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Background: Little is known about the impacts at an individual level of long-term antibiotic consumption. We explored health outcomes of long-term antibiotic therapy prescribed to a cohort of patients to suppress infections deemed incurable. Methods: We conducted a 5-year longitudinal study of patients on long-term antibiotics at Monash Health, a metropolitan tertiary-level hospital network in Australia. Adults prescribed antibiotics for >12 months to suppress chronic infection or prevent recurrent infection were included. A retrospective review of medical records and a descriptive analysis was conducted. Results: Twenty-seven patients were followed up during the study period, from 29 patients originally identified in Monash Health in 2014. Seven of the 27 patients (26%) died from causes unrelated to the suppressed infection, six (22%) ceased long-term antibiotic therapy and two (7%) required treatment modification. Fifteen (56%) were colonised with multiresistant microorganisms, including vancomycin resistant Enterococci, methicillin resistant <i>Staphylococcus aureus</i>, and carbapenem resistant Enterobacteriaciae. Conclusions: This work highlights the potential pitfalls of long-term antibiotic therapy, and the frailty of this cohort, who are often ineligible for definitive curative therapy.