This study investigated the antibiotic susceptibilities of 67 isolates of viridans streptococci from 61 cases of bacteraemia in immunocompromised paediatric patients with malignancy. The majority of patients (87%) had received prior courses of empirical antibiotic therapy, which consisted of ceftazidime plus amikacin during period 1 and piperacillin/tazobactam plus amikacin during period 2. Susceptibility to vancomycin and quinupristin/dalfopristin was 100%. Susceptibility to beta-lactam antibiotics varied. For period 1, the geometric mean MICs of all beta-lactams tested against blood culture isolates (n = 31) exceeded those against isolates (n = 36) collected from blood after the change in empirical therapy (by 3.3-fold for ceftazidime, 2.8-fold for piperacillin/tazobactam and 1.6-fold for penicillin). The selection of a beta-lactam antibiotic for empirical therapy must be made with care, as repeated courses of certain agents may be more likely to select for viridans streptococci with diminished susceptibility.