Analysis of finger sweat detected isoniazid in adults with tuberculosis (TB) for ≤ 6 hours after administration, based on data from a new pilot study.
Risk factors for TB treatment failure include poor medication compliance and insufficient exposure to medications, but measurement of drugs in samples of blood, saliva, or sweat can help assess adherence and inform dose adjustments, wrote Katherine Longman, a PhD student at the University of Surrey, Guildford, United Kingdom, and colleagues.
Although TB is treatable, “it is well known that insufficient drug dosing leads to treatment failure and drug resistance, and so ensuring that patients are have sufficient drug exposure is important,” corresponding author Melanie J. Bailey, PhD, also of the University of Surrey, said in an interview.
“This can be carried out using blood, but blood is painful to collect and difficult to transport. Finger sweat offers a completely noninvasive way to sample patients,” but its use to determine medication adherence has not been examined, she said.
In a pilot study published in the International Journal of Antimicrobial Agents, the researchers reviewed data from 10 adults with TB who provided finger sweat, blood, and saliva samples at several timepoints ≤ 6 hours after receiving a controlled dose of isoniazid (median of 300 mg daily). They used liquid chromatography–mass spectrometry to examine the samples.
Overall, “isoniazid and acetyl isoniazid were detected in at least one finger sweat sample from all patients,” with detection rates of 96% and 77%, respectively, the researchers wrote. Given the short half-life of isoniazid, they used a window of 1-6 hours after administration. Isoniazid was consistently detected between 1 and 6 hours after administration, while acetyl isoniazid had a noticeably higher detection rate at 6 hours.
The researchers also examined creatinine to account for variability in volume of sweat samples, and found that finger sweat was significantly correlated to isoniazid concentration. The maximum isoniazid to creatinine ratio in finger sweat occurred mainly in the first hour after drug administration, and the activity of isoniazid in finger sweat over time reflected isoniazid concentration in serum more closely after normalization to creatinine, they said. The Pearson’s correlation coefficient (r) was 0.98 (P P = .051).
The study findings were limited by several factors including the lack of knowledge of the last drug dose and lack of confirmation testing with an established method of analysis, the researchers noted. However, the results support the potential of the finger sweat test as a screening tool to indicate patients’ nonadherence or to identify patients at risk of low medication exposure, they wrote in their discussion.
“We were surprised that we were able to detect the drug in so many patient samples because the sample volume is so low, and so detection is challenging,” Bailey told Medscape Medical News. “We were also surprised that fingerprint and drug levels correlated so well after normalizing to creatinine. This is exciting as it unlocks the possibility to test drug levels, as well as providing a yes/no test,” she said.
In practice, the finger sweat technique could reduce the burden on clinics by offering a completely noninvasive way to test a patient’s medication adherence. Looking ahead, more research is needed to explore whether creatinine normalization is widely applicable, such as whether it works for patients with abnormal kidney function, she added.
Noninvasive Option May Mitigate Treatment Challenges
The current study presents a strategy that might address current limitations in TB management, said Krishna Thavarajah, MD, a pulmonologist and director of the interstitial lung disease program at Henry Ford Hospital, Detroit, Michigan, in an interview.
Both self-administered treatment and directly-observed therapy (DOT) for TB therapy have limitations, including adherence as low as 50% for TB regimens, she said. In addition, “DOT availability and efficacy can be limited by cost, personnel availability from an administration perspective, and by distrust of those being treated,” she noted.
In the current study, “I was struck by the correlation between the sweat and serum values of INH [isoniazid] and by the level of sophistication of noninvasive testing, being able to normalize for creatinine to account for different volumes of sweat,” Thavarajah told Medscape Medical News. In clinical practice, finger sweat isoniazid could potentially serve as an adjunct or alternative to DOT in patients with TB, she said.
Although adherence to the sampling protocol and possible patient distrust of the process (such as concerns over what else is being collected in their sweat) might be barriers to the use of a finger sweat strategy in the clinical setting, appropriate patient selection, patient training, and encouraging clinicians to incorporate this testing into practice could overcome these barriers, said Thavarajah.
However, more research is needed to study the finger sweat strategy in larger, real-world samples and to study accuracy and treatment adherence with monitoring in a population undergoing DOT, she said.
The study was supported by the Engineering & Physical Sciences Research Council and by Santander PhD Mobility Awards 2019. The researchers had no financial conflicts to disclose. Thavarajah had no financial conflicts to disclose.