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Single-dose gentamicin therapy of recurrent urinary tract infection in patients with normal urinary tracts
PEDIATRIC PHARMACOLOGY AND THERAPEUTICS
Single-dose gentamicin therapy of recurrent urinary tract infection in patients with normal urinary tracts Results of single-dose therapy of urinary tract infections in pediatric patients have been contradictoP/mainly because of selection criteria. We evaluated the efficacy of a Single dose of gentamicin in patients with normal urinary tracts and in whom urinary tract Infections were recurrent. Twenty-one patients were included in th@study, and a similar number in a conventional groUp given treatment for 10 days. Cure rate was 100% in both groups. The recurrence rates of 67% in the stUdy and 52% in the conventional group were comparable. Single-dose therapy seems to have a role in the treatment of urinary tract infeCtion in the absence of urinary tract malformation. (J PEDIATR1987;110:131-5)
Abdul J. Khan, M.D., Kusum Kumar, M.D., and Hugh E. Evans, M.D. From the Department of Pediatrics, Interfaith Medical Center, State University of New York/Downstate Medical Center, Brooklyn
Single-dose antimicrobial therapy has been found to be as effective as conventional 10-day therapy in adult patients with uncomplicated lower urinary tract infection.1,2 Similar studies in pediatric patients have had divergent results, 36 apparently because of the lack of uniformity in patient selection. Inclusion of patients with possible upper UTI or urinary tract malformation may have been responsible for poor outcome in some studies, 6 whereas selection of patients with initial UTI 4 led to excellent results. In acute symptomatic initial UTI, single-dose therapy cannot be used with confidence because there is no rapid, reliable test to identify upper UTI and because of the increased prevalence of underlying structural anomalies in children. Tests of upper UTI such as the antibody-coated bacteria test 7 and serum CRP concentration8are unreliable in pediatric patients. 7-9We believe that single-dose therapy may be appropriate for treatment of recurrent UTI in selected patients with normal urinary tracts, and have designed this study to evaluate the possibility.
Submitted for publication March 24, 1986; accepted July 14, 1986. Reprint requests: Abdul J. Khan, M.D., Department of Pediatrics, Interfaith Medical Center, 1545 Atlantic Ave., Brooklyn, NY 11213.
METHODS Fifty-six episodes of recurrent UTI were treated prospectively on an alternate basis with either a single intramuscular dose of gentamicin (28 episodes) or a 10-day orally administered course with various antimicrobial agents selected empirically (28 episodes). All patients had received treatment for previous UTIs and observed in the pediatric renal clinic. Most patients had symptoms suggestive of lower UTI (Table I). Eight patients without symptoms had symptomatic UTI treated in the past. In
ESR UTI
Erythrocyte sedimentation rate Urinary tract infection
most, examination of fresh urine (performed routinely) revealed actively motile organisms. The diagnosis in each patient was based on at least two consecutive positive urine cultures, defined as growth of ~ 105 organisms per milliliter of urine collected by the clean-catch method, in which the same organism was grown in pure culture. All patients had presumed lower UTI on the basis of clinical symptoms such as dysuria and frequency (Table I), lack of systemic signs and symptoms such as fever (temperature >38 ~ C rectal or >37 ~ C oral), vomiting, clinical toxicity, or
131
13 2
Khan, Kumar, and Evans
The Journal o f Pediatrics January 1987
T a b l e I. Results of single-dose and conventional therapy of recurrent urinary tract infection 10-Day conventional
Single-dose gentamicin (n = 21) n
Age (yr) (+__1SD) Previous UT!s ( _+1 SD) Symptomatic Asymptomatic Normal IVP and VCU Pathogens Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa
Other Cure Recurrence rate (cumulative) 2-4 days 1-2 weeks 3-4 weeks 4-6 weeks 6-12 weeks Relapse Reinfection total Different organism Same organism, different biotype
(n = 21)
%
7.8 + 3.0 5.0 + 3.1
7.5 + 3.3 6.0 +__3.6 18 3 21 21 15
%
n
76 24 100 100 86
86 14 100 100 71
16 5 21 21 18
5 10
---
3 21
14 100
3 21
14 100
0 3 9I" 11~ 141 0 14 5t 9
0 14 43 52 67 0 100 36 64
1 2 5:~ 8~ 11:~ 0 11 2:~ 9
5 10 24 38 52 0 100 18 72
1 2
IVP, intravenouspyelogram;UTI, urinarytract infection;vcu, voidingcystourethrogram. *Dysuria,frequency,abdominalpain. "~vs :~, P >0.1.
