Microneedle Beta-Lactam Biosensor Passes First-in-Human Test

By Anne Harding

October 12, 2019

NEW YORK (Reuters Health) - A solid microneedle biosensor can continuously monitor penicillin levels in extracellular fluid (ECF) in real-time, a new proof-of-concept study in healthy volunteers shows.

"Microneedle sensors were able to monitor changing antibiotic concentrations in tissue fluid with a similar accuracy as the current gold standard," Dr. Alison H. Holmes of the Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Hammersmith Hospital in London told Reuters Health by email.

"This study provides evidence to support the wider exploration of microneedle antibiotic monitoring in patients and for a broader range of antimicrobial drugs," Dr. Holmes and her team write in The Lancet Digital Health, online September 30. "It is also the first step towards automated, individualised antibiotic dosing in humans through the application of closed-loop control systems."

Better drug monitoring methods are needed to help optimize antibiotic dosing, which could in turn reduce toxicity and antimicrobial resistance (AMR), the researchers note. They previously developed a solid microneedle beta-lactam biosensor for in-vivo monitoring of penicillin levels in ECF, and validated it in vitro

In the new study, 10 healthy volunteers wore two microneedle arrays, one containing three enzyme-coated sensors and one containing a control sensor, while receiving oral phenoxymethylpenicillin. They also underwent blood sampling via cannula and microdialysis monitoring of ECF.

The authors were able to analyze data from 25 of the 30 sensors. Maximum phenoxymethylpenicillin concentrations were 0.74 mg/L with microdialysis and 0.64 mg/L with the microneedle (P=0.53).

Likewise, there was no significant difference between in time to maximum concentration and area under the concentration-time curve (AUC) with microdialysis and microneedle monitoring, or in phenoxymethylpenicillin AUCs with free serum and microneedle measurement.

All monitoring methods were well tolerated, and all showed significant variation in pharmacokinetics from person to person, as has been found previously with phenoxymethylpenicillin, the authors note.

"Microneedle sensing provides an opportunity to monitor antibiotic levels outside of specialist settings and in real-time," Dr. Holmes said. "We envisage that this technology could be used to optimise doses for patients being treated on the ward, and also those being treated as an outpatient. The application will also enable the provision of a rich source of data to better inform prescribing. Linked to closed-loop control systems this will provide the ability to be able to deliver automated drug monitoring and dose adjustment to achieve therapeutic antibiotic levels."

She and her colleagues are now planning to test the sensors in sick, hospitalized patients, and to expand their research to include antibiotics active against resistant bugs.

In an accompanying editorial, Dr. Daniel C. Richter and Dr. Markus A. Weigand of Heidelberg University Hospital in Germany write, "It will be interesting to see how the microneedle biosensor will perform in a population with infections and, especially, in critically ill patients in the intensive-care unit, where real-time measurement of concentrations would be important."

Another question, they note, is whether the sensors could be placed at the site of infection to "aid clinicians in determining the effectiveness of the antimicrobial therapy."

The technology has potential usefulness as "the mainstay of a closed-loop system for automated drug delivery," the editorialists add, but the benefits of continuous therapeutic drug monitoring have not been established.

"We don't know whether continuous measurement is superior to serial measurement every day or twice a day," Dr. Weigand told Reuters Health by phone. "We have no data on that so far."

He and Dr. Richter conclude, "Further investigation will show if this technology will find its way into clinical practice and we anticipate that this tool has the potential to change the way we do antimicrobial treatment."

SOURCE: https://bit.ly/2nlpduw and https://bit.ly/2o4tkLC

Lancet Dig Health 2019.