Vol. 105, April Printed in U.S.A.
THE JouRNAL oF UROLOGY
Copyright © 1971 by The Williams & Wilkins Co.
URINARY TRACT INFECTION IN CHILDREN: A RETROSPECTIVE STUDY JOSEPH W. SEGURA, PANAYOTIS P. KELALIS, GUNNAR B. STICKLER EDMUND C. BURKE
AND
From the Departments of Urologic Surgery and Pediatrics, Mayo Graduate School of Medicine and lhe Mayo Clinic and Mayo Foundation, Rochester, Minnesota
The various symptoms indicative of urinary tract infection in children often have been considered to be poor indicators of the specific anatomic abnormality of the urinary tract possibly associated with infection. Kunin and Paquin did not consider history and symptomatology helpful in determining which girls with bacteriuria would have calicectasis, reflux or an abnormal bladder. 1 Spence and associates referred to a retrospective study of children hospitalized for urinary tract infection in whom the precise urologic diagnosis could not be predicted from the history. 2 We have attempted to determine whether the presence or absence of specific urologic abnormalities can be predicted on the basis of the patient's history or symptoms. The symptoms and findings in 100 consecutive histories of children with urinary tract infection seen at the Mayo Clinic from late 1967 through April 1969 were analyzed and the results of urological diagnostic study were evaluated.
abdominal pain, dribbling, enuresis, malodorous urine, day wetting, hematuria, high fever, presence of congenital (externally visible) anomalies related to the urogenital tract and a family history of urologic disease. Frequency, urgency and dysuria occurred in nearly every case and were not evaluated. Diagnostic study included cystoscopic examination of all children, excretory urography (IVP) of 99 and cine-cystourethrography of 85. :\Iidstream urine cultures were obtained at the first clinic visit. Urine specimens for culture were also obtained at cystoscopy. Vaginal cultures were obtained at cystoscopy in 57 of 82 girls. Findings on the cine-cystourethrogram were considered abnormal if reflux was demonstrated, if para-ureteral diverticula were present or if more than minimal trabeculation was noted. Abnormal IVP findings included duplicated collecting systems and minimally dilated ureters. All IVPs were interpreted by the same urologist.
METHOD
RESULTS
The study included 100 children (82 girls and 18 boys). All boys with a history or symptoms of 1 or more urinary tract infections and all girls with 2 or more infections had undergone urologic evaluation. Children with myelodysplasia and those who had had previous surgical procedures of the urogenital tract were excluded from the study. Previous cystoscopic examination was not a contraindication to inclusion. Histories were reviewed specifically for the number of previous infections, age at onset of symptoms, flank pain,
More than 75 per cent of the 100 children had had 3 or more infections when they were seen at this clinic (table 1). Girls had a higher incidence of enuresis and day wetting but anomalies of the urogenital tract were found more often in boys. :VIalodorous urine was a symptom in girls only. Abdominal or flank pain and a positive family history showed no predilection for either sex. Several symptoms were more likely to occur together~fever was associated with abdominal pain but was unlikely to be assor-iated with enuresis and enuresis was frequently found in children who also had day wetting and malodorous urine. These associations were statistically significant. We were not able to predict the outcome of diagnostic study when the aforementioned factors were present in the history with 2 exceptions (table 2). 1) Children with histories of multiple infections (3 or more) had much less chance of having cortical scarring than those with only 1 or
Accepted for publication May 26, 1970. Read at annual meeting of North Central Section, American Urological Association, Milwaukee, Wisconsin, September 24-27, 1969. 1 Kunin, C. M. and Paquin, A. J., Jr.: Urinary tract disease in school girls with bacteriuria. Ann. N. Y. Acad. Sci., 142: 640, 1967. 2 Spence, H. M., Murphy, J. J., JVIcGovern, J. H., Hendren, W. H. and Pryles, C. V.: Urinary tract infections in infants and children. J. Urol., 91: 623, 1964.
591
592
SEGURA AND ASSOCIATES
TABLE
1. Symptoms in 100 consecutive cases of children with urinary tract infection Symptom
% 51
Fever: High Low Infections: 3 or more 1 or 2 Not known Enuresis Positive family history Day wetting Abdominal pain Flank pain Malodorous urine Dribbling
24 27 100 78 16 6 43 32 22 22 13 14 12
2. Relationship of infections and malodorous urine findings to diagnostic study in 100 consecutive cases of children with urinary tract infection
TABLE
Abnormal (%) No. Pts.