costovertebral angle tenderness. In addition, all had an ESR of ~ 2 0 mm/hr. Twelve patients were excluded, 10 (four in single-dose group and six in 10-da.y therapy group) because of elevated ESR (>21mm) and two (single-dose group) because of lack of positive culture in urine collected prior to treatment. Two additional patients, both boys, one in each group, were also dropped, to make it an all-girl study. All patients had normal intravenous pyelograms and voiding cystourethrograms. Patients younger than 6 months and older than 15 years, those with elevated serum creatinine values, renal failure, nephropathies, or those given antimicrobial agents in the past 2 weeks were not included. Written informed consent was obtained from the parents of those given a single dose. The two groups, with 21 patients in each, were comparable in age and clinical characteristics of UTI, including the number of previous episodes (Table I). Patients in the study group were given a single intramuscular injection of gentamicin in a dose of 5 mg/kg body weight (maximum of 300 mg). The conventional treatment group was given standard doses of various antimicrobial agents for 10 days, including trimethoprim-sulfamethoxazole in t l , ampicillin in five, and a cephalosporin in five. The organ-
isms in the single-dose group were susceptible to gentamicin, and those in the conventional treatment group were susceptible to the agent selected, using the disk method. Compliance in those given treatment for 10 days was monitored by careful questioning and by checking medication supplies. Pathogens were identified by standard microbiologic techn!ques, including API (Analylab Products, Plainview, N.Y.) biotyping. Urine culture in each patient was repeated between 2 and 4 days, and at 1 week, 2 weeks, 4 to 6 weeks, and 8 to 12 weeks after therapy. The two groups were compared for frequency of cure and recurrences, including relapse or reinfection at various follow-up intervals. Cure was defined as eradication of the primary pathogen at the first follow-up visit. Posttherapy recurrent infections were identified as relapse or reinfection based on API biotyping and the antibiotic sensitivity pattern of the organisms. Recurrence caused by a n organism belonging to same species, having similar biotype and sensitivity pattern as the pretherapy pathogen, was considered a relapse; and recurrence caused by an organism of a different species or same species but having a different biotype and sensitivity pattern was considered a reinfection. The results were compared utilizing the chi-square test and Fisher exact test.
V o l u m e 110 Number 1
Gentamicin
for recurrent
Table II. Posttherapy recurrence rates in urinary tract infection caused by E s c h e r i c h i a Single-dose therapy No. treated E s c h e r i c h i a coil
Other Klebsiella pneumoniae P s e u d o m o n a s aeruginosa Proteus mirabilis Staphylococcus epidermidis Enterococcus
Total
15 6
No. recurred
9* 5t
1 2 1 1 1
0 2 1 1 1
21
14
urinary
coil
tract infection
13 3
and other pathogens
10-Day therapy
Percent
No. treated
No. recurred
Percent
P
60 83
18 3
10" 1~"
56 33
>0.1 >0.1
--1 -2
--1 -0
21
11
67
------
52
>0.1
* vs ~, p > 0 . 1 .
