Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Cost-Effectiveness Comparison of Single and Multiple-Dose Antibiotic Treatment of Lower Uncomplicated Urinary Tract Infections S. Capri, G.P. Del Bono & R. Dellamano To cite this article: S. Capri, G.P. Del Bono & R. Dellamano (1992) Cost-Effectiveness Comparison of Single and Multiple-Dose Antibiotic Treatment of Lower Uncomplicated Urinary Tract Infections, Journal of Chemotherapy, 4:3, 171-175, DOI: 10.1080/1120009X.1992.11739159 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739159
Published online: 15 Jul 2016.
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Citing articles: 2 View citing articles
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Date: 01 September 2017, At: 11:01
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Journal of Chemotherapy
Cost-Effect iveness Comparison of Single and Multiple-Dose Antibiotic Treatment of Lower Uncomplicated Urinary Tract Infections S. CAPRI * - G.P. DEL BONO ** R. DELLAMANO ***
Summary --------------- --------------- This study analyzed the cost-effectiveness of antibiotic treatments of different durations for acute cystitis in nonpregnant females. Questionnaires were sent to 400 practitioners evenly distributed throughout Italy. Data are reported from 2,069 patients. The clinical bacteriological efficacy at 1015 days was 86.4% for single-dose treatment with fosfomy· cin-trometamol (FT), and 81.8% for the multiple-dose antibiotics group (MDAG). Disappearance of symptoms occurred in 2.1 days with FT and 3.4 days with MDAG. With FT 93.8% of patients were free of adverse events and 86.9% with MDAG. Analysis of the cost-effectiveness indicators for cure rate and absence of adverse events showed that treat· ment costs were similar for all antibiotics. FT needed less time interval for symptoms to disappear with a slighdy higher cost than for MDAG, which had a better cost/effectiveness ratio. Key words: urinary tract infections, cost-effectiveness, fosfomycin trometamol, cost of antibiotic therapy.
* Institute of Biometrics, University of Milan and National Cancer Institute of Milan, Italy. ** Clinical Development Direction, ZAMBON RESEARCH, Bresso, Milan, Italy. *** Independent Health Economist, Milan, Italy. Correspondence: Stefano Capri MSc, Health Economist, Institute of Biometrics, University of Milan, Via Venezian 1, 20133 Milano, Italy.- Tel. 02/23.90.294- Fax. 02/26.66.234. © Edizioni Riviste Scientifiche - Firenze
Vol. 4 - n. 3 (171-175) - 1992
INTRODUCTION
Economic studies have recently been focusing increasingly on urinary tract infections (UTI) 1 " 4 with debate over the choice between alternative treatments. The discussion involves whether the gain, in terms of effectiveness, is worth the cost. An economic assessment of pharmacological therapy requires clear identification of the clinical objectives, and the cost of resources consumed. Urinary infections are one of the most common diseases requiring prescription of antibiotics in Italy. It has been estimated that 2030% of adult women experience one or more episodes of dysuria per year. Thus a large number of women seek medical advice for symptoms of urinary infection; most of these are considered to be uncomplicated UTI. Conventionally, antibiotic therapy is prescribed for 5-10 days, but in recent years there has been a tendency to employ short-term therapy, from a single dose to a 3-day schedule. The present study involved female patients attending out-patient clinics, with symptoms of acute uncomplicated UTI. Specifically, singledose treatment with fosfomycin-trometamol (FT) and the most widely prescribed multipledose antibiotics were compared. Any assessment of a given treatment using cost-effectiveness information involves comparing the success of the results and the conditions in which results and costs arise. PATIENTS AND METHODS
A questionnaire was sent out early in 1989 to 400 physicians in Italy (255 general practiISSN 1120-009X
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
17-~
