© 2017, EDIMES Edizioni Medico Scientifiche. All rights reserved.After experiencing a high rate of carbapenem-resistant Gram-negative bacilli infections in febrile neutropenic patients, a two-stage intervention was introduced in the haematopoietic stem cell transplantation (HSCT) centre. During the first eight months of 2014, carbapenems remained the first choice for the empirical treatment of febrile neutropenia while the use of piperacillin/tazobactam (TZP) was encouraged in patients with stable clinical condition. When blood cultures were reported as negative and the patient was clinically stable the carbapenem/TZP treatment was stopped regardless of continuous fever and neutrophil count. From October 2014, TZP (with prolonged infusion) with or without amikacin replaced carbapenems as the first line therapy of neutropenic fever except for high-risk patients previously known as colonized or infected with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae, who presented with severe sepsis, septic shock or nosocomial pneumonia, and recently transferred from the intensive care unit with a high endemicity of multidrug-resistant Gram-negative bacilli. Vancomycin or teicoplanin was used when there was suspicion of septic shock or detection of severe mucositis and central-line associated bacteraemia. The antibacterial therapy was escalated or de-escalated in culture-positive patients according to the antimicrobial susceptibility reports and clinical progress. Daily defined dosages (DDD) per 1000 patient days were calculated for all antibiotics by the hospital pharmacist for each year. A total of 913 admissions with 11,544 patient-days were followed in 2013; and 1,072 admissions with 11,843 patient-days were followed in 2014. The rate of ESBL production in Enterobacteriaceae bacteraemia was as 31.8% in 2013 and 47.3% in 2014. All staphylococci isolated from blood culture were methicillin-resistant for both years. All Enterococcus faecium isolates but one from blood cultures were resistant to ampicillin. The number of the patients who died during hospitalization was 24 in 2013, and 17 patients died in 2014. The DDDs/1000 patient days for imipenem, meropenem, vancomycin, daptomycin, linezolid, piperacillin/ tazobactam and amikacin in 2013 and 2014 were respectively as follows; 201 vs 19 (p<0.001); 1,578 vs 1,092 (p<0.001); 533 vs 251 (p<0.001); 56 vs 14 (p<0.001); 76 vs 26 (p<0.001); 157 vs 254 (p<0.001); and 5 vs 41 (p<0.001). While there was a decreasing trend for consumption of teicoplanin (205 versus 159) and colistin (188 versus 254), this was not statistically significant. Our study showed that a febrile neutropenia pathway guided by local epidemiology and international guidelines can reduce the use of antibiotics in haematological cancer or HSCT patients. The sustainability of such an intervention requires strong multidisciplinary cooperation.