Antibiotic resistance can come at a high cost, both in terms of fitness for the pathogen and poorer outcomes for patients. The fitness landscape encountered by bacterial pathogens varies greatly throughout patient populations in terms of host immunity as well as the duration and spectrum of antibiotics encountered. Severely immunocompromised patients present a favorable environment for antibiotic resistance to emerge due to lack of immune-mediated competition and increased opportunities to evolve both on-target and compensatory mutations. Such patients may present unique pathways for antibiotic resistance to emerge.