On-patch detection of meropenem using hydrogel-forming microneedles and near-infrared spectroscopy for enhanced therapeutic drug monitoring

Abstract

Meropenem, a broad-spectrum carbapenem antibiotic, is commonly used for critically ill patients with hospital-acquired infections, where pharmacokinetic changes can lead to inadequate dosages. A rapid and facile point-of-care test is essential for tailoring antimicrobial therapy to improve patient outcomes. We introduce a novel approach combining hydrogel-forming microneedles (MNs) integrated with near-infrared (NIR) spectroscopy for on-patch detection, enabling rapid and direct assay at the point-of-care without the need of sample preparation. MNs offer a minimally invasive approach for microsampling dermal interstitial fluid (ISF), contributing to eco-conscious healthcare solutions. The optimal MN formulation, developed using response surface methodology, included 5.00 % w/w hyaluronic acid, 1.50 % w/w Gantrez™ S-97, and 0.15 % w/w xanthan gum, allowing extraction of >200 μL ISF. Using these MNs for NIR on-patch detection, the optimum partial least squares regression (PLSR) model covering meropenem concentration in the therapeutic range, using standard normal variate (SNV) and orthogonal signal correction (OSC), achieved a root mean square error of prediction (RMSEP) of 1.2147 μg/mL and bias of −0.3581 μg/mL, with latent factor 1. A Pearson R² of 0.8952 was obtained for 20 ex vivo dermal interstitial fluid (ISF) samples. Comparison of meropenem concentrations from NIR spectroscopy and fluorescence assay showed no significant difference (p-value >0.05). This method enables real-time, low-waste, and cost-effective β-lactam antibiotic measurement with a short turnaround time, enhancing outcomes in vulnerable patients.