In this limited patient population, prophylactic antimicro- bial therapy should be directed against viridans group strep- tococci. During the past 2 decades, there has been a signifi- cant increase in the percentage of strains of viridans group streptococci resistant to antibiotics recommended in previous AHA guidelines for the prevention of IE. Prabhu et al135 studied susceptibility patterns of viridans group streptococci recovered from patients with IE diagnosed during a period from 1971 to 1986 and compared these susceptibilities with those of viridans group streptococci from patients with IE diagnosed from 1994 to 2002. In that study, none of the strains of viridans group streptococci were penicillin resistant in the early time period compared with 13% of strains that were intermediately or fully penicillin resistant during the later time period. In that study, macrolide resistance increased from 11% to 26% and clindamycin resistance from 0% to 4%. Among 352 blood culture isolates of viridans group strep- tococci, resistance rates were 13% for penicillin, 15% for amoxicillin, 17% for ceftriaxone, 38% for erythromycin, and 96% for cephalexin.136 The rank order of decreasing level of activity of cephalosporins in that study was cefpodoxime equal to ceftriaxone, greater than cefprozil, and equal to cefuroxime, and cephalexin was the least active. In other studies, resistance of viridans group streptococci to penicillin ranged from 17% to 50%137 142 and resistance to ceftriaxone ranged from 22% to 42%.131,140 Ceftriaxone was 2 to 4 times more active in vitro than cefazolin.131,140 Similarly high rates of resistance were reported for macrolides, ranging from 22% to 58%137,141,143,144; resistance to clindamycin ranged from Most of the strains of viridans group streptococci in the above-cited studies were recovered from patients with serious underlying illnesses, including malignancies and febrile neu- tropenia. 