2. BY Moftah M. Rabeea Ped. Nephrology Al-Azhar Univ.

3. UTI

4.  UTI: Combination of clinical features and presence of bacteria in the urine.  Asymptomatic bacteriuria: Presence of bacteria in the urine but no symptoms.  Unresolved bacteriuria: Presence of the same organism and it is mainly due to inadequate antimicrobial therapy. Infection typically resolves after treatment based on C/S of urine.  Bacterial persistence: Re-infection with the same organism after sterilization of the urine has been documented (-ve culture). The nidus of infection in UT is not eradicated. Surgical intervention may be required to eradicate infection.  UTI: Combination of clinical features and presence of bacteria in the urine.  Asymptomatic bacteriuria: Presence of bacteria in the urine but no symptoms.  Unresolved bacteriuria: Presence of the same organism and it is mainly due to inadequate antimicrobial therapy. Infection typically resolves after treatment based on C/S of urine.  Bacterial persistence: Re-infection with the same organism after sterilization of the urine has been documented (-ve culture). The nidus of infection in UT is not eradicated. Surgical intervention may be required to eradicate infection.

5.  Recurrent UTI: Re-infection by different organisms documented on proper urine culture with each new UTI. You should suspect UT abnormalities specially in infants and young children.  Recurrence of infection:  Two or more episodes of acute pyelonephritis (upper UTI).  Three or more episodes of cystitis (lower UTI).  One episode of upper UTI + one or more episodes of cystitis.  Recurrent UTI: Re-infection by different organisms documented on proper urine culture with each new UTI. You should suspect UT abnormalities specially in infants and young children.  Recurrence of infection:  Two or more episodes of acute pyelonephritis (upper UTI).  Three or more episodes of cystitis (lower UTI).  One episode of upper UTI + one or more episodes of cystitis.

6. Atypical UTI includes:  Seriously ill child or infant.  Poor urine flow.  Abdominal or bladder mass.  Raised creatinine.  Septicaemia.  Failure to respond to treatment with suitable antibiotics within 48 hours.  Infection with non-E.coli organisms.  Seriously ill child or infant.  Poor urine flow.  Abdominal or bladder mass.  Raised creatinine.  Septicaemia.  Failure to respond to treatment with suitable antibiotics within 48 hours.  Infection with non-E.coli organisms.

7. Complicated infections are: A.Patients with pyelonephritis. B.Children with known mechanical or functional obstruction of the UT. C.All febrile infants especially neonates with suspected UTI are likely to be complicated and should be treated as such. Children with complicated UTI require hospitalization. Uncomplicated UTI:  Lower UTI  easily managed. Complicated infections are: A.Patients with pyelonephritis. B.Children with known mechanical or functional obstruction of the UT. C.All febrile infants especially neonates with suspected UTI are likely to be complicated and should be treated as such. Children with complicated UTI require hospitalization. Uncomplicated UTI:  Lower UTI  easily managed.

8. Risk factors for UTI:  Poor urine flow.  Neonates and young infants.  History suggesting previous UTI or confirmed previous UTI.  Recurrent fever of uncertain origin.  Antenatally diagnosed renal abnormality.  Family history of vesicoureteric reflux (VUR) or renal disease.  Constipation.  Foreskin.  Dysfunctional voiding.  Enlarged bladder or abdominal mass.  Evidence of spinal lesion.  Immunocompromised children.  High blood pressure. Risk factors for UTI:  Poor urine flow.  Neonates and young infants.  History suggesting previous UTI or confirmed previous UTI.  Recurrent fever of uncertain origin.  Antenatally diagnosed renal abnormality.  Family history of vesicoureteric reflux (VUR) or renal disease.  Constipation.  Foreskin.  Dysfunctional voiding.  Enlarged bladder or abdominal mass.  Evidence of spinal lesion.  Immunocompromised children.  High blood pressure.

