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Evidence Basis for Individualized Evaluation and Less Imaging in Febrile Urinary Tract Infection
Evidence Basis for Individualized E v aluatio n an d L es s I m a gi n g i n F e b r i l e U r i n a r y Tr a c t I n f e c t i o n An Editorial Commentary Thomas B. Newman,
MD, MPH
a,
*
KEYWORDS Urinary tract infection Vesicoureteral reflux Voiding cystourethrogram Urine testing KEY POINTS The past decade has seen a remarkable retreat from previous dogma regarding urinary tract infections (UTIs). The lack of evidence that treatment affects long term outcomes suggests urine testing decisions should be based primarily on patient preferences and estimated short-term benefits. Short-term benefits of diagnosing UTIs are limited in children with mild illness, because most UTIs resolve without treatment. An individualized approach to urine testing that is less aggressive than previous recommendations is warranted.
In this issue Drs Koyle and Shifrin1 provided a thoughtful review on febrile urinary tract infections (UTIs) in children, acknowledging the uncertainty around many of the questions we used to think we knew the answers to. They concluded that there is not a single algorithm that fits all patients and that clinicians and parents should have an open and cooperative approach. I would like to expand on that conclusion in this commentary and focus on febrile infants younger than 2 years, for whom decisions are most difficult because the children cannot reliably report UTI symptoms, and obtaining the urine sample from this age group is often time consuming and unpleasant.
This editorial commentary was written in response to the article by Drs Martin Koyle and Donald Shifrin, entitled “Issues in Febrile Urinary Tract Infection Management” in Pediatric Clinics of North America (59:4), August 2012. a Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA 94143, USA * Department of Epidemiology & Biostatistics, UCSF Box 0560, San Francisco, CA 94143. E-mail address: [email protected] Pediatr Clin N Am 59 (2012) 923–926 doi:10.1016/j.pcl.2012.05.016 pediatric.theclinics.com 0031-3955/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.
924
Newman
It is clear from recent studies highlighted in Koyle and Shifrin’s review that the past decade has seen a remarkable retreat from previous dogmas regarding UTIs. There are no good data demonstrating a relationship between febrile UTIs and subsequent renal diseases, and if there is such a relationship, it must be weak.2,3 Although we know that vesicoureteral reflux (VUR) is frequently found in children with a history of febrile UTIs, we admit that most VUR resolves spontaneously and that we do not have evidence as to whether treatment of the rest improves outcome.4 These changes in the outlook toward UTIs are reflected in new, more conservative imaging recommendations, but their implications have not yet been sufficiently appreciated for the decisions pediatricians face most often when evaluating a young child with a fever: whether to obtain a urine sample, and if so, how to do so. The decision to obtain a urine sample for testing should be based on both the probability of UTI and the projected health benefit of diagnosing it at the current visit. The former can be estimated by considering clinical and demographic risk factors, including absence of another likely source for the fever, fever duration, race, sex, and circumcision status.4,5 The health benefit of early diagnosis of UTI is the improvement in health outcomes that can be accomplished by treatment. Now that we acknowledge that we do not know the extent to which imaging or treatment of UTI actually prevents late adverse outcomes, we can focus on short-term outcomes, such as reduction of symptoms and prevention of immediate complications, such as sepsis or meningitis. Because febrile UTIs are easily treated, the benefit of reducing symptoms is directly related to symptom severity. Patients who present with high temperature, flank pain, and longer duration of illness (suggesting that their UTI is not resolving spontaneously) have the most to gain from having their UTIs diagnosed and treated sooner. Serious complications of UTI, such as bacteremia and meningitis, are rare and largely seen in infants younger than 6 months, especially those younger than 2 months.6–8 It makes sense to test more aggressively for UTI in these infants. What happens to children in whom a UTI is initially missed? In a prospective study of 15,781 episodes of febrile illness in children younger than 5 years, even those children whose bacterial infections were not initially diagnosed and treated did well.9 Data from the Pediatric Research in Office Settings (“PROS”) Febrile Infant Study suggest that even in the highest risk 0- to 3-month age group (in whom I recommend urine testing), the outcome is generally benign.6 In this study, there were 807 infants aged 0 to 3 months with a temperature greater than or equal to 38 C, whose practitioners did not initially order for any urine tests, who were not initially treated with antibiotics, and were followed up until resolution of their illness. Based on the demographic and clinical risk factors for UTI recorded at their initial visit, about 61 patients (7.6%) would have had a UTI diagnosed if a urine test had been ordered. However, only 2 patients were diagnosed with UTI; both were treated and did