Objective: To assess the relative cost effectiveness of cephalosporin monotherapy options and aminoglycoside/ureidopenicillin combination therapy for the treatment of febrile episodes in adult patients with neutropenia.
Design and setting: This was a retrospective cost-effectiveness analysis conducted from the institutional perspective.
Methods: The analysis was based on 741 febrile episodes in adult patients with neutropenia enrolled in 5 randomised trials: 3 comparing monotherapy with ceftazidime or cefepime, and 2 comparing cefepime monotherapy versus aminoglycoside/ ureidopenicillin combination therapy. Resource utilisation included costs for study antibacterials, treatment of adverse effects and failures, and hospitalisation. The primary end-point was the overall cost of treatment per patient. Cost-effectiveness ratios were also analysed.
Results: No significant differences in clinical success rates were detected. Median per-patient costs in the monotherapy comparisons were $US7849 for cefepime and $US7788 for ceftazidime [1997 values; not significantly different (NS)]. Corresponding costs for the monotherapy versus combination therapy comparisons were $US9780 for cefepime and $US10 159 for gentamicin/ureidopenicillin (NS). Despite a higher acquisition cost for cefepime, there were no statistically significant differences in cost effectiveness compared with either ceftazidime monotherapy or gentamicin/ureidopenicillin combination therapy. Sensitivity analyses revealed that monotherapy can be cost effective compared with combination therapy in many situations.
Conclusion: There were no economic differences between the 3 regimens tested. Therefore, drug cost should not be a deciding factor when choosing antibacterial therapy for the treatment of febrile episodes in adult patients with neutropenia.
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The authors thank Lynn Jagodzinski for her technical assistance. This work was funded in part by an unrestricted grant from Bristol-Myers Squibb Company.
Pizzo PA. Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med 1993; 328: 1323–32PubMedCrossRefGoogle Scholar
Giamarellou H. Empiric therapy for infections in the febrile, neutropenic, compromised host. Med Clin North Am 1995; 79: 559–80PubMedGoogle Scholar
Pizzo PA, Ladisch S, Simon RM, et al. Increasing incidence of Gram-positive sepsis in cancer patients. Med Pediatr Oncol 1978; 5: 241–4PubMedCrossRefGoogle Scholar
Bochud PY, Eggiman PH, Calandra TH, et al. Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin Infect Dis 1994; 18: 25–31PubMedCrossRefGoogle Scholar
Chow JW, Fine MJ, Shlaes DM, et al. Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med 1991; 115: 585–90PubMedGoogle Scholar
Ramphal R, Gucalp R, Rotstein C, et al. Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient. Am J Med 1996; 100 Suppl. 6A: 83S-9SCrossRefGoogle Scholar
Rolston KV, Berkey P, Bodey GP, et al. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients. Arch Intern Med 1992; 152: 283–91PubMedCrossRefGoogle Scholar
Wade JC, Johnson DE, Bustamante CI. Monotherapy for empiric treatment of fever in granulocytopenic cancer patients. Am J Med 1986; 80 Suppl. 5C: 85–95Google Scholar
DePauw B, Deresinski S, Feld R, et al. Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer: a multicenter randomized trial. Ann Intern Med 1994; 120: 834–44Google Scholar
The Infectious Diseases Society of America. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Clin Infect Dis 1997; 25: 551–73CrossRefGoogle Scholar
Leese B. The costs of treating febrile neutropenia in six UK hospitals. Eur J Cancer 1993; 29A Suppl. 7: S15–8CrossRefGoogle Scholar
Glaspy JA, Jakway J. Cost considerations in therapy with myeloid growth factors. Am J Hosp Pharm 1993; 50 Suppl. 3: 519–26Google Scholar
Holdsworth MT, Duncan MH. Health care outcomes case study: febrile neutropenia. Am J Health-Syst Pharm 1995; 52 Suppl. 4: S15–8Google Scholar
Paladino JA. Cost-effectiveness comparison of cefepime and ceftazidime using decision analysis. Pharmacoeconomics 1994; 5: 505–12PubMedCrossRefGoogle Scholar
Clarke MJ, Paladino JA. Pharmacoeconomic comparison of cefepime versus ceftazidime in septic patients. J Infect Dis Pharmacother 1996; 2: 1–17CrossRefGoogle Scholar
Bristol-Myers Squibb Pharmaceutical Research Institute. New Drug Application 50–679. Maxipimer (cefepime HCl) for injection; empiric therapy in febrile neutropenic patients. Wallingford (CT): Bristol-Myers Squibb Pharmaceutical Research Institute, 1996: Suppl. 4Google Scholar
