Artificial intelligence discovers new antibiotic candidate

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Scientists doing cutting-edge research
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A team of researchers from McMaster University in Toronto and the Massachusetts Institute of Technology say they have discovered, with the help of artificial intelligence (AI), a new antibiotic with the potential to fight a multidrug-resistant bacterial pathogen.

In a paper published yesterday in Nature Chemical Biology, the researchers described their use of a machine-learning model to screen 7,684 small molecules for those that inhibit the growth of Acinetobacter baumannii, a gram-negative pathogen that commonly displays multidrug resistance and is associated with more than 300,000 deaths a year globally. The data obtained from the screening was then fed into an algorithm that could predict whether structurally new compounds may display activity against A baumannii.

The model was than applied to 6,680 compounds it had not seen before, which yielded 240 molecules that could be tested in the lab. Of the nine antibiotics in this group, a compound the researchers named abaucin showed narrow-spectrum activity against A baumannii but had no effect on other bacterial species, including Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, and Staphylococcus aureus. In addition, it had minimal impact on commensal gut bacteria.

Subsequent testing showed abaucin, which works by disrupting a process known as lipoprotein trafficking, could treat wound infections in mice, and lab tests demonstrated activity against drug-resistant A baumannii strains from human patients.

This work validates the benefits of machine learning in the search for new antibiotics.

The study authors say the research demonstrates that AI approaches can enable researchers to screen hundreds of millions of molecules with antibacterial properties more efficiently and less expensively than traditional methods.

"This work validates the benefits of machine learning in the search for new antibiotics," Jonathan Stokes, PhD, lead author on the paper and an assistant professor in McMaster's Department of Biomedicine and Biochemistry, said in a university press release. "Using AI, we can rapidly explore vast regions of chemical space, significantly increasing the chances of discovering fundamentally new antibacterial molecules."

US COVID indicators remain low

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SARS-CoV-2 under microscope

On the eve of the Memorial Day weekend, the two main metrics that the Centers for Disease Control and Prevention (CDC) uses to track US COVID-19 activity—hospitalizations and deaths—continue to decline, according to the latest data. Hospitalizations for COVID are down 11% compared to a week ago, and deaths from the virus are down 13.3%.

The hospitalization map, which reflects activity by county, replaces the CDC's earlier community levels, and there are currently only a few hot spots, some in Texas and in small portions of Nebraska and Louisiana.

Early indicators—regional test positivity and emergency department (ED) visits—also show no signs of increase. Test positivity at the national level is 4.3%, down 0.7% from a week ago. The only region showing a slight increase is the part of the Southwest that includes California, Nevada, and Arizona. Only 0.5% of ED visits last week were due to COVID, down 10.8% from the previous week. There are no major rises in COVID positivity in wastewater surveillance.

The CDC also released its latest variant proportion estimates, which show a handful of newer XBB Omicron subvariants continuing to chip away at the XBB 1.5 dominance, which has declined to 53.8%. The XBB subvariants showing small but steady increases include XBB.1.16 (15.1%), XBB.1.9.1 (11.8%), XBB.1.9.2 (6.1%), and XBB.2.3 (4.8%).

CDC details outbreak at its conference

The CDC today shared its findings in its investigation into a COVID-19 outbreak in people who attended its Epidemic Intelligence Service conference in Atlanta from April 24 to April 27. Among 1,443 survey respondents, there were 181 COVID infections (13%), and those who tested positive were much more likely to have attended 3 or more days of the event. No hospitalizations were reported.

The findings ... support previous data that demonstrate that COVID-19 vaccines, antiviral treatments, and immunity from previous infection continue to provide people with protection against serious illness.

Nearly all case-patients had received at least one vaccine dose, and 49 (27%) received antiviral treatment. When asked about masks, 70% said they didn't wear one. The conference in Atlanta was held when community levels were low, for which masking wasn't recommended according to CDC guidance. "The findings of this rapid assessment support previous data that demonstrate that COVID-19 vaccines, antiviral treatments, and immunity from previous infection continue to provide people with protection against serious illness," the agency said.

COVID-19 death, hospitalization rates fell from 2020 to 2022

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From 2020 to early 2022 in England, the COVID-19 infection-fatality ratio (IFR) decreased from 0.67% to 0.10%, and the infection-hospitalization ratio (IHR) declined from 2.60% to 0.76%, with increases during the SARS-CoV-2 Alpha and Delta variant surges, estimates a study published yesterday in PLOS Biology.

Imperial College London researchers estimated COVID-19 infections in England each month from May 2020 to March 2022 to analyze the evolving relationship between case rates and deaths and hospitalizations. They also estimated the case-ascertainment rate, or the ratio of detected infections to the true number of cases, using data from the country's mass testing program.

Reliable IFR and IHR estimates, "along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand," the study authors wrote.

Cases dropped amid vaccination, Omicron

The COVID-19 IFR declined from 0.67% in 2020 to 0.10% in 2022, and the IHR fell from 2.60% to 0.76% over the same period.

The average case-ascertainment rate during the entire study period was estimated at 36.1%—signifying that actual cases were more than a third higher than reported—but the authors noted significant variation in continuous estimates of this rate. Continuous IFR and IHR estimates rose during the Alpha and Delta variant waves and fell during the COVID-19 vaccine rollout and the emergence of the Omicron variant.