well. The other approximately 59 infants (97%) recovered uneventfully, without ever having their UTIs diagnosed. Given this benign outcome in a group at highest risk of complications, it seems that the short-term risk of failing to diagnose UTI at the initial clinic visit is extremely low. Hence, the benefit of early diagnosis of UTI is primarily the opportunity to reduce symptoms sooner and prevent a small number of return visits for persistent fever. An open question is at what risk of UTI these modest benefits justify the cost, discomfort, and inconvenience of urine testing, as well as the accompanying risk of false-positive results. The American Academy of Pediatrics practice guideline suggests that this point is 1% to 2%, implying that it is worth performing urine tests on 50 to 100 children to identify a UTI (sooner) in 1 child. This seems like a very low threshold (and high number needed to test) to me.10 However, this threshold varies
Febrile Urinary Tract Infection
with the treatment and risk preferences of the family and clinician, as suggested by Drs Koyle and Shifrin. Families and clinicians will also have a range of preferences regarding the relative value of a more accurate urine culture result obtainable by urethral catheterization weighed against the invasiveness of the procedure11 and the risk of introducing a UTI.12,13 Greater certainty is required if the consequence of a positive culture is to be imaging, particularly with a voiding cystourethrogram (VCUG). On the other hand, if the main decision made as a result of the urine culture is whether to discontinue antibiotics (already started because of a positive urinalysis result), it may not be worth doing about 20 urethral catheterizations to avoid administering antibiotics for an additional 8 days in 1 child.14 SUMMARY
There is growing consensus that most infants and children with UTI do not need invasive imaging, at least initially.15–19 The importance of ultrasonography and VCUG after recurrence of UTI is uncertain.10,17 The weak and uncertain relationship between diagnosing and treating UTI and the prevention of future renal diseases suggests that decisions about whether and how to obtain urine samples should depend on estimated shortterm benefits3 and patient values. As stated by Koyle and Shifrin, while guidelines can be helpful, “they should not serve as rigid rules requiring emphatic adherence.” REFERENCES
1. Craig JC, Irwig LM, Knight JF, et al. Does treatment of vesicoureteric reflux in childhood prevent end-stage renal disease attributable to reflux nephropathy? Pediatrics 2000;105:1236–41. 2. Salo J, Ikaheimo R, Tapiainen T, et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics 2011;128:840–7. 3. Craig JC, Williams GJ. Denominators do matter: it’s a myth—urinary tract infection does not cause chronic kidney disease. Pediatrics 2011;128:984–5. 4. Finnell S, Downs S, Carroll A. Technical report: the diagnosis and management of the initial urinary tract infection in febrile infants and young children. Pediatrics 2011;128:e749–70. 5. Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA 2007;298:2895–904. 6. Newman TB, Bernzweig JA, Takayama JI, et al. Urine testing and urinary tract infections in febrile infants seen in office settings: the Pediatric Research in Office Settings’ Febrile Infant Study. Arch Pediatr Adolesc Med 2002;156:44–54. 7. Schnadower D, Kuppermann N, Macias CG, et al. Febrile infants with urinary tract infections at very low risk for adverse events and bacteremia. Pediatrics 2010;126:1074–83. 8. Herz AM, Greenhow TL, Alcantara J, et al. Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J 2006;25: 293–300. 9. Craig JC, Williams GJ, Jones M, et al. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses. BMJ 2010;340:c1594. 10. Newman TB. The new American Academy of Pediatrics urinary tract infection guideline. Pediatrics 2011;128(3):572–5.
925
926
Newman
11. Merritt KA, Ornstein PA, Spicker B. Children’s memory for a salient medical procedure: implications for testimony. Pediatrics 1994;94:17–23. 12. Lohr JA, Downs SM, Dudley S, et al. Hospital-acquired urinary tract infections in the pediatric patient: a prospective study. Pediatr Infect Dis J 1994;13:8–12. 13. Lohr JA, Portilla MG, Geuder TG, et al. Making a presumptive diagnosis of urinary tract infection by using a urinalysis performed in an on-site laboratory. J Pediatr 1993;122:22–5. 14. Schroeder AR, Newman TB, Wasserman RC, et al. Choice of urine collection methods for the diagnosis of urinary tract infection in young, febrile infants. Arch Pediatr Adolesc Med 2005;159:915–22. 15. Newman TB. Evidence does not support American Academy of Pediatrics recommendation for routine imaging after a first urinary tract infection. Pediatrics 2005;116:1613–4. 16. Newman TB. Much pain, little gain from voiding cystourethrograms after urinary tract infection. Pediatrics 2006;118:2251. 17. National Collaborating Centre for Women’s and Children’s Health. Urinary tract infection in children: diagnosis, treatment and long-term management. National Institute for Health and Clinical Excellence Clinical Guideline. London: RCOG Press; 2007. 18. Schroeder AR, Abidari JM, Kirpekar R, et al. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Arch Pediatr Adolesc Med 2011;165:1027–32. 19. Schroeder AR, Harris SJ, Newman TB. Safely doing less: a missing component of the patient safety dialogue. Pediatrics 2011;128:e1596–7.