RESULTS The most common organism in each group was E s c h e r i c h i a c o l i (Table I). Initial response to therapy was favorable in each group, with sterilization of urine demonstrated at 2 to 4 days after therapy, thus achieving a 100% cure rate in each group (Table I). One patient in the conventional therapy group, a 15-year-old girl, developed an early recurrence. P r o t e u s m i r a b i l i s , the primary pathogen, was eradicated by the fourth day of therapy, but at that time the urine grew P s e u d o m o n a s a e r u g i n o s a , indicating reinfection. Recurrence rates at 2 weeks of followup were also similar, 14% and 10% with single-dose and 10-day therapy, respectively. At 3 to 4 weeks follow-up, the cumulative recurrence rate increased to 43% in the singledose group and to 24% in the conventional group; by the end of 12 weeks, 67% and 52% of patients in the singledose and 10-day therapy groups, respectively, had developed recurrent infection. The difference in recurrence rates throughout the follow-up period remained insignificant (P >0.1 in each instance). However, the power of the test with 1 degree of freedom is only 0.26, and the difference in the final recurrence rates would achieve significance at the 0.05 level, using a power of 0.80, if the sample size were increased to 103 patients in each group. All the recurrent episodes encountered during the observation period after therapy in both groups were reinfections (Table I). Recurrence rates were similar whether the treated episodes were caused by E . c o l i or by other pathogens. Thus, 60% of patients with UTI caused by E. c o l i (Table II) in the single-dose group and 56% in the conventional group developed recurrences (P >0.1). Results were similar in patients with E . c o l i compared with those infected with other pathogens in both the single-dose and 10-day therapy groups (Table II). Medications, including the single dose of gentamicin, were well tolerated
by all. No untoward side effects, including skin rash and swelling or abscess at the injection site, were reported or observed. DISCUSSION In this study, single-dose therapy was as effective as 10 days of conventional therapy in the treatment of an acute recurrent episode of UTI in patients with normal urinary tracts; cure and recurrence rates were comparable. The recurrence rates (67% and 52%) in the two groups were higher than reported previously,4'5 but were not unexpected, because all these patients had a history of recurrent UTI, with an average of five to six episodes per patient (Table I). Comparison of our results with those of previous studies is difficult because of differences in selection criteria. 3-e A review (Table III) indicates that in most studies the treated episodes were initial UTIs 4 only or a mixture of recurrent and initial UTIs. 5,6 In addition, in most the urinary tract was not completely examined.3-5In one study6 in which urinary tract investigation was part of the protocol, patients with possible upper UTI and urinary tract malformation were not excluded. Among these (Table III), the study of K/illenius and Winberg3 is the only one that included recurrent UTIs exclusively. They utilized low ESR as evidence of lower UTI; their cure rate (100%) and recurrence rate (55%) were similar to our own findings. Their study was uncontrolled, however, and the urinary tract was not investigated. The study of Wallen et al. 4 somewhat resembles ours in using an aminoglycoside as a single dose, but included patients with initial UTIs. The cure rate in their study was similar to our own (Table III) but the recurrence rate (26%) was lower, reemphasizing the observation that patients with a history of recurrent UTIs have a higher prevalence of recurrences regardless of duration of therapy.
134
Khan, Kumar, and Evans
The Journal of Pediatrics January 1987
T a b l e III. Comparison of efficacy of single-dose therapy in various studies Characteristics of urinary tract infection Therapy group
Reference
Khan et al.
(1986)
K~illenius and Winberg 3 Wallen et al.4
(1979) (1983)
Shapiro and Wal@
(1983)
Avner et al. 6
(1983)
Initial or recurrent
Upper or lower
Cr|teria for localization
Lower Lower Lower Lower Lower Lower Lower Mixed Mixed
Clinical (ESR) Clinical (ESR) Clinical (ESR) Clinical (ESR) Clinical (ESR) Clinical Clinical Clinical (ESR) Antibody-coated bacteria Clinical (ESR) Antibody-coated bacteria
Single-dose 10-day Single-dose Single-dose 10-Day Single-dose 10-Day Single-dose
(n (n (n (n
(n = 18) (n = 17) (n = 24)
Recurrent Recurrent Recurrent Initial Initial Mixed Mixed Unknown
10-Day
(n = 25)
Unknown
= = = =
21) 21) 29) 26)
(n =
25)
*Sterile. tlnfected urine at 2 to 6 days follow-up.
