Guidelines for the Management of Acute Urinary Tract Infection in Childhood

Chronic pyelonephritis (reflux nephropathy) is found in about 20% of children and adults with end stage renal failure[1]. Prospective studies have shown that children who presented up to 30 years ago with urinary infection and chronic pyelonephritis now have a 20% risk of hypertension and a 10% risk of chronic renal failure[2][3][4][5]. The considerable variation in man-
agement of acute urinary tract infections in childhood [bib_ref] Current practice in managing urinary tract infections in children, Smyth [/bib_ref] prompted the Research Unit of the Royal College of Physicians to convene a Working Group to consider guidelines for good practice, to identify areas where more research is needed and to develop procedures that could be used for audit.
In this report, a statement supported by research is followed by a reference number, statements recognising the need for further research by , and subjects suitable for audit are indicated by . A list of proposed audit measures is given in Appendix 1.

## Diagnosis of urinary tract infection
As most scars are present at the first investigation [bib_ref] Reflux nephropathy: a personal historical review, Hodson [/bib_ref] [bib_ref] Natural history of pyelonephritic scarring, Hodson [/bib_ref] , early diagnosis and prompt treatment are especially important during the first year of life. At home, any infant with a rectal temperature above 38.5?C with no definite cause should have a urine sample collected within 24 hours [bib_ref] Study of childhood urinary tract infection in general practice, Mond [/bib_ref]. In all infants and children admitted to hospital with pyrexia, even with another diagno- The yield of positive results when urine specimens are taken at home for the above indications, including fever, would be a suitable research project (R).
Taking a specimen A clean-catch urine in an infant or a mid-stream urine specimen in an older child is the ideal. Only social cleanliness and dryness are required [bib_ref] Study of childhood urinary tract infection in general practice, Mond [/bib_ref]. If these techniques are not effective, a bag urine should be obtained while the infant is held upright [bib_ref] Natural history of pyelonephritic scarring, Hodson [/bib_ref] and the specimen transferred from the bag as soon as it is passed [bib_ref] Study of childhood urinary tract infection in general practice, Mond [/bib_ref]. A negative result (see below) from a bag urine specimen is reliable, but a positive result should be confirmed by a clean-catch specimen or, in infants, with suprapubic puncture or rarely by a catheter specimen (A). If suprapubic aspiration is needed, the infant should be referred to hospital for day-care or inpatient investigation.

## Criteria for diagnosis of urinary tract infection
The diagnosis of urinary infection is confirmed if in one specimen there is a pure growth of more than 105 bacteria per microlitre. Lower counts of bacteria may be found persistently in urinary tract infection, particularly in boys [bib_ref] Urinary infection in boys: a threeyear prospective study, Hallett [/bib_ref]. This will be an indication for repeating the culture or obtaining a suprapubic aspiration. Pyuria (>10 white blood cells per microlitre of uncentrifuged urine) is usually found in the presence of acute symptoms but is not diagnostic [bib_ref] The measurement and monitoring of pyuria, Stansfield [/bib_ref]. Pus cells suggest inflammation and may be a helpful indicator in the absence of genital inflammation or when antibiotics have already been prescribed. The absence of pus cells [bib_ref] Urine microscopy as an aid to detection of bacteriuria, Robins [/bib_ref] or the presence of a mixed growth of bacteria is evidence against, but does not exclude, an infection. A urinary infection can only be ruled out if a urine culture before treatment is sterile. Any growth on culture of a catheter or suprapubic specimen is usually clinically significant. The number of colonies of pathogens isolated from suprapubic specimens needs to be compared with results from clean-catch specimens (R).
Urine microscopy can make a useful contribution to diagnosis, especially when urgent treatment must be initiated without awaiting culture results. It has an acceptably low false negative rate and the technique is easily learnt [bib_ref] Urine microscopy as an aid to detection of bacteriuria, Robins [/bib_ref].
The nitrite test is a reliable sign of infection when positive but has up to a 48% false negative rate [bib_ref] Urinary nitrite in symptomatic and asymptomatic urinary infections, Powell [/bib_ref] ; other studies have shown a substantially lower false negative rate [bib_ref] Dipstick analysis for screening of paediatric urine, Borland [/bib_ref]. A prerequisite of the test is that the urine must have been in the bladder for at least an hour so that there is time for bacterial conversion of nitrate into nitrite . If so, the false negative rate is considerably lower. In addition, routine bacteriological examination must always be performed (A). Other chemical tests, eg for hypoglycosuria, are less satisfactory [bib_ref] Screening methods for covert bacteriuria in schoolgirls, Edwards [/bib_ref]. Although proteinuria occurs in advanced reflux nephropathy [bib_ref] End-stage reflux nephropathy, Bailey [/bib_ref] , it is not diagnostic of acute urinary infection (R).

