News Scan for Apr 19, 2021

News brief

CARB-X to fund development of bacteriophage-based drug

CARB-X announced today that it is awarding Phico Therapeutics of Cambridge, United Kingdom, up to $5.3 million to develop an intravenous bacteriophage drug to treat ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

The award will support development of Phico's SASPject PT 3.9 project, which combines engineered bacteriophages with antibacterial small acid-soluble spore proteins (SASPs) to target and inactivate P aeruginosa bacteria. Phico says SASPs are unaffected by the sequence of bacterial DNA, which makes it unlikely that bacteria could develop resistance.

The project will be eligible for an additional $12.86 million in funding from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) if the project progresses successfully to phase 1 clinical trials.

"This approach has the potential to target the bacteria without damaging other cells or contributing to the rise of resistance," CARB-X Research and Development Chief Erin Duffy, PhD, said in a CARB-X press release. "If successful, this new intravenous drug could transform the way patients with ventilator-associated pneumonia are treated in hospitals, and save lives."

The Centers for Disease Control and Prevention estimates there were 32,600 multidrug-resistant P aeruginosa infections and 2,700 deaths in US hospitals in 2017.
Apr 19 CARB-X press release

Review finds increased MRSA risk from dog ownership

A review and meta-analysis of previously published studies has identified dog ownership as a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) colonization, German researchers reported last week in the Journal of Antimicrobial Chemotherapy.

To get a better understanding of the risk for multidrug-resistant organism (MDROs) colonization posed by pet ownership, the researchers conducted three separate reviews and meta-analyses of literature on pet ownership and MRSA, third-generation cephalosporin-resistant Enterobacterales (3GCRE) and carbapenem-resistant Enterobacterales (CRE), and vancomycin-resistant Enterococcus (VRE). The primary outcome was the relative risk of carrying an MDRO in humans with pet contact (including dogs, cats, rodents, birds, and reptiles) compared with those without pet contact.

The researchers calculated an increased risk of MRSA carriage for dog owners, with a risk ratio (RR) of 2.28 (95% confidence interval [CI], 1.47 to 3.56), but not for other pet owners. The meta-analysis for 3GCRE/CRE did not show a significantly higher risk for colonization among pet owners compared with non-pet owners, with an RR of 1.18 (95% CI, 0.83 to 1.68) for pet owners in general. For VRE, there were insufficient data to perform a meta-analysis.

The study authors say the MRSA risk among dog owners is higher than found in literature reviews and, because of limitations concerning study populations and study designs, may be an overestimate. The data suggest that transmission occurs primarily from humans to dogs, who then may serve as a reservoir for reinfection and transmission to other household members. In addition, dogs may be a vector for livestock-associated strains of MRSA.

"If indeed pets play a role as a risk factor for MDRO acquisition in humans, our meta-analyses only suggested this relation for the transmission of MRSA via dogs," they wrote.
Apr 17 J Antimicrob Chemother abstract

COVID-19 Scan for Apr 19, 2021

News brief

Study: Indoor school sports most likely to spread COVID-19

A study in an Atlanta school district revealed that the highest secondary COVID-19 attack rates were in indoor, high-contact sports settings (23.8%), staff meetings or lunches (18.2%), and elementary school classrooms (9.5%), and that staff were more susceptible to COVID-19 than students were.

The study, published late last week in Clinical Infectious Diseases, tracked COVID-19 cases and case contacts from Dec 11, 2020, through Jan 22, 2021, in a district that included eight elementary schools, two middle schools, and one high school. Students were in-person 4 days per week and wore masks, and desks were spaced 3 to 6 feet apart.

All cases were confirmed by polymerase chain reaction testing. Secondary attack rate (SAR)—which is the percent of case contacts who become infected—was calculated by setting (classroom, bus, indoor sports), index case roll (student or staff), symptom status (asymptomatic or symptomatic), and time of exposure. Eighty-six primary cases were included in the analysis, involving 33 staff and 53 students, who generated 1,119 contacts (112 staff and 1,007 students).

Among contacts, 9.8% tested positive. The overall SAR was 8.7% (95% confidence interval [CI], 6.8% to 10.9%).

SAR was highest in indoor sports settings (including basketball, wrestling, and cheerleading) (23.8%; 95% CI, 12.7%–33.3%), interactions among staff (group lunches, staff meetings) (18.2%; 95% CI, 4.5%–31.8%), and in elementary school classrooms (9.5%; 95% CI, 6.5%–12.5%).

Symptomatic index cases had a higher SAR than asymptomatic cases—10.9% versus 3.0%.

"Staff were overrepresented among index cases; while they made up approximately 20% of persons attending school in person, they accounted for nearly 40% of cases," the authors concluded. "This may, in part, be because adults are more likely to be symptomatic, and having symptoms is associated with a higher risk of transmission both in this investigation and others."
Apr 17 Clin Infect Dis study

COVID vaccine may trigger less immune response in blood cancer patients

mRNA COVID-19 vaccines may not fully protect people with the blood cancers chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), according to two studies released late last week in Blood.

The first study found that only 39.5% of 167 Israelis studied who had CLL had a positive antibody-mediated response to the Pfizer/BioNTech COVID-19 vaccine, compared with 100% of 53 controls.

CLL patients currently undergoing cancer treatment had significantly lower response rates to the vaccine than people who had completed treatment and were in remission (16% vs 79%). Patients who hadn't yet begun treatment had a 55.5% immune response rate. Likewise, people who had completed treatment at least 1 year before vaccination had a 94% response rate, compared with 50% among those undergoing treatment within the last year.

Because clinical trials of coronavirus vaccines didn't include people with blood cancers, who are prone to severe illness and complications, measuring their effectiveness in this population is important, the researchers said. They said a booster dose of the vaccine may be needed for CLL patients and that similar results would be expected for the Moderna vaccine, which they didn't test.

"Even though response rates were not optimal, patients with CLL should still get the vaccine and, if appropriate, it may be better to do so before CLL treatment starts although the disease itself may affect the response," lead author Yair Herishanu, MD, said in an American Society of Hematology news release.

The second study, from Greece, provided similar results after one dose of the Pfizer vaccine in older MM patients. Twenty-two days after the first dose of the vaccine, measurable neutralizing antibodies were found in 20.6% of 48 MM patients, compared with 32.5% of 104 healthy controls. Median patient age was 83.

Of the MM patients, 72.9% were receiving chemotherapy, four were in remission and not receiving therapy, and nine had precancerous MM. The authors said that chemotherapy appears to blunt production of neutralizing antibodies after one vaccine dose and that older MM patients would need a second dose for a more robust immune response.
Apr 16 Blood CLL study and MM study
Apr 16 American Society of Hematology news release