cilastatin--imipenem-drug-combination and Lymphoma--Non-Hodgkin

Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile neutropenic cancer patients. We noted in a previous study that response to empiric therapy was related more to disease classification (solid tumors vs. leukemia) than to the regimen chosen. In the present study we based empiric monotherapy on the underlying disease in treating 240 episodes of fever and neutropenia in 145 children. Patients with leukemia or Stage III/IV non-Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin, whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk group) received ceftriaxone. The regimens were modified in 15% of lower risk and 45% of higher risk episodes. Overall successful outcomes were obtained in 93.2% of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes. The two groups differed significantly in duration of neutropenia, frequency of positive blood cultures and superinfection and the need for modification of the monotherapy (P < 0.05). Empiric monotherapy based on primary disease appears to be safe and effective for febrile neutropenic children with cancer at our Brazilian institution. Further studies will be needed before these findings can be generalized to patient populations in other settings.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Female; Fever; Humans; Imipenem; Infant; Leukemia; Lymphoma, Non-Hodgkin; Male; Neoplasms; Neutropenia

The pharmacokinetics of imipenem/cilastatin were studied in febrile neutropenic patients with haematological malignancies. The peak plasma concentrations (36.4 +/- 4.96 mg/l), plasma half-life (60 min), volume of distribution (0.28 +/- 0.02 l/kg) and plasma clearance (3.23 +/- 0.38 ml/min/kg) were comparable with those in normal healthy volunteers suggesting that the drug handling is not appreciably altered in this group of patients. The administration of 12.5 mg/kg (max 1 g), 6-hourly achieved levels that were up to 3.5 times MICs of most relevant bacteria. The drug therefore has a potential use as empirical monotherapy in febrile neutropenic patients.

Topics: Acute Disease; Adult; Agranulocytosis; Blood Preservation; Chromatography, High Pressure Liquid; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Half-Life; Humans; Imipenem; Leukemia; Lymphoma, Non-Hodgkin; Male; Metabolic Clearance Rate; Middle Aged; Neutropenia