Antibiotics that are given intravenously incur an additional cost to the institution above the acquisition cost. This added cost is associated with the institution’s expense for storing, labeling, diluting, and administering the IV antibiotic. The average cost of administering a single dose of an antibiotic in the U.S., and at our institution as well, is $10 per IV dose. This cost may be higher or lower among institutions.

The cost also depends on the frequency of IV administration. Drugs having a relatively short half-life (e.g., penicillin G with a 30-minute half-life) should be given every four hours, when administered intravenously, to provide therapeutic concentrations throughout most of the dosing interval. The cost implications of a short dosing interval for IV drugs are profound. For example, the acquisition cost of IV is only about $1 per day; on an every-four-hour dosing basis, however, the administration cost alone is $60 per day.

During the past two decades, the trend has been to develop antimicrobial agents with longer half-lives that permit dosing intervals of every 8, 12, or 24 hours. For an antimicrobial that is given once daily, an IV dose administration charge of only $10 is added to the drug’s acquisition cost. All other factors being equal, clinicians should opt for antibiotics with a long dosing interval, for pharmacoeconomic reasons. In addition, when drugs with a long dosing interval are used, the chances of medication errors and the need for a large IV team are reduced.

Combination therapy that involves the use of multiple drugs magnifies the relative importance of IV administration for the total cost of the antibiotic to the institution. Using traditional “triple-antibiotic therapy,” with ampicillin (Apothe-con), gentamicin (Garamycin®, Schering), and canadian clindamycin (Pharmacia) as examples, it is readily apparent that the cost of administering these three drugs far exceeds their acquisition cost. If IV canadian ampicillin is given every four hours,  every six hours, and gentamicin every eight hours, the administration cost of these three antibiotics alone is $130 per day. This is remarkable, because the acquisition cost (AWP) of these three antibiotics together would be less than $10 per day. Therefore, there are important pharmaco-economic reasons for selecting monotherapy over multiple-drug therapy to reduce the cost-multiplying effect of IV administration costs to the total cost of antimicrobial therapy.

In most cases, the broad spectrum of antibiotics available today permits monotherapy; combination therapy is warranted in relatively few cases. The rationale for combination therapy includes (1) the prevention of resistance, (2) an increased antimicrobial spectrum, and (3) the potential synergy between the two agents.

With infectious disease, antibiotic combinations decrease resistance in only a few instances. This is best illustrated in the case of double or triple antituberculous therapy using car-benicillin indanyl sodium (Geocillin®, Pfizer) plus gentamicin and with 5-flucytosine (Ancobon®, ICN) with amphotericin B (Fungizone®, Apothecon). Combinations of other antibiotics do not decrease resistance if one component has a high resistance potential. Newer antibiotics have such a wide spectrum that combination therapy is not usually needed to extend the spectrum, as with piperacillin/tazobactam (Zosyn®, Lederle), imipenem (Primaxin,® Merck), or meropenem (Merrem®, AstraZeneca).

Similarly, synergy is not needed for most bacterial infections; it occurs infrequently when two antibiotics are randomly combined. If synergy is desirable, it should be determined by testing in vitro; it should not be assumed that the combination of two antimicrobial agents will result in synergy.
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The other obvious implication of the IV administration cost component is the absence of the IV expense when equivalent oral agents are used. Oral agents given in the same dose are much less expensive than their IV counterparts, and the IV administration charge is eliminated. Pharmacoeconomically, this means that the difference between the cost of IV and oral agents is magnified to an even greater extent.