gms | German Medical Science

Background: Altered pathophysiological conditions in febrile neutropenic patients with severe sepsis resulting in variations in pharmacokinetics are important factors determining the therapeutic success of antibiotics.

Objective: The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) of imipenem in serious bacteremia in febrile neutropenic patients.

Methods: The study was conducted in ten febrile neutropenic patients with severe sepsis. The patients were randomised into two groups: Group I received a 0.5-h infusion of 0.5 g of imipenem every 6 h (q6h) for 8 doses; and Group II received a 4-h infusion of 0.5 g of imipenem q6h for 8 doses. The pharmacokinetic studies were carried out during the 8^th dose of both groups and a Monte Carlo simulation was performed to determine the PTA.

Results: The population pharmacokinetics of imipenem were; k₁₂ = 0.32±2.29 h^-1, k₂₁ = 2.10±2.22 h^-1, k₁₃ = 1.02±2.22 h^-1, k₃₁ = 1.25±2.46 h^-1, k_e = 1.12±1.37 h^-1, Vd = 20.78±1.35 L and CL = 23.19±1.34 L/h.

By using the EUCAST susceptibility patterns to determine the CFR of imipenem, only a 4-h infusion of all simulated regimens achieved targets (CFR≥90%) against Escherichia coli and Klebsiella spp. The PTAs for selected regimens over a range of MICs were as illustrated in Table 1 [Tab. 1].

Conclusion: The results indicate that a higher than recommended dosage regimen for the treatment of serious infections in this patient population is required to maximize the activity of imipenem.