In 2020, the interval between a positive COVID-19 test and hospitalization was 19 days, and the lag between positivity and death was 26 days. The intervals declined to 7 days for hospitalization and 18 days for deaths by late 2021 and early 2022.

As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship.

"Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR," the researchers wrote. "As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation."

COVID-related cancer screening delays will lead to later diagnoses, experts note

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Mammogram on iPadDelayed diagnoses of lung, breast, and colorectal cancers will likely be on the rise as a direct consequence of missed cancer screenings during the COVID-19 pandemic, write researchers in the Journal of the American College of Surgeons.

Researchers at Boston University created a predictive statistical model to quantify missed diagnoses of lung, breast, and colorectal cancers by comparing observed cancer rates in 2020 with pre-pandemic cancer rates in the previous decade (2010-2019).

"These are all cancers that have very profound incidences in our patient population across the U.S. They are much better managed and often curable when found early, and devastating when caught late," said senior author Teviah E. Sachs, MD, MPH, an associate professor of surgery at Boston University in a press release from the American College of Surgeons, which publishes the journal. "In addition, these are all screening tests that were likely put off during COVID-19 because they require patients to come into the hospital setting."

These are all cancers that have very profound incidences in our patient population across the U.S.

Sachs and his colleagues used the National Cancer Database to track the observed incidence of the three cancer types in 2020.

The observed 2020 incidence was 66.888, 152.059, and 36.522 per 100,000 compared with predicted 2020 incidence of 81.650, 178.124, and 44.837 per 100,000, for lung, breast, and colorectal cancer, respectively. The observed incidence for colorectal cancer decreased by 18.6%, by 18.1% for lung cancer, and by 14.6% for breast cancer.

For breast and lung cancer, the discrepancies were seen mostly in adults ages 65 and older, and for those under 65 for colorectal cancer.

"In addition to the human toll, this will further burden the healthcare system and increase future healthcare costs," the authors concluded. "It is imperative that providers empower patients to schedule cancer screenings to flatten this pending oncological wave."

Hospital intervention reduces unnecessary screening, antibiotics for bacteriuria

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Removing urinalysis and urine cultures from preoperative checklists for cardiac surgery was associated with a significant decrease in antibiotic prescriptions for bacteriuria, researchers reported today in Antimicrobial Stewardship & Healthcare Epidemiology.

In the single-center study, conducted at Massachusetts General Hospital, researchers assessed the proportion of patients undergoing screening for asymptomatic bacteriuria (ASB) in the 6 months prior to and after modification of the preoperative checklist for all patients undergoing cardiac artery bypass grafting (CABG).

Prior to the intervention, preoperative ASB screening was a routine step aimed at preventing postoperative infection, despite national guidelines recommending against the practice. The researchers also evaluated the impact of removing urinalysis and urine culture from the preoperative checklist on costs, antibiotic prescriptions, and postoperative infections.

A total of 502 patients were included in the study, with 254 in the preintervention group and 248 in the postintervention group. Comparison of the two groups showed a 76.5% decline in urinalyses and an 87.0% decline in urine cultures in the postintervention group, with an estimated cumulative cost savings of $8,090.38 and 50% fewer antibiotic prescriptions for bacteriuria. No increase in surgical-site infections, central line-associated bloodstream infections, catheter-associated urinary tract infections, or Clostridioides difficile infection was observed.

Removal of unnecessary orders from a preoperative checklist after a short education session targeted at wasteful laboratory testing was a highly effective strategy.

"Removal of unnecessary orders from a preoperative checklist after a short education session targeted at wasteful laboratory testing was a highly effective strategy to reduce unnecessary preoperative testing prior to CABG surgeries," the study authors wrote.

Quick takes: Polio in DRC, more US fungal meningitis, France avian flu vaccine results in ducks

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  • Only one country—the Democratic Republic of the Congo (DRC)—reported new polio cases this week, according to the latest update from the Global Polio Eradication Initiative (GPEI). The country reported three more cases involving circulating vaccine-derived poliovirus type 1 (cVDPV1) and nine due to circulating vaccine-derived poliovirus type 2 (cVDPV2). In related developments this week, Afghanistan reported its third wild poliovirus type 1 (WPV1) case of the year, according to a media report, and Pakistan reported a second armed attack on polio vaccinators in as many weeks, according to a separate report, which said the attack wounded three police officers who were guarding the immunizers.
  • The number of US patients who are suspected to have fungal meningitis infections linked to contaminated spinal anesthesia products administered during cosmetic surgery in at least two clinics in Matamoros, Mexico, has risen to nine, with nine additional cases listed as probable, meaning spinal tap results suggest meningitis, the Centers for Disease Control and Prevention (CDC) said this week in its latest update. Two deaths have been reported among patients with probable cases. A total of 206 US cases are under investigation. The CDC first described details of the outbreak in a May 17 Health Advisory Network notice.
  • France's agriculture ministry today said its goal is to launch an avian influenza vaccine campaign in poultry in the fall, following promising vaccine effectiveness findings in ducks, according to Reuters. The European Union last year backed a plan to introduce vaccination in poultry, starting with France.

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