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(Health Rounds is published Tuesdays and Thursdays. Think your friend or colleague should know about us? Send them this newsletter. They can also subscribe here.) by Nancy Lapid
Hello Health Rounds readers! Today we present preliminary data in rodents and animals that could portend important advances in combating antibiotic-resistant microbes and improving the delivery of chemotherapy drugs. We also present long-term data on the world’s best-selling prescription drug, Merck & Co MRK.N cancer immunotherapy Keytruda.
Vaccines can help fight antibiotic resistance
Thanks to a new approach to vaccine development, researchers may have found a solution to the problem of antibiotic-resistant bacteria.
Their experimental vaccine gave mice high levels of immunity against deadly levels of Staphylococcus aureus and its “superbug” form, methicillin-resistant S. aureus, or MRSA, the researchers reported Wednesday in the journal Nature Communications.
Overuse of antibiotics has contributed to the evolution of superbugs that are resistant to most common treatments. New antibiotics or other solutions are badly needed, health experts say.
To develop a vaccine, researchers must identify a molecule that the body will signal as foreign. These molecules, or antigens, trigger the immune system to create antibodies to fight future infection.
While most vaccines rely on protein antigens, the new vaccine uses a carbohydrate called poly-beta-(1-6)-N-acetylglucosamine, or PNAG, found on the cell wall of many bacteria.
The scientists were able to identify 32 PNAG carbohydrates, all composed of five sugars, but with different patterns of certain molecular components that are either linked to another small molecule called an acetyl group or are not linked to anything else.
The team found two versions of PNAG that were particularly promising and attached them to a virus that infects bacteria.
Combined with the virus, the two PNAG combinations provided mice with “nearly complete protection” against S. aureus and MRSA infections, with minimal impact on healthy organisms that live in the intestines, the researchers said.
The widespread presence of PNAG in many bacteria “makes it an attractive target for vaccine development,” they added.
Closed-loop chemotherapy infusions could improve cancer treatment
Doctors could one day use continuous monitoring systems for chemotherapy to continuously track the amount of drug in a patient’s blood and automatically adjust the dose when needed, researchers say.
Similar to what exists today for diabetic patients who use insulin, their experimental “closed loop” system would make it possible to continuously monitor and adjust drug infusions in order to maintain the dose within this which we call the therapeutic range, that is to say where it is supposed to be the most effective without being toxic.
Current dosing of chemotherapy drugs may be inaccurate and based on unreliable formulas.
In proof-of-concept testing in rabbits, the amount of 5-fluorouracil circulating in the body was analyzed every five minutes using high-performance liquid chromatography and mass spectroscopy. According to a report published Wednesday in the journal Med, the system helped keep blood levels of the drug within the target range nearly 45 percent of the time, compared with 13 percent of the time in animals not using the system.
The researchers made some components of the system manually for their current experiments, but “each step could potentially be fully automated using commercially available devices, enabling fully autonomous, closed-loop control of drug concentrations” , they said.
Current methods for calculating doses of chemotherapy drugs, generally based on patients’ height and weight, do not take into account differences that can affect how the drug is distributed in the body, nor genetic variations that influence how the The body uses it, the researchers said.
Additionally, the levels of enzymes that affect chemotherapeutic drug concentrations are known to fluctuate depending on the time of day. During a single infusion, circadian rhythms can cause tenfold fluctuations in blood concentrations of the commonly used drug 5-fluorouracil, the researchers said.
A patient “can have treatment cycles with minimal toxicity and then have one cycle with miserable toxicity,” study leader Dr. Douglas Rubinson of the Dana-Farber Cancer Institute in Boston, said in a statement.
“Something has changed in the way the patient metabolizes chemotherapy from one cycle to the next. Our archaic dosages do not account for this change and patients suffer as a result.”
Benefit of Keytruda for kidney cancer patients lasts for years
Kidney cancer patients continued to experience a survival advantage from postoperative treatment with Merck’s Keytruda, more than four years after enrolling in a randomized trial, researchers reported Wednesday in The New England Journal of Medicine.
The drug’s use after surgery for renal cell carcinoma was approved by the U.S. Food and Drug Administration in 2021 based on the trial, but the duration of the survival benefit was uncertain, they said. Researchers.
In total, 496 participants received Keytruda and 498 received a placebo. At 48 months, the estimated overall survival rate was 91.2% in the Keytruda group and 86.0% in the placebo group.
The researchers also found that the pattern was similar across various subsets of patients.
Because half of the patients were followed for more than 57 months and individual risk factors were taken into account, the risk of death during the study period was 38% lower in the Keytruda group, according to the report.
Side effect rates were 20.7% in the Keytruda group and 18.6% in the placebo group. ) “This is the first study to show a statistically and clinically significant improvement in survival with postoperative treatment (in kidney cancer,” said Dr. Toni Choueiri of the Dana-Farber Cancer Institute, head of the study, discussing the trial results at a symposium earlier this year.
