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Background: Staphylococcus aureus (S. aureus) is one of the pathogens strongly implicated in hospital infections. Data on the resistance and molecular characteristics of this bacterium are rare in Mali., Objective: This study aimed to evaluate the antibiotic resistance patterns, virulence factors of S. aureus isolates from pleural fluid infections in hospitalized patients., Methods: Pleural effusion samples were obtained by thoracentesis for bacteriological examination from October 2021 to December 2022 at the "Hôpital du Mali" teaching hospital. Comorbidities such as HIV/AIDS and diabetes were assessed. Standard microbiological procedures were used for bacterial identification. The disk diffusion method was used to identify methicillin-resistant S. aureus . The PCR amplification method was used to detect the following genes: lukE/D , sek , bsa , sel , and sep ., Results: This study analyzed 6096 samples from inpatients and found a pooled frequency of bacterial pleuritis of 526 (8.6%) in thoracic surgery and pediatric wards. S. aureus was isolated in 52 (9.88%) cases, of which 39 (75%) isolates were MRSA. There was no significant difference between the sexes ( p = 1.00 ). The median age of the patients was 30 years. All S. aureus isolates showed resistance to penicillin-G. The leucocidin lukE/D toxin was detected in 7.7% of thoracic surgery patients, but sek , bsa , sel , and sep toxins were not found., Conclusion: In this study, we found a high frequency of S. aureus (and MRSA) in pleurisy patients at the "Hôpital du Mali". Only the leukocidin lukE/D was found. The empirical treatment protocol for pleurisy may need revision. Clindamycin, linezolid, teicoplanin, daptomycin, fosfomycin, vancomycin, moxifloxacin and fusidic acid were the most active antibiotics on our isolates in this study. Infection prevention measures, active surveillance, and effective therapeutic options are recommended., Competing Interests: Competing interests The authors declare no competing interests.