tioners, 95 obstetricians, 50 urologists), the sample being spread proportionally around the country. Questions referred to their specialization, number of years in the medical profession, treatments usually prescribed and number of patients with UTI treated monthly. Each physician was also sent copies of a questionnaire to be completed for each patient examined during the study period (first quarter of 1989). The first part, to be completed during the first visit, asked for the patient's demographic data: age, occupation, pregnancy and clinical data of first episode of UTI or relapse, number of days with relevant symptoms, urine culture and treatment prescribed. At the next visit, the second part of the questionnaire included the duration of symptoms, adverse events, treatment duration, results, and any further treatment in case of failure. From the 4,000 patient records distributed, almost 2,500 were returned and 2,249 were eligible for analysis. Pregnant patients were excluded since only a small sample were evaluable, so analysis was done on a population of 2,069 patients. The characteristics of the physicians responding (65%) were: mean age 42 years; mean interval from graduation 15 years; 87% practiced almost entirely in out-patient clinics; each physician had an average of 1,250 subjects registered for health care through the Italian National Health Service and 50% saw at least 10 patients with UTI per month. The clinical objectives checked were the outcome of treatment, clinical/bacteriological cure at 10-15 days, the incidence of adverse events and duration of symptoms. The time patients spent travelling to the physician's office was not taken into account . The cost of each treatment was taken as the mean market price of the different drug packages used, multiplied by the number of packages needed. This cost analysis was based on drug cost only, since administrative costs (e.g. physician's time/workload) were assumed to be the same for each antibiotic regimen. An estimate of indirect costs such as time lost from work and psychological and physical costs (mostly intangible) would have required quite a different approach. Costs are expressed in Italian liras (1,000 liras = US $0.78 according to the average 1989 exchange rate). The indicators employed were derived to
S. CAPRI - G.P. DEL BONO - R. DELLAMANO
compare single-dose treatment (FT, Zambon) with multiple-dose treatments, relating the costs to the specific results. The first indicator was the ratio of cost of therapy to the percentage of clinical/bacteriological cure (i.e. total symptom remission or bacteriological cure); the second was the cost of therapy related to the absence of adverse events (as a percentage of patients); the third indicator showed the extra cost of the single-dose treatment to achieve more rapid disappearance of symptoms than the other treatments and is expressed as cost/day.
RESULTS
The total of 2,069 patients received 33 different drug treatments. Analysis was restricted to the 15 most widely used drugs, collecting the other 18 in the "other antibiotics" category (Table 1). The distribution of patients at the beginning of therapy in regard to first UTI episodes or relapses was, on average, the same for each category: 52% for first episodes and 48% for relapses. The short-term results of treatment in the FT (single-dose) group were better (86.4%) than the multiple-dose antibiotics group (MDAG) (81.4%), except for piperacillin that achieved a 100% cure rate (Table 2).
TABLE 1 - Treatment distribution . No. Patients
Treatment
%
Pipemidic acid Norfloxacin Cinoxacin Cotrimoxazole Aztreonam Aminoglycosides Nitrofurantoin Enoxacin Cephalosporin Injectables Oral Broad-Spect.Penicillin Nalidixic Acid Ofloxacin Other Antibiotics Piperacillin
13 .6 13 .2 4.3 4.0 3.9 2.9 1.8 1.4 1.3 1.1 0.9 0.6 0 .5 0.4
Multiple-dose Antibiotics Group Fosfomycin Trometamol Group
50.1 49.9
1037 1032
100.0
2069
Total
282 . 274 89 82 81 60 38 30 27 22 19 13 11 9
173
COST-EFFECTIVENESS COMPARISON OF SINGLE AND MULTIPLE-DOSE ANTIBIOTIC TREATMENT, ETC.
