When investigating a possible cluster of infections, an infection preventionist (IP) follows a structured epidemiological approach to identify the cause and implement control measures. The Certification Board of Infection Control and Epidemiology (CBIC) outlines this process within the "Surveillance and Epidemiologic Investigation" domain, which aligns with the Centers for Disease Control and Prevention (CDC) guidelines for outbreak investigation. The steps typically include defining and identifying cases, formulating a hypothesis, testing the hypothesis, and implementing control measures. The question specifies the next step after defining and identifying cases, requiring an evaluation of the logical sequence.

Option C, "A hypothesis that will explain the majority of cases," is the next critical step. After confirming a cluster through case definition and identification (e.g., by time, place, and person), the IP should develop a working hypothesis to explain the observed pattern. This hypothesis might propose a common source (e.g., contaminated equipment), a mode of transmission (e.g., airborne), or a specific population at risk. The CDC’s "Principles of Epidemiology in Public Health Practice" (3rd Edition, 2012) emphasizes that formulating a hypothesis is essential to guide further investigation, such as identifying risk factors or environmental sources. This step allows the IP to focus resources on testing the most plausible explanation before proceeding to detailed analysis or interventions.

Option A, "The route of transmission," is an important element of the investigation but typically follows hypothesis formulation. Determining the route (e.g., contact, droplet, or common vehicle) requires data collection and analysis to test the hypothesis, making it a subsequent step rather than the immediate next action. Option B, "An appropriate control group," is relevant for analytical studies (e.g., case-control studies) to compare exposed versus unexposed individuals, but this is part of hypothesis testing, which occurs after the hypothesis is established. Selecting a control group prematurely, without a hypothesis, lacks direction and efficiency. Option D, "Whether observed incidence exceeds expected incidence," is a preliminary step to define a cluster, often done during case identification using baseline data or statistical thresholds (e.g., exceeding the mean plus two standard deviations). Since the question assumes cases are already defined and identified, this step is complete, and the focus shifts to hypothesis development.

The CBIC Practice Analysis (2022) and CDC guidelines prioritize hypothesis formulation as the logical next step after case identification, enabling a targeted investigation. This approach ensures that the IP can efficiently address the cluster’s cause, making Option C the correct answer.