The aim of this study was to assess community members' knowledge and awareness levels, attitudes, and practices of Drug Resistant Tuberculosis. A quantitative descriptive cross sectional study was carried out in the Eastern Cape Province of South Africa. The sample size consisted of four hundred (400) respondents aged 18 years and above on their last birthday who were purposively and conveniently selected from Port Elizabeth area in the Nelson Mandela Municipality. Data were collected using close-ended questions, which were administered by the researcher and two research assistants to the selected respondents. Data were analysed using descriptive statistics. The results of this study show poor knowledge and awareness levels, unfavourable attitudes, but good prevention practices of Drug Resistant Tuberculosis among Port Elizabeth community members. This study also found a statistically significant association between knowledge and attitudes (p value = <0.001), and no statistically significant association between knowledge and practices and attitude and practices, respectively (p values = 0.120 and 0.136). The study also revealed low literacy levels, inadequate information, misconceptions and erroneous beliefs about causes, transmission, prevention, treatment, and management of Drug Resistant Tuberculosis among the respondents. This study also highlighted the use and existence of dual healthcare system (traditional spiritual and western).The study found that the main source of Drug Resistant TB information was radio and television among the majority of research respondents. It is recommended that in future health education interventions and awareness campaigns need to be intensified in the area so that misconceptions and erroneous beliefs that exist in society can be addressed. It is also recommended that training programs that are culturally sensitive should be developed and delivered taking into account different languages and literacy levels that exist in society. Such education interventions should be facilitated in collaboration with people living with Drug Resistant Tuberculosis. A multidisciplinary approach should be fostered and collaborations with spiritual healers and various congregational leaders, traditional health practitioners, community leaders, and government leaders in the health sector should be promoted in order to deal with Drug Resistant Tuberculosis. It is also recommended that a similar study be conducted using a qualitative research approach in urban and rural areas of the Eastern Cape. Lastly, assessment of knowledge, attitudes, and practices of spiritual and traditional healers with regard to Drug Resistant Tuberculosis should be conducted as they can influence health-seeking behaviour.

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