TWENTY-EIGHT-DAY COURSES OF ANTIBIOTICS FOR URINARY TRACT INFECTION* MALCOLM CHERI
D. COSGROVE,
M.D.
GAULT, R.N.
NOEMI DANIEL
FIORENTINO IVLER,
PH.D.
From the Departments of Urology and Pediatric Microbiology, Los Angeles County-University of Southern California Medical Center, Los Angeles, California
ABSTRACT -A prospective double-blind study was performed in which 30 adult patients with recurrent urinary tract infections due to Escherichia coli, and Proteus mirabilis organisms were treated by twenty-eight-day courses of either ampicillin, 500 mg. four times a day, or trimethoprimsulphamethoxazole, 2 tablets twice a day. In terms of freedom from infection fifty-six days after the cessation of treatment in both complicated and uncomplicated infections, trimethoprimsulphamethoxazole yielded results superior to those of ampicillin. In comparing the results of this study with those of a similar study in which the same agents were given fm ten-day courses it appears that only in the complicated infection is there an advantage in giving a prolonged course of trimethoprimsulphamethoxazole. This study did not generate any evidence to support the extension of ampicillin therapy for urinary tract infection beyond ten days.
The combination trimethoprim-sulphamethoxazole is gaining acceptance as a useful agent for the treatment of urinary tract infections. In a recent cooperative study comparing the efficacy of the trimethoprim-sulphamethoxazole against ampicillin in ten-day courses in patients with urinary infections, it was found that the former was more successful in eradicating infections, particularly those due to Escherichia coli.’ In another report it appeared that in infections complicated by urologic disorders neither of the two agents was successful when given in ten-day courses.2 To determine whether or not these results could be improved on by increasing the treatment period beyond ten days, a further study was undertaken in which patients with urinary tract infections were treated with ampicillin or trimethoprim-sulphamethoxazole in fixed dosage for periods of twenty-eight days. The results of this study are presented. *This work is part of a cooperative study sponsored by Roche Laboratories, the manufacturers of trimethoprimsulphamethoxazole (Bactrim).
156
Material and Method Thirty adult patients of both sexes suffering from recurrent urinary tract infection were selected for the study. All had significant bacteriuria with E. coli or Proteus mirabilis organisms in colony counts of lo5 or greater in two successive clean voided urine samples within one week of start of therapy. It was not necessary for the organisms to be sensitive in vitro to ampicillin or trimethoprim-sulphamethoxazole although disk sensitivity testing was performed on all pathogens cultured. Patients were excluded from the study if they were known or suspected to be allergic to either drug or the penicillin group of drugs. Also excluded were patients with indwelling urethral catheters or condom drainage as well as those who required urethral instrumentation or urologic surgery during the period of treatment or followup observation. Patients who were pregnant or breast feeding were also excluded as were those with impaired renal function as manifested by an elevated serum creatinine. Patients with known or suspected inadequate folate stores or with
UROLOGY
/ FEBRUARY
1976 / VOLUME
VII. NUMBER
2
Fifteen cases of complicated infections
TABLE I. Cause
No. of Cases
Calculous disease Urethral Stricture Prostatic carcinoma Neurogenic bladder Ileocystoplasty
8 3 2 1
1
TOTAL
15
known glucose-6-phosphate dehydrogenase deficiency were also excluded as were patients with depression of the hematocrit, or elevations of serum bilirubin, serum glutamic oxaloacetic transaminase, or alkaline phosphatase levels, so also were patients with known or suspected systemic lupus erythematosus. Pretreatment laboratory values were obtained for the complete blood and platelet counts, serum glutamic oxaloacetic transaminase, alkaline phosphatase, serum bilirubin, and creatinine, and routine urinalysis was performed. Patients were subjected to complete physical examination with particular emphasis on the urinary tract. Intravenous pyelography with postvoiding films was obtained if a patient had not undergone such roentgenographic study within the previous three months. If a patient satisfied the bacteriologic, clinical, urologic, and biochemical criteria and was in addition deemed reliable and cooperative enough to return for the required