Positive MidStream Cys- Cys- Culture IVP toure- tos(%) thro- copy Cine-
Renal Units With Cortica Scarring (%)
gram
- - -- -- -- - - -No. infections: 1 or 2 3 or more Not known Malodorous urine: No Yes
16 78 6
73 51
64 69
-
86 14
59 36
* Significantly different (p
<
27* 5*
-
75 88 -
54 34 -
-
73* 21 *
88* 64*
34 46
11* O*
stenosis, stricture or vesical neck obstruction, was made in 20 cases. Eight (40 per cent) of these 20 children had reflux. Urethral valves were found in 5 boys. Thus, the incidence of reflux in children with obstructive disease was no higher than in children without obstructive problems. Other diagnoses included such anomalies as neurogenic bladder and congenital megaloureter. The number of anatomic abnormalities was about the same for each sex: 60 girls (74 per cent) and 15 boys (84 per cent). Cortical scarring was found much more often in children with reflux than in children without reflux, occurring in 19 of the 78 renal units in which reflux was present (table 4). There was no difference in concentrating ability or degree of pyuria in patients with or without reflux. Reflux was noted in 15 of 19 instances in which hyaline or granular casts were revealed by urinalysis. Most of these children had only occasional casts per high power field; only 1 child had grade 1 or 1 to 10 casts per high power field. IVP revealed no anatomic abnormality in 44 of 99 children (table 5). In 21 of these 44 children reflux was present. Cystoscopy revealed abnormality in 35 (80 per cent) of these children whether or not the urographic findings were normal. Findings on IVP were likely to be abnormal whether findings on the cine-cystoureTABLE
0.05).
2 episodes. This fact is in contrast to what would be expected if the assumption is made that frequent infections cause cortical scarring. 2) In children with complaints that included foulsmelling urine, the results of cine-cystourethrography and cystoscopic examination were more likely to be normal than abnormal; further, no child with foul-smelling urine had renal cortical scarring. Differences noted with respect to urographic findings and to the urine culture were not statistically significant. Reflux, the most common urologic finding, was seen in 54 per cent of the children (table 3). Reflux was bilateral in 24 instances, on the left side in 17 and on the right side in 13. Some patients had evidence of infection or minor pathologic change such as minimal bladder trabeculation but no other anatomic abnormality could be determined. Diagnosis of obstructive diseases, such as urethral valves and severe distal urethral
3. Diagnoses in 100 consecutive cases of children with urinary tract infection Diagnosis
%
Reflux Cortical scarring Distal urethral stenosis Urethral valves Obstruction of vesical neck Urinary tract infection-no anatomic abnormality Normal urogenital tract-no evidence of urinary tract infection Other
54
TABLE
15 12 5
2 20 3
7
4. Reflux in 100 consecutive cases of children with urinary tract infections Urine
Reflux
Pyuria (grade No. Cortical Pts. Scarring Sped2 or fie Casts higher) Gravity
-- -Yes No
54 46
Height and Weight
Crea tinine Urea
--- - - - - - - - - - - - - 12* 3*
1.016 1.016
* Significantly different (p
15* 4*
16 12
< 0.05).
Normal Normal
Normal Normal
593
URINARY TRACT INFECTION IN CHILDREN
5. Relat,:onship of !VP findings to reflux ancl cystoscopic findings in 100 consecutive cases of children with urinary tract infection
TABLE
Normal IVP
No. Pts.
Reflux No.(%)
Abnormal Cystoscopy No.(%)
Yes No Not done
44 55
21 (48) 33 (60)
35 (80) 49 (89)
6. Relationship of dne-cystourethrographic findings to IVP and cystoscopic findings in 100 consecutive cases of children with urinary tract infection
Bacteria were found in 48 of 84 children in whom a mid-stream urine culture had been made when the patient was first examined at our clinic. Colony counts were greater than 100,000 in 30 of the 48 children (table 8). The number of abnormal results in the diagnostic study was the same regardless of whether there was significant bacteriuria when the child came for medical study. Those children who had had previous cystoscopy were infected no more frequently than those who had not.
TABLE
IVP
Cystoscopy
Normal Cine-Cysto- No. Pts. urethrogram
No Yes Not done
TABLIG
Abnormal (%)
Normal Abnormal J\Tormal Abnormal No.(%) No.(%) No.(%) No.(%) --~ - - - - - - - - - - - 53 22 (42) 31 (58) 0 53 (100) 15 (47) 32 17 (53) 8 (25) 24 (75) 15 -
7. Age of patient at onset of symptoms and
presence of reflux in 100 consecutive cases of urinary tract infection Age (yrs.)
No.
Less than 1
14 9 17 18 16
2
3 4
8 7
8-14
2 6
Unknown Total
8. Relationship of culture of mid-stream urine specimen to diagnostic study in 100 consecutive cases of children with urinary tract infection
TABLE
100
Reflux No.(%) 9
(64)
7
(78)
(41) (50) (56) (50) (44) (50) 2 (33) 1 (100)
7
9 10 4
54
(54)
throgram were normal or abnormal (table 6). Whenever the cine-cystourethrogram showed an abnormality, cystoscopy also demonstrated one. Cystoscopic findings were normal in 8 of 30 children for whom results of cine-cystourethrogra phic study were normal. Expression cystography was done in 44 children and reflux was confirmed in 14. In only one instance did expression cystography reveal reflux when this was not also demonstrated on cine-cystourethrography. Reflux was found in a high proportion of children who became symptomatic before they were 3 years old; only 2 of the 40 children who were less than 3 years old at the time of the first infection had normal urinary tracts (table 7).