The shortest interval between drug intake and remission of symptoms was with FT (singledose): 2.1 days. The weighted mean for the MDAG was 3.4 days (Table 3). Treatment was, as expected, shorter with FT - 1. 7 days whereas for MDAG the mean was 7.4 days (range 5 .4-8 .1 days). It is perhaps worth mentioning that since the FT package contains two sachets, the mean prescription of 1. 7 sachets
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
TABLE 2 - Results of short-term (10-15 days) treatment. Treatment
Pi peracillin Oral Broad-Spectrum Penicillin Pipemidic Acid Ofloxacin Nalidixic Acid Aztreonam Enoxacin Aminoglycosides Norfloxacin Cotrimoxazole Cinoxacin Cephalosporin Injectable Other Antibiotics Nitrofurantoi n
Clinical/ Bacteriological Cure (% ) 100.0 86.3 85.1 84 .7 84.2 83.9 83.4 83.3 82.2 78.1 77.5 74.0
TABLE 4 - Adverse events (A.E.) by treatment. A.E. Present (% ) A.E. Absent
Treatment
Cephalosporin Injectable Piperacillin Oral Broad-Spect.Penicillin Aztreonam Nalidixic Acid Pipemidic Acid Aminoglycosides Enoxacin N orfloxaci n Cinoxacin Cotrimoxazole Other Antibiotics Nitrofurantoin Ofloxacin Multiple-dose Antibiotics Group (weighted mean) Fosfomycin Trometamol Group (mean)
%
Gastrointestinal tract
Other
100.0 100.0 90.9 90.1 89 .5 86 .9 86.7 86.7 86.5 85.4 85.4 81.8 78.9 76.9
0.0 0.0 9.1 8.6 5.3 10.6 10.0 6.7 8.8 11.2 9.8 9.1 18.4 15.4
0.0 0.0 0.0 1.2 5.3 2.5 3.3 6.6 4.8 3.3 4.9 9.1 2.6 7.7
86.9
9.6
3.5
93.8
5.1
1.1
TABLE 5 - Drug costs per treatment.
72.8
63.2 Treatment
Multiple-dose Antibiotics Group (weighted mean) Fosfomycin Trometamol Group (mean)
81.8 86.4
TABLE 3 - Time needed for symptoms to disappear, by treatment. Treatment
Days
Ami nag! ycosides Aztreonam Oral Broad-S pectrum Penicillin Piperacillin Nalidixic Acid Cotri moxazole Pipemidic Acid Norfloxacin Cinoxacin Enoxacin Ofloxacin Nitrofurantoin Cephalosporin Injectable Other Antibiotics
2.9 2.9 3.1 3.1 3.2 3.2 3.4 3.4 3.5 3.5 3.5 3.7 4.2 4.3
Multiple-dose Antibiotics Group (weighted mean) Fosfomycin Trometamol Group (mean)
3.4 2.1
Aztreonam Cephalosporin Injectable Piperacillin Aminoglycosides Ofloxacin Enoxacin Cinoxacin Norfloxacin Other Antibiotics Fosfomycin Trometamol Group Oral Broad-S pectrum Penicillin Pipemidic Acid Nalidixic Acid Cotrimoxazole Nitrofurantoin Multiple-dose Antibiotics Group (weighted mean)
Italian Liras (1989) 379,781 210,271 165,870 143,931 59,057 54,219 38,867 36,936 25,832 23,823 21,480 14,946 9,791 7,958 5,242 66,106
might be attributable to physicians' reluctance at that time to accept the concept of single-dose treatment for acute cystitis. For the same year, data from a larger panel of physicians gave a mean prescription of 1.2 sachets.
174
S. CAPRI - G.P. DEL BONO - R. DELLAMANO
The cost per therapy of a single-dose is low and only pipemidic acid was a more effective and less expensive treatment: 14,946 liras versus 23,823 liras for FT. The weighted mean for the MDAG was 66,106 liras (Table 5). Given the similar effectiveness of most of the antibiotic therapies presented, the differences in cost/therapy in relation to the percentage of success were highly dependent on the cost of therapy. Therefore tha lowest cost/therapy for cure was obtained with nitrofurantoin (8,294 liras per success obtained) while FT was the sixth least expensive (27,573 liras). The indicator ranged from 8,294-454,659 liras (Table 6). The ranking was the same for cost of therapy in relation to absence of adverse events (Table 6). Based on these results, a marginal analysis was made for the cost-per-day achieved which was free of symptoms. This was done specifically for therapies that were more cost-effective than the single-dose schedule with FT (Table 7). Given the average number of days necessary for remission of symptoms with each of the most cost-effective treatments, and their respective cost/therapy, we calculated the days gained free of symptoms with FT. Then, from the difference in cost/therapy, we calculated the marginal cost (direct cost in terms of drug therapy only) of using single-dose FT instead of ~ther drugs to gain a day free of symptoms (Table 7). The range of extra cost was 2,343-14,442 liras, which did not seem excessive in terms of a day gained which was free of discomfort.
