Of 41 patients with bone-related infections who were treated for > or =10 days with piperacillin-tazobactam, 14 (34%) developed neutropenia. Cumulative doses of piperacillin administered to neutropenic patients were higher than those administered to nonneutropenic ones (330 vs. 237 g; P=.008), and an inverse correlation was detected between the absolute neutrophil count at the end of treatment and the cumulative dose of piperacillin (r=-0.47, P=.002). Moreover, the incidence of piperacillin-tazobactam-induced neutropenia increased with an increase in the cumulative dose of piperacillin: 0% of patients in the first quartile of cumulative piperacillin doses, 33.3% in the second quartile, 40% in the third quartile, and 66.7% in the fourth quartile.