The combination of penicillin or ceftriaxone with gentamicin results in synergistic killing in animal models of VGS or S gallolyticus (bovis) experimental IE. In selected patients, treatment with a 2-week regimen with either penicil- lin or ceftriaxone combined with an aminoglycoside resulted in cure rates that are similar to those after monotherapy with penicillin or ceftriaxone administered for 4 weeks.83,120 Studies performed in Europe, South America, and the United States demonstrated that the combination of once-daily ceftriaxone with either netilmicin or gentamicin administered once daily was equivalent in efficacy to 2 weeks of therapy with peni- cillin with an aminoglycoside administered in daily divided The 2-week regimen of penicillin or ceftriaxone combined with single daily-dose gentamicin is reasonable for uncomplicated cases of IE caused by highly penicillin-suscep- tible VGS or S gallolyticus (bovis) in patients at low risk for adverse events caused by gentamicin therapy (Table 7). This 2-week regimen is not recommended for patients with known extracardiac infection or those with a creatinine clearance of <20 mL/min. Although the two, 4-week -lactam containing regi- mens shown in Table 7 produce similar outcomes, each regi- men has advantages and disadvantages. Monotherapy with either penicillin or ceftriaxone for 4 weeks avoids the use of gentamicin, which is potentially ototoxic and nephrotoxic. Compared with penicillin, the advantage of once-daily cef- triaxone is its simplicity for use in therapy administered to Both penicillin and ceftriaxone are overall well tolerated but, like all antimicrobials, have the potential for causing adverse drug events; some of the more common ones include rash, fever, diarrhea, and neutropenia. Liver function abnormalities can be seen with ceftriaxone use and are sometimes associated with sludging of drug in the For patients who are unable to tolerate penicillin or ceftriax- one, vancomycin is a reasonably effective alternative. 