outpatient follow-up visits for up to twelve weeks from the initiation of the treatment, he was asked to sign the informed consent form for the study. Each patient was then allocated in double-blind fashion to one of two treatment groups, either 2 tablets of trimethoprim-sulphamethoxazole twice a day for twenty-eight days, or I 500-mg. capsule of ampicillin four times a day for twenty-eight days. No other antimicrobial drug was given over the course of the study, and all the laboratory studies were repeated at one week, two weeks, and four weeks after onset of treatment. Voided urine samples were collected one, two, four, six, eight, and twelve weeks after the initiation of treatment for culture and sensitivity testing. If any of these urine samples yielded a significant growth of bacteria, a second urine sample was obtained for confirmation. Ifat any time up to twelve weeks after the initiation of treatment a patient was confirmed to be growing lo5 or more organisms of any kind in the urine, he was de-
UROLOGY
/ FEBRUARY1976
/ VOLUMEVII,
NUMBER2
clared a treatment failure. A therapeutic success was one in which no urine sample up to and including the one taken twelve weeks after the initiation of treatment contained significant infection. Patients were categorized as having complicated urinary tract infection if there was any evidence of structural abnormalities of the urinary tract such as calculous disease, stricture, diverticulum, and so on. An uncomplicated infection was one in which there was no associated radiologic or clinical abnormality of the urinary tract. At the end of the 30-patient study, the treatment code was broken to determine what medication each patient had received and the results were analyzed. Results There were 21 female and 9 male patients in the study. The ages ranged from twenty-two to seventy-four years, with an average of forty-five years. There were fifteen uncomplicated and fifteen complicated infections. Twenty patients were infected with E. coli and 10 with P. mirabilis organisms. Fifteen patients were treated with ampicillin and 15 with trimethoprimsulphamethoxazole. Of the 15 patients suffering from a complicated urinary tract infection, 8 had urinary tract calculi (Table I). All 8 patients were infected with P. mirabilis organisms. The remaining 7 complicated cases were infected with E. coli. Thus, of the 20 E. coli infections, 13 were uncomplicated whereas of the 10 P. mirabilis infections only 2 were associated with uncomplicated infections. Nine of the complicated infections were treated with ampicillin and 6 with trimethoprimsulphamethoxazole. Therapeutic success, as defined by freedom from infection twelve weeks after the initiation of treatment, is expressed in Table II. Of the 30 patients only 11 were free of infection at twelve
Results of treatment in 30 patients twelve weeks after start of therapy
TABLE II.
Treatment Ampicillin Trimethoprimsulphamethoxazole TOTALS
Uncomplicated
Complicated
Cure
Failure
Cure
2
4
_& 8
3 ?
1
Failure 8
2
4
3
12
157
TABLE III.
Results of treatment of 15 uncomplicated and 15 complicated infections according to pathogen
Pathogen Uncomplicated E. Coli P. mirabilis TOTALS Complicated E. coli P. mirabilis TOTALS
No. of
Cases
-AmpicillinCure
13 2 15
2 0 z
3 1 4
5
3
_L 6
0 3
7 8
1 0 i-
3
1
2
s 8
r 2
2 4
15
weeks. Of the 11, 8 were in the trimethoprimsulphamethoxazole group and 3 in the ampicillintreated group. It appears that the success rate for trimethoprim-sulphamethoxazole is greater than that of ampicillin in both the uncomplicated and the complicated groups of cases. The results of the two treatments in terms of the infecting organism for both complicated and uncomplicated infections are expressed in Table III. Trimethoprim-sulphamethoxazole appeared to be superior to ampicillin in all instances although the number of patients in each group is too small for statistical analysis. The clinical side effects noted in 30 patients were a skin rash and palpitations in 1 patient who received ampicillin and nausea in 1 patient taking trimethoprim-sulphamethoxazole. The effects were transient in both patients and were not the reason for discontinuation of treatment. No abnormal blood chemistries were noted in any of the patients treated. However, in 5 patients receiving trimethoprim-sulphamethoxazole and 1 on ampicillin minor hematologic effects, such as depression of the platelet count and the white cell count, were noted. These hematologic abnormalities were transient in all instances, reverted to normal in all cases within a few weeks, and resulted in no clinical problems. Treatment success rates, expressed as percentages, are shown in Table IV in which the data from the present study are compared with those of a similar study by the same author2 on a similar group of patients treated with the same dosages of the same antibiotics for a ten-day course as opposed to a twenty-eight-day course. The results are expressed as freedom from infection fifty-six days after the cessation of treatment, The only other difference between the two protocols is that in the ten-day course all infecting organisms had to be sensitive in vitro to ampicillin whereas this 158
