Continuous infusion of ceftazidime in febrile neutropenic patients with acute myeloid leukemia

Abstract

Twelve febrile patients with severe neutropenia, who had undergone aggressive chemotherapy for acute myeloid leukemia, were treated empirically with a continuous infusion of ceftazidime 100 mg/kg/day after a 500 mg loading dose, in order to study the pharmacokinetics of ceftazidime after continuous infusion and to examine the clinical applicability of continuous infusion in this patient population. Three patients had a slight decrease in renal function. All patients attained a steady-state ceftazidime serum level of > 20 micrograms/ml within 180 to 240 min, which was considered effective against most pathogens in neutropenic patients. The median volume of distribution for the patient group was 29.1 l, the elimination half-life was 2.5 h and the clearance of ceftazidime was 7.7 l/h. A subnormal kidney function influenced half-lives and clearance (but not volume of distribution), as expected. When precautions were taken to avoid known interactions between ceftazidime and other compounds to be infused simultaneously, continuous infusion of ceftazidime was applicable for treatment of neutropenic patients without major side effects.

Ceftazidime in Acute Myeloid Leukemia Patients with Febrile Neutropenia: Helpfulness of Continuous Intravenous Infusion in Maximizing Pharmacodynamic Exposure

“…Ceftazidime's pharmacokinetic parameters are in agreement with other authors' findings showing that an enlarged volume of distribution and/or increased renal clearance may occur in patients with hematological malignancies (6,14). Consistently, in order to maintain an appropriate t Ͼ MIC, higher intermittent dosages were advocated (14).…”

Randomized, Open-Label, Comparative Study of Piperacillin-Tazobactam Administered by Continuous Infusion versus Intermittent Infusion for Treatment of Hospitalized Patients with Complicated Intra-Abdominal Infection

“…Although the concept of continuous infusion is supported by ␤-lactam pharmacodynamics (8,27), suggesting that maximization of the fT Ͼ MIC should be a critical factor for a positive outcome, clinical studies supporting this are limited. The majority of supporting data have been derived from either in vitro or animal models of infection, which demonstrated equivalent or improved end points with continuous infusion (2,25,26), or from small case reports, retrospective studies, or prospective observational trials (1,9,10,11,14,20,22,28). In one randomized, comparative trial of 100 febrile neutropenic patients, intermittent carbenicillin infusion plus continuous cefamandole infusion achieved a greater effectiveness than intermittent carbenicillin infusion plus intermittent cefamandole infusion in the subgroup of patients with agranulocytosis (absolute neutrophil count, Ͻ100/mm 3 ) (4).…”

“…The superior effectiveness of continuous infusion over intermittent infusion has been demonstrated for ␤-lactams in animal studies (2,8,25,26); however, clinical data comparing continuous and intermittent infusions are limited and consist primarily of data from small studies and case reports (1,3,6,9,10,11,19,22,28). In most of these studies, similar clinical and microbiological outcomes have been observed for the two administration techniques, but none of the studies have had sufficient power to conclude noninferiority.…”

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

“…Many clinical studies assessing continuous and prolonged infusion were conducted through the 1990s, but only a few were clinical randomized controlled trials, mostly addressing only pharmacologic endpoints (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49), and only two reported patients' outcomes. In 1979, Bodey and colleagues found that an antibiotic combination containing continuous-infusion cefamandole achieved the greatest cure rates in 490 febrile episodes with neutropenia (48).…”