We evaluated the efficacy and safety of a monotherapy by piperacillin and sulbactam potentially associated to vancomycin as an empiric antimicrobial therapy in febrile neutropenic patients treated with nephrotoxic chemotherapy for solid tumors. Twenty-three patients were treated during 32 episodes with piperacillin 4 g i.v. every 8 hours and sulbactam 1 g IV every 8 hours. If the patient remained febrile after 48 hours, 1 g of vancomycin i.v. was added every 12 hours as indicated by our study design. The mean duration of neutropenia was 5.5 days (2-13 days). In ten episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in seven episodes (22%) with six Gram negative bacilli and 3 Gram positive cocci. There were 19 apyrexia with piperacillin and sulbactam (59%) and further seven were resolved by the addition of vancomycin (total success: 81%). Failure was observed in six episodes consecutive to germ resistance (one episode), clinical deterioration (one episode), relapsing fever related to Pseudomonas infection (one episode), persistent fever despite withdrawal of neutropenia and no microbiological documentation (two episodes) and protocol violation (one episode). Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe in short period febrile neutropenic episodes in patients heavily treated with nephrotoxic chemotherapy for solid tumors.