Failure
Trimethoprimsulphamethoxazole Cure Failure
was not necessary in the twenty-eight-day study. In the over-all results there did not appear to be any difference in efficacy for each antibiotic between a ten-day course and a twenty-eight-day course. The superiority of trimethoprim-sulphamethoxazole to ampicillin was apparent. This superiority in the uncomplicated infection was of the order of 2 to 1 in favor of trimethoprimsulphamethoxazole in both studies. There is no evidence from this ‘comparison that for an uncomplicated infection a twenty-eight-day course of either antibiotic is superior to a ten-day course of the same drug. In the complicated infection, however, it appears that while the twentyeight-day course of ampicillin yielded as dismal results as the ten-day course of either agent, the twenty-eight-day course of trimethoprimsulphamethoxazole resulted in an improved cure rate. Comment At the present time in the United States the combination trimethoprim-sulphamethoxazole is available for the treatment of urinary tract infection and the recommended course is ten to fourteen days. The combination has been shown in one recent cooperative study3 to be more effective than sulphonamide alone and in another report1 to be superior also to ampicillin in the eradication of chronic bacteriuria in the recommended dosage. Previous reports by Wren4 and Brumfitt and Pursel15 confirm the superiority of trimethoprimsulphamethoxazole to ampicillin against urinary tract pathogens in standard courses. The purpose of the present work which is part of a multi-institutional cooperative group study was to determine whether or not the efficacy of either treatment could be further enhanced by prolonging the course of therapy to twenty-eight days. Although a few reports6J have suggested
UROLOGY/ FEBRUARY 1976 / VOLUMEVII, NUMBER2
TABLE IV.
Comparison of success rates in twenty-eight-day and ten-day courses of treatment*
Duration (Days) 10
28
Treatment
Uncomplicated (Per Cent)
Complicated (Per Cent)
Over-all (Per Cent)
43
12
27
87 33
14 11
53 20
66
33
55
Ampicillin Trimethoprimsulphamethoxazole Ampicillin Trimethoprimsulphamethoxazole
*All results at fifty-six days after termination of therapy.
that trimethoprim-sulphamethoxazole may be usefully employed in more extensive courses for the treatment of recurrent or chronic urinary tract infection, there have been no reported doubleblind studies comparing an extended course of trimethoprim-sulphamethoxazole with any other antibiotic. Both medications were tolerated well by most of the patients, and the side effects noted were not serious, numerous, or lasting. Whether or not more significant problems would have arisen had patients with impaired renal function been included for study is speculative. A recent report urged caution in prescribing the combination trimethoprim-sulphamethoxazole in patients with impaired renal function.8 It should be noted that the patients in the present study all had normal renal and hepatic function prior to therapy, did not undergo instrumentation of the urinary tract, nor did they have indwelling catheters. This makes it a rather select group of patients. These conditions, however, were the same for both standard and prolonged treatment groups. Comparison of the data from the present study with those from a previous ten-day comparative study is, we think, valid because the studies were both performed by the same investigator in the same institution with similar groups of patients under very similar circumstances. From Table III it would appear that there is no advantage in prescribing ampicillin in a twentyeight-day course rather than a ten-day course for the treatment of urinary tract infections. In the uncomplicated infection there appears likewise to be no advantage in prescribing trimethoprimsulphamethoxazole in a twenty-eight-day course compared with a ten-day course.
