Background: Tuberculosis (TB) is an infectious disease is endemic in Sub-Saharan Africa including Ethiopia together with HIV infection in the past decades.

Objective:-To assess the magnitude of Mycobacterium tuberculosis, drug-resistance pattern, and associated factors among patients referred to St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia.

Methods: A cross-sectional study was conducted at SPHMMC, Addis Ababa, Ethiopia from Jan to July 2019.  Socio-demographic data were collected by using structured questionnaire in face to face interview. Sputum and non-sputum samples were also collected. All clinical samples were processed using the standard operating procedures (SOPs) and examined using Ziehl-Neelsen technique, analyzed X-pert MTB/RIF assay, and culture using Lowenstein-Jensen (LJ) and positive culture results were tested for drug resistance pattern using Line probe Assay (LPA).

Results: The totals of 436 respondents were included in the study. Of the total, 374(85.8%) were diagnosed for pulmonary tuberculosis, and 130 (30%) were HIV positive individuals. The overall LJ culture confirmed Mycobacterium tuberculosis was 27 (6.2%), and three isolates were resistant for either INH or RIF drug, while two of them were MDR-TB based on line probe assays method. In a bivariate logistic regression analysis, having a previous TB-contact history, patient weight loss, having pneumonia with chest X-ray diagnosis, and having CD4⁺ T-cells  count 200-350/mm³ of blood were significantly associated.

Conclusion: The magnitude of M. tuberculosis and MDR TB in this study highlights the need for further extended early case detection and managing MDR TB cases to minimize transmission and the suffering of patients.