MD, MPH
a,
*
KEYWORDS Urinary tract infection Vesicoureteral reflux Voiding cystourethrogram Urine testing KEY POINTS The past decade has seen a remarkable retreat from previous dogma regarding urinary tract infections (UTIs). The lack of evidence that treatment affects long term outcomes suggests urine testing decisions should be based primarily on patient preferences and estimated short-term benefits. Short-term benefits of diagnosing UTIs are limited in children with mild illness, because most UTIs resolve without treatment. An individualized approach to urine testing that is less aggressive than previous recommendations is warranted.
In this issue Drs Koyle and Shifrin1 provided a thoughtful review on febrile urinary tract infections (UTIs) in children, acknowledging the uncertainty around many of the questions we used to think we knew the answers to. They concluded that there is not a single algorithm that fits all patients and that clinicians and parents should have an open and cooperative approach. I would like to expand on that conclusion in this commentary and focus on febrile infants younger than 2 years, for whom decisions are most difficult because the children cannot reliably report UTI symptoms, and obtaining the urine sample from this age group is often time consuming and unpleasant.
This editorial commentary was written in response to the article by Drs Martin Koyle and Donald Shifrin, entitled “Issues in Febrile Urinary Tract Infection Management” in Pediatric Clinics of North America (59:4), August 2012. a Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA 94143, USA * Department of Epidemiology & Biostatistics, UCSF Box 0560, San Francisco, CA 94143. E-mail address: [email protected] Pediatr Clin N Am 59 (2012) 923–926 doi:10.1016/j.pcl.2012.05.016 pediatric.theclinics.com 0031-3955/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.
924
Newman
It is clear from recent studies highlighted in Koyle and Shifrin’s review that the past decade has seen a remarkable retreat from previous dogmas regarding UTIs. There are no good data demonstrating a relationship between febrile UTIs and subsequent renal diseases, and if there is such a relationship, it must be weak.2,3 Although we know that vesicoureteral reflux (VUR) is frequently found in children with a history of febrile UTIs, we admit that most VUR resolves spontaneously and that we do not have evidence as to whether treatment of the rest improves outcome.4 These changes in the outlook toward UTIs are reflected in new, more conservative imaging recommendations, but their implications have not yet been sufficiently appreciated for the decisions pediatricians face most often when evaluating a young child with a fever: whether to obtain a urine sample, and if so, how to do so. The decision to obtain a urine sample for testing should be based on both the probability of UTI and the projected health benefit of diagnosing it at the current visit. The former can be estimated by considering clinical and demographic risk factors, including absence of another likely source for the fever, fever duration, race, sex, and circumcision status.4,5 The health benefit of early diagnosis of UTI is the improvement in health outcomes that can be accomplished by treatment. Now that we acknowledge that we do not know the extent to which imaging or treatment of UTI actually prevents late adverse outcomes, we can focus on short-term outcomes, such as reduction of symptoms and prevention of immediate complications, such as sepsis or meningitis. Because febrile UTIs are easily treated, the benefit of reducing symptoms is directly related to symptom severity. Patients who present with high temperature, flank pain, and longer duration of illness (suggesting that their UTI is not resolving spontaneously) have the most to gain from having their UTIs diagnosed and treated sooner. Serious complications of UTI, such as bacteremia and meningitis, are rare and largely seen in infants younger than 6 months, especially those younger than 2 months.6–8 It makes sense to test more aggressively for UTI in these infants. What happens to children in whom a UTI is initially missed? In a prospective study of 15,781 episodes of febrile illness in children younger than 5 years, even those children whose bacterial infections were not initially diagnosed and treated did well.9 Data from the Pediatric Research in Office Settings (“PROS”) Febrile Infant Study suggest that even in the highest risk 0- to 3-month age group (in whom I recommend urine testing), the outcome is generally benign.6 In this study, there were 807 infants aged 0 to 3 months with a temperature greater than or equal to 38 C, whose practitioners did not initially order for any urine tests, who were not initially treated with antibiotics, and were followed up until resolution of their illness. Based on the demographic and clinical risk factors for UTI recorded at their initial visit, about 61 patients (7.6%) would have had a UTI diagnosed if a urine test had been ordered. However, only 2 patients were diagnosed with UTI; both were treated and did well. The other approximately 59 infants (97%) recovered uneventfully, without ever having their UTIs diagnosed. Given this benign outcome in a group at highest risk of complications, it seems that the short-term risk of failing to diagnose UTI at the initial clinic visit is extremely low. Hence, the benefit of early diagnosis of UTI is primarily the opportunity to reduce symptoms sooner and prevent a small number of return visits for persistent fever. An open question is at what risk of UTI these modest benefits justify the cost, discomfort, and inconvenience of urine testing, as well as the accompanying risk of false-positive results. The American Academy of Pediatrics practice guideline suggests that this point is 1% to 2%, implying that it is worth performing urine tests on 50 to 100 children to identify a UTI (sooner) in 1 child. This seems like a very low threshold (and high number needed to test) to me.10 However, this threshold varies