## Specimen transport
The specimen of urine should ideally be collected in a sterile container, chilled immediately to 4?C and examined in the laboratory within 2 hours (A). The method and time of collection must be stated on the , pathology request to enable the microbiologist to give an accurate opinion (A). An alternative is to refrigerate the specimen at 4?C in the main compartment of a domestic refrigerator for at most 48 hours before examination. The temperature of the general practice refrigerator should be checked regularly (A).
Another possibility is to transport the urine in 1.8% boric acid, but the correct amount of urine must be added to the bottle to ensure the correct concentration of boric acid (A). There are some data [bib_ref] Boric acid preservation of urine samples, Porter [/bib_ref] which suggest that boric acid preserves pus cells and bacteria, and does not inhibit the growth of pathogens, but more research is needed in this area in children (R).

## Dipslide
The dipslide is a miniature culture plate which is immersed in the urine immediately after voiding. This eliminates the delay so often incurred during transport of the specimen to the laboratory. It has been fully tested in 'field' conditions amongst primary schoolgirls who collected their own samples at home without vulval cleansing. This study showed a nil false negative rate, together with an acceptably low false positive rate [bib_ref] Screening methods for covert bacteriuria in schoolgirls, Edwards [/bib_ref].
Dipslides can also be inoculated by voiding urine directly on to the culture medium ('Dipstream'); this makes the method simpler and cheaper but yields a somewhat higher false positive rate; this can be minimised by disregarding micro-organisms such as coagulase negative staphylococci which are not recognised as common urinary pathogens in childhood [bib_ref] Screening methods for covert bacteriuria in schoolgirls, Edwards [/bib_ref]. However, this method has the disadvantage that it does not provide a urine specimen for microscopy. Dipslides have failed to gain popularity in practice perhaps because their comparatively short shelf life (A) precludes bulk purchase by general practitioners. Nevertheless, they are an efficient and reliable means of documenting bacteriuria before treatment is initiated. Management of the infant or child with acute symptomatic urinary tract infection Management is greatly helped by detailed discussion with the parents and child, supplemented by written guidelines (Appendix 2).
After an appropriate specimen of urine has been obtained, treatment should immediately be started, especially in infants under 2 years old, with the 'best guess' antibacterial agent in full dosage (A). It can be changed if necessary after 48 hours when drug sensitivities of the organism are available or if there has been no clinical response (A). Drugs suitable for oral administration for short full-dose courses include cotrimoxazole, trimethoprim, nitrofurantoin and orally administered cephalosporins. The sulphonamide component of co-trimoxazole is more likely to result in adverse effects, but resistance to trimethoprim in the community may be higher [bib_ref] Trimethoprim resistance and single agent use, Maskell [/bib_ref]. However, the Working Group did not reach consensus on this point as some members held that co-trimoxazole and trimethoprim were no different in tolerance, compliance, side effects or emergence of resistance [bib_ref] Prophylactic co-trimoxazole in the management of urinary tract infections in children, Smellie [/bib_ref]. Resistance of urinary pathogens to amoxycillin, even in primary care, is currently too high for this drug to be used as a first choice (A). A course of 5-7 days is usually prescribed but the optimum length of treatment is not known (R). After the short course of treatment the urine should be examined to ensure that the infection has been eradicated (A). Prophylactic antibiotics should not be stopped while the urine is collected (A). A low dose of a suitable antibacterial drug should be continued prophylactically at least until investigation of the urinary tract has been completed. The drug dose should be adjusted to the child's weight (A). Agents currently suitable for prophylaxis include trimethoprim (1-2 mg/kg/day), co-trimoxazole (trimethoprim 1-2 mg and sulphamethoxazole 5-10 mg/kg/day) and nitrofurantoin (1 mg/kg/day). Amoxycillin is not satisfactory (A). To reduce the risk of dental decay, liquid preparations of these drugs must be sugar-free and must not be diluted with sugarcontaining diluents. In children with minor symptoms it is acceptable to wait for the results of the urine culture (which may need to be repeated) before starting treatment.
In children under [bib_ref] The long-term followup of surgically treated vesico-ureteric reflux, Wallace [/bib_ref] should be collected except from children who presented with obvious symptoms, for example those over 5 years old with dysuria, or fever and malaise. The reason for this suggestion is that there is evidence that asymptomatic urinary infection without scars does not affect prognosis, although there may be some slight decline in renal function in adult life [bib_ref] The effects of covert bacteriuria in schoolgirls on renal function at 18..., Davison [/bib_ref]. However, following the use of antibiotics for other infections in the presence of asymptomatic bacteriuria, the child is more likely subsequently to be infected with a more virulent organism [bib_ref] Untreated asymptomatic bacteriuria in girls; 1: Stability of urinary isolates, Hansson [/bib_ref] [bib_ref] Untreated asymptomatic bacteriuria in girls; II: Effect of phenoxymethylpenicillin and erythromycin given..., Hansson [/bib_ref]. The long-term management of children with recurrent infection, renal scars or vesicoureteric reflux was not discussed by the Working Group.