UROLOGY /
FEBRUARY 1976 /
VOLUME VII, NUMBER 2
However, where there is a structural abnormality of the urinary tract causing a complicated urinary tract infection it may well be advantageous to continue trimethoprim-sulphamethoxazole treatment to twenty-eight days. If the results of the entire cooperative group substantiate this recommendation, a significant therapeutic advance will have been made in the difficult area of treating the complicated urinary tract infection. Box 85, 1200 N. State Street Los Angeles, California 90033 References 1. GLECKMAN, R. A. : Trimethoprim-sulfamethoxazole vs. ampicillin in chronic urinary tract infections: a doubleblind multicenter cooperative controlled study, J.A.M.A. 233: 427 (1975). 2. COSGROVE, M. D., and MORROW, J, W.: Ampicillin versus trimethoprim/sulfamethoxazole in chronic urinary tract infection, J. Urol. 111:670 (1974). R. A.: A cooperative controlled study of 3. GLECKMAN, the use of trimethoprim-sulfamethoxazole in chronic urinary tract infections, J, Infect. Dis. 128 (suppl.): 5647 (1973). Double blind trial comparing 4. WREN, B. G.: trimethoprim-sulfamethoxazole (Bactrim) with ampicillin in treating urinary infections, Med. J. Aust. 1:261(1972). 5. BRUMFITT, W., and PURSELL, R. : Double blind trial to compare ampicillin, cephalexin, co-trimoxazole and trimethoprim in treatment of urinary infection, Br. Med. J. 2: 673 (1972). 6. GAVRAS,H., LAWSON,D. H., and LINTON, A. L.: Extended therapy with a trimethoprim-sulphonamide for the treatment ofestablished urinary tract infection, Scott. Med. J. 6: 506 (1971). New trimethoprim-sulfa7. FJELLSTROEM, K. E.: methoxazole antimicrobial assessed at symposium, Infect. Dis. 2: 1, 18 (1972). 8. KALOWSKI, S., MATHEW, T. H., NANRA, R. S., and KINCAID-SMITH,P.: Deterioration in renal function in association with co-trimoxazole therapy, Lancet 1: 394 (1973).
159
D. COSGROVE,
M.D.
GAULT, R.N.
NOEMI DANIEL
FIORENTINO IVLER,
PH.D.
From the Departments of Urology and Pediatric Microbiology, Los Angeles County-University of Southern California Medical Center, Los Angeles, California
ABSTRACT -A prospective double-blind study was performed in which 30 adult patients with recurrent urinary tract infections due to Escherichia coli, and Proteus mirabilis organisms were treated by twenty-eight-day courses of either ampicillin, 500 mg. four times a day, or trimethoprimsulphamethoxazole, 2 tablets twice a day. In terms of freedom from infection fifty-six days after the cessation of treatment in both complicated and uncomplicated infections, trimethoprimsulphamethoxazole yielded results superior to those of ampicillin. In comparing the results of this study with those of a similar study in which the same agents were given fm ten-day courses it appears that only in the complicated infection is there an advantage in giving a prolonged course of trimethoprimsulphamethoxazole. This study did not generate any evidence to support the extension of ampicillin therapy for urinary tract infection beyond ten days.
The combination trimethoprim-sulphamethoxazole is gaining acceptance as a useful agent for the treatment of urinary tract infections. In a recent cooperative study comparing the efficacy of the trimethoprim-sulphamethoxazole against ampicillin in ten-day courses in patients with urinary infections, it was found that the former was more successful in eradicating infections, particularly those due to Escherichia coli.’ In another report it appeared that in infections complicated by urologic disorders neither of the two agents was successful when given in ten-day courses.2 To determine whether or not these results could be improved on by increasing the treatment period beyond ten days, a further study was undertaken in which patients with urinary tract infections were treated with ampicillin or trimethoprim-sulphamethoxazole in fixed dosage for periods of twenty-eight days. The results of this study are presented. *This work is part of a cooperative study sponsored by Roche Laboratories, the manufacturers of trimethoprimsulphamethoxazole (Bactrim).
