Scandinavian Journal of Infectious Diseases
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Double Blind Comparison of Short and Medium Term Sulfonamides, Sulfamethizole and Sulfamethoxazole, in Uncomplicated Acute Urinary Tract Infections Tom Bergan & Ove Skjerven To cite this article: Tom Bergan & Ove Skjerven (1979) Double Blind Comparison of Short and Medium Term Sulfonamides, Sulfamethizole and Sulfamethoxazole, in Uncomplicated Acute Urinary Tract Infections, Scandinavian Journal of Infectious Diseases, 11:3, 219-223, DOI: 10.3109/inf.1979.11.issue-3.08 To link to this article: http://dx.doi.org/10.3109/inf.1979.11.issue-3.08
Published online: 02 Jan 2015.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [University of California, San Diego]
Date: 20 April 2016, At: 08:32
Scand J Infect Dis 11: 219-223, 1979
Double Blind Comparison of Short and Medium Term Sulfonamides, Sulfamethizole and Sulfamethoxazole, in Uncomplicated Acute Urinary Tract Infections TOM BERGAN' and OVE SKJERVEN2
Downloaded by [University of California, San Diego] at 08:32 20 April 2016
From the 'Department of Microbiology, University Hospital and Institute of Medical Biology, University of Tromsi and Department of Microbiology, Institute of Pharmacy, University of Oslo, and the 2Tromsi District of the National Public Health Service, Tromsi, Norway
ABSTRACT. Sulfamethizoleand sulfamethoxazde were compared in a prospective, randomized, double blind study on uncomplicated, acute urinary tract infections. 59 patients were evaluable for therapeutic effect of sulfamethizole and 53 for sulfamethoxazole. The cure rates were 91.5 and 92.5 % respectively for sulfamethizole and sulfamethoxazole. The rates of side effects were the same in the two groups, 5.4% and 4.2%. Also instances where the infecting bacteria were sulfonamide-resistantwere cured.
INTRODUCTION Sulfonamides were the first effective antibacterial agents to be employed systematically against bacterial infections in man. After his experiments with streptococci in mice, Domagk (8) is credited with the discovery that this class of compounds is valuable against infections. The first human case, reported in 1933 by Foerster (18), was a 10-month old infant with staphylococcal septicaemia cured by Prontosil. Although other antimicrobials are now more important in the cure of infections, sulfonamides have maintained their role as effective agents in urinary tract infections (UTI). They are generally recommended for acute, uncomplicated UTI. Many investigators are of the opinion that sulfonamides are first choice agents in uncomplicated UTI (18). This view dominates in Scandinavia (1, 14, 15). Mabeck (14) compared sulfonamides and antibiotics regarding therapeutic effect and development of resistance in 214 patients and concluded that sulfonamides lead to a good response in uncomplicated UTI acquired outside hospital. What sulfonamide to choose among the large number now available is a more difficult matter, except that the slowly excreted agents like sulfamethoxypyridazine, sulfamethoxydiazine, and sulfadimethoxine are undesirable because of a low urinary excretion rate and severe hypersensitivity reactions (5, 6, 18). There are theoretical reasons for preferring
sulfonamides with a medium duration (serum halflife (fh) values of 8-16 h) over those of a short duration ( t i under 8 h). The former have more sustained urine and serum levels, and give higher concentrations in renal lymph since more of the antibacterially active portion is reabsorbed in the tubuli (1, 2). Also, compliance stands a better chance with the medium term agents since the dosage schedule is simpler than with those of short duration. There is little clinical evidence to support this contention, however. The first sulfonamides were such marvellous wonders that no lengthy analyses or comparisons seemed necessary to document their valuable properties when they were first introduced. Even the later sulfonamides appeared before our present more elaborate protocols of comparing anti-infectious agents. Older studies are often difficult to assess and frequently do not answer questions which seem relevant today. Most clinical sulfonamide studies have concentrated on single agents, a circumstance which hampers comparisons between them. The closest we come to controlled studies in UTI treated with sulfonamides are works by Bunger (7) and Kriiger-Thiemer & Bunger (12) who ran independent investigations on different sulfonamides, but with the same methodology. Their results indicate that the long term sulfalen has about half the cure rate of the medium term sulfamethoxazole (7, 10). Scand J Infect Dis I I
220
T . Bergan and 0 . Skjerven
Table I. No. of patients evaluable or non-evaluable f o r therapeutic effect Treatment with Sulfamethizole
Sulfamethoxazole
89
88
17
20
1 1
1
The mean age of the patients in the sulfamethizole group was 38 years and in the sulfamethoxazole group 36 years. In the former 69 females and 5 males were evaluable for therapy and/or side effects. In the latter group, 72 females only were evaluable.
