antibiotic restriction can be useful in maintaining bacterial susceptibility. the objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (nicu), would ameliorate broad-spectrum susceptibility of gram-negative isolates. nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: group 1 (n=396) comprised patients admitted from january 2002 to december 2003, period in which cefepime was the most used broad-spectrum antibiotic. patients in group 2 (n=349) were admitted when piperacillin/tazobactam replaced cefepime (january to december 2004) and in group 3 (n=250) when cefepime was reintroduced (january to september 2005). meropenem was the alternative third-line antibiotic for all groups. multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. statistics involved kruskal-wallis, mann-whitney and logrank tests, kaplan-meier analysis. groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. ninety-eight gram-negative isolates were analyzed. patients were more likely to remain free of multiresistant isolates by kaplan-meier analysis in group 2 when compared to group 1 (p=0.017) and group 3 (p=0.003). there was also a significant difference in meropenem resistance rates. cefepime has a greater propensity to select multiresistant gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.