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Infective endocarditis (IE) The most common overall cause of IE is Streptococcus viridans. The most common cause of IE in injection drug users is Staphylococcus aureus. The most common cause of IE in patients with prosthetic valves is also Staphylococcus species; in the first two months postop coag-negative Staphylococcus predominates, and after that the most common causes are Staphylococcus aureus, Streptococcus viridans, and enterococcus. In treating IE of prosthetic valves and/or in injection drug users, the addition of rifampin to the standard regimen of nafcillin/vancomycin + gentamycin is often recommended in order to add additional gram positive coverage.