Comparison of the pharmacodynamics of imipenem in patients with ventilator-associated pneumonia following administration by 2 or 0.5 h infusion

Abstract

The 2 h infusions of imipenem resulted in greater t > MICs than the 0.5 h infusion. For infections caused by pathogens with high MICs, a 2 h infusion of 1 g of imipenem every 6 h can provide plasma concentrations above the MIC of 4 mg/L for 60% of a 6 h interval.

Optimisation of imipenem regimens in patients with impaired renal function by pharmacokinetic-pharmacodynamic target attainment analysis of plasma and urinary concentration data

“…0.5-h versus 3-h infusions [19,20]. In contrast, the current results (Table 3) indicated that the effects of infusion time on PK-PD breakpoints depended on CL Cr , and a prolonged infusion did not improve the PK-PD breakpoints in typical patients with a CL Cr of 20 mL/min and 60 mL/min.…”

“…These inconsistent findings may be explained by the patient demographics. In the abovementioned studies [19,20], healthy subjects and patients with ventilator-associated pneumonia were recruited and their CL Cr was 91.1 ± 8.2 mL/min and ≥60 mL/min, whereas the patients enrolled in the current study had CL Cr ranging from 8.7 mL/min to 130 mL/min. Given that IPM is a time-dependent killing antibiotic Table 3 Pharmacokinetic-pharmacodynamic (PK-PD) breakpoints for the dosing regimens of imipenem (0.5-h and 1.5-h infusions) in patient populations with varying renal function as determined by creatinine clearance (CLCr).…”

Evaluation of Updated Interpretative Criteria for Categorizing Klebsiella pneumoniae with Reduced Carbapenem Susceptibility

“…Based upon our findings, an understanding of the enzymatic mechanism of resistance mediated by KPC, and the initial limited expression of KPC by many strains, resulting in MICs that are raised but still in the susceptible range, patients infected with KPC-producing K. pneumoniae are unlikely to respond to carbapenems, even if these antibiotics are dosed according to the level of susceptibility manifested by the pathogen and appropriate pharmacokinetic/pharmacodynamic targets are achieved (37,43). On the other hand, infections due to isolates with Omp loss and coproduction of ESBLs might be treatable with carbapenems if MICs are in the susceptible range based on pharmacokinetic/pharmacodynamic targets (17,18,21,23,(29)(30)(31)(32)38). Further studies are needed to define these relationships and to determine if there is a clinical need to differentiate between the KPC-Kp and ESBL/Omp groups.…”

Pharmacodynamics of meropenem in critically ill patients with febrile neutropenia and bacteraemia

“…The studies found that a 3-h infusion of meropenem gives greater values for T > MIC than a bolus injection [12,13]. Other studies have found that a 2-h infusion of imipenem and a 4-h infusion of doripenem provide greater values for T > MIC than a bolus injection [14][15][16]. We have therefore suggested that administration by prolonging intermittent infusion may offer the opportunity to increase the T > MIC within the limitations of stability at room temperature.…”