Acta Psediatr 81: 695-7. 1992
Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections P Gaudreault, M Beland, JB Girodias and RL Thivierge Department of Puediatrics, University of Montreal and Suinte-Justine Hospital. Montreal. Canada
Gaudreault P, Beland M, Girodias JB, Thivierge RL. Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections. Acta Pzediatr 1992;81:695-7. Stockholm. ISSN 08035253
We conducted a prospective randomized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 m g / k of sulphadiazine for three (group 1) or 10 days (group 2) in the treatment of uncomplicated urinary tract infections in children. Forty patients (nine boys and 31 girls) aged 2.5-18 years, presenting with a urinary tract infection were allocated to one of the two groups. Patients were seen three, 10, and 2 38 days after the initiation of treatment. Control urine cultures were negative in all patients at days 3 and 10. Two patients in group 1 and one patient in group 2 suffered a relapse within a month. Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children. 0 Single daily dose, trimethoprim/sulphadiazine,urinary tract infection P Gaudreault, Department of Paediatrics, Sainte-Justine Hospital, 31 75 Cote Ste-Catherine, Montreal. Canada, H3T IC.5
Treatment modifications that reduce the frequency or the duration of the administration of medications improve patient compliance, reduce risks of developing side effects and reduce costs. In recent years, several studies have evaluated the possibility of reducing the duration of treatment of uncomplicated urinary tract infections (1-6). In adults, urinary tract infections have been treated successfully with single daily doses of the combination trimethoprim/sulphadiazine for three or 10 days instead of fractionated doses every 12 h (7,8). In children such a study has never been performed. We conducted this study to evaluate the efficacy of a single daily dose of the combination trimethoprim/ sulphadiazine administered for three days in eradicating the bacteria causing the urinary tract infection and in preventing early recurrences of such infections in children and compared it to a single daily dose administered for 10 days.
Patients and methods We studied 40 patients aged between 2.5 and 18 years of age presenting to our emergency room with sign(s) and/ or symptom(s) suggestive of uncomplicated urinary tract infections. The diagnosis of urinary tract infection was confirmed by an abnormal urine analysis and a positive urine culture defined as a growth in pure culture 2 lo5 organisms/ml of urine collected by the cleancatch method. Patients with urinary tract malformations, a urinary tract infection in the last six months or abnormal serum creatinine or BUN were excluded. Furthermore, patients vomiting or with signs suggestive
of pyelonephritis such as costovertebral angle tenderness or fever > 39°C and leucocytosis 2 20 000 were also excluded. Written informed consent was obtained for each child. Patients were distributed at random into two groups but were not blinded as to the length of duration of their treatment. Patients in group 1 received a single daily dose of 4 mg/kg trimethoprim together with 17.5 mg/kg sulphadiazine for three days. Patients in group 2 received the same dose but for 10 days. The medication was administered as a suspension. Patients were seen three and 10 days after the beginning of their antiobiotic therapy and at least 28 days after the end of their treatment. During those visits urinary tract symptoms, temperature and side effects were recorded, and a urine culture was performed. Echographic studies were performed on all patients. Voiding cystograms were carried out in patients who presented with a recurrence of their urinary tract infection, in all boys and in girls when parents consented to the procedure. All statistical analyses were performed using chi-square test (with Yates’ correction) or the student’s t-test (two-tailed).
Results Fifty-seven patients were enrolled in the study. Seventeen patients were excluded because their initial urine culture was negative ( 1 1 patients), the bacteria were resistant to the antibiotic used (one), or they were lost during follow-up (five). All patients lost during followup had negative urine cultures at their last visit to the clinic. Parents of these patients were contacted. They
696
P Gaudreault et al.