Finding
, - - - - - - - - , Urethral No. Pts. Cine- Cys- Stenosis IVP tos(%) gram copy
u;'.[tt~;-
Positive* Negative Not done
30 54 16
53 49
63 69
87 85
Cortical Scarring (%)
13
10
11
11
* Counts greater than 100,000 colonies. TABLE
9. Results of vaginal culture in 57 patients with urinary tract infection Organism
No. Pts.
Escherichia coli Group D streptococci Staphylococcus epidermidis Corynebacterium Streptococcus viridans Proteus Staphylococcus (coagulase-negative) Staphylococcus aureus Klebsiella Pseudomonas Mixed flora
31 27
TABLE
22
17 11 8
4 4 5 1 2
10. Organisms in urine culture not found in the vaginal culture in 57 patients with urinary tract infection
Specimen and Organism
Mid-stream specimen: Escherichia coli Proteus Klebsiella Providentia Pseudomonas Enterobacter Catheter specimen: Klebsiella Enterobacter Herellea vaginicola
Counts <100,000
> 100,000
0 0
0
594
SEGURA AND ASSOCIATES
The most commonly cultured organisms from the vagina were Escherichia coli, group D streptococci and Staphylococcus epidermidis (table 9). In 9 cases mid-stream urine culture produced an organism that was not found in the vagina and in 4 cases the catheterized specimen yielded bacteria that was not found in the vagina (table 10). COMMENT
From the symptomatology of children with urinary tract infection, it is not possible to predict which patients will have significant anatcmic abnormalities. The observation of malodorous urine in the history of girls only appears to indicate disease confined to the lower urogenital tract. In predicting the result of positive urologic findings, we found that the history of documented urinary tract infections was as useful as the actual observation of a urinary bacterial colony count greater than 100,000. Reflux was found most often in children who had hyaline or granular casts in the urine. Hyaline casts are precipitates of albumin formed during passage through the tubules arid when seen only occasionally in the high power field these casts are considered normal.3 Granular casts result from degenerate-formed elements of renal origin and are considered abnormal, although non-specific. 4 The association of these elements with reflux may indicate early subclinical parenchymal damage. The IVP was not helpful in predicting reflux or cystoscopic abnormalities despite the high incidence of reflux and other urologic findings. As noted by Meadows, reflux can occur in radiographically normal urinary tracts. 5 We believe that cine-cystourethrography as a diagnostic procedure in children with urinary tract infection is probably as useful as the IVP. Expression cystography was not as reliable an indicator of reflux as the cine-cystourethrogram. 3 Hepler, 0. E.: Manual of Clinical Laboratory Methods, 4th ed. Springfield, Illinois: Charles C Thomas, Publisher, 1949. 4 Hamburger, J., Richet, G., Crosnier, J., Funck-Brentano, J. L., Antoine, B., Ducrot, H., Mery, J.P. and de Montera, H.: Nephrology. (Translated by A. Walsh.) Philadelphia: W. B. Saunders Co., vol. 1, 1968. 5 Meadows, J. A., Jr.: Cystourethrography in infants and children: patterns of voiding and urinary tract infections. Southern Med. J., 60: 1171. 1967.
Cystoscopy revealed some abnormality in 85 per cent of children with history of urinary tract infection. Most children with reflux had the welldescribed changes of the orifices and trigone. 6 Cortical scarring is not likely to be seen in the absence of reflux. Children with reflux had no deficit in urinary concentrating ability and they did not differ from normal children in physical development. There was no relationship between the occurrence of reflux and the presence of pyuria or obstructive disease. The organism involved in infected urine probably will be one of the organisms found in the vaginal culture. In several girls in our series organisms isolated from the urine did not appear in the vaginal culture; this was noticed slightly more often with the enterobacter organisms. However, it is most probable that the causative organism would be found in the vagina, if only because of the recurrent contact of the vagina with urine. In addition, the organism presumably would have originated in this region. Symptoms indicative of a urinary tract infection frequently begin in infancy. Williams and Eckstein noted that 71 of 276 children become symptomatic in the first year of life.7 It seems likely that all children less than 3 years old who have urinary tract infection should have a complete diagnostic study. SUMMARY
The records of 100 children referred for urologic evaluation of urinary tract infection were reviewed. Relationships between symptoms, between symptoms and diagnostic study and within the diagnostic study were studied. Several symptoms were more likely to occur concurrently but it was not possible to predict which patients would have significant anatomic abnormalities. Malodorous urine was a symptom in girls only and indicated disease confined to the lower urinary tract. Casts in the urine were associated with reflux. The IVP was not a useful indicator of cystoscopic abnormalities or of reflux. Probably all children less than 3 years old who have urinary tract infection should be evaluated urologically. 6 Lyon, R. P., Marshall, S. and Tanagho, E. A.: The ureteral orifice: its configuration and competency. J. Urol., 102: 504, 1969. 7 Williams, D. I. and Eckstein, H.B.: Surgical treatment of reflux in children. Brit. J. Urol., 37: 13, 1965.