There are few published reports of large case series evaluating management strategies for IE caused by these microorganisms. Results of logistic regression analysis of clinical variables from cases of pneumococcal IE demonstrated the potential value of valve replacement in preventing early death in 1 investigation.129 For patients with NVE caused by highly penicillin-susceptible S pneumoniae, it is reasonable to administer 4 weeks of anti- microbial therapy with penicillin, cefazolin, or ceftriaxone. Vancomycin is reasonable only for patients who are unable to tolerate -lactam therapy. Six weeks of therapy is reasonable for patients with prosthetic valve endocarditis (PVE). Pneumococci with intermediate penicillin resistance (MIC >0.1 1.0 g/mL) or high penicillin resistance (MIC 2.0 g/mL) are recovered uncommonly from patients with Moreover, cross-resistance of pneumococci to other antimicrobial agents such as cephalosporins, mac- rolides, fluoroquinolones, carbapenems, and even vanco- mycin is increasing in frequency. In 1 multicenter study131 with a relatively large number of patients with IE caused by Table 8. Therapy of NVE Caused by Strains of VGS and Streptococcus gallolyticus (bovis) Relatively Resistant to Penicillin Regimen Dose* and Route Duration, wk Strength of Recommendation Comments Aqueous crystalline penicillin G sodium 24 million U/24 h IV either continuously or in 4 6 equally divided doses 4 Class IIa; Level of Evidence B It is reasonable to treat patients with IE caused penicillin-resistant (MIC 0.5 g/mL) VGS strains with a combination of ampicillin or penicillin plus gentamicin as done for enterococcal IE with infectious diseases consultation (Class IIa; Level of Evidence C). Ampicillin 2 g IV every 4 h is a reasonable alternative to penicillin if a penicillin shortage exists. 