ACTA PRDIATR 81 (1992)
Table I . Trimethoprim/sulphadiazinein uncomplicated urinary tract infections. Mean ( f SD)patientscharacteristics, bacteria encountered and the efficacy of treatment (UTI = urinary tract infection).
diazine for three or 10 days are effective in eliminating the bacteria causing uncomplicated urinary tract infections and improve the clinical status of the patients. 3-day group 10-day group Indeed all patients were cured within three days and the Criteria (n =20) (n =20) urine cultures remained negative in all patients at 10 days. Symptoms disappeared in all patients within 10 Sex days. These results demonstrate that single daily doses Female 16 15 of the combination trimethoprim/sulphadiazine are 4 5 Male effective in the treatment of uncomplicated urinary tract 5.5f3.3 7.8f4.3 Age (year) 21f11 Weight (kg) 28f12 infections in children as in adults (7). Furthermore, Temperature (“C) 36.9 f I .O 37.6f0.9 these results demonstrate that divided doses of this 11.5 k5.2 kucocytosis ( x 10)) 13f3.6 combination offer no advantages over single daily doses BUN since the cure rate (100%) is the same for both regimens 4.6 f I .O (mmol/l) 4.3 f 1.3 (12.1f3.7) (12.9f2.7) (mg/dl) (8). Creatinine Another goal of the treatment of urinary tract 44.2f8.8 53 f 8.8 (pmol/l) infections is the prevention of early recurrences. We (0.5f0.1) (0.6f0.1) (mg/dl) evaluated the efficacy of our treatments in preventing 2 I Previous UTI recurrence within a month of the end of treatment Bacteria E. coli 19 17 because most recurrences occur within a month of the P. mirabilis I I end of antibiotic therapy (3). In our study there were no S. saprophyticus 2 significant differences between the recurrence rate of Treatment efficacy urinary tract infections of patients treated for three or 10 20 (100%) Cure 20 (100%) 2 (10%) 1(5%) Recurrence ( < 1 month) days. These results are similar to those obtained by Helin (8). As pointed out by recent reviews of previous published studies, the number of patients we have evaluated is too small to state with confidence that the reported that their children did not present any symp- two treatments are equivalent (9, 10). However, these toms of recurrence but failed to come back for follow-up results demonstrate that many patients with uncomplivisits. The two groups were similar with regard to sex cated urinary tract infections do not require a 10-day distribution, mean age and weight, temperature, white course of therapy to prevent early recurrence. blood cell counts, renal function tests and previous Several authors are reluctant to use three-day course urinary tract infections (Table I ) . The causative organ- therapy fearing that their patients might be suffering isms were Escherichia coli, Proteus mirabilis and Staphy- from pyelonephritis instead of only a lower urinary tract loccocus saprophyticus (Table 1). infection. There is no single clinical or laboratory test Urine cultures were negative in all patients at their capable of determining kidney involvement during a control visits, three and 10 days after the initiation of urinary tract infection. Although we tried to eliminate their treatment. Three patients had a recurrence of their patients with suggestive signs of kidney involvement urinary tract infection within a month of the end of their it is possible that a few patients we treated had pyelotreatment; two patients in group 1 and one patient in nephritis. However, all patients were cured and none group 2 (Table 1). The bacteria recovered had the same developed any signs of worsening of their clinical antibiogram as the one present at the first urine culture. status. Urinary symptoms disappeared in 30 patients within These data demonstrate that single daily doses of the three days of the beginning of their treatment and in all combination trimethoprim/sulphadiazineare effective within 10 days. The only side effect encountered was one in treating uncomplicated paediatric urinary tract infecepisode of vomiting in two patients. tions. Furthermore, our data confirm that a three-day Renal echographic studies performed on all patients course therapy is effective in preventing early recurdid not demonstrate any significant kidney malforma- rences for a large proportion of children suffering from tions except for a small kidney in one patient; her uncomplicated urinary tract infections. However, larger voiding cystogram was normal. Voiding cytograms were groups of patients are required to demonstrate that performed in 20 patients. Only one of the two patients of three- and 10-day course therapies are equivalent in group 1 who developed a recurrence of his urinary tract preventing early recurrences of urinary tract infections. infection demonstrated bilateral vesicoureteral reflux. The reduction of the frequency of administration of medications and the reduction of duration of treatment improve patients compliance, reduce the risk of developing side effects and reduce costs.
