- Email: [email protected]
The conversion of cefoxitin usage to cefotetan: An interdisciplinary approach
6. Smith BR, LeFrock JL, Thyrum PT, et al. Cefotetan pharmocokinetics in volunteers with various degrees of renal function. Antimicrob Agents Chemother 1986; 29: 887-93. 7. Nakagawa K, Koyama M, Tachibana A, Komiya M, Kikuchi Y, Yano K. Pharmacokinetics of cefotetan (YM 09330) in humans. Antimicrob Agents Chemother 1982; 22:935-41. 8. Yates RA, Adam HK, Donnelly RJ, Houghton HL, Chartesworth EA, Lows EA. Pharmacokinetics of single intravenous doses of cefotetan disodium in male Caucasian volunteers. J Antimicrob Chemother 1983; 11 (suppl A): 185-91. 9. Snedecor GW, Cochran WG. Statistical methods. 6th ed. Ames, Iowa: Iowa State University Press, 1987: 130-2, 550. 10. Colquhoun D. Lectures on biostatistics. Oxford: Clarendon
Press, 1971: 117-23, 127-32.
11. Moleski RJ, Andriole VT. Role of the infectious disease specialist in containing costs of antibiotics in the hospital. Rev Infect Dis 1986; 8: 488-93. 12. Hemsell DL, Gall SA, Gibbs RS, et al. Multicenter comparison of cefotetan and cefoxitin in the treatment of obstetric and gynecologic infections (abstr). Efficacy and cost implications of the new cephalosporins. Vancouver, British Columbia, 1987: 33. 13. PoindexterAN, Castetlano A, Faro S, et al. Results of noncomparative studies in the treatment of obstetric and gynecologic infections (abstr). Efficacy and cost implications of the new cephalosporins. Vancouver, British Columbia, 1987:
34.
FOCUS
The Conversion of Cefoxitin Usage to Cefotetan: An Interdisciplinary Approach
Charles H. Nightingale, PhD, Karen S. Smith, BS, Richard Quintiliani, MD, Laurie L. Briceland, PharmD, and Brian Cooper, MD, Hartford, Connecticut
This report describes the experience at Hartford Hospital 1 year after cefoxitin was replaced by cefotetan on the hospital formulary. In approving a recommendation to replace cefoxitin with cefotetan for prophylaxis and therapy effective August 1, 1986, the medical staff agreed that both drugs were similar in antimicrobial activity and had a similar safety profile, although hypoprothrombinemias are a potential problem with cefotetan therapy due to the N-methylthiotetrazole substitution present in the chemical structure [1-3]. When antibiotics have been demonstrated to be clinically equal in terms of efficacy and toxicity, cost then becomes the predominant determinant in the selection of drugs for inclusion in the hospital formulary. Although cefotetan costs approximately the same as cefoxitin on a per-gram basis, the longer half-life allows for a twice-daily dosing regimen compared with a 6 hour dosing regimen for cefoxitin. Program Description
Therapeutic interchange was implemented through use of automatic substitution supplemented by intense educational programs, such as in-service presentations to medical and nursing staff by infectious disease specialists and clinical pharmacists. These techniques emphasized the clinical literature supporting the therapeutic interFrom the Department of Pharmacy Services and Division of Infectious Disease, Hartford Hospital, Hartford, Connecticut and the University of Connecticut, Storrs, Connecticut. Requests for reprints should be addressed to Charles H. Nightingale, PhD, Vice President, Hartford Hospital, 80 Seymour Street, Hartford, Connecticut 06115.
Volume 155 (SA), May 31, 1988
changeability of the two antibiotics and stressed the anticipated annual savings of approximately $140,000 based on previous cefoxitin usage (Table I). To evaluate clinical efficacy, safety, and savings, two separate retrospective reviews of patient medical records were performed. The first audit consisted of 100 patients who had received cefotetan and 100 randomly chosen cefoxitin-treated patients [4]. Subsequently, 154 additional patient medical charts were reviewed, comparing 1 g or 2 g of cefotetan every 12 hours with combination therapy of an aminoglycoside with either mezlocillin or clindamycin. The aminoglycoside dosing regimen varied for each patient according to the recommendations of the pharmacokinetics monitoring service. Clindamycin was commonly administered as 600 mg or 900 mg every 6 or 8 hours, and mezlocillin was dosed at 5 g every 8 hours due to a previous decision made by the Pharmacy and Therapeutics Committee [5]. Program E x p e r i e n c e
A total of 960 patients were treated with cefotetan last year; no unexpected difficulties with clinical efficacy or safety were encountered. In the audit, an empiric cure or clinical improvement was noted in 95.7 percent and 80 percent of patients treated with cefotetan or cefoxitin, respectively. The second retrospective review produced similar clinical assessments. Clinical outcomes were classified as an empiric cure or improvement for 99 percent, 97.2 percent, and 95.5 percent of patients treated with cefotetan or an aminoglycoside combined with either clindamycin or mezlocillin, respectively.
