Once-Daily vs. Continuous Infusion of Beta-Lactams

Source: Hitt CM, et al. Cost comparison of single daily IV doses of ceftriaxone versus continuous infusion of cefotaxime. Am J Health-Syst Pharm 1997;54:1614-1618.

This article reports on a complete cost analysis performed by comparing the daily delivery of single, 1 g doses of ceftriaxone given as a 30-minute infusion vs. the delivery of 2 g of cefotaxime given as a continuous infusion. The study by Hitt and colleagues looked at all costs associated with each drug, including pharmacy, nursing, and supply costs. They also compared different types of minibag delivery systems and the cost savings associated with using bulk vs. single-dose medication vials. Hitt et al concluded that, after the first day of therapy, the continuous delivery of cefotaxime was approximately $8-$10 less expensive than ceftriaxone. The increased cost of cefotaxime delivery on the first day of therapy was due to the administration of a loading dose of 1 g of cefotaxime.

COMMENT BY THOMAS SCHLEIS, MS, RPh

The theoretical advantages of administering beta-lactam antibiotics as a continuous infusion have been reported in the literature.1,2 This method of delivery has also begun to gain acceptance with trials going on at a number of institutions throughout the nation. Some of the results of these trials have been reported,3-8 and Hoescht-Roussel now has approval in their package insert for the delivery of cefotaxime by continuous infusion.

While this study performs a complete and accurate analysis of the costs associated with the two methods of delivery in a hospital setting, the choice of a 2 g dose of cefotaxime for continuous infusion daily may not be an appropriate dose under all circumstances. Although animal and human studies demonstrate that a smaller total daily dose of a beta-lactam may be given as a continuous infusion vs. intermittent dosing, serum levels still vary widely among patients,3,4 and the minimal inhibitory concentration (MIC) of the bacteria causing the infection may not be known. Nix9 further reported that cefotaxime at the dose of 2 g daily as a continuous infusion given to volunteers resulted in inhibitory activity that was lower than that seen with 4 g per day. He also noted that, with the 2 g per day regimen, inhibitory activity occasionally dropped to less than 1:2 for E. cloacae and S. aureus. If the dose of cefotaxime were increased to 3-4 g daily and compared to 1 g of ceftriaxone, any cost advantage of cefotaxime would be eliminated.

There are indications that continuous infusion of beta-lactams should be the preferred method of administration under most circumstances. Unfortunately, until controlled studies where infections are treated at different continuous infusion dosages are performed and reported, the optimal dose of continuously infused beta-lactam antibiotics will not be known. Without this information, the use of continuous infusion will not gain national acceptance. Now that the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has mandated that healthcare organizations be involved in outcomes research, there is additional incentive to perform meaningful outcomes studies such as the type needed here. This is an area that is sure to be reported on in the future.

References

    1. Moellering RC, et al. Continuous vs. intermittent infusion of beta-lactam antibiotics: A potential advance. Infections in Medicine 1992;9[suppl B]:1-34.

    2. Craig WA, Ebert SC. Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother 1992;36: 2577-2583.

    3. Daenen S, de Vries-Hospers H. Cure of Pseudomonas aeruginosa infection in neutropenic patients by continuous infusion of ceftazidime. Lancet 1988;I:937.

    4. David TJ, Devlin J. Continuous infusion of ceftazidime in cystic fibrosis. Lancet 1988;I:1454-1455.

    5. Vinks AA, et al. Pharmacokinetics of ceftazidime in adult cystic fibrosis patients during continuous infusion and ambulatory treatment at home. Ther Drug Monit 1994; 16(4):341-348.

    6. Richelieu W, et al. Cefotaxime by continuous infusion a new standard of care? Proceedings of the ASHP Midyear Clinical Meeting. 1995;23:P275(E).

    7. Carlson RH. Continuous infusion less costly, equally effective. Pharmacy Practice News, March 1996:6.

    8. Richards B. Greenbrier Valley Medical Center adopts continuous antibiotic infusion protocol for pneumonia patients. Quality Time (a quarterly update of the West Virginia Medical Institute's Health Care Quality Improvement Program), January/February/March 1996: 2-3.

    9. Nix DE. Continuous infusion of beta-lactams: Cidal actions and pharmacokinetics/pharmacodynamics in volunteers. Symposium Presented at the ASHP Midyear Clinical Meeting, December 6, 1992.

Dr. Schleis is Director of Pharmacy Services, Infections Limited, Tacoma, WA.