9. Symptoms and signs suggesting UTI Infants < 3mo of age Infants and children 3mo or older but <3 years Children 3 years or older Gen. nonspecific symptom Specific “localizing” & nonspecific symptoms and signs Specific symptom and signs "common" Gen. nonspecific symptoms and signs "less common"

10. Urine-testing strategies for infants younger than 3 months:  All infants younger than 3 months with suspected UTI should be referred to paediatric specialist care.  Urine sample should be sent for urgent microscopy and culture.  IV antibiotics should be started. Urine-testing strategies for infants younger than 3 months:  All infants younger than 3 months with suspected UTI should be referred to paediatric specialist care.  Urine sample should be sent for urgent microscopy and culture.  IV antibiotics should be started.

11. Urine-testing for infants and children 3 months or older but younger than 3 years: Urgent microscopy and culture is the preferred method for diagnosing UTI in this age group. If the infant or child has specific urinary symptoms  Urgent microscopy and culture should be arranged and antibiotic treatment should be started.  When urgent microscopy is not available, a urine sample should be sent for microscopy and culture, and antibiotic treatment should be started. If the symptoms are non- specific to UTI  For an infant or child with a high, to intermediate risk of serious illness: the infant or child should be urgently referred to a pediatric specialist.  Urgent microscopy and culture for urine.  Antibiotic treatment (IV) should be started.  When urgent microscopy is not available, dipstick testing may act as a substitute. A positive test  infection.  For an infant or child with a low risk of serious illness: microscopy and culture should be arranged. Antibiotic treatment should only be started if microscopy or culture is positive.

12. Urine-testing for children 3 years or older. Dipstick testing for leucocyte esterase and nitrite is diagnostically as useful as microscopy and culture, and can safely be used. If both leucocyte esterase and nitrite are positive  The child should be regarded as having UTI and antibiotic treatment should be started.  If a child has a high or intermediate risk of serious illness, a urine samples should be sent for culture. If leucocyte esterase is negative and nitrite is positive  Antibiotic treatment should be started if fresh urine was tested.  A urine sample should be sent for culture.  Subsequent management will depend upon the result of urine culture.

13. Urine-testing for children 3 years or older (Cont. ). If leucocyte esterase is positive and nitrite is negative  A urine sample should be sent for microscopy and culture.  Antibiotic treatment should not be started unless there is good clinical evidences of UTI.  Leucocyte esterase may be indicative of an infection outside the urinary tract which may need to be managed differently. If both lucocyte esterase and nitrite are negative  The child should not be regarded as having UTI.  Antibiotic treatment for UTI should not be started, and a urine sample should not be sent for culture.  Other causes of illness should be explored.

14. Guidance on the interpretation of microscopy results: Microscopy results Pyuria positivePyuria negative Bacteriuria positive The infant or child should be regarded as having UTI Bacteriuria negative Antibiotic treatment should be started if clinically UTI The infant or child should be regarded as not having UTI

15. Indication for culture:  Diagnosis of acute pyelonephritis.  Presence of high to intermediate risk of serious illness.  In infants and children younger than 3 years.  A single positive result for leucocyte esterase or nitrite.  In infants and children with recurrent UTI.  Infection that does not respond to treatment within 24-48 hours.  When clinical symptoms and dipstick tests do not correlate. Indication for culture:  Diagnosis of acute pyelonephritis.  Presence of high to intermediate risk of serious illness.  In infants and children younger than 3 years.  A single positive result for leucocyte esterase or nitrite.  In infants and children with recurrent UTI.  Infection that does not respond to treatment within 24-48 hours.  When clinical symptoms and dipstick tests do not correlate.

16. Acute management: If there is a high risk of serious illness* or infant younger than 3 mo.  Immediately refer to hospital.  Urine for urgent microscopy and culture.  Treatment with broad spectrum parenteral antibiotics. If the infant or child is 3 months or older with acute pyelonephritis /upper UTI  Consider referral to paediatric.  Urine C/S if not already done.  Treat with oral antibiotics for 7-10 days.  If oral antibiotics cannot be used, refer to hospital for IV antibiotics for 2-4 days followed by oral antibiotics for a total duration of 10 days. If the infant or child is 3 months or older with cystitis/ lower UTI  Treat with oral antibiotics for 3 days.  If the child is still unwell after 24-48 hours they should be reassessed.  If no alternative diagnosis, send urine for culture. * If there is doubt about the level of risk of serious illness  manage as higher risk level.