We conclude that single-dose therapy is effective for the treatment of recurrent episodes of lower U T I in those patients with normal urinary tracts. Because most recurrences are reinfections with a new organism derived from fecal flora, the preferred form of therapy for these patients may be a single dose. In certain patients with frequent recurrent UTIs, therapy may include long-term prophylaxis. Single-dose treatment might be useful also in these patients for treating breakthrough, recurrent episodes of UTI. In addition to being cost effective, single-dose therapy has other advantages, such as assured compliance, decreased drug toxicity, z and decreased likelihood of resistance. The choice of single-dose therapy could be one of the orally administered medications, including ampicillin 5.6 or a sulfonamide, or a parenterally administered aminoglycoside, including amikacin 4 or gentamicin. We consider a
single dose of an aminoglycoside to be safe and not to require any precautions, including posttherapy determination of serum creatinine concentration, in patients with normal renal function. In previous studies we had observed that amikacin, 1~ gentamicin, or netilmicin 11 was safe for the treatment of UT1 for as long as 10 days. However, aminoglycosides have their own limitations. They should be avoided in patients with impaired renal function and associated urinary tract malformations. If U T I is thought to be a lower tract infection and if serum creatinine concentration and urinary tract are normal, gentamicin may be considered for single-dose therapy and is as effective as conventional management. If the cost and discomfort of an intramuscular injection are unacceptable, orally administered medication may be chosen.
Volume 110 Number 1
Gentamicin f o r recurrent urinary tract infection
Results
Urinary tract Studied
(%)
135
Abnormal
(%)
Cure"
(%)
Failure
Recurrence rate
(%)
%
Duration
Drug
100 100 0 24 16 Unknown Unknown 100
0 0 Unknown Unknown Unknown Unknown Unknown 20
100 100 100 92 96 78 88 63
0 0 0 8 8 22 12 37
67 52 55 26 19 39 24 50
12 wk 12 wk 3 mo 40 day 40 day 3 mo 3 mo 4 wk
Gentamicin IM Three drugs vo Sulfonamide vo Amikacin IM Sulfonamide vo Amoxicillin vo Amoxicillin vo Amoxicillin vo
100
16
92
8
36
4 wk
Amoxicillin vO
REFERENCES
1. Roland AR, Boutros PL, Mourtada H. Bacteriuria localization and response to single dose therapy in women. JAMA 1976;235:1854. 2. Fang LST, Tolkoff-Rubin NH, Rubin RH. Efficacy of single dose and conventional amoxicillin therapy in urinary tract infection localized by the antibody coated bacteria technique. N Engl J Med 1978;298:413. 3. K~illenius G, Winberg J. Urinary tract infections treated with single dose of short-acting sulphonamide. Br Med J 1979; 1:1175. 4. Wallen L, Zeller P, Goessler M, et al. Single dose amikacin treatment of first childhood E. coli lower urinary tract infection. J PEDIATR 1983;103:316. 5. Shapiro ED, Wald ER. Single dose amoxicillin treatment of urinary tract infections. J PEDIATR 1981;99:989. 6. Avner ED, Ingelfinger JR, Herrin JT, et al. Single dose amoxicillin therapy of uncomplicated pediatric urinary tract infections. J PEDIATR 1983;102:623.