101
Nightingale et al
TABLE I
Comparative Costs of Cefoxitin and Cefotetan Antibiotic
Dosing Regimen
Total Daily Cost*
Total Annual Costt
Cefoxitin Cefotetan Cefoxitin Cefotetan Total predicted s a v i n g s
1g/6h lg/12h 2g/6h 2g/12h . .
$38.72 $21.20 $65.72 $37.10 . .
$56,730 $30,320 $260,080 $143,680
.
.
.
.
Predicted Annual Savings $26,410 $11(~,400 ... $142,810
.
* Includes drug acquisition costs, supply costs, and the cost of nursing and pharmacy labor. Cefoxitin data reflect actual usage, cefotetan data reflect projected usage.
TABLE II
Comparative Costs of Antibiotic Therapy From Second Retrospective Audit
Antibiotic
Mean No. of Doses
Cefotetan Aminoglycoside/ clindamycin Aminoglycoside/ mezlocillin
10 14.8 16.9 11.3 14.7
Study Drug Costs* $189.64 4- 79.96 $295.07 -I- 135.48 $307.64 -I- 168.53
* Values given as the mean 4- the standard deviation.
In the 960 patients who have received cefotetan to date, the nursing, pharmacy, and medical staffs have voluntarily reported 32 adverse events possibly related to cefotetan therapy (an incidence of 3.2 percent). These adverse reactions coincide with those reported in the package insert and with those associated with other cephalosporins and beta-lactams in general [6]. Coagulopathy occurred in 18 patients; clinical bleeding was reported in 7 of these patients, but in only 1 was it believed to be related to antibiotic therapy. In the second audit, the average cost of cefotetan therapy ($189.64) was substantially lower than that of either of the other two antibiotic regimens ($295.07 and $307.64, respectively), demonstrating the cost-effectiveness of cefotetan therapy (Table II).
102
The propriety of the decision for the therapeutic replacement of cefotetan for cefoxitin has been verified over the course of the year. No difficulties in either efficacy or clinical safety of cefotetan therapy have been observed. Based on the data analysis of cefotetan usage for the 12 month period, the actual annual savings resulting from the therapeutic substitution of cefotetan for cefoxitin was $124,961.
References 1. Ward A, Richards DM. Cefotetan: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1985; 30: 382-426. 2. Stuart Pharmaceuticals. Cefotetan package insert. Wilmington, Delaware: March 1986. 3. Quintiliani R, French M, Nightingale CH. First and second generation cephalosporins. Med Clin North Am 1982; 66: 183-97. 4. Quintiliani R, Cooper BW, Briceland LL, Nightingale CH. Formulary replacement policies: cefotetan vs cefoxitin. Infections in Med 1987; 275-9. 5. Briceland LL, Nightingale CH, Quintiliani R, Cooper BW. Costeffective dosage modification of mezlocillin utilizing dosedependent pharmacokinetic principles. Accepted for poster presentation. A.S.H.P. 22nd annual midyear clinical meeting, Atlanta, Georgia. 6. Midtvedt T. Penicillins, cephalosporins and tetracyclines. In: Dukes MNG, Beeley L, eds. Side effects of drugs: annual 11. Amsterdam: Elsevier Science Publishers, 1987: 223-30.
The AmericanJournalof Surgery
Press, 1971: 117-23, 127-32.
11. Moleski RJ, Andriole VT. Role of the infectious disease specialist in containing costs of antibiotics in the hospital. Rev Infect Dis 1986; 8: 488-93. 12. Hemsell DL, Gall SA, Gibbs RS, et al. Multicenter comparison of cefotetan and cefoxitin in the treatment of obstetric and gynecologic infections (abstr). Efficacy and cost implications of the new cephalosporins. Vancouver, British Columbia, 1987: 33. 13. PoindexterAN, Castetlano A, Faro S, et al. Results of noncomparative studies in the treatment of obstetric and gynecologic infections (abstr). Efficacy and cost implications of the new cephalosporins. Vancouver, British Columbia, 1987:
34.
FOCUS
The Conversion of Cefoxitin Usage to Cefotetan: An Interdisciplinary Approach
Charles H. Nightingale, PhD, Karen S. Smith, BS, Richard Quintiliani, MD, Laurie L. Briceland, PharmD, and Brian Cooper, MD, Hartford, Connecticut
This report describes the experience at Hartford Hospital 1 year after cefoxitin was replaced by cefotetan on the hospital formulary. In approving a recommendation to replace cefoxitin with cefotetan for prophylaxis and therapy effective August 1, 1986, the medical staff agreed that both drugs were similar in antimicrobial activity and had a similar safety profile, although hypoprothrombinemias are a potential problem with cefotetan therapy due to the N-methylthiotetrazole substitution present in the chemical structure [1-3]. When antibiotics have been demonstrated to be clinically equal in terms of efficacy and toxicity, cost then becomes the predominant determinant in the selection of drugs for inclusion in the hospital formulary. Although cefotetan costs approximately the same as cefoxitin on a per-gram basis, the longer half-life allows for a twice-daily dosing regimen compared with a 6 hour dosing regimen for cefoxitin. Program Description
Therapeutic interchange was implemented through use of automatic substitution supplemented by intense educational programs, such as in-service presentations to medical and nursing staff by infectious disease specialists and clinical pharmacists. These techniques emphasized the clinical literature supporting the therapeutic interFrom the Department of Pharmacy Services and Division of Infectious Disease, Hartford Hospital, Hartford, Connecticut and the University of Connecticut, Storrs, Connecticut. Requests for reprints should be addressed to Charles H. Nightingale, PhD, Vice President, Hartford Hospital, 80 Seymour Street, Hartford, Connecticut 06115.