17. Some empiric parenteral antibiotics in pediatric UTI. Drug Dose mg/kg/d Comment Ampicillin and Gentamicin 50-100 5-7 Monitor gentamicin level Ampecillin Cefotaxime 50-100 50-150 Cefotaxime and Ceftriaxone 50-150 50-75 No pseudomonas or enterococcus cover-age ceftriaxone is contraindicated in hyperbilirubinemia N.B.: Patients should be hospitalised

18. Some empiric oral antibiotics in pediatric UTI (out-patient) N.B.: If IV route is not available or there is emesis, intramuscular injection is indicated. Drug Dose mg/kg/d Comment TMP/SMX8 Contraindicated infant <2 mo. Amoxicillin40-50  resistance by E-coli Nitrofurantoin5-7 Not adequate in pyelonephritis Oral cephalosporins Cefixime Cephalexin Cefaclor 8 25-50 20 No enterococcus or pseudomonas coverage

19. Accurate imaging tests for assessing UTI: 1)Ultrasound  structure of UT. 2)MCUG and indirect radionuclide cystography  detection of VUR. 3)DMSA  detection of renal parenchymal defects. Accurate imaging tests for assessing UTI: 1)Ultrasound  structure of UT. 2)MCUG and indirect radionuclide cystography  detection of VUR. 3)DMSA  detection of renal parenchymal defects.

20. Recommended imaging schedule for infants younger than 6 months: Imaging Test Responds well to treatment within 48 hours A typical UTI Recurrent UTI Ultrasound during the acute infection NoYes Ultrasound within 6 weeks Yes*No DMSA 4-6 months following the acute infection NoYes MCUGNoYes * If abnormal consider MCUG

21. Recommended imaging schedule for infants and children 6 months or older but younger than 3 years. Test Responds well to treatment within 48 hours A typical UTI Recurrent UTI Ultrasound during the acute infection NoYesNo Ultrasound within 6 weeks No Yes DMSA 4-6 months following the acute infection NoYes MCUGNoNo* * Consider MCUG if: - U/S is abnormal. - Family history of VUR.- Poor urine flow. * Consider MCUG if: - U/S is abnormal. - Family history of VUR.- Poor urine flow.

22. Recommended imaging schedule for children 3 years or older: Test Responds well to treatment within 48 hours A typical UTI Recurrent UTI Ultrasound during the acute infection NoYesNo Ultrasound within 6 weeks No Yes DMSA 4-6 months following the acute infection No Yes MCUGNo

23. Prophylaxis I) Antibiotic prophylaxis is recommended in: Prophylaxis I) Antibiotic prophylaxis is recommended in:  Neonates and infants after treatment for first time UTI until thorough evaluation of UT, is completed.  Structural abnormalities of UT, VUR or urinary obstruction.  Functional abnormalities of UT.  Immunocompromised children.  Recurrent UTI even with normal anatomy and function of UT.  Atypical UTI. N.B.: Asymptomatic bacteriuria shouldn't be treated with prophylactic antibiotics.  Neonates and infants after treatment for first time UTI until thorough evaluation of UT, is completed.  Structural abnormalities of UT, VUR or urinary obstruction.  Functional abnormalities of UT.  Immunocompromised children.  Recurrent UTI even with normal anatomy and function of UT.  Atypical UTI. N.B.: Asymptomatic bacteriuria shouldn't be treated with prophylactic antibiotics.

24. Prophylactic antibiotics. Drug Dose mg/kg/d Comment Cephalexin2-3 Nitrofurantoin1-2 TMP/SMX1-2 Contraindicated in infant <2mo Ciprofloxacin--- Safety not accurately proved in children

25. II) Non-antibiotic strategy for preventing recurrence: The following steps can help in preventing recurrence of UTI:  Dysfunctional elimination syndromes and constipation should be addressed in infants and children who have had a UTI.  Children who have had a UTI should be encouraged to drink an adequate amount.  Children who have had a UTI should have ready access to clean toilets when required and should not be expected to delay voiding. II) Non-antibiotic strategy for preventing recurrence: The following steps can help in preventing recurrence of UTI:  Dysfunctional elimination syndromes and constipation should be addressed in infants and children who have had a UTI.  Children who have had a UTI should be encouraged to drink an adequate amount.  Children who have had a UTI should have ready access to clean toilets when required and should not be expected to delay voiding.