7. Hellerstein S, Kennedy E, Nussbaum L, et al. Localization of the site of urinary tract infection by means of antibody coated bacteria in the urinary sediment. J PEDIATR 1978;92:188. 8. Jodal U, Lindberg U, Lincoln K. Level diagnosis of symptomatic urinary tract infection in childhood. Acta Paediatr Scand 1975;64:201. 9. Hellerstein S, Duggan E, Welchert E, Mansour F. Serum C-reactive protein and the site of urinary tract infections. J PEDIATR 1982;100:21. 10. Khan AJ, Evans HE, Jhaveri R, Chang P, Hochstein L. Amikacin pharmacokinetics in the therapy of childhood urinary tract infections. Pediatrics 1976;58:873. 11. Varghese M, Khan A J, Kumar K, Schaeffer HA, Evans HE. Comparison of pharmacokinetics and safety of netilmicin and gentamicin in infants and children. Curr Ther Res 1983; 34:124.
Single-dose gentamicin therapy of recurrent urinary tract infection in patients with normal urinary tracts Results of single-dose therapy of urinary tract infections in pediatric patients have been contradictoP/mainly because of selection criteria. We evaluated the efficacy of a Single dose of gentamicin in patients with normal urinary tracts and in whom urinary tract Infections were recurrent. Twenty-one patients were included in th@study, and a similar number in a conventional groUp given treatment for 10 days. Cure rate was 100% in both groups. The recurrence rates of 67% in the stUdy and 52% in the conventional group were comparable. Single-dose therapy seems to have a role in the treatment of urinary tract infeCtion in the absence of urinary tract malformation. (J PEDIATR1987;110:131-5)
Abdul J. Khan, M.D., Kusum Kumar, M.D., and Hugh E. Evans, M.D. From the Department of Pediatrics, Interfaith Medical Center, State University of New York/Downstate Medical Center, Brooklyn
Single-dose antimicrobial therapy has been found to be as effective as conventional 10-day therapy in adult patients with uncomplicated lower urinary tract infection.1,2 Similar studies in pediatric patients have had divergent results, 36 apparently because of the lack of uniformity in patient selection. Inclusion of patients with possible upper UTI or urinary tract malformation may have been responsible for poor outcome in some studies, 6 whereas selection of patients with initial UTI 4 led to excellent results. In acute symptomatic initial UTI, single-dose therapy cannot be used with confidence because there is no rapid, reliable test to identify upper UTI and because of the increased prevalence of underlying structural anomalies in children. Tests of upper UTI such as the antibody-coated bacteria test 7 and serum CRP concentration8are unreliable in pediatric patients. 7-9We believe that single-dose therapy may be appropriate for treatment of recurrent UTI in selected patients with normal urinary tracts, and have designed this study to evaluate the possibility.
Submitted for publication March 24, 1986; accepted July 14, 1986. Reprint requests: Abdul J. Khan, M.D., Department of Pediatrics, Interfaith Medical Center, 1545 Atlantic Ave., Brooklyn, NY 11213.
METHODS Fifty-six episodes of recurrent UTI were treated prospectively on an alternate basis with either a single intramuscular dose of gentamicin (28 episodes) or a 10-day orally administered course with various antimicrobial agents selected empirically (28 episodes). All patients had received treatment for previous UTIs and observed in the pediatric renal clinic. Most patients had symptoms suggestive of lower UTI (Table I). Eight patients without symptoms had symptomatic UTI treated in the past. In
ESR UTI
Erythrocyte sedimentation rate Urinary tract infection
most, examination of fresh urine (performed routinely) revealed actively motile organisms. The diagnosis in each patient was based on at least two consecutive positive urine cultures, defined as growth of ~ 105 organisms per milliliter of urine collected by the clean-catch method, in which the same organism was grown in pure culture. All patients had presumed lower UTI on the basis of clinical symptoms such as dysuria and frequency (Table I), lack of systemic signs and symptoms such as fever (temperature >38 ~ C rectal or >37 ~ C oral), vomiting, clinical toxicity, or
131
13 2
Khan, Kumar, and Evans
The Journal o f Pediatrics January 1987
T a b l e I. Results of single-dose and conventional therapy of recurrent urinary tract infection 10-Day conventional
Single-dose gentamicin (n = 21) n
Age (yr) (+__1SD) Previous UT!s ( _+1 SD) Symptomatic Asymptomatic Normal IVP and VCU Pathogens Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa
Other Cure Recurrence rate (cumulative) 2-4 days 1-2 weeks 3-4 weeks 4-6 weeks 6-12 weeks Relapse Reinfection total Different organism Same organism, different biotype
(n = 21)
%
7.8 + 3.0 5.0 + 3.1
7.5 + 3.3 6.0 +__3.6 18 3 21 21 15
%
n
76 24 100 100 86
86 14 100 100 71
16 5 21 21 18
5 10
---
3 21
14 100
3 21
14 100
0 3 9I" 11~ 141 0 14 5t 9
0 14 43 52 67 0 100 36 64
1 2 5:~ 8~ 11:~ 0 11 2:~ 9
5 10 24 38 52 0 100 18 72
1 2
IVP, intravenouspyelogram;UTI, urinarytract infection;vcu, voidingcystourethrogram. *Dysuria,frequency,abdominalpain. "~vs :~, P >0.1.