## Imaging studies
As a significant number of important abnormalities will be detected in both sexes, all children diagnosed as having a urinary tract infection should have some form of imaging after the first proved infection [bib_ref] Investigation of urinary tract infection, Haycock [/bib_ref]. Although guidance on the most suitable types of imaging in the various age groups was agreed by the majori- The results of ultrasound scanning depend on the experience and skill of the operator (A); small focal scars may not be detected even by the best operator [bib_ref] Sonography as a substitute for excretion urography in children with urinary tract..., Leonidas [/bib_ref]. Such small scars in older children may not be of therapeutic importance, since the risk of further scarring developing after 7 years of age is small (R) [bib_ref] Development of new renal scars: a collaborative study, Smellie [/bib_ref]. The IVU produces poor renal outlines in the first year of life, even when the staff are experienced (R). It can provide information on pelvicalyceal appearances and ureteric calibre, and sometimes a reduced nephrogram or enlargement of the affected kidney can be seen.

## ?
In some cases an abnormality shown on DMSA scanning (due to hypoperfusion) shortly after the beginning of an infection has resolved 3 months later [bib_ref] The DMSA scan and intravenous urography in the detection of renal scarring, Smellie [/bib_ref] [bib_ref] Serial DMSA scans after urinary infections presenting before the age of 5..., Verber [/bib_ref]. These early reversible changes may indicate a vulnerable kidney or may be of no clinical importance (R). An IVU performed during an acute infection may fail to detect the inflammatory change preceding a scar (R).
? Units carrying out these investigations may not have enough patients to provide appropriate experience (A).
The contrast micturating cystourethrogram (MCU) is the only technique that shows the urethra or reflux into the lower third of the ureter, but it does require a urethral catheter. The radiation dosage is about twenty times the dose of a direct radionuclide cystogram (DRC) which uses a radioactive tracer instead of contrast medium [bib_ref] Radionuclide cystography in the investigation of vesico-ureteric reflux in children, Rothwell [/bib_ref] [fig_ref] Table 1: Comparison of radiation dosage sustained in the course of various imaging procedures... [/fig_ref]. The indirect radionuclide cystogram (IRC) is particularly useful in the toilet-trained child because the tracer is given intravenously and does not involve inserting a catheter into the bladder. The DRC has higher sensitivity than the MCU for detection of vesicoureteric reflux [bib_ref] Effectiveness of direct and indirect radionuclide cystography in detecting vesico-ureteral reflux, Conway [/bib_ref] [bib_ref] Radionuclide voiding cystography, Willi [/bib_ref] When to suspect urinary tract infection in a child or baby Your child or baby may have infected urine without having the fishy smell and burning pain on passing urine that occurs in adults with cystitis. In a baby or toddler you should think of urinary infection if your child is unwell and has a high temperature, unless there is clear evidence for some other explanation. You should also think of it in a baby that has repeated bouts of fever, or vomiting, jaundice or poor weight gain, and, of course, in any child that does have symptoms related to passing urine.
What to do if you think your child might have a urine infection It is important to treat urinary tract infection quickly, particularly in very young children because prolonged infection may make them quite ill, and delay in treatment may damage the kidneys. You should contact your doctor as soon as you suspect that your baby or child might have infected urine and ask for an urgent appointment and urine test.