26. Significance of UTI in children: UTI can lead to:  Permanent renal parenchymal damage.  It is often a pointer to an associated UT malformations or VUR  Significant cause of ESRD in young adults.   incidence of hypertension.   incidence of toxemia of pregnancy and fetal loss. Significance of UTI in children: UTI can lead to:  Permanent renal parenchymal damage.  It is often a pointer to an associated UT malformations or VUR  Significant cause of ESRD in young adults.   incidence of hypertension.   incidence of toxemia of pregnancy and fetal loss.

27. Follow up:  Infants and children who do not undergo imaging should not routinely be followed up.  When results are normal, a follow-up outpatient appointment is not routinely required.  Infants and children who have recurrent UTI or abnormal imaging results should be assessed by a paediatric specialist.  Assessment of infants and children with renal parenchymal defects should include height, weight, blood pressure and routine testing for proteinuria. Follow up:  Infants and children who do not undergo imaging should not routinely be followed up.  When results are normal, a follow-up outpatient appointment is not routinely required.  Infants and children who have recurrent UTI or abnormal imaging results should be assessed by a paediatric specialist.  Assessment of infants and children with renal parenchymal defects should include height, weight, blood pressure and routine testing for proteinuria.

28.  Infants and children with a minor, unilateral renal parenchymal defect do not need long-term follow-up unless they have recurrent UTI or family history or risk factors for hypertension.  Infants and children who have bilateral renal abnormalities, impaired kidney function, raised blood pressure and/or proteinuria should be managed by a paediatric nephrologist.  Infants and children who are asymptomatic following an episode of UTI should not routinely have their urine re- tested for infection.  Asymptomatic bacteriuria is not an indication for follow-up.  Parents or carers should be informed of the results of all investigations in writing.  Infants and children with a minor, unilateral renal parenchymal defect do not need long-term follow-up unless they have recurrent UTI or family history or risk factors for hypertension.  Infants and children who have bilateral renal abnormalities, impaired kidney function, raised blood pressure and/or proteinuria should be managed by a paediatric nephrologist.  Infants and children who are asymptomatic following an episode of UTI should not routinely have their urine re- tested for infection.  Asymptomatic bacteriuria is not an indication for follow-up.  Parents or carers should be informed of the results of all investigations in writing.

29. Note:  You should maintain a high index of suspicion to diagnose UTI specially in neonates and infants.  UTI should be suspected in any infant or child with unexplained fever (38  C or more).  UTI must be considered in all children with serious illness even if there is a strong evidence of infection outside the UT.  Infants and children with UT abnormalities or VUR should be individually evaluated. Surgery may be indicated and early consultation is important. Note:  You should maintain a high index of suspicion to diagnose UTI specially in neonates and infants.  UTI should be suspected in any infant or child with unexplained fever (38  C or more).  UTI must be considered in all children with serious illness even if there is a strong evidence of infection outside the UT.  Infants and children with UT abnormalities or VUR should be individually evaluated. Surgery may be indicated and early consultation is important.

30. Patient flow pathway: Assess symptoms and sings.  Assess the risk of serious illness.  Test the urine using the method recommended according to the age of the infant or child and severity of illness.  Assess symptoms and signs to identify or exclude acute pyelonephritis.  Provide acute management according to age group and presence or absence of acute pyelonephritis.  Arrange imaging tests according to age, type of UTI and severity of illness.  Arrange follow up for infants and children with recurrent UTI, risk factors, atypical illness and abnormal imaging. Assess symptoms and sings.  Assess the risk of serious illness.  Test the urine using the method recommended according to the age of the infant or child and severity of illness.  Assess symptoms and signs to identify or exclude acute pyelonephritis.  Provide acute management according to age group and presence or absence of acute pyelonephritis.  Arrange imaging tests according to age, type of UTI and severity of illness.  Arrange follow up for infants and children with recurrent UTI, risk factors, atypical illness and abnormal imaging.