Infective endocarditis is a disease with high mortality and morbidity, generally caused by a wide range of organisms. Prophylaxis with penicillins, cefalosporins, macrolides, or vancomycin is highly recommended for the patients with endocarditis, prosthetic heart valves. An 83-year-old man admitted with fever, fatigue, and joint pain and reported dental intervention following amoxicillin prophylaxis fortyfive days ago. Patient history indicated acute rheumatoid arthritis, bacterial endocarditis, and mitral and aortic valve replacement. S. Sanguinis was detected in the blood culture of the patient, which was resistant to penicillin and ampicillin. He was given meropenem, the clinical status was improved and no microorganisms were detected in two follow-up blood cultures. Endocarditis prophylaxis should be individualized considering the globally high penicillin resistance, especially for the patients with prosthetic valves and/or infective endocarditis history. In addition, to decrease the bacterial load of the oral flora before elective dental or respiratory intervention is recommended with antibiotic prophylaxis.