TABLE 6 - Cost/effectiveness indicators. Treatment cost*
Treatment cost*
Cure (%)
Absence of adverse events (%)
454,659 284,150 172,786 165,870 69,725 65,011 50,151 44,934 35,484 27,573 24,890 17,563 11,628 10,190 8,294
421,511 210,271 166,010 165,870 76,797 62,536 45 ,5 12 42,701 31,579 25,398 23,630 17,199 10,940 9,319 6,644
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
Treatment
Aztreonam Cephalosporin Injectable Aminoglycosides Pi peracillin Ofloxacin Enoxacin Cinoxacin Norfloxacin Other Antibiotics Fosfomycin Trometamol Oral Broad-Spect.Penicillin Pipemidic Acid Nalidixic Acid Cotrimoxazole Nitrofurantoin * 1989 Italian liras (1000
us
$ 0 .78) .
Piperacillin and the cephalosporins gave the highest percentages of patients free from adverse events (100%), followed by FT with 93.8%; the weighted mean for the MDAG was 86.9% (Table 4). Most of the adverse events involved the gastrointestinal tract and FT caused only 5.1%, compared to the MDAG average of 9.6%. The therapeutic effectiveness of single-dose FT thus appeared slightly better than the MDAG therapies. The relation to cost data was therefore calculated.
TABLE 7 - Treatment with a better cost-effectiveness ratio than fosfomycin trometamol (FT) . Days to disappearance of symptoms
Treatments
Difference in days to Difference in cost-therapy * disappearance of symptoms (FT - Multiple dose (Multiple dose an tibio tics) antibiotics - FT)
Cost/day * gained without sympto ms with FT
Fosfomycin Trometamol
2.1
Oral Broad-Spect.Penicillin
3.1
1.0
2,343
2,343
Nalidixic Acid
3.2
1.1
14,032
12,756
Cotrimoxazole
3.2
1.1
15,865
14,422
Piperni die Acid
3 .4
1.3
8,877
6,828
Nitrofurantoin
3. 7
1.6
18,581
11,613
* 1000 Italian liras
US $ 0.78 (1989 exchange rate).
COST-EFFECTIVENESS COMPARISON OF SINGLE AND MULTIPLE-DOSE ANTIBIOTIC TREATMENT, ETC.
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
DISCUSSION
In the present study, 1,032 women with UTI receiving FT as single-dose oral antibiotic treatment were compared to 1,03 7 patients receiving multiple-dose antibiotic treatments (the 15 most widely prescribed antibiotics). Since the analysis was made on the basis of the general practice of 260 physicians distributed uniformly throughout Italy the results are in terms of effectiveness, not just efficacy (the former relating to results assessed under normal operat~ ing conditions, the latter to results obtained under controlled experiments or trials). They therefore seem more reliable, particularly when related to costs. Besides our analysis of the cost of drug therapy, information was obtained on the physicians' practice, and the average frequency of UTI cases treated was about ten cases/month. Cost-effectiveness, in terms of clinical/bacteriological cure and absence of adverse events, was best for a group of low cost treatments, comprising nitrofurantoin, cotrimoxazole, nalidixic acid, pipemidic acid, oral broad-spectrum
175
penicillins, FT and some other antibiotics. Finally, the interval between infection and remission of symptoms was shortest with FT (at least one day less than with the most effective multiple-dose antibiotics), so the cost of gaining an extra day free of symptoms with the singledose schedule ranged from 2,343-14,422 liras or about US $1.88 to $11.25. ACKNOWLEDGEMENT - This study was supported by a grant from ZAMBON GROUP (Milan), Italy.
REFERENCES ' Patton JP, Nash DB, Abrutyn E. Urinary tract infection : economic considerations. Med Clin North Am 1991; 75: 495 -5 13. ' Capri S. A framework for an economic appraisal of single-dose drug. In : Neu HC, Wi.UiamsJD, eds. New Trends in Urinary Tract Infections. Basel : Karger, 1989: 110-115 . ' Bailey RR. Cost-benefit considerations in the management of uncomplicated urinary tract infections in sexually active women. NZ Med J 1987; 100: 680-683 . ' Carlson KJ. Cost-effectiveness analysis of single-dose therapy of urinary tract infection compared to conventional treatment. Eur Urol 1987; 135 : 45-47.