## How to diagnose urinary tract infection
Urinary infection can only be diagnosed with certainty if a clean urine sample is collected in a sterile container and sent without delay to the laboratory for examination. The full result will not be available for 48 hours. In babies and toddlers an adhesive plastic bag can be used to collect the sample.

## Treatment
In babies and toddlers who are unwell and any child with distressing symptoms, your doctor will not wait for the laboratory results but will straight away start treatment with antibiotic, most commonly Trimethoprim. It may be necessary to change the antibiotic after 48 hours if the child is not obviously better. In this case the laboratory result will probably show that the germ causing the infection is not sensitive to the antibiotic first chosen, and will also indicate what other antibiotic to choose. Full treatment should be continued for 5-10 days; after that, all children under 5, and older children who have been quite unwell, should continue to take a small regular dose of antibiotic (Nitrofurantoin or Trimethoprim) until the kidneys and bladder have been checked.
What to expect after treatment Doctors believe that all young children who have had a urinary tract infection should have simple tests to check the kidneys and bladder are normal. If any abnormality is found, suitable tests will be arranged.
For children the tests should include an ulrasound scan of the kidneys (like the scans used to measure the baby during pregnancy) and an x-ray to show the kidneys. Further tests will be necessary in very young children and when the ultrasound scan is abnormal.
Older children with recurrent distressing symptoms may also need further tests. When the tests have been completed make sure that you understand the results, and the reason why further tests and treatment may be necessary.
What may happen in the future Boys rarely get further infections, and if they do, it usually happens quite soon after the first one. But girls often do get further infections. It does not necessarily mean that there is something seriously wrong, but it might be an indication for further investigation and a new treatment plan. In some children, long-term, low dose antibiotic treatment is used to reduce the risk of further infections, particularly in very young children who may have some abnormality of the urinary tract (such as vesicoureteric reflux). Ask enough questions so that you understand the reasons for your child's need for prolonged treatment and can help your child to get better.
1. Encourage regular bladder emptying 4 hourly or before each meal and before going to bed. 2. To make sure that the bladder is completely empty ask your child to try again after 5-10 minutes. 3. Treat constipation adequately with diet and laxatives. [bib_ref] Outcome of childhood vesico-ureteric reflux and urinary tract infection: a follow-up study..., Smellie [/bib_ref]. Avoid tight trousers. 5. Bath regularly, dry carefully afterwards. 6. Avoid highly scented soap, do not use bubble bath or wash hair in the bath. [bib_ref] Natural history of pyelonephritic scarring, Hodson [/bib_ref]. Wipe bottom clean from front to back.. Use soft absorbant toilet paper.
10 Ensure easy access to satisfactory toilets at school. [bib_ref] Urinary infection in boys: a threeyear prospective study, Hallett [/bib_ref]. Treat thrush and thread worms.
[table] Table 1: Comparison of radiation dosage sustained in the course of various imaging procedures of the urinary tract in child- [/table]
[table] .: Many institutions have compared the IRC with both the MCU and the DRC In six reported studies, the sensitivity of the IRC is as good as that of the DRC and the MCU[36,37] Only one study reported poor results for the IRC[38]The Working Group agreed that all boys having their first cystourethrogram should have an MCU (A)If nuclear medicine facilities are available, the DRC has the advantage of a lower radiation dose The IRC is particularly useful for studies in older children to The Research Unit of the Royal College of Physicians is supported in part by the Wolfson and Welton Foundations The Working Group thanks Dr I Gordon and Mr K Evans of the Hospital for Sick Children, London, for preparingTable 1 [/table]