156
Material and Method Thirty adult patients of both sexes suffering from recurrent urinary tract infection were selected for the study. All had significant bacteriuria with E. coli or Proteus mirabilis organisms in colony counts of lo5 or greater in two successive clean voided urine samples within one week of start of therapy. It was not necessary for the organisms to be sensitive in vitro to ampicillin or trimethoprim-sulphamethoxazole although disk sensitivity testing was performed on all pathogens cultured. Patients were excluded from the study if they were known or suspected to be allergic to either drug or the penicillin group of drugs. Also excluded were patients with indwelling urethral catheters or condom drainage as well as those who required urethral instrumentation or urologic surgery during the period of treatment or followup observation. Patients who were pregnant or breast feeding were also excluded as were those with impaired renal function as manifested by an elevated serum creatinine. Patients with known or suspected inadequate folate stores or with
UROLOGY
/ FEBRUARY
1976 / VOLUME
VII. NUMBER
2
Fifteen cases of complicated infections
TABLE I. Cause
No. of Cases
Calculous disease Urethral Stricture Prostatic carcinoma Neurogenic bladder Ileocystoplasty
8 3 2 1
1
TOTAL
15
known glucose-6-phosphate dehydrogenase deficiency were also excluded as were patients with depression of the hematocrit, or elevations of serum bilirubin, serum glutamic oxaloacetic transaminase, or alkaline phosphatase levels, so also were patients with known or suspected systemic lupus erythematosus. Pretreatment laboratory values were obtained for the complete blood and platelet counts, serum glutamic oxaloacetic transaminase, alkaline phosphatase, serum bilirubin, and creatinine, and routine urinalysis was performed. Patients were subjected to complete physical examination with particular emphasis on the urinary tract. Intravenous pyelography with postvoiding films was obtained if a patient had not undergone such roentgenographic study within the previous three months. If a patient satisfied the bacteriologic, clinical, urologic, and biochemical criteria and was in addition deemed reliable and cooperative enough to return for the required outpatient follow-up visits for up to twelve weeks from the initiation of the treatment, he was asked to sign the informed consent form for the study. Each patient was then allocated in double-blind fashion to one of two treatment groups, either 2 tablets of trimethoprim-sulphamethoxazole twice a day for twenty-eight days, or I 500-mg. capsule of ampicillin four times a day for twenty-eight days. No other antimicrobial drug was given over the course of the study, and all the laboratory studies were repeated at one week, two weeks, and four weeks after onset of treatment. Voided urine samples were collected one, two, four, six, eight, and twelve weeks after the initiation of treatment for culture and sensitivity testing. If any of these urine samples yielded a significant growth of bacteria, a second urine sample was obtained for confirmation. Ifat any time up to twelve weeks after the initiation of treatment a patient was confirmed to be growing lo5 or more organisms of any kind in the urine, he was de-
UROLOGY
/ FEBRUARY1976
/ VOLUMEVII,
NUMBER2
clared a treatment failure. A therapeutic success was one in which no urine sample up to and including the one taken twelve weeks after the initiation of treatment contained significant infection. Patients were categorized as having complicated urinary tract infection if there was any evidence of structural abnormalities of the urinary tract such as calculous disease, stricture, diverticulum, and so on. An uncomplicated infection was one in which there was no associated radiologic or clinical abnormality of the urinary tract. At the end of the 30-patient study, the treatment code was broken to determine what medication each patient had received and the results were analyzed. Results There were 21 female and 9 male patients in the study. The ages ranged from twenty-two to seventy-four years, with an average of forty-five years. There were fifteen uncomplicated and fifteen complicated infections. Twenty patients were infected with E. coli and 10 with P. mirabilis organisms. Fifteen patients were treated with ampicillin and 15 with trimethoprimsulphamethoxazole. Of the 15 patients suffering from a complicated urinary tract infection, 8 had urinary tract calculi (Table I). All 8 patients were infected with P. mirabilis organisms. The remaining 7 complicated cases were infected with E. coli. Thus, of the 20 E. coli infections, 13 were uncomplicated whereas of the 10 P. mirabilis infections only 2 were associated with uncomplicated infections. Nine of the complicated infections were treated with ampicillin and 6 with trimethoprimsulphamethoxazole. Therapeutic success, as defined by freedom from infection twelve weeks after the initiation of treatment, is expressed in Table II. Of the 30 patients only 11 were free of infection at twelve
Results of treatment in 30 patients twelve weeks after start of therapy
TABLE II.