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Cost-Effectiveness Comparison of Single and Multiple-Dose Antibiotic Treatment of Lower Uncomplicated Urinary Tract Infections S. Capri, G.P. Del Bono & R. Dellamano To cite this article: S. Capri, G.P. Del Bono & R. Dellamano (1992) Cost-Effectiveness Comparison of Single and Multiple-Dose Antibiotic Treatment of Lower Uncomplicated Urinary Tract Infections, Journal of Chemotherapy, 4:3, 171-175, DOI: 10.1080/1120009X.1992.11739159 To link to this article: http://dx.doi.org/10.1080/1120009X.1992.11739159
Published online: 15 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [Australian Catholic University]
Date: 01 September 2017, At: 11:01
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
Journal of Chemotherapy
Cost-Effect iveness Comparison of Single and Multiple-Dose Antibiotic Treatment of Lower Uncomplicated Urinary Tract Infections S. CAPRI * - G.P. DEL BONO ** R. DELLAMANO ***
Summary --------------- --------------- This study analyzed the cost-effectiveness of antibiotic treatments of different durations for acute cystitis in nonpregnant females. Questionnaires were sent to 400 practitioners evenly distributed throughout Italy. Data are reported from 2,069 patients. The clinical bacteriological efficacy at 1015 days was 86.4% for single-dose treatment with fosfomy· cin-trometamol (FT), and 81.8% for the multiple-dose antibiotics group (MDAG). Disappearance of symptoms occurred in 2.1 days with FT and 3.4 days with MDAG. With FT 93.8% of patients were free of adverse events and 86.9% with MDAG. Analysis of the cost-effectiveness indicators for cure rate and absence of adverse events showed that treat· ment costs were similar for all antibiotics. FT needed less time interval for symptoms to disappear with a slighdy higher cost than for MDAG, which had a better cost/effectiveness ratio. Key words: urinary tract infections, cost-effectiveness, fosfomycin trometamol, cost of antibiotic therapy.
* Institute of Biometrics, University of Milan and National Cancer Institute of Milan, Italy. ** Clinical Development Direction, ZAMBON RESEARCH, Bresso, Milan, Italy. *** Independent Health Economist, Milan, Italy. Correspondence: Stefano Capri MSc, Health Economist, Institute of Biometrics, University of Milan, Via Venezian 1, 20133 Milano, Italy.- Tel. 02/23.90.294- Fax. 02/26.66.234. © Edizioni Riviste Scientifiche - Firenze
Vol. 4 - n. 3 (171-175) - 1992
INTRODUCTION
Economic studies have recently been focusing increasingly on urinary tract infections (UTI) 1 " 4 with debate over the choice between alternative treatments. The discussion involves whether the gain, in terms of effectiveness, is worth the cost. An economic assessment of pharmacological therapy requires clear identification of the clinical objectives, and the cost of resources consumed. Urinary infections are one of the most common diseases requiring prescription of antibiotics in Italy. It has been estimated that 2030% of adult women experience one or more episodes of dysuria per year. Thus a large number of women seek medical advice for symptoms of urinary infection; most of these are considered to be uncomplicated UTI. Conventionally, antibiotic therapy is prescribed for 5-10 days, but in recent years there has been a tendency to employ short-term therapy, from a single dose to a 3-day schedule. The present study involved female patients attending out-patient clinics, with symptoms of acute uncomplicated UTI. Specifically, singledose treatment with fosfomycin-trometamol (FT) and the most widely prescribed multipledose antibiotics were compared. Any assessment of a given treatment using cost-effectiveness information involves comparing the success of the results and the conditions in which results and costs arise. PATIENTS AND METHODS
A questionnaire was sent out early in 1989 to 400 physicians in Italy (255 general practiISSN 1120-009X
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
17-~