Febrile Urinary Tract Infection
with the treatment and risk preferences of the family and clinician, as suggested by Drs Koyle and Shifrin. Families and clinicians will also have a range of preferences regarding the relative value of a more accurate urine culture result obtainable by urethral catheterization weighed against the invasiveness of the procedure11 and the risk of introducing a UTI.12,13 Greater certainty is required if the consequence of a positive culture is to be imaging, particularly with a voiding cystourethrogram (VCUG). On the other hand, if the main decision made as a result of the urine culture is whether to discontinue antibiotics (already started because of a positive urinalysis result), it may not be worth doing about 20 urethral catheterizations to avoid administering antibiotics for an additional 8 days in 1 child.14 SUMMARY
There is growing consensus that most infants and children with UTI do not need invasive imaging, at least initially.15–19 The importance of ultrasonography and VCUG after recurrence of UTI is uncertain.10,17 The weak and uncertain relationship between diagnosing and treating UTI and the prevention of future renal diseases suggests that decisions about whether and how to obtain urine samples should depend on estimated shortterm benefits3 and patient values. As stated by Koyle and Shifrin, while guidelines can be helpful, “they should not serve as rigid rules requiring emphatic adherence.” REFERENCES
1. Craig JC, Irwig LM, Knight JF, et al. Does treatment of vesicoureteric reflux in childhood prevent end-stage renal disease attributable to reflux nephropathy? Pediatrics 2000;105:1236–41. 2. Salo J, Ikaheimo R, Tapiainen T, et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics 2011;128:840–7. 3. Craig JC, Williams GJ. Denominators do matter: it’s a myth—urinary tract infection does not cause chronic kidney disease. Pediatrics 2011;128:984–5. 4. Finnell S, Downs S, Carroll A. Technical report: the diagnosis and management of the initial urinary tract infection in febrile infants and young children. Pediatrics 2011;128:e749–70. 5. Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA 2007;298:2895–904. 6. Newman TB, Bernzweig JA, Takayama JI, et al. Urine testing and urinary tract infections in febrile infants seen in office settings: the Pediatric Research in Office Settings’ Febrile Infant Study. Arch Pediatr Adolesc Med 2002;156:44–54. 7. Schnadower D, Kuppermann N, Macias CG, et al. Febrile infants with urinary tract infections at very low risk for adverse events and bacteremia. Pediatrics 2010;126:1074–83. 8. Herz AM, Greenhow TL, Alcantara J, et al. Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J 2006;25: 293–300. 9. Craig JC, Williams GJ, Jones M, et al. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses. BMJ 2010;340:c1594. 10. Newman TB. The new American Academy of Pediatrics urinary tract infection guideline. Pediatrics 2011;128(3):572–5.
925
926
Newman
11. Merritt KA, Ornstein PA, Spicker B. Children’s memory for a salient medical procedure: implications for testimony. Pediatrics 1994;94:17–23. 12. Lohr JA, Downs SM, Dudley S, et al. Hospital-acquired urinary tract infections in the pediatric patient: a prospective study. Pediatr Infect Dis J 1994;13:8–12. 13. Lohr JA, Portilla MG, Geuder TG, et al. Making a presumptive diagnosis of urinary tract infection by using a urinalysis performed in an on-site laboratory. J Pediatr 1993;122:22–5. 14. Schroeder AR, Newman TB, Wasserman RC, et al. Choice of urine collection methods for the diagnosis of urinary tract infection in young, febrile infants. Arch Pediatr Adolesc Med 2005;159:915–22. 15. Newman TB. Evidence does not support American Academy of Pediatrics recommendation for routine imaging after a first urinary tract infection. Pediatrics 2005;116:1613–4. 16. Newman TB. Much pain, little gain from voiding cystourethrograms after urinary tract infection. Pediatrics 2006;118:2251. 17. National Collaborating Centre for Women’s and Children’s Health. Urinary tract infection in children: diagnosis, treatment and long-term management. National Institute for Health and Clinical Excellence Clinical Guideline. London: RCOG Press; 2007. 18. Schroeder AR, Abidari JM, Kirpekar R, et al. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Arch Pediatr Adolesc Med 2011;165:1027–32. 19. Schroeder AR, Harris SJ, Newman TB. Safely doing less: a missing component of the patient safety dialogue. Pediatrics 2011;128:e1596–7.