This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 ± 18.6 ml/min and 2.46 ± 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 ± 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 ± 2.7 μg/ml, and trough levels after 6 h of CVVH were 6.6 ± 1.5 μg/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 ± 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

Abstract. Levels of procalcitonin (ProCT) have been found to be elevated in individuals with severe bacterial infections such as sepsis and peritonitis, and this correlates well with the severity of the disease. Recently, increased levels have been described in melioidosis and Plasmodium falciparum malaria. In this study ProCT levels were measured in 27 Thai patients with complicated malaria before and during/after treatment with artesunate and mefloquine. Initial parasite counts averaged 290,680/l (range ϭ 533-1,147,040). On admission, ProCT levels were elevated in all but one patient (median ϭ 40 ng/ml, range ϭ 0.04-662, normal values Ͻ 0.5 ng/ml). With treatment, levels decreased to 1.3 ng/ml (range ϭ 0.01-6.5). Nitrite/nitrate levels in patients were higher than in controls throughout the study. The ProCT levels correlated with initial parasite density (P Ͻ 0.05), which is a marker of disease severity, and with nitrite/nitrate levels (P Ͻ 0.05). Based on the changes of ProCT levels over the course of the disease a possible role in the acute-phase reaction seems likely.

Unlike Cohn-like fractionation, chromatography-based IVIG manufacturing processes do not have an intrinsic capacity for isoagglutinin reduction. The addition of dedicated isoagglutinin reduction steps may help minimize the potential risk of hemolysis in IVIG-treated patients.

Introducing an isoagglutinin-specific IAC step in the manufacturing process of Privigen is an efficient strategy for reduction of anti-A and anti-B titers. Such reductions might help minimize the risk of hemolytic events in patients receiving IVIG therapy.