tioners, 95 obstetricians, 50 urologists), the sample being spread proportionally around the country. Questions referred to their specialization, number of years in the medical profession, treatments usually prescribed and number of patients with UTI treated monthly. Each physician was also sent copies of a questionnaire to be completed for each patient examined during the study period (first quarter of 1989). The first part, to be completed during the first visit, asked for the patient's demographic data: age, occupation, pregnancy and clinical data of first episode of UTI or relapse, number of days with relevant symptoms, urine culture and treatment prescribed. At the next visit, the second part of the questionnaire included the duration of symptoms, adverse events, treatment duration, results, and any further treatment in case of failure. From the 4,000 patient records distributed, almost 2,500 were returned and 2,249 were eligible for analysis. Pregnant patients were excluded since only a small sample were evaluable, so analysis was done on a population of 2,069 patients. The characteristics of the physicians responding (65%) were: mean age 42 years; mean interval from graduation 15 years; 87% practiced almost entirely in out-patient clinics; each physician had an average of 1,250 subjects registered for health care through the Italian National Health Service and 50% saw at least 10 patients with UTI per month. The clinical objectives checked were the outcome of treatment, clinical/bacteriological cure at 10-15 days, the incidence of adverse events and duration of symptoms. The time patients spent travelling to the physician's office was not taken into account . The cost of each treatment was taken as the mean market price of the different drug packages used, multiplied by the number of packages needed. This cost analysis was based on drug cost only, since administrative costs (e.g. physician's time/workload) were assumed to be the same for each antibiotic regimen. An estimate of indirect costs such as time lost from work and psychological and physical costs (mostly intangible) would have required quite a different approach. Costs are expressed in Italian liras (1,000 liras = US $0.78 according to the average 1989 exchange rate). The indicators employed were derived to
S. CAPRI - G.P. DEL BONO - R. DELLAMANO
compare single-dose treatment (FT, Zambon) with multiple-dose treatments, relating the costs to the specific results. The first indicator was the ratio of cost of therapy to the percentage of clinical/bacteriological cure (i.e. total symptom remission or bacteriological cure); the second was the cost of therapy related to the absence of adverse events (as a percentage of patients); the third indicator showed the extra cost of the single-dose treatment to achieve more rapid disappearance of symptoms than the other treatments and is expressed as cost/day.
RESULTS
The total of 2,069 patients received 33 different drug treatments. Analysis was restricted to the 15 most widely used drugs, collecting the other 18 in the "other antibiotics" category (Table 1). The distribution of patients at the beginning of therapy in regard to first UTI episodes or relapses was, on average, the same for each category: 52% for first episodes and 48% for relapses. The short-term results of treatment in the FT (single-dose) group were better (86.4%) than the multiple-dose antibiotics group (MDAG) (81.4%), except for piperacillin that achieved a 100% cure rate (Table 2).
TABLE 1 - Treatment distribution . No. Patients
Treatment
%
Pipemidic acid Norfloxacin Cinoxacin Cotrimoxazole Aztreonam Aminoglycosides Nitrofurantoin Enoxacin Cephalosporin Injectables Oral Broad-Spect.Penicillin Nalidixic Acid Ofloxacin Other Antibiotics Piperacillin
13 .6 13 .2 4.3 4.0 3.9 2.9 1.8 1.4 1.3 1.1 0.9 0.6 0 .5 0.4
Multiple-dose Antibiotics Group Fosfomycin Trometamol Group
50.1 49.9
1037 1032
100.0
2069
Total
282 . 274 89 82 81 60 38 30 27 22 19 13 11 9
173
COST-EFFECTIVENESS COMPARISON OF SINGLE AND MULTIPLE-DOSE ANTIBIOTIC TREATMENT, ETC.
