Chronic Suppurative Otitis Media (CSOM) is a widely prevalent disease, which is a leading cause of acquired deafness worldwide, and is associated with complications with significant mortality and morbidity. It often responds poorly to standard of care therapy and places a disproportionate burden on at-risk populations. The microbiology and antibiotic resistance of CSOM varies based on local factors, including health care access, comorbidities, and antibiotic prescribing practices. We evaluated the role and feasibility of using routine culture for the treatment of CSOM in rural areas as a means of improving treatment of CSOM. More than 400 patients were screened in a rural clinic in South Africa over six weeks, and 14 met study criteria and consented for participation. Gram-negative organisms predominated overall, although Staphylococcus aureus was the most commonly isolated single species. A majority of the pathogens were relatively sensitive to commonly prescribed antibiotics, but two cases of methicillin resistant Staphylococcus aureus were cultured, and one patient grew a Scedosporium species. Treatment on follow-up was able to be directed by culture results, suggesting routine culture at the initial point of contact with the health care system may play a pivotal role in addressing this widely prevalent and devastating disease.