Volume 155 (SA), May 31, 1988
changeability of the two antibiotics and stressed the anticipated annual savings of approximately $140,000 based on previous cefoxitin usage (Table I). To evaluate clinical efficacy, safety, and savings, two separate retrospective reviews of patient medical records were performed. The first audit consisted of 100 patients who had received cefotetan and 100 randomly chosen cefoxitin-treated patients [4]. Subsequently, 154 additional patient medical charts were reviewed, comparing 1 g or 2 g of cefotetan every 12 hours with combination therapy of an aminoglycoside with either mezlocillin or clindamycin. The aminoglycoside dosing regimen varied for each patient according to the recommendations of the pharmacokinetics monitoring service. Clindamycin was commonly administered as 600 mg or 900 mg every 6 or 8 hours, and mezlocillin was dosed at 5 g every 8 hours due to a previous decision made by the Pharmacy and Therapeutics Committee [5]. Program E x p e r i e n c e
A total of 960 patients were treated with cefotetan last year; no unexpected difficulties with clinical efficacy or safety were encountered. In the audit, an empiric cure or clinical improvement was noted in 95.7 percent and 80 percent of patients treated with cefotetan or cefoxitin, respectively. The second retrospective review produced similar clinical assessments. Clinical outcomes were classified as an empiric cure or improvement for 99 percent, 97.2 percent, and 95.5 percent of patients treated with cefotetan or an aminoglycoside combined with either clindamycin or mezlocillin, respectively.
101
Nightingale et al
TABLE I
Comparative Costs of Cefoxitin and Cefotetan Antibiotic
Dosing Regimen
Total Daily Cost*
Total Annual Costt
Cefoxitin Cefotetan Cefoxitin Cefotetan Total predicted s a v i n g s
1g/6h lg/12h 2g/6h 2g/12h . .
$38.72 $21.20 $65.72 $37.10 . .
$56,730 $30,320 $260,080 $143,680
.
.
.
.
Predicted Annual Savings $26,410 $11(~,400 ... $142,810
.
* Includes drug acquisition costs, supply costs, and the cost of nursing and pharmacy labor. Cefoxitin data reflect actual usage, cefotetan data reflect projected usage.
TABLE II
Comparative Costs of Antibiotic Therapy From Second Retrospective Audit
Antibiotic
Mean No. of Doses
Cefotetan Aminoglycoside/ clindamycin Aminoglycoside/ mezlocillin
10 14.8 16.9 11.3 14.7
Study Drug Costs* $189.64 4- 79.96 $295.07 -I- 135.48 $307.64 -I- 168.53
* Values given as the mean 4- the standard deviation.
In the 960 patients who have received cefotetan to date, the nursing, pharmacy, and medical staffs have voluntarily reported 32 adverse events possibly related to cefotetan therapy (an incidence of 3.2 percent). These adverse reactions coincide with those reported in the package insert and with those associated with other cephalosporins and beta-lactams in general [6]. Coagulopathy occurred in 18 patients; clinical bleeding was reported in 7 of these patients, but in only 1 was it believed to be related to antibiotic therapy. In the second audit, the average cost of cefotetan therapy ($189.64) was substantially lower than that of either of the other two antibiotic regimens ($295.07 and $307.64, respectively), demonstrating the cost-effectiveness of cefotetan therapy (Table II).
102
The propriety of the decision for the therapeutic replacement of cefotetan for cefoxitin has been verified over the course of the year. No difficulties in either efficacy or clinical safety of cefotetan therapy have been observed. Based on the data analysis of cefotetan usage for the 12 month period, the actual annual savings resulting from the therapeutic substitution of cefotetan for cefoxitin was $124,961.
References 1. Ward A, Richards DM. Cefotetan: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1985; 30: 382-426. 2. Stuart Pharmaceuticals. Cefotetan package insert. Wilmington, Delaware: March 1986. 3. Quintiliani R, French M, Nightingale CH. First and second generation cephalosporins. Med Clin North Am 1982; 66: 183-97. 4. Quintiliani R, Cooper BW, Briceland LL, Nightingale CH. Formulary replacement policies: cefotetan vs cefoxitin. Infections in Med 1987; 275-9. 5. Briceland LL, Nightingale CH, Quintiliani R, Cooper BW. Costeffective dosage modification of mezlocillin utilizing dosedependent pharmacokinetic principles. Accepted for poster presentation. A.S.H.P. 22nd annual midyear clinical meeting, Atlanta, Georgia. 6. Midtvedt T. Penicillins, cephalosporins and tetracyclines. In: Dukes MNG, Beeley L, eds. Side effects of drugs: annual 11. Amsterdam: Elsevier Science Publishers, 1987: 223-30.
The AmericanJournalof Surgery