The shortest interval between drug intake and remission of symptoms was with FT (singledose): 2.1 days. The weighted mean for the MDAG was 3.4 days (Table 3). Treatment was, as expected, shorter with FT - 1. 7 days whereas for MDAG the mean was 7.4 days (range 5 .4-8 .1 days). It is perhaps worth mentioning that since the FT package contains two sachets, the mean prescription of 1. 7 sachets
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
TABLE 2 - Results of short-term (10-15 days) treatment. Treatment
Pi peracillin Oral Broad-Spectrum Penicillin Pipemidic Acid Ofloxacin Nalidixic Acid Aztreonam Enoxacin Aminoglycosides Norfloxacin Cotrimoxazole Cinoxacin Cephalosporin Injectable Other Antibiotics Nitrofurantoi n
Clinical/ Bacteriological Cure (% ) 100.0 86.3 85.1 84 .7 84.2 83.9 83.4 83.3 82.2 78.1 77.5 74.0
TABLE 4 - Adverse events (A.E.) by treatment. A.E. Present (% ) A.E. Absent
Treatment
Cephalosporin Injectable Piperacillin Oral Broad-Spect.Penicillin Aztreonam Nalidixic Acid Pipemidic Acid Aminoglycosides Enoxacin N orfloxaci n Cinoxacin Cotrimoxazole Other Antibiotics Nitrofurantoin Ofloxacin Multiple-dose Antibiotics Group (weighted mean) Fosfomycin Trometamol Group (mean)
%
Gastrointestinal tract
Other
100.0 100.0 90.9 90.1 89 .5 86 .9 86.7 86.7 86.5 85.4 85.4 81.8 78.9 76.9
0.0 0.0 9.1 8.6 5.3 10.6 10.0 6.7 8.8 11.2 9.8 9.1 18.4 15.4
0.0 0.0 0.0 1.2 5.3 2.5 3.3 6.6 4.8 3.3 4.9 9.1 2.6 7.7
86.9
9.6
3.5
93.8
5.1
1.1
TABLE 5 - Drug costs per treatment.
72.8
63.2 Treatment
Multiple-dose Antibiotics Group (weighted mean) Fosfomycin Trometamol Group (mean)
81.8 86.4
TABLE 3 - Time needed for symptoms to disappear, by treatment. Treatment
Days
Ami nag! ycosides Aztreonam Oral Broad-S pectrum Penicillin Piperacillin Nalidixic Acid Cotri moxazole Pipemidic Acid Norfloxacin Cinoxacin Enoxacin Ofloxacin Nitrofurantoin Cephalosporin Injectable Other Antibiotics
2.9 2.9 3.1 3.1 3.2 3.2 3.4 3.4 3.5 3.5 3.5 3.7 4.2 4.3
Multiple-dose Antibiotics Group (weighted mean) Fosfomycin Trometamol Group (mean)
3.4 2.1
Aztreonam Cephalosporin Injectable Piperacillin Aminoglycosides Ofloxacin Enoxacin Cinoxacin Norfloxacin Other Antibiotics Fosfomycin Trometamol Group Oral Broad-S pectrum Penicillin Pipemidic Acid Nalidixic Acid Cotrimoxazole Nitrofurantoin Multiple-dose Antibiotics Group (weighted mean)
Italian Liras (1989) 379,781 210,271 165,870 143,931 59,057 54,219 38,867 36,936 25,832 23,823 21,480 14,946 9,791 7,958 5,242 66,106
might be attributable to physicians' reluctance at that time to accept the concept of single-dose treatment for acute cystitis. For the same year, data from a larger panel of physicians gave a mean prescription of 1.2 sachets.
174
S. CAPRI - G.P. DEL BONO - R. DELLAMANO
The cost per therapy of a single-dose is low and only pipemidic acid was a more effective and less expensive treatment: 14,946 liras versus 23,823 liras for FT. The weighted mean for the MDAG was 66,106 liras (Table 5). Given the similar effectiveness of most of the antibiotic therapies presented, the differences in cost/therapy in relation to the percentage of success were highly dependent on the cost of therapy. Therefore tha lowest cost/therapy for cure was obtained with nitrofurantoin (8,294 liras per success obtained) while FT was the sixth least expensive (27,573 liras). The indicator ranged from 8,294-454,659 liras (Table 6). The ranking was the same for cost of therapy in relation to absence of adverse events (Table 6). Based on these results, a marginal analysis was made for the cost-per-day achieved which was free of symptoms. This was done specifically for therapies that were more cost-effective than the single-dose schedule with FT (Table 7). Given the average number of days necessary for remission of symptoms with each of the most cost-effective treatments, and their respective cost/therapy, we calculated the days gained free of symptoms with FT. Then, from the difference in cost/therapy, we calculated the marginal cost (direct cost in terms of drug therapy only) of using single-dose FT instead of ~ther drugs to gain a day free of symptoms (Table 7). The range of extra cost was 2,343-14,442 liras, which did not seem excessive in terms of a day gained which was free of discomfort.