costovertebral angle tenderness. In addition, all had an ESR of ~ 2 0 mm/hr. Twelve patients were excluded, 10 (four in single-dose group and six in 10-da.y therapy group) because of elevated ESR (>21mm) and two (single-dose group) because of lack of positive culture in urine collected prior to treatment. Two additional patients, both boys, one in each group, were also dropped, to make it an all-girl study. All patients had normal intravenous pyelograms and voiding cystourethrograms. Patients younger than 6 months and older than 15 years, those with elevated serum creatinine values, renal failure, nephropathies, or those given antimicrobial agents in the past 2 weeks were not included. Written informed consent was obtained from the parents of those given a single dose. The two groups, with 21 patients in each, were comparable in age and clinical characteristics of UTI, including the number of previous episodes (Table I). Patients in the study group were given a single intramuscular injection of gentamicin in a dose of 5 mg/kg body weight (maximum of 300 mg). The conventional treatment group was given standard doses of various antimicrobial agents for 10 days, including trimethoprim-sulfamethoxazole in t l , ampicillin in five, and a cephalosporin in five. The organ-
isms in the single-dose group were susceptible to gentamicin, and those in the conventional treatment group were susceptible to the agent selected, using the disk method. Compliance in those given treatment for 10 days was monitored by careful questioning and by checking medication supplies. Pathogens were identified by standard microbiologic techn!ques, including API (Analylab Products, Plainview, N.Y.) biotyping. Urine culture in each patient was repeated between 2 and 4 days, and at 1 week, 2 weeks, 4 to 6 weeks, and 8 to 12 weeks after therapy. The two groups were compared for frequency of cure and recurrences, including relapse or reinfection at various follow-up intervals. Cure was defined as eradication of the primary pathogen at the first follow-up visit. Posttherapy recurrent infections were identified as relapse or reinfection based on API biotyping and the antibiotic sensitivity pattern of the organisms. Recurrence caused by a n organism belonging to same species, having similar biotype and sensitivity pattern as the pretherapy pathogen, was considered a relapse; and recurrence caused by an organism of a different species or same species but having a different biotype and sensitivity pattern was considered a reinfection. The results were compared utilizing the chi-square test and Fisher exact test.
V o l u m e 110 Number 1
Gentamicin
for recurrent
Table II. Posttherapy recurrence rates in urinary tract infection caused by E s c h e r i c h i a Single-dose therapy No. treated E s c h e r i c h i a coil
Other Klebsiella pneumoniae P s e u d o m o n a s aeruginosa Proteus mirabilis Staphylococcus epidermidis Enterococcus
Total
15 6
No. recurred
9* 5t
1 2 1 1 1
0 2 1 1 1
21
14
urinary
coil
tract infection
13 3
and other pathogens
10-Day therapy
Percent
No. treated
No. recurred
Percent
P
60 83
18 3
10" 1~"
56 33
>0.1 >0.1
--1 -2
--1 -0
21
11
67
------
52
>0.1
* vs ~, p > 0 . 1 .
