Cefotaxime: A Pharmacoeconomic Review of its Use in the Treatment of Infections
Greg L. Plosker
Rachel H. Foster
Cefotaxime is a parenterally administered third generation cephalosporin with a broad spectrum of antimicrobial activity. After more than a decade of use, cefotaxime continues to play an important role in the treatment of patients with serious infections, particularly those caused by Gram-negative bacteria. Clinical trials of cefotaxime have demonstrated clinical and/or bacteriological success rates usually between 75 and 100% in hospitalised patients with infections such as pneumonia, complicated urinary tract infections and bacteraemia. In general, comparative trials have shown that cefotaxime has equivalent clinical efficacy to ceftriaxone. Although cefotaxime was traditionally administered at 6- or 8-hourly intervals, evaluations of twice daily regimens have demonstrated the feasibility of using this extended dosage interval in selected patients. Like other parenterally administered cephalosporins, cefotaxime is well tolerated. Cefotaxime does not cause a significant incidence of coagulopathies, as observed with some cephalosporins (e.g. cefamandole and cefoperazone), nor is it associated with the development of pseudocholelithiasis as seen with ceftriaxone. Some hospitals have achieved significant cost savings by implementing programmes or policies involving replacement of prescriptions for ceftriaxone with those for cefotaxime; however, other institutions have shown cost savings when cefotaxime is replaced by ceftriaxone. Similarly, conflicting results were seen in studies that assessed only the drug acquisition and administration supply costs (with or without inclusion of labour costs), highlighting the difficulty in applying pharmacoeconomic data from one clinical setting to another. A limited number of detailed pharmacoeconomic analyses of cefotaxime have been conducted. One analysis, in patients with pneumonia or other serious infections, incorporated published clinical trial data as well as published or estimated cost data (from 1992 or earlier) for the US healthcare setting. Total treatment costs per patient-day were $US25.21 for cefotaxime 1g twice daily and $US37.23 for cefotaxime 1g 3 times daily, compared with $US69.97 for ceftriaxone 2g once daily and $US74.57 for ceftriaxone 1g twice daily. Costs included those associated with drug acquisition, administration and preparation, laboratory monitoring and adverse events. A large retrospective analysis was conducted between 1989 and 1993 in a US hospital. Patients treated with cefotaxime twice daily had similar clinical outcomes, including duration of hospital stay (7.21 vs 7.24 days), to those receiving antimicrobials other than cefotaxime. However, when a model was applied to determine attributable differences, a trend was demonstrated towards reduced length of hospitalisation (mean reduction 0.5 days) and total cost of hospitalisation (mean reduction $US623 per patient) with cefotaxime. In a Canadian clinical decision-analysis model of initial empirical monotherapy for an average infectious disease state (costs for serious lower respiratory tract infection, urinary tract infection, sepsis, skin/soft tissue infection and febrile neutropenia were weighted according to the incidence of each infection and combined to give a single value), the average total cost per patient for cefotaxime was $Can4099 (1994 dollars). This was lower than that for ceftriaxone ($Can4257) but higher than that for cefepime ($Can3945), ciprofloxacin ($Can4008) and ceftazidime ($Can4086). Costs included those related to drug acquisition, preparation and administration, bacterial culture and sensitivity testing, hospitalisation and adverse events. An analysis conducted in France demonstrated that cefotaxime 1g 3 times daily was associated with total treatment costs equal to or lower than those for ceftriaxone 2g once daily. The study also evaluated total costs of cefotaxime 1g twice daily and ceftazidime 1g 3 times daily; treatment costs associated with cefotaxime were less than one-third of those associated with ceftazidime. The choice of dosage regimen appears to be particularly important in determining the cost effectiveness of cefotaxime. All pharmacoeconomic analyses of twice daily administration of cefotaxime produced results that favoured the drug over comparators. In conclusion, parenteral cefotaxime has been shown to have economic advantages over other broad spectrum antimicrobials, including ceftriaxone, in selected clinical settings. Clearly, choosing the most cost-effective treatment requires institution-specific pharmacoeconomic data. Many local variables, including drug acquisition costs and the dosage schedule, influence whether cefotaxime has a cost advantage.
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