The frequency of neutropenia in patients receiving long-term cefepime therapy for osteomyelitis compared with that in patients receiving other antimicrobials was studied. A comparative case review was conducted of home infusion patients receiving cefepime and patients receiving other antimicrobials for osteomyelitis. All courses of antimicrobial therapy for osteomyelitis between January 2001 and December 2002 were evaluated. The duration of prescribed therapy was approximately six weeks. Weekly laboratory tests included complete blood counts with differential. A total of 134 courses of antimicrobial therapy were reviewed (13 courses of cefepime therapy in 12 patients and 121 courses of therapy with other i.v. antimicrobials in 120 patients). Eight (62%) of the cefepime courses resulted in neutropenia, compared with none in the courses of other antimicrobials. Neutropenia was detected after 17-30 days of cefepime therapy. Blood counts returned to normal within one week of cefepime discontinuation. Eight of 13 courses of extended therapy with i.v. cefepime for osteomyelitis resulted in neutropenia, compared with none of 121 courses of other antimicrobials. Clinicians should exercise extreme caution when prescribing cefepime for longer than 14 days.