RESULTS The most common organism in each group was E s c h e r i c h i a c o l i (Table I). Initial response to therapy was favorable in each group, with sterilization of urine demonstrated at 2 to 4 days after therapy, thus achieving a 100% cure rate in each group (Table I). One patient in the conventional therapy group, a 15-year-old girl, developed an early recurrence. P r o t e u s m i r a b i l i s , the primary pathogen, was eradicated by the fourth day of therapy, but at that time the urine grew P s e u d o m o n a s a e r u g i n o s a , indicating reinfection. Recurrence rates at 2 weeks of followup were also similar, 14% and 10% with single-dose and 10-day therapy, respectively. At 3 to 4 weeks follow-up, the cumulative recurrence rate increased to 43% in the singledose group and to 24% in the conventional group; by the end of 12 weeks, 67% and 52% of patients in the singledose and 10-day therapy groups, respectively, had developed recurrent infection. The difference in recurrence rates throughout the follow-up period remained insignificant (P >0.1 in each instance). However, the power of the test with 1 degree of freedom is only 0.26, and the difference in the final recurrence rates would achieve significance at the 0.05 level, using a power of 0.80, if the sample size were increased to 103 patients in each group. All the recurrent episodes encountered during the observation period after therapy in both groups were reinfections (Table I). Recurrence rates were similar whether the treated episodes were caused by E . c o l i or by other pathogens. Thus, 60% of patients with UTI caused by E. c o l i (Table II) in the single-dose group and 56% in the conventional group developed recurrences (P >0.1). Results were similar in patients with E . c o l i compared with those infected with other pathogens in both the single-dose and 10-day therapy groups (Table II). Medications, including the single dose of gentamicin, were well tolerated
by all. No untoward side effects, including skin rash and swelling or abscess at the injection site, were reported or observed. DISCUSSION In this study, single-dose therapy was as effective as 10 days of conventional therapy in the treatment of an acute recurrent episode of UTI in patients with normal urinary tracts; cure and recurrence rates were comparable. The recurrence rates (67% and 52%) in the two groups were higher than reported previously,4'5 but were not unexpected, because all these patients had a history of recurrent UTI, with an average of five to six episodes per patient (Table I). Comparison of our results with those of previous studies is difficult because of differences in selection criteria. 3-e A review (Table III) indicates that in most studies the treated episodes were initial UTIs 4 only or a mixture of recurrent and initial UTIs. 5,6 In addition, in most the urinary tract was not completely examined.3-5In one study6 in which urinary tract investigation was part of the protocol, patients with possible upper UTI and urinary tract malformation were not excluded. Among these (Table III), the study of K/illenius and Winberg3 is the only one that included recurrent UTIs exclusively. They utilized low ESR as evidence of lower UTI; their cure rate (100%) and recurrence rate (55%) were similar to our own findings. Their study was uncontrolled, however, and the urinary tract was not investigated. The study of Wallen et al. 4 somewhat resembles ours in using an aminoglycoside as a single dose, but included patients with initial UTIs. The cure rate in their study was similar to our own (Table III) but the recurrence rate (26%) was lower, reemphasizing the observation that patients with a history of recurrent UTIs have a higher prevalence of recurrences regardless of duration of therapy.
134
Khan, Kumar, and Evans
The Journal of Pediatrics January 1987
T a b l e III. Comparison of efficacy of single-dose therapy in various studies Characteristics of urinary tract infection Therapy group
Reference
Khan et al.
