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By Nancy Lapid
April 25 (Reuters) - Hello Health Rounds Readers! Today we have some early rodent and animal data that may portend important advances in tackling antibiotic resistant bugs and better delivery of chemotherapy drugs. We also cover some long-term data on the world's top-selling prescription medicine, Merck & Co's cancer immunotherapy Keytruda.
Vaccines may help tackle antibiotic resistance
Using a new approach to vaccine development, researchers may have come up with a potential solution to the problem of antibiotic-resistant bacteria.
Their experimental vaccine provided mice with high levels of immunity from lethal levels of Staphylococcus aureus and its “superbug” form methicillin-resistant S. aureus, or MRSA, researchers reported on Wednesday in Nature Communications.
Overuse of antibiotics has helped lead to the evolution of superbugs resistant to most commonly available 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 flag 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 polysaccharide poly-beta-(1−6)-N-acetylglucosamine, or PNAG, which is present on the cell wall of many bacteria.
The scientists were able to identify 32 PNAG carbohydrates, all comprised of five sugars but with differing patterns of certain molecular components that are either bound to another small molecule called an acetyl group, or that are not bound to anything else.
The team found two PNAG versions that were especially promising and attached them to a virus that infects bacteria.
Coupled with the virus, the two PNAG combos provided mice with “near complete protection” against infections by S. aureus and MRSA, with minimal impact on the healthy organisms that live in the intestines, the researchers said.
The widespread presence of PNAG in multiple bacteria “render it an attractive target for vaccine development,” they added.
Closed-loop chemo infusions may improve cancer treatment
Doctors may someday use continuous-monitoring systems for chemotherapy to keep constant track of how much of the drugs is present in the patient’s blood and automatically adjust the dose if more or less is needed, researchers say.
Similar to what’s available now for patients with diabetes who use insulin, their experimental “closed-loop” system would allow for continuous monitoring and adjusting of drug infusions to keep the dose in the so-called therapeutic range, where it’s believed to be most effective without being toxic.
Current dosing of chemotherapy drugs can be inexact and based on unreliable formulas.
In proof of concept tests in rabbits, the amount of the chemo drug 5-fluorouracil circulating in the body was analyzed every five minutes using high-performance liquid chromatography mass spectroscopy. The system kept blood levels of the drug within the target range nearly 45% of the time compared with 13%
of the time in animals not using the system, according to a report published on Wednesday in Med.
The researchers performed some components of the system manually for their present experiments, however "each step could potentially be fully automated using commercially available devices, thereby enabling fully autonomous, closed-loop control of drug concentrations,” they said.
Current methods of calculating chemotherapy drug dosages, usually based on patients’ height and weight, don’t account for differences that can affect how the drug spreads through the body, or genetic variations that influence how the body uses it, the researchers said.
Furthermore, levels of enzymes that affect chemotherapy drug levels are known to fluctuate based on time of day. During the course of a single infusion, circadian rhythms can lead to tenfold fluctuations in blood levels of the commonly used drug 5-fluorouracil, the researchers said.
One patient “can have cycles of treatment with minimal toxicity and then have a cycle with miserable toxicity,” study leader Dr. Douglas Rubinson of Dana-Farber Cancer Institute in Boston said in a statement.
“Something changed in how that patient metabolized chemo from one cycle to the next. Our antiquated dosing fails to capture that change, and patients suffer as a result.”
Keytruda benefit for kidney cancer patients lasts years
Patients with kidney cancer were still seeing a survival benefit from postoperative treatment with Merck’s Keytruda more than four years after enrollment in a randomized trial, researchers reported on Wednesday in The New England Journal of Medicine.
Use of the drug after surgery for renal cell carcinoma was approved by the U.S. Food and Drug Administration in 2021 on the basis of the trial, but how long the survival advantage would last had been uncertain, the researchers said.
Overall, 496 participants received Keytruda and 498 received placebo. At 48 months, the estimated overall survival rate was 91.2% in the Keytruda group and 86.0% in the placebo group.
The pattern was similar in various subsets of patients, the researchers also found.
With half the patients followed for more than 57 months, and with individual risk factors taken in to account, the odds of death during the study period were 38% lower in the Keytruda group, according to the report.
Rates of side effects were 20.7% with Keytruda and 18.6% with placebo.
“This is the first study to show a statistically significant and clinically meaningful survival improvement with any (postoperative) therapy in kidney cancer,” study leader Dr. Toni Choueiri of Dana-Farber Cancer Institute said of the trial results at a symposium earlier this year.
(Reporting by Nancy Lapid; Editing by Bill Berkrot)
((nancy.lapid@thomsonreuters.com))
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