Discussion
Our study demonstrated that single daily doses of 4 mg/ 17.5 mg/kg of the combination trimethoprim/sulpha-
Acknowledgements.-This study was supported in part by a grant from Jouveinal Inc.
ACTA PKDIATR 8 I ( 1992)
References I . Fang LST, Talkoff-Rubin NE, Rubin RH. Efficacy of single-dose and conventional amoxicillin therapy in urinary tract infection localized by theantibody coated bacteria technique. N Engl J Med 1978;298:4 I3 2. Avner ED, Ingelfinger JR, Herring JT, et al. Single-dose amoxicillin therapy of uncomplicated pediatric urinary tract infections. J Pediatr 1983;102:623-7 3. Khan AJ, Kumar K, Evans HE. Three-day antimicrobial therapy of urinary tract infection. J Pediatr 1981;99:9924 4. Stahl GE, Topf P, Fleisher GR, et al. Single-dose treatment of uncomplicated urinary tract infections in children. Ann Emerg Med 1984;13:705-8 5. Pitt WR, Dyer SA, McNee JL, et al. Single dose trimethoprimsulphamethoxazole treatment of symptomatic urinary infection. Am J Dis Child 1982;57:229-39
Short-course antibiotic therapy for urinary tract infections
697
6. Helin I. Three-day therapy with cephalexin for lower urinary tract infections in children. Scand J Infect Dis 1984;16:305-7 7. Guibert J, Bamberg P, Acar J. Study of the efficacy and tolerance of co-trimazine given once or twice daily in urinary tract infections. Infection 198 1;9:96-8 8. Helin I. Short-term treatment of lower urinary tract infections in children with trimethoprim/sulphadiazine. Infection 1981;9: 249-5 1 9. Fihn SD, Stamm WE. Interpretation and comparison of treatment studies for uncomplicated urinary tract infections in women. Rev Infect Dis 1985;7:468-78 10. Moffat M, Embree J, Grimm P, Law B. Short-course antibiotic therapy for urinary tract infections in children. Am J Dis Child 1988;142:57-61
Received Aug. 29, 1990. Accepted Feb. 26, 1992
Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections P Gaudreault, M Beland, JB Girodias and RL Thivierge Department of Puediatrics, University of Montreal and Suinte-Justine Hospital. Montreal. Canada
Gaudreault P, Beland M, Girodias JB, Thivierge RL. Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections. Acta Pzediatr 1992;81:695-7. Stockholm. ISSN 08035253
We conducted a prospective randomized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 m g / k of sulphadiazine for three (group 1) or 10 days (group 2) in the treatment of uncomplicated urinary tract infections in children. Forty patients (nine boys and 31 girls) aged 2.5-18 years, presenting with a urinary tract infection were allocated to one of the two groups. Patients were seen three, 10, and 2 38 days after the initiation of treatment. Control urine cultures were negative in all patients at days 3 and 10. Two patients in group 1 and one patient in group 2 suffered a relapse within a month. Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children. 0 Single daily dose, trimethoprim/sulphadiazine,urinary tract infection P Gaudreault, Department of Paediatrics, Sainte-Justine Hospital, 31 75 Cote Ste-Catherine, Montreal. Canada, H3T IC.5
Treatment modifications that reduce the frequency or the duration of the administration of medications improve patient compliance, reduce risks of developing side effects and reduce costs. In recent years, several studies have evaluated the possibility of reducing the duration of treatment of uncomplicated urinary tract infections (1-6). In adults, urinary tract infections have been treated successfully with single daily doses of the combination trimethoprim/sulphadiazine for three or 10 days instead of fractionated doses every 12 h (7,8). In children such a study has never been performed. We conducted this study to evaluate the efficacy of a single daily dose of the combination trimethoprim/ sulphadiazine administered for three days in eradicating the bacteria causing the urinary tract infection and in preventing early recurrences of such infections in children and compared it to a single daily dose administered for 10 days.