Downloaded by [University of California, San Diego] at 08:32 20 April 2016
Clinical evaluation Total no. of patients No. of dropouts due to Insignificant growth Therapy discontinued due to side effect Bacterial resistance Missing control visit Incomplete compliance Total no. of dropouts No. of patients evaluable for treatment effect
1
4 7 30 (33.7%)
7 6 35 (39.8%)
59 (66.3%)
53 (60.2 %)
A double blind study comparing short and medium term sulfonamides is needed to assess rates of both cure and side effects. The present investigation is a randomized, double blind, prospective comparison between sulfamethizole (t4=2.5 h) and sulfamethoxazole (t4=8-12 h) (1, 2, 3, 17). MATERIALS AND METHODS Plan of study. The study was camed out as a randomized, double blind comparison of sulfamethizole and sulfamethoxazole for UTI. After admission to the study, the patients were allocated to either sulfonamide group according to a randomized scheme. The drugs were distributed to the patients in identically looking parcels packed by Roche, Norway. Place of srudy. The study took place in the general domiciliary practice of the Tromsa district, National Public Health Service. The region covers a large area which is mostly rural except the town of Tromsa with 20000 inhabitants. Part of the patients came from surrounding districts including the numerous islands along the coast. It takes some 5 h to travel to the doctor from the most remote settlements. Patients. Considered for admission to the study were consecutive patients above 15 years who visited the general practice and were diagnosed as uncomplicated, acute UTI. The diagnosis was based upon clinical symptoms, urine microscopy, and bacteriological examination. Among the patients satisfying these criteria, selection was only exercised to exclude patients with anatomical defects or calculi of the urinary tract, hypersensitivity to sulfonamides, reduced renal function (serum creatinine, blood urea), evidence of liver malfunction (alkaline phosphatase or known liver ailment), pregnancy, severe systemic diseases like cancer, leukemia, diabetes, or gastrointestinal diseases. In all, 177 patients were admitted to the study. 89 patients received sulfamethizole and 88 sulfamethoxazole.
Therapeutic effecr. Patients who had significant bacteruria, a full 14 days treatment, and reported for control examination 5-21 days after the end of therapy, were evaluated for therapeutic effect. A number of patients could not be evaluated (Table I), most of them having insignificant bacteruria (
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Double Blind Comparison of Short and Medium Term Sulfonamides, Sulfamethizole and Sulfamethoxazole, in Uncomplicated Acute Urinary Tract Infections Tom Bergan & Ove Skjerven To cite this article: Tom Bergan & Ove Skjerven (1979) Double Blind Comparison of Short and Medium Term Sulfonamides, Sulfamethizole and Sulfamethoxazole, in Uncomplicated Acute Urinary Tract Infections, Scandinavian Journal of Infectious Diseases, 11:3, 219-223, DOI: 10.3109/inf.1979.11.issue-3.08 To link to this article: http://dx.doi.org/10.3109/inf.1979.11.issue-3.08
Published online: 02 Jan 2015.
Submit your article to this journal
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [University of California, San Diego]
Date: 20 April 2016, At: 08:32
Scand J Infect Dis 11: 219-223, 1979
Double Blind Comparison of Short and Medium Term Sulfonamides, Sulfamethizole and Sulfamethoxazole, in Uncomplicated Acute Urinary Tract Infections TOM BERGAN' and OVE SKJERVEN2
Downloaded by [University of California, San Diego] at 08:32 20 April 2016
From the 'Department of Microbiology, University Hospital and Institute of Medical Biology, University of Tromsi and Department of Microbiology, Institute of Pharmacy, University of Oslo, and the 2Tromsi District of the National Public Health Service, Tromsi, Norway
ABSTRACT. Sulfamethizoleand sulfamethoxazde were compared in a prospective, randomized, double blind study on uncomplicated, acute urinary tract infections. 59 patients were evaluable for therapeutic effect of sulfamethizole and 53 for sulfamethoxazole. The cure rates were 91.5 and 92.5 % respectively for sulfamethizole and sulfamethoxazole. The rates of side effects were the same in the two groups, 5.4% and 4.2%. Also instances where the infecting bacteria were sulfonamide-resistantwere cured.
