Preventing Nephrotoxicity of Vancomycin and Attenuating Deep Tissue Infections by Methicillin-Resistant <i>Staphylococcus aureus</i> via Needle-Free Drug Delivery by the Droplette Micromist Technology Device

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing wound infections. The use of vancomycin, a glycopeptide antibiotic, is a last resort treatment against MRSA. However, systemic administration of vancomycin causes nephrotoxicity. Currently, no effective strategies are available to deliver the high molecular weight drug vancomycin topically across the outermost layer of the epidermis, the stratum corneum, to treat deep tissue infections by MRSA. We reported previously on the use of localized, needle-free transdermal delivery of high molecular weight antibiotics by the Droplette micromist technology device (DMTD) to successfully treat deep tissue infections by gram-negative bacteria. We hypothesized that DMTD delivery of vancomycin would successfully attenuate deep tissue infections by MRSA without causing nephrotoxicity. A mouse model (n = 15 per experimental group) for deep skin wound infection by MRSA was treated with vancomycin (300 mg/kg; 3 treatments) delivered via either transdermal DMTD delivery or systemic delivery by intraperitoneal (IP) injection. Saline-treated mice with MRSA infection were used as a positive control for untreated MRSA infection. The number of colony-forming units of MRSA in the skin wound tissue 2 days post-infection was determined to evaluate attenuation of MRSA infection. Histopathological scoring of kidney tissues was used to evaluate vancomycin-induced nephrotoxicity. Both IP- and DMTD-delivered vancomycin attenuated MRSA deep skin infection similarly as compared to saline-treated control (P < .001), but hematoxylin and eosin staining of kidney tissues revealed acute tubular necrosis evidenced by vacuolization of tubular cells, tubular lumen dilation, and tubular cell necrosis only in the mice that received IP-delivered vancomycin. These results confirm that transdermal delivery of vancomycin by the DMTD successfully attenuates deep skin infection by MRSA without causing nephrotoxicity. This novel drug delivery device can have a significant impact on wound care in general, but especially in the austere environment of battlefield hospitals.