Patients and methods We studied 40 patients aged between 2.5 and 18 years of age presenting to our emergency room with sign(s) and/ or symptom(s) suggestive of uncomplicated urinary tract infections. The diagnosis of urinary tract infection was confirmed by an abnormal urine analysis and a positive urine culture defined as a growth in pure culture 2 lo5 organisms/ml of urine collected by the cleancatch method. Patients with urinary tract malformations, a urinary tract infection in the last six months or abnormal serum creatinine or BUN were excluded. Furthermore, patients vomiting or with signs suggestive
of pyelonephritis such as costovertebral angle tenderness or fever > 39°C and leucocytosis 2 20 000 were also excluded. Written informed consent was obtained for each child. Patients were distributed at random into two groups but were not blinded as to the length of duration of their treatment. Patients in group 1 received a single daily dose of 4 mg/kg trimethoprim together with 17.5 mg/kg sulphadiazine for three days. Patients in group 2 received the same dose but for 10 days. The medication was administered as a suspension. Patients were seen three and 10 days after the beginning of their antiobiotic therapy and at least 28 days after the end of their treatment. During those visits urinary tract symptoms, temperature and side effects were recorded, and a urine culture was performed. Echographic studies were performed on all patients. Voiding cystograms were carried out in patients who presented with a recurrence of their urinary tract infection, in all boys and in girls when parents consented to the procedure. All statistical analyses were performed using chi-square test (with Yates’ correction) or the student’s t-test (two-tailed).
Results Fifty-seven patients were enrolled in the study. Seventeen patients were excluded because their initial urine culture was negative ( 1 1 patients), the bacteria were resistant to the antibiotic used (one), or they were lost during follow-up (five). All patients lost during followup had negative urine cultures at their last visit to the clinic. Parents of these patients were contacted. They
696
P Gaudreault et al.
ACTA PRDIATR 81 (1992)
Table I . Trimethoprim/sulphadiazinein uncomplicated urinary tract infections. Mean ( f SD)patientscharacteristics, bacteria encountered and the efficacy of treatment (UTI = urinary tract infection).
diazine for three or 10 days are effective in eliminating the bacteria causing uncomplicated urinary tract infections and improve the clinical status of the patients. 3-day group 10-day group Indeed all patients were cured within three days and the Criteria (n =20) (n =20) urine cultures remained negative in all patients at 10 days. Symptoms disappeared in all patients within 10 Sex days. These results demonstrate that single daily doses Female 16 15 of the combination trimethoprim/sulphadiazine are 4 5 Male effective in the treatment of uncomplicated urinary tract 5.5f3.3 7.8f4.3 Age (year) 21f11 Weight (kg) 28f12 infections in children as in adults (7). Furthermore, Temperature (“C) 36.9 f I .O 37.6f0.9 these results demonstrate that divided doses of this 11.5 k5.2 kucocytosis ( x 10)) 13f3.6 combination offer no advantages over single daily doses BUN since the cure rate (100%) is the same for both regimens 4.6 f I .O (mmol/l) 4.3 f 1.3 (12.1f3.7) (12.9f2.7) (mg/dl) (8). Creatinine Another goal of the treatment of urinary tract 44.2f8.8 53 f 8.8 (pmol/l) infections is the prevention of early recurrences. We (0.5f0.1) (0.6f0.1) (mg/dl) evaluated the efficacy of our treatments in preventing 2 I Previous UTI recurrence within a month of the end of treatment Bacteria E. coli 19 17 because most recurrences occur within a month of the P. mirabilis I I end of antibiotic therapy (3). In our study there were no S. saprophyticus 2 significant differences between the recurrence rate of Treatment efficacy urinary tract infections of patients treated for three or 10 20 (100%) Cure 20 (100%) 2 (10%) 1(5%) Recurrence ( < 1 month) days. These results are similar to those obtained by Helin (8). As pointed out by recent reviews of previous published studies, the number of patients we have evaluated is too small to state with confidence that the reported that their children did not present any symp- two treatments are equivalent (9, 10). However, these toms of recurrence but failed to come back for follow-up results demonstrate that many patients with uncomplivisits. The two groups