This document is intended for use by state and local health departments and healthcare facilities and serves as general guidance for the initial response for the containment of novel or targeted multidrug-resistant organisms (MDROs) or resistance mechanisms. It is not intended to describe all the actions that might be required for control of an outbreak (e.g., sustained transmission within a facility or region). In addition, further evaluation might be required based on the findings of the initial response described in this document.