Breen J, Ramphal R, Cometta A, et al. Cefepime versus ceftazidime in the empiric therapy of febrile episodes in neutropenic patients. In: Klastersky JA, editor. Febrile neutropenia. Berlin: Springer, 1997: 63–74CrossRefGoogle Scholar
Yamamura D, Gucalp R, Carlisle P, et al. Open, randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients. Antimicrob Agents Chemother 1997; 41: 1704–8PubMedGoogle Scholar
Eggiman P, Glauser MP, Aoun M, et al. Cefepime monotherapy for the empirical treatment of fever in granulocytopenic cancer patients. J Antimicrob Chemother 1993; 32 Suppl.B: 151–63CrossRefGoogle Scholar
Bohme A, Shah PM, Stille W, et al. Piperacillin-tazobactam versus cefepime as initial empiric antimicrobial therapy in febrile neutropenic patients: a prospective randomized pilot study. Eur J Med Res 1998; 3: 324–30PubMedGoogle Scholar
The Infectious Diseases Society of America. General guidelines for the evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Clin Infect Dis 1992; 15 Suppl. 1: S206–15CrossRefGoogle Scholar
The Immunocompromised Host Society. The design, analysis and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient: report of a consensus panel. J Infect Dis 1990; 161: 397–401CrossRefGoogle Scholar
Paladino JA, Fell PE. Pharmacoeconomic analysis of cefmenoxime dual individualization in the treatment of nosocomial pneumonia. Ann Pharmacother 1994; 28: 384–9PubMedGoogle Scholar
Katz DA, Welch HG. Discounting in cost-effectiveness analysis of healthcare programmes. Pharmacoeconomics 1993; 3: 276–85PubMedCrossRefGoogle Scholar
Clemens K, Townsend R, Luscombe F, et al. Methodological and conduct principles for pharmacoeconomic research. Pharmacoeconomics 1995; 8: 169–74PubMedCrossRefGoogle Scholar
Foran RM, Brett JL, Wulf PH. Evaluating the cost impact of intravenous antibiotic dosing frequencies. DICP Ann Pharmacother 1991; 25: 546–52Google Scholar
Smith CF, Amen RJ. Comparison of seven methods of preparing and administering small-volume injections. Am J Hosp Pharm 1988; 45: 1896–901PubMedGoogle Scholar
Tanner DJ. Cost containment of reconstituted parenteral antibiotics: personnel and supply costs associated with preparation, dispensing, and administration. Rev Infect Dis 1984; 6 Suppl. 4: S924–37CrossRefGoogle Scholar
Cardinale V, editor. Drug topics red book 1996. Oradelle (NJ): Medical Economics Data, 1996Google Scholar
Garrelts JC, Horst WD, Silkey B, et al. A pharmacoeconomic model to evaluate antibiotic costs. Pharmacotherapy 1994; 14: 438–45PubMedGoogle Scholar
McKinnon PS, Paladino JA, Grayson ML, et al. Cost-effectiveness comparison of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients. Clin Infect Dis 1997; 24: 57–63PubMedCrossRefGoogle Scholar
Anaissie EJ, Vadhan-Raj S. Is it time to redefine the management of febrile neutropenia in cancer patients? [editorial].Am J Med 1995; 98: 221–3PubMedCrossRefGoogle Scholar
Eisenberg JM. Clinical economics: a guide to the economic analysis of clinical practices. JAMA 1989; 262: 2879–86PubMedCrossRefGoogle Scholar
Jolicoeur LM, Jones-Grizzle AJ, Boyer JG. Guidelines for performing a pharmacoeconomic analysis. Am J Hosp Pharm 1992; 49: 1741–7PubMedGoogle Scholar
D’Argenio DZ, Schumitzky A. ADAPT II user’s guide, release 4. Los Angeles (CA):Biomedical Simulations Resource, University of Southern California, 1997Google Scholar
Paladino JA, Kapfer JA, Dibona JR. Bedside estimation of creatinine clearance: which method is most accurate while least complex? Hosp Formul 1986; 21: 709–15Google Scholar
Canaday BR, Poe TE, Sawyer WT, et al. Fractional adjustment of predicted creatinine clearance in females. Am J Hosp Pharm 1984; 41: 1842–3PubMedGoogle Scholar
Dranitsaris G. Clinical and economic considerations of empirical antibacterial therapy of febrile neutropenia in cancer. Pharmacoeconomics 1999; 16: 343–53PubMedCrossRefGoogle Scholar
Obadina M, Cho C, Oketunji A, et al. Neutropenia and fever in patients receiving chemotherapy in a community teaching hospital: results of a retrospective chart review. Maryland Med J 1994; 43: 977–80Google Scholar
Pizzo PA. Evaluation of fever in the patient with cancer. Eur J Cancer Clin Oncol 1989; 25 Suppl. 2: S9–16Google Scholar
Pizzo PA, Hathorn JW, Hiemenz J, et al. A randomized trial comparing ceftazidime alone with combination antibiotic therapy in cancer patients with fever and neutropenia. N Engl J Med 1986: 315: 552–8PubMedCrossRefGoogle Scholar
American Hospital Association. American Hospital Association hospital statistics. Chicago (IL): American Hospital Association, 1996–1997Google Scholar
Jensen KM, Paladino JA. Cost effectiveness of abbreviating the duration of intravenous antibiotic therapy with oral fluoroquinolones. Pharmacoeconomics 1997; 11: 64–74PubMedCrossRefGoogle Scholar