Imipenem/Cilastatin

Abstract

Synopsis

Imipenem/cilastatin possesses a very broad spectrum of antibacterial activity that encompasses the range of Gram—negative and Gram—positive aerobes and anaerobes usually associated with intra—abdominal and other polymicrobial infections. Its therapeutic efficacy is comparable to that of aminoglycoside/antianaerobe combination regimens, and the most commonly reported adverse effects are similar to those of other β—lactam antibacterials and are generally of a non—serious nature.

The acquisition cost of imipenem/cilastatin is generally greater than that of aminoglycoside/ antianaerobe combination regimens, but treatment with the latter incurs the additional costs of multiple intravenous administration, aminoglycoside pharmacokinetic and other monitoring, and possible nephrotoxicity and ototoxicity. The available pharmacoeconomic studies show a trend towards lower total treatment costs with imipenem/cilastatin compared with gentamicin plus c/indamycin. Results from other sources suggest that imipenem/cilastatin may achieve forther cost savings through reduced duration of hospitalisation. Although forther study is required to confirm these trends, it appears that the total treatment cost of imipenem/cilastatin does not exceed that of usual combination therapy and the risk of aminoglycoside—induced toxicity is avoided.

Disease Considerations

Most intra—abdominal infections are polymicrobial, and Bacteroides fragilis and Escherichia coli are the most frequently isolated aerobes and anaerobes, respectively. Severe infection carries the risk of sepsis—induced multiple organ failure and requires early treatment. The major factors contributing toward the total direct cost of treatment include diagnostic procedures, surgery, hospitalisation, resuscitation and nutritional support, and adjunctive antibacterial therapy. The latter requires a broad spectrum regimen suitable for empirical administration.

Intravenous administration of an aminoglycoside in combination with an antianaerobe, such as metronidazole or clindamycin, is a widely used and effective treatment. However, administration costs are greater for a multiple versus single agent intravenous regimen, and aminoglycoside treatment increases the cost of pharmacokinetic monitoring and may also result in costs due to nephrotoxicity or ototoxicity. Thus, it is appropriate to evaluate alternative antibacterial regimens, particularly from a pharmacoeconomic standpoint.

Pharmacoeconomic Benefits and Costs

The economic potential ofimipenem/cilastatin hinges on its ability to be as effective as standard combination regimens but to incur lower overall treatment costs. Imipenem/cilastatin possesses an extremely broad spectrum of antibacterial activity that covers the range of Gram—negative and Gram—positive aerobes and anaerobes usually associated with intra—abdominal infections. In comparative trials involving patients with intra—abdominal or other polymicrobial infections intravenous imipenem/cilastatin (usually 0.5g every 6 hours) exhibited comparable efficacy to various combination regimens. The latter most frequently comprised clindamycin plus an aminoglycoside such as gentamicin or tobramycin.

In general, preparation and administration costs of intravenous monotherapy are lower than those of combination treatment. Imipenem/cilastatin eliminates the costs of pharmacokinetic monitoring as well as the risk of additional costs incurred from aminoglycoside toxicity. There is also some evidence that there may be fewer costs due to treatment failure with imipenem/ cilastatin. A few studies have reported a reduction in hospital length of stay with imipenem/ cilastatin treatment but the available evidence is insufficient to be considered conclusive.

The acquisition cost of daily therapy with imipenem/cilastatin is generally greater than that of a typical combination regimen. Costs due to adverse events are not expected to be significant with imipenem/cilastatin, although on rare occasions the cost of seizure will be an important consideration.

Pharmacoeconomic Analysis

The available comparative pharmacoeconomic data are limited to 3 cost—minimisation studies. While there appears to be a trend toward lower total treatment costs with imipenem/cilastatin compared with gentamicin plus c1indamycin, there is insufficient evidence to demonstrate a definite cost advantage favouring the former treatment.

Formulary decisions on the choice of antibacterial agent for the treatment of intra—abdominal infection should be based on institution—specific data. When this is not available, and in view of the above findings, the deciding factor might well be the risk of aminoglycoside—induced toxicity.