Treatment Ampicillin Trimethoprimsulphamethoxazole TOTALS
Uncomplicated
Complicated
Cure
Failure
Cure
2
4
_& 8
3 ?
1
Failure 8
2
4
3
12
157
TABLE III.
Results of treatment of 15 uncomplicated and 15 complicated infections according to pathogen
Pathogen Uncomplicated E. Coli P. mirabilis TOTALS Complicated E. coli P. mirabilis TOTALS
No. of
Cases
-AmpicillinCure
13 2 15
2 0 z
3 1 4
5
3
_L 6
0 3
7 8
1 0 i-
3
1
2
s 8
r 2
2 4
15
weeks. Of the 11, 8 were in the trimethoprimsulphamethoxazole group and 3 in the ampicillintreated group. It appears that the success rate for trimethoprim-sulphamethoxazole is greater than that of ampicillin in both the uncomplicated and the complicated groups of cases. The results of the two treatments in terms of the infecting organism for both complicated and uncomplicated infections are expressed in Table III. Trimethoprim-sulphamethoxazole appeared to be superior to ampicillin in all instances although the number of patients in each group is too small for statistical analysis. The clinical side effects noted in 30 patients were a skin rash and palpitations in 1 patient who received ampicillin and nausea in 1 patient taking trimethoprim-sulphamethoxazole. The effects were transient in both patients and were not the reason for discontinuation of treatment. No abnormal blood chemistries were noted in any of the patients treated. However, in 5 patients receiving trimethoprim-sulphamethoxazole and 1 on ampicillin minor hematologic effects, such as depression of the platelet count and the white cell count, were noted. These hematologic abnormalities were transient in all instances, reverted to normal in all cases within a few weeks, and resulted in no clinical problems. Treatment success rates, expressed as percentages, are shown in Table IV in which the data from the present study are compared with those of a similar study by the same author2 on a similar group of patients treated with the same dosages of the same antibiotics for a ten-day course as opposed to a twenty-eight-day course. The results are expressed as freedom from infection fifty-six days after the cessation of treatment, The only other difference between the two protocols is that in the ten-day course all infecting organisms had to be sensitive in vitro to ampicillin whereas this 158
Failure
Trimethoprimsulphamethoxazole Cure Failure
was not necessary in the twenty-eight-day study. In the over-all results there did not appear to be any difference in efficacy for each antibiotic between a ten-day course and a twenty-eight-day course. The superiority of trimethoprim-sulphamethoxazole to ampicillin was apparent. This superiority in the uncomplicated infection was of the order of 2 to 1 in favor of trimethoprimsulphamethoxazole in both studies. There is no evidence from this ‘comparison that for an uncomplicated infection a twenty-eight-day course of either antibiotic is superior to a ten-day course of the same drug. In the complicated infection, however, it appears that while the twentyeight-day course of ampicillin yielded as dismal results as the ten-day course of either agent, the twenty-eight-day course of trimethoprimsulphamethoxazole resulted in an improved cure rate. Comment At the present time in the United States the combination trimethoprim-sulphamethoxazole is available for the treatment of urinary tract infection and the recommended course is ten to fourteen days. The combination has been shown in one recent cooperative study3 to be more effective than sulphonamide alone and in another report1 to be superior also to ampicillin in the eradication of chronic bacteriuria in the recommended dosage. Previous reports by Wren4 and Brumfitt and Pursel15 confirm the superiority of trimethoprimsulphamethoxazole to ampicillin against urinary tract pathogens in standard courses. The purpose of the present work which is part of a multi-institutional cooperative group study was to determine whether or not the efficacy of either treatment could be further enhanced by prolonging the course of therapy to twenty-eight days. Although a few reports6J have suggested
UROLOGY/ FEBRUARY 1976 / VOLUMEVII, NUMBER2
TABLE IV.
