Continuous versus intermittent infusion of temocillin in intensive care unit patients

Abstract

Background and goal β-lactams are time-dependent antibiotics and show little gain in activity once their concentration exceeds the minimum inhibitory concentration about fourfold, which suggests their administration by continuous infusion. We have studied the stability, the compatibility with other drugs, and the pharmacokinetics of continuous or intermittent administration of temocillin (a β-lactam active against Gram-negative organisms). Methods Temocillin was assayed by HPLC. Temocillin stability was measured over 24 hours after its solution in water at 37°C. Compatibility with several frequently used drugs on the ICU was determined under conditions mimicking their clinical use. Temocillin was measured in plasma samples from ICU patients with normal renal function, randomly assigned to receive a continuous (n = 6; 2 g every 12 hours; 5 day sample observation) or intermittent (n = 6; 2 g over 30 minutes twice daily; consecutive samples before and after dose 1 and 9) schedule. Results Recovery after storage for 24 hours at 37°C of both R and S isomers of temocillin exceeded 90%, which is better among other studied β-lactams. Temocillin was compatible with most frequently used drugs on the ICU with the exception of clarithromycin, ciprofloxacin, meropenem, imipenem, piperacillin/tazobactam, vancomycin, amoxicillin/acid clavulanic acid, propofol, midazolam, piritramide, nicardipine, milrinone, and ranitidine. In patients with normal renal function, plasma levels of temocillin were above 50 mg/l in the continuous group, and 90% of the time above the breakpoint of 16 mg/l with peak levels of 120 mg/l after the first and ninth dose in the intermittent group. Conclusion Temocillin can be used safely in the ICU, either with an intermittent or continuous schedule. The latter may be preferred based on pharmacodynamic considerations.