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Continuous Dosing of Antibiotics for Pneumonia

　　In a subsequent discussion, David P. Nicolau, PharmD,[10] of Hartford Hospital in Hartford, Connecticut, presented intriguing information about drug delivery.
　　For beta lactam drugs, antibacterial activity is time-dependent rather than concentration-dependant. This is in contrast to aminoglycosides and quinolones, where antibacterial activity is concentration-dependent. In animal models, the antimicrobial effect of beta lactam drugs can be improved (ie, animal survival can be improved by increasing the number of hours per day that the serum antibiotic level is above the minimum inhibitory concentration [MIC] of the causative organism). Increasing the number of hours with a serum concentration above the MIC of the organism does not necessarily imply that the dose of drug should be increased. In fact, the method of drug delivery may be more important (ie, providing a continuous infusion of drug rather than a higher bolus dose or a higher total daily dose. These continuous infusions are practical in the hospital with infusion pumps. They may also allow lower, rather than higher, daily drug doses, thus saving money on drug acquisition costs.
　　Dr. Nicolau recommended that when administering parenteral beta lactam drugs for patients with life-threatening infections, the period of time that the serum antibiotic concentration is over the MIC of the causative organism be at least 50% of the 24-hour period (ie, at least 12 hours). He reported data on piperacillin-tazobactam used to treat Pseudomonas infections.[11] Continuous infusions can also be used with certain drugs, which have been considered unstable at room temperature, by utilizing an imaginative approach. His group has tried putting an ice pack in the infusion pump when infusing meropenem. This approach allowed the drug to remain stable over an extended period of time.
　　Continuous infusion of beta lactam drugs is, thus, a logical approach that can reduce drug acquisition and delivery costs. It should be noted that it is difficult to demonstrate enhanced efficacy with this approach, or even to prove that this approach is equally effective at producing clinical efficacy, minimizing toxicity, or preventing resistance.