Comparison of success rates in twenty-eight-day and ten-day courses of treatment*
Duration (Days) 10
28
Treatment
Uncomplicated (Per Cent)
Complicated (Per Cent)
Over-all (Per Cent)
43
12
27
87 33
14 11
53 20
66
33
55
Ampicillin Trimethoprimsulphamethoxazole Ampicillin Trimethoprimsulphamethoxazole
*All results at fifty-six days after termination of therapy.
that trimethoprim-sulphamethoxazole may be usefully employed in more extensive courses for the treatment of recurrent or chronic urinary tract infection, there have been no reported doubleblind studies comparing an extended course of trimethoprim-sulphamethoxazole with any other antibiotic. Both medications were tolerated well by most of the patients, and the side effects noted were not serious, numerous, or lasting. Whether or not more significant problems would have arisen had patients with impaired renal function been included for study is speculative. A recent report urged caution in prescribing the combination trimethoprim-sulphamethoxazole in patients with impaired renal function.8 It should be noted that the patients in the present study all had normal renal and hepatic function prior to therapy, did not undergo instrumentation of the urinary tract, nor did they have indwelling catheters. This makes it a rather select group of patients. These conditions, however, were the same for both standard and prolonged treatment groups. Comparison of the data from the present study with those from a previous ten-day comparative study is, we think, valid because the studies were both performed by the same investigator in the same institution with similar groups of patients under very similar circumstances. From Table III it would appear that there is no advantage in prescribing ampicillin in a twentyeight-day course rather than a ten-day course for the treatment of urinary tract infections. In the uncomplicated infection there appears likewise to be no advantage in prescribing trimethoprimsulphamethoxazole in a twenty-eight-day course compared with a ten-day course.
UROLOGY /
FEBRUARY 1976 /
VOLUME VII, NUMBER 2
However, where there is a structural abnormality of the urinary tract causing a complicated urinary tract infection it may well be advantageous to continue trimethoprim-sulphamethoxazole treatment to twenty-eight days. If the results of the entire cooperative group substantiate this recommendation, a significant therapeutic advance will have been made in the difficult area of treating the complicated urinary tract infection. Box 85, 1200 N. State Street Los Angeles, California 90033 References 1. GLECKMAN, R. A. : Trimethoprim-sulfamethoxazole vs. ampicillin in chronic urinary tract infections: a doubleblind multicenter cooperative controlled study, J.A.M.A. 233: 427 (1975). 2. COSGROVE, M. D., and MORROW, J, W.: Ampicillin versus trimethoprim/sulfamethoxazole in chronic urinary tract infection, J. Urol. 111:670 (1974). R. A.: A cooperative controlled study of 3. GLECKMAN, the use of trimethoprim-sulfamethoxazole in chronic urinary tract infections, J, Infect. Dis. 128 (suppl.): 5647 (1973). Double blind trial comparing 4. WREN, B. G.: trimethoprim-sulfamethoxazole (Bactrim) with ampicillin in treating urinary infections, Med. J. Aust. 1:261(1972). 5. BRUMFITT, W., and PURSELL, R. : Double blind trial to compare ampicillin, cephalexin, co-trimoxazole and trimethoprim in treatment of urinary infection, Br. Med. J. 2: 673 (1972). 6. GAVRAS,H., LAWSON,D. H., and LINTON, A. L.: Extended therapy with a trimethoprim-sulphonamide for the treatment ofestablished urinary tract infection, Scott. Med. J. 6: 506 (1971). New trimethoprim-sulfa7. FJELLSTROEM, K. E.: methoxazole antimicrobial assessed at symposium, Infect. Dis. 2: 1, 18 (1972). 8. KALOWSKI, S., MATHEW, T. H., NANRA, R. S., and KINCAID-SMITH,P.: Deterioration in renal function in association with co-trimoxazole therapy, Lancet 1: 394 (1973).
159