TABLE 6 - Cost/effectiveness indicators. Treatment cost*
Treatment cost*
Cure (%)
Absence of adverse events (%)
454,659 284,150 172,786 165,870 69,725 65,011 50,151 44,934 35,484 27,573 24,890 17,563 11,628 10,190 8,294
421,511 210,271 166,010 165,870 76,797 62,536 45 ,5 12 42,701 31,579 25,398 23,630 17,199 10,940 9,319 6,644
Downloaded by [Australian Catholic University] at 11:01 01 September 2017
Treatment
Aztreonam Cephalosporin Injectable Aminoglycosides Pi peracillin Ofloxacin Enoxacin Cinoxacin Norfloxacin Other Antibiotics Fosfomycin Trometamol Oral Broad-Spect.Penicillin Pipemidic Acid Nalidixic Acid Cotrimoxazole Nitrofurantoin * 1989 Italian liras (1000
us
$ 0 .78) .
Piperacillin and the cephalosporins gave the highest percentages of patients free from adverse events (100%), followed by FT with 93.8%; the weighted mean for the MDAG was 86.9% (Table 4). Most of the adverse events involved the gastrointestinal tract and FT caused only 5.1%, compared to the MDAG average of 9.6%. The therapeutic effectiveness of single-dose FT thus appeared slightly better than the MDAG therapies. The relation to cost data was therefore calculated.
TABLE 7 - Treatment with a better cost-effectiveness ratio than fosfomycin trometamol (FT) . Days to disappearance of symptoms
Treatments
Difference in days to Difference in cost-therapy * disappearance of symptoms (FT - Multiple dose (Multiple dose an tibio tics) antibiotics - FT)
Cost/day * gained without sympto ms with FT
Fosfomycin Trometamol
2.1
Oral Broad-Spect.Penicillin
3.1
1.0
2,343
2,343
Nalidixic Acid
3.2
1.1
14,032
12,756
Cotrimoxazole
3.2
1.1
15,865
14,422
Piperni die Acid
3 .4
1.3
8,877
6,828
Nitrofurantoin
3. 7
1.6
18,581
11,613
* 1000 Italian liras
US $ 0.78 (1989 exchange rate).
COST-EFFECTIVENESS COMPARISON OF SINGLE AND MULTIPLE-DOSE ANTIBIOTIC TREATMENT, ETC.
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DISCUSSION
In the present study, 1,032 women with UTI receiving FT as single-dose oral antibiotic treatment were compared to 1,03 7 patients receiving multiple-dose antibiotic treatments (the 15 most widely prescribed antibiotics). Since the analysis was made on the basis of the general practice of 260 physicians distributed uniformly throughout Italy the results are in terms of effectiveness, not just efficacy (the former relating to results assessed under normal operat~ ing conditions, the latter to results obtained under controlled experiments or trials). They therefore seem more reliable, particularly when related to costs. Besides our analysis of the cost of drug therapy, information was obtained on the physicians' practice, and the average frequency of UTI cases treated was about ten cases/month. Cost-effectiveness, in terms of clinical/bacteriological cure and absence of adverse events, was best for a group of low cost treatments, comprising nitrofurantoin, cotrimoxazole, nalidixic acid, pipemidic acid, oral broad-spectrum
175
penicillins, FT and some other antibiotics. Finally, the interval between infection and remission of symptoms was shortest with FT (at least one day less than with the most effective multiple-dose antibiotics), so the cost of gaining an extra day free of symptoms with the singledose schedule ranged from 2,343-14,422 liras or about US $1.88 to $11.25. ACKNOWLEDGEMENT - This study was supported by a grant from ZAMBON GROUP (Milan), Italy.
REFERENCES ' Patton JP, Nash DB, Abrutyn E. Urinary tract infection : economic considerations. Med Clin North Am 1991; 75: 495 -5 13. ' Capri S. A framework for an economic appraisal of single-dose drug. In : Neu HC, Wi.UiamsJD, eds. New Trends in Urinary Tract Infections. Basel : Karger, 1989: 110-115 . ' Bailey RR. Cost-benefit considerations in the management of uncomplicated urinary tract infections in sexually active women. NZ Med J 1987; 100: 680-683 . ' Carlson KJ. Cost-effectiveness analysis of single-dose therapy of urinary tract infection compared to conventional treatment. Eur Urol 1987; 135 : 45-47.