were similar with regard to sex cated urinary tract infections do not require a 10-day distribution, mean age and weight, temperature, white course of therapy to prevent early recurrence. blood cell counts, renal function tests and previous Several authors are reluctant to use three-day course urinary tract infections (Table I ) . The causative organ- therapy fearing that their patients might be suffering isms were Escherichia coli, Proteus mirabilis and Staphy- from pyelonephritis instead of only a lower urinary tract loccocus saprophyticus (Table 1). infection. There is no single clinical or laboratory test Urine cultures were negative in all patients at their capable of determining kidney involvement during a control visits, three and 10 days after the initiation of urinary tract infection. Although we tried to eliminate their treatment. Three patients had a recurrence of their patients with suggestive signs of kidney involvement urinary tract infection within a month of the end of their it is possible that a few patients we treated had pyelotreatment; two patients in group 1 and one patient in nephritis. However, all patients were cured and none group 2 (Table 1). The bacteria recovered had the same developed any signs of worsening of their clinical antibiogram as the one present at the first urine culture. status. Urinary symptoms disappeared in 30 patients within These data demonstrate that single daily doses of the three days of the beginning of their treatment and in all combination trimethoprim/sulphadiazineare effective within 10 days. The only side effect encountered was one in treating uncomplicated paediatric urinary tract infecepisode of vomiting in two patients. tions. Furthermore, our data confirm that a three-day Renal echographic studies performed on all patients course therapy is effective in preventing early recurdid not demonstrate any significant kidney malforma- rences for a large proportion of children suffering from tions except for a small kidney in one patient; her uncomplicated urinary tract infections. However, larger voiding cystogram was normal. Voiding cytograms were groups of patients are required to demonstrate that performed in 20 patients. Only one of the two patients of three- and 10-day course therapies are equivalent in group 1 who developed a recurrence of his urinary tract preventing early recurrences of urinary tract infections. infection demonstrated bilateral vesicoureteral reflux. The reduction of the frequency of administration of medications and the reduction of duration of treatment improve patients compliance, reduce the risk of developing side effects and reduce costs.
Discussion
Our study demonstrated that single daily doses of 4 mg/ 17.5 mg/kg of the combination trimethoprim/sulpha-
Acknowledgements.-This study was supported in part by a grant from Jouveinal Inc.
ACTA PKDIATR 8 I ( 1992)
References I . Fang LST, Talkoff-Rubin NE, Rubin RH. Efficacy of single-dose and conventional amoxicillin therapy in urinary tract infection localized by theantibody coated bacteria technique. N Engl J Med 1978;298:4 I3 2. Avner ED, Ingelfinger JR, Herring JT, et al. Single-dose amoxicillin therapy of uncomplicated pediatric urinary tract infections. J Pediatr 1983;102:623-7 3. Khan AJ, Kumar K, Evans HE. Three-day antimicrobial therapy of urinary tract infection. J Pediatr 1981;99:9924 4. Stahl GE, Topf P, Fleisher GR, et al. Single-dose treatment of uncomplicated urinary tract infections in children. Ann Emerg Med 1984;13:705-8 5. Pitt WR, Dyer SA, McNee JL, et al. Single dose trimethoprimsulphamethoxazole treatment of symptomatic urinary infection. Am J Dis Child 1982;57:229-39
Short-course antibiotic therapy for urinary tract infections
697
6. Helin I. Three-day therapy with cephalexin for lower urinary tract infections in children. Scand J Infect Dis 1984;16:305-7 7. Guibert J, Bamberg P, Acar J. Study of the efficacy and tolerance of co-trimazine given once or twice daily in urinary tract infections. Infection 198 1;9:96-8 8. Helin I. Short-term treatment of lower urinary tract infections in children with trimethoprim/sulphadiazine. Infection 1981;9: 249-5 1 9. Fihn SD, Stamm WE. Interpretation and comparison of treatment studies for uncomplicated urinary tract infections in women. Rev Infect Dis 1985;7:468-78 10. Moffat M, Embree J, Grimm P, Law B. Short-course antibiotic therapy for urinary tract infections in children. Am J Dis Child 1988;142:57-61
Received Aug. 29, 1990. Accepted Feb. 26, 1992
