findings were published today in Pediatrics.

The study was the largest to date to describe ANS following HUS, and showed a strong correlation between increased multiple neurological symptoms and mortality. The authors used the Pediatric Health Information System database to identify HUS-related inpatient visits between 2004 and 2018.

Among 3,915 patients included in the analysis, acute neurologic manifestation (ANM) was noted in 10.4% (409) patients, the authors found, and encephalopathy (245) and seizures (108) were the most common ANMs recorded. The median age for patients with at least one ANM was 3.3 years.

Mortality was significantly higher among patients with an ANM compared with patients without an ANM (13.9% vs 1.8%; P < .001). Brain hemorrhage (odds ratio [OR], 3.09; 95% confidence interval [CI], 1.40–6.82; P = .005), brain infarction (OR, 2.64; 95% CI, 1.10–6.34; P = .03), anoxic brain injury (OR, 3.92; 95% CI, 1.49–10.31; P = .006), and brain edema (OR, 4.81; 95% CI, 1.82–12.71; P = .002) were independently associated with mortality.

"Knowledge of these risk factors can help clinicians prognosticate clinical course and appropriately counsel families," the authors write.
Feb 15 Pediatrics study

COVID-19 Scan for Feb 15, 2021

News brief

High SARS-CoV-2 loads tied to B117 variant, potential super-spreaders

B117, a SARS-CoV-2 variant believed to have increased infectivity, is linked to high viral loads in COVID-19 patients in the United Kingdom, while a small number of patients with extremely high viral loads could have largely driven the second wave of the pandemic in Houston, according to two new studies in the Journal of Infectious Diseases.

In the first study, a team led by researchers from Public Health England tested 641 respiratory samples collected from COVID-19 patients from Oct 25 to Nov 25, 2020, for B117 viral loads. They found that those infected with the variant had up to 10,000-fold higher viral loads than those infected with other virus strains.

The authors said that although similar viral loads were observed in non-B117 samples, "the significantly higher number of subjects having an extreme viral load is of great concern." They called for further research into the possibility that either high short-term viral load or a longer period of infectious viral emission during acute illness may also have a role in increasing the variant's transmissibility.

First discovered in the United Kingdom in December 2020, B117 has spread rapidly throughout the country and to many other parts of the world, including the United States.

In the second study, researchers at Baylor College of Medicine, compared SARS-CoV-2 loads in 1,319 COVID-19 patients from Mar 18 to Aug 15, 2020, in Houston. In the second pandemic wave, a small number of patients had extremely high average viral loads, meaning that they could have been super-spreaders, or those who transmit the virus to a large number of other people—even though they are not sick or only mildly ill.

The potential super-spreaders were most likely to be otherwise healthy women who didn't require hospitalization. The length of viral shedding was similar in patients with no symptoms and those with mild to moderate illness.

"Many were asymptomatic or had mild illness indicating that without appropriate viral detection, social distancing and quarantine, individuals who have extremely high or high viral load will be able to spread SARS-CoV-2 and sustain the current COVID-19 pandemic," the authors wrote. "We believe that these individuals' characteristics could be consistent with the super-spreader phenomenon and that greater awareness of the social dynamics of these individuals is needed to understand the spread of SARS-CoV-2."
Feb 13 J Infect Dis UK study
Feb 15 J Infect Dis
Houston study


CDC data: COVID vaccine-related anaphylaxis in less than 4 per million

Pfizer/BioNTech's and Moderna's mRNA COVID-19 vaccines have been associated with 4.7 cases of anaphylaxis per million doses and 2.5 cases per million, respectively, according to data published by Centers for Disease Control and Prevention scientists in JAMA late last week.

Sixty-six total cases have occurred in the United States through Jan 18, 2021, making the cumulative frequency 3.8 cases per million doses. No known deaths have been reported.

Anaphylaxis is a severe allergic reaction that can include swelling, hives, lowered blood pressure, and shock. Of the 66 people who experienced this outcome, 52 (78.8%) had prior allergies or allergic reactions and 21 (31.8%) had prior anaphylaxis events. Three-quarters occurred within 15 minutes of vaccine receipt.

The researchers say the clinical characteristics of anaphylaxis were similar between the two vaccines and whether the person had symptom onset within 30 minutes of being vaccinated or later. All 66 people received treatment in a healthcare setting, and 61 (92.4%) received epinephrine, 18 (27.3%) needed intensive care unit admission, and 7 (10.6%) needed endotracheal intubation.

The researchers used data from the Vaccine Adverse Event Reporting System (VAERS) from Dec 14, 2020, through Jan 18, 2021 (the first mRNA vaccine [Pfizer] received emergency-use authorization on Dec 11, 2020). During this time, 9,943,247 Pfizer/BioNTech doses and 7,581,429 Moderna doses were administered.
Feb 12 JAMA article

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