INTRODUCTION Sulfonamides were the first effective antibacterial agents to be employed systematically against bacterial infections in man. After his experiments with streptococci in mice, Domagk (8) is credited with the discovery that this class of compounds is valuable against infections. The first human case, reported in 1933 by Foerster (18), was a 10-month old infant with staphylococcal septicaemia cured by Prontosil. Although other antimicrobials are now more important in the cure of infections, sulfonamides have maintained their role as effective agents in urinary tract infections (UTI). They are generally recommended for acute, uncomplicated UTI. Many investigators are of the opinion that sulfonamides are first choice agents in uncomplicated UTI (18). This view dominates in Scandinavia (1, 14, 15). Mabeck (14) compared sulfonamides and antibiotics regarding therapeutic effect and development of resistance in 214 patients and concluded that sulfonamides lead to a good response in uncomplicated UTI acquired outside hospital. What sulfonamide to choose among the large number now available is a more difficult matter, except that the slowly excreted agents like sulfamethoxypyridazine, sulfamethoxydiazine, and sulfadimethoxine are undesirable because of a low urinary excretion rate and severe hypersensitivity reactions (5, 6, 18). There are theoretical reasons for preferring
sulfonamides with a medium duration (serum halflife (fh) values of 8-16 h) over those of a short duration ( t i under 8 h). The former have more sustained urine and serum levels, and give higher concentrations in renal lymph since more of the antibacterially active portion is reabsorbed in the tubuli (1, 2). Also, compliance stands a better chance with the medium term agents since the dosage schedule is simpler than with those of short duration. There is little clinical evidence to support this contention, however. The first sulfonamides were such marvellous wonders that no lengthy analyses or comparisons seemed necessary to document their valuable properties when they were first introduced. Even the later sulfonamides appeared before our present more elaborate protocols of comparing anti-infectious agents. Older studies are often difficult to assess and frequently do not answer questions which seem relevant today. Most clinical sulfonamide studies have concentrated on single agents, a circumstance which hampers comparisons between them. The closest we come to controlled studies in UTI treated with sulfonamides are works by Bunger (7) and Kriiger-Thiemer & Bunger (12) who ran independent investigations on different sulfonamides, but with the same methodology. Their results indicate that the long term sulfalen has about half the cure rate of the medium term sulfamethoxazole (7, 10). Scand J Infect Dis I I
220
T . Bergan and 0 . Skjerven
Table I. No. of patients evaluable or non-evaluable f o r therapeutic effect Treatment with Sulfamethizole
Sulfamethoxazole
89
88
17
20
1 1
1
The mean age of the patients in the sulfamethizole group was 38 years and in the sulfamethoxazole group 36 years. In the former 69 females and 5 males were evaluable for therapy and/or side effects. In the latter group, 72 females only were evaluable.
Downloaded by [University of California, San Diego] at 08:32 20 April 2016
Clinical evaluation Total no. of patients No. of dropouts due to Insignificant growth Therapy discontinued due to side effect Bacterial resistance Missing control visit Incomplete compliance Total no. of dropouts No. of patients evaluable for treatment effect
1
4 7 30 (33.7%)
7 6 35 (39.8%)
59 (66.3%)
53 (60.2 %)
A double blind study comparing short and medium term sulfonamides is needed to assess rates of both cure and side effects. The present investigation is a randomized, double blind, prospective comparison between sulfamethizole (t4=2.5 h) and sulfamethoxazole (t4=8-12 h) (1, 2, 3, 17). MATERIALS AND METHODS Plan of study. The study was camed out as a randomized, double blind comparison of sulfamethizole and sulfamethoxazole for UTI. After admission to the study, the patients were allocated to either sulfonamide group according to a randomized scheme. The drugs were distributed to the patients in identically looking parcels packed by Roche, Norway. Place of srudy. The study took place in the general domiciliary practice of the Tromsa district, National Public Health Service. The region covers a large area which is mostly rural except the town of Tromsa with 20000 inhabitants. Part of the patients came from surrounding districts including the numerous islands along the coast. It takes some 5 h to travel to the doctor from the most remote settlements. Patients. Considered for admission to the study were consecutive patients above 15 years who visited the general practice and were diagnosed as uncomplicated, acute UTI. The diagnosis was based upon clinical symptoms, urine microscopy, and bacteriological examination. Among the patients satisfying these criteria, selection was only exercised to exclude patients with anatomical defects or calculi of the urinary tract, hypersensitivity to sulfonamides, reduced renal function (serum creatinine, blood urea), evidence of liver malfunction (alkaline phosphatase or known liver ailment), pregnancy, severe systemic diseases like cancer, leukemia, diabetes, or gastrointestinal diseases. In all, 177 patients were admitted to the study. 89 patients received sulfamethizole and 88 sulfamethoxazole.
Therapeutic effecr. Patients who had significant bacteruria, a full 14 days treatment, and reported for control examination 5-21 days after the end of therapy, were evaluated for therapeutic effect. A number of patients could not be evaluated (Table I), most of them having insignificant bacteruria (
