An imaging system and method provides automated microbial growth detection for antibiotic sensitivity testing. A processing system having an image sensor for capturing images of an inoculated culture plate having antibiotic disks disposed on the culture media captures images of the plate at separate times (e.g., first and second images). The system generates pixel characteristic data for pixels of the second image from a comparison of the first image and second image. The pixel characteristic data may be indicative of plate growth. The system may access growth modeling data concerning the antibiotic disk(s) and generate simulated image data with a growth model function. The growth model function uses the growth modeling data. The simulated image data simulates growth on the plate relative to the disk(s). The system compares the simulated image and the pixel characteristic data to identify pixel region(s) of the second image that differ from the simulated image.