Stability of meropenem in a portable infusion device in a cold pouch.

Grant EM, Zhong MK, Ambrose PG, Nicolau DP, Nightingale CH, Quintiliani R.

Continuous infusion of time-dependent or concentration-independent antibiotics, such as [beta]-lactams, cephalosporins, and carbapenems, is gaining popularity, particularly for pharmacoeconomic reasons. Time-dependent antibiotics cause bacterial death when their serum concentrations are above the minimum inhibitory concentration (MIC) for the organism. Once the concentration exceeds two to four times the MIC, the rate of bacterial killing is maximized. The best predictor of clinical outcome is usually the amount of time that the concentration remains above the MIC (t > MIC) during the dosage interval, not the degree to which these levels exceed the MIC. While the minimum t > MIC varies with different drug-bacterium combinations, it appears that an acceptable clinical response occurs when t > MIC is >=50% of the dosage interval in patients with intact or functioning immune systems. For immunocompromised patients, bacterial eradication is maximized by achieving an antibiotic concentration two to four times the MIC for the entire dosage interval. Since continuous infusion allows the serum concentration of an antibiotic to remain above the MIC throughout the dosage interval, the bactericidal effect is maximized. Although most studies have not found a significant increase in clinical response with continuous infusion, it is associated with decreased length of stay, decreased duration of treatment, lower total dose, fewer adverse effects, and lower labor and supply costs compared with intermittent infusion.

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