Emergence of Rapid-Onset Ototoxicity Following Three Doses of Vancomycin: A Unique Case Report in the Context of Normal Renal Function and Therapeutic Dosing.

Vancomycin, a potent glycopeptide antibiotic renowned for its efficacy against methicillin-resistant Staphylococcus aureus, also harbors the potential for adverse reactions. While its use is often associated with infusion-related events and nephrotoxicity, ototoxicity has emerged as a noteworthy but rare concern. This adverse effect, characterized by a spectrum of transient to permanent hearing loss or damage, typically surfaces in patients receiving excessive doses, those undergoing concomitant therapy with other ototoxic agents such as aminoglycosides, or individuals with baseline hearing impairment or renal dysfunction. This report highlights the possibility of ototoxicity in the setting of normal renal function and therapeutic dosing. We report a case of a 58-year-old male patient with a complex medical history, who presented with sepsis, respiratory failure, and a constellation of underlying conditions. His treatment regimen encompassed intravenous vancomycin administration, which led to an unexpected development-severe-to-profound bilateral conductive and sensorineural hearing loss after three doses. The absence of concurrent ototoxic agents and Bayesian dosing software predicting an acceptable AUC/MIC ratio complicates the understanding of this adverse event. Amid this complex scenario, the case underscores the evolving landscape of vancomycin-induced ototoxicity, encouraging heightened vigilance, thorough audiometric monitoring, and an in-depth exploration of potential mechanisms underlying this adverse reaction. Early audiometric testing and referral to otolaryngology may allow for early intervention with high-dose steroids to mitigate the ototoxicity.

Patterning Neuroepithelial Cell Sheet via a Sustained Chemical Gradient Generated by Localized Passive Diffusion Devices.

Recent advances in human pluripotent stem cells (hPSCs)-derived in vitro models open a new avenue for studying early stage human development. While current approaches leverage the self-organizing capability of hPSCs, it remains unclear whether extrinsic morphogen gradients are sufficient to pattern neuroectoderm tissues in vitro. While microfluidics or hydrogel-based approaches to generate chemical gradients are well-established, these systems either require continuous pumping or encapsulating cells in gels, making it difficult for adaptation in standard biology laboratories and downstream analysis. In this work, we report a new device design that leverages localized passive diffusion, or LPaD for short, to generate a stable chemical gradient in an open environment. As LPaD is operated simply by media changing, common issues for microfluidic systems such as leakage, bubble formation, and contamination can be avoided. The device contains a slit carved in a film filled with solid gelatin and connected to a static aqueous morphogen reservoir. Concentration gradients generated by the device were visualized via DAPI fluorescent intensity and were found to be stable for up to 168 h. Using this device, we successfully induced cellular response of Madin-Darby canine kidney (MDCK) cells to the concentration gradient of a small-molecule drug, cytochalasin D. Furthermore, we efficiently patterned the dorsal-ventral axis of hPSC-derived forebrain neuroepithelial cells with the sonic hedgehog (Shh) signal gradient generated by the LPaD devices. Together, LPaD devices are powerful tools to control the local chemical microenvironment for engineering organotypic structures in vitro.