(1986)
K~illenius and Winberg 3 Wallen et al.4
(1979) (1983)
Shapiro and Wal@
(1983)
Avner et al. 6
(1983)
Initial or recurrent
Upper or lower
Cr|teria for localization
Lower Lower Lower Lower Lower Lower Lower Mixed Mixed
Clinical (ESR) Clinical (ESR) Clinical (ESR) Clinical (ESR) Clinical (ESR) Clinical Clinical Clinical (ESR) Antibody-coated bacteria Clinical (ESR) Antibody-coated bacteria
Single-dose 10-day Single-dose Single-dose 10-Day Single-dose 10-Day Single-dose
(n (n (n (n
(n = 18) (n = 17) (n = 24)
Recurrent Recurrent Recurrent Initial Initial Mixed Mixed Unknown
10-Day
(n = 25)
Unknown
= = = =
21) 21) 29) 26)
(n =
25)
*Sterile. tlnfected urine at 2 to 6 days follow-up.
We conclude that single-dose therapy is effective for the treatment of recurrent episodes of lower U T I in those patients with normal urinary tracts. Because most recurrences are reinfections with a new organism derived from fecal flora, the preferred form of therapy for these patients may be a single dose. In certain patients with frequent recurrent UTIs, therapy may include long-term prophylaxis. Single-dose treatment might be useful also in these patients for treating breakthrough, recurrent episodes of UTI. In addition to being cost effective, single-dose therapy has other advantages, such as assured compliance, decreased drug toxicity, z and decreased likelihood of resistance. The choice of single-dose therapy could be one of the orally administered medications, including ampicillin 5.6 or a sulfonamide, or a parenterally administered aminoglycoside, including amikacin 4 or gentamicin. We consider a
single dose of an aminoglycoside to be safe and not to require any precautions, including posttherapy determination of serum creatinine concentration, in patients with normal renal function. In previous studies we had observed that amikacin, 1~ gentamicin, or netilmicin 11 was safe for the treatment of UT1 for as long as 10 days. However, aminoglycosides have their own limitations. They should be avoided in patients with impaired renal function and associated urinary tract malformations. If U T I is thought to be a lower tract infection and if serum creatinine concentration and urinary tract are normal, gentamicin may be considered for single-dose therapy and is as effective as conventional management. If the cost and discomfort of an intramuscular injection are unacceptable, orally administered medication may be chosen.
Volume 110 Number 1
Gentamicin f o r recurrent urinary tract infection
Results
Urinary tract Studied
(%)
135
Abnormal
(%)
Cure"
(%)
Failure
Recurrence rate
(%)
%
Duration
Drug
100 100 0 24 16 Unknown Unknown 100
0 0 Unknown Unknown Unknown Unknown Unknown 20
100 100 100 92 96 78 88 63
0 0 0 8 8 22 12 37
67 52 55 26 19 39 24 50
12 wk 12 wk 3 mo 40 day 40 day 3 mo 3 mo 4 wk
Gentamicin IM Three drugs vo Sulfonamide vo Amikacin IM Sulfonamide vo Amoxicillin vo Amoxicillin vo Amoxicillin vo
100
16
92
8
36
4 wk
Amoxicillin vO
REFERENCES
1. Roland AR, Boutros PL, Mourtada H. Bacteriuria localization and response to single dose therapy in women. JAMA 1976;235:1854. 2. Fang LST, Tolkoff-Rubin NH, Rubin RH. Efficacy of single dose and conventional amoxicillin therapy in urinary tract infection localized by the antibody coated bacteria technique. N Engl J Med 1978;298:413. 3. K~illenius G, Winberg J. Urinary tract infections treated with single dose of short-acting sulphonamide. Br Med J 1979; 1:1175. 4. Wallen L, Zeller P, Goessler M, et al. Single dose amikacin treatment of first childhood E. coli lower urinary tract infection. J PEDIATR 1983;103:316. 5. Shapiro ED, Wald ER. Single dose amoxicillin treatment of urinary tract infections. J PEDIATR 1981;99:989. 6. Avner ED, Ingelfinger JR, Herrin JT, et al. Single dose amoxicillin therapy of uncomplicated pediatric urinary tract infections. J PEDIATR 1983;102:623.
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