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Para el manejo de las ITUS

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  • 1. Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis andManagement of the Initial UTI in Febrile Infants and Children 2 to 24 Months SUBCOMMITTEE ON URINARY TRACT INFECTION and STEERING COMMITTEE ON QUALITY IMPROVEMENT AND MANAGEMENT Pediatrics; originally published online August 28, 2011; DOI: 10.1542/peds.2011-1330 The online version of this article, along with updated information and services, is located on the World Wide Web at: PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 2. FROM THE AMERICAN ACADEMY OF PEDIATRICSCLINICAL PRACTICE GUIDELINEUrinary Tract Infection: Clinical Practice Guideline forthe Diagnosis and Management of the Initial UTI inFebrile Infants and Children 2 to 24 MonthsSUBCOMMITTEE ON URINARY TRACT INFECTION, STEERINGCOMMITTEE ON QUALITY IMPROVEMENT AND MANAGEMENT abstractKEY WORDSurinary tract infection, infants, children, vesicoureteral reflux, OBJECTIVE: To revise the American Academy of Pediatrics practicevoiding cystourethrography parameter regarding the diagnosis and management of initial urinaryABBREVIATIONS tract infections (UTIs) in febrile infants and young children.SPA—suprapubic aspiration METHODS: Analysis of the medical literature published since the lastAAP—American Academy of PediatricsUTI—urinary tract infection version of the guideline was supplemented by analysis of data providedRCT—randomized controlled trial by authors of recent publications. The strength of evidence supportingCFU—colony-forming unit each recommendation and the strength of the recommendation wereVUR—vesicoureteral refluxWBC—white blood cell assessed and graded.RBUS—renal and bladder ultrasonography RESULTS: Diagnosis is made on the basis of the presence of bothVCUG—voiding cystourethrography pyuria and at least 50 000 colonies per mL of a single uropathogenicThis document is copyrighted and is property of the American organism in an appropriately collected specimen of urine. After 7 to 14Academy of Pediatrics and its Board of Directors. All authorshave filed conflict of interest statements with the American days of antimicrobial treatment, close clinical follow-up monitoringAcademy of Pediatrics. Any conflicts have been resolved through should be maintained to permit prompt diagnosis and treatment ofa process approved by the Board of Directors. The American recurrent infections. Ultrasonography of the kidneys and bladderAcademy of Pediatrics has neither solicited nor accepted anycommercial involvement in the development of the content of should be performed to detect anatomic abnormalities. Data from thethis publication. most recent 6 studies do not support the use of antimicrobial prophy-The recommendations in this report do not indicate an exclusive laxis to prevent febrile recurrent UTI in infants without vesicoureteralcourse of treatment or serve as a standard of medical care. reflux (VUR) or with grade I to IV VUR. Therefore, a voiding cystoure-Variations, taking into account individual circumstances, may be thrography (VCUG) is not recommended routinely after the first UTI;appropriate. VCUG is indicated if renal and bladder ultrasonography reveals hydro-All clinical practice guidelines from the American Academy ofPediatrics automatically expire 5 years after publication unless nephrosis, scarring, or other findings that would suggest either high-reaffirmed, revised, or retired at or before that time. grade VUR or obstructive uropathy and in other atypical or complex clinical circumstances. VCUG should also be performed if there is a recurrence of a febrile UTI. The recommendations in this guideline do not indicate an exclusive course of treatment or serve as a standard of care; variations may be appropriate. Recommendations about antimi- crobial prophylaxis and implications for performance of VCUG are based on currently available evidence. As with all American Academy of Pediatrics clinical guidelines, the recommendations will be routinely and incorporate new evidence, such as data from the Ran-doi:10.1542/peds.2011-1330 domized Intervention for Children With Vesicoureteral Reflux (RIVUR) study.PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).Copyright © 2011 by the American Academy of Pediatrics CONCLUSIONS: Changes in this revision include criteria for the diag-COMPANION PAPERS: Companions to this article can be found nosis of UTI and recommendations for imaging. Pediatrics 2011;128:on pages 572 and e749, and online at 595–610doi/10.1542/peds.2011-1818 and Volume 128, Number 3, September 2011 595 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 3. INTRODUCTION for use in a variety of clinical settings ness of prophylactic antimicrobialSince the early 1970s, occult bactere- (eg, office, emergency department, or therapy to prevent recurrence of fe-mia has been the major focus of con- hospital) by clinicians who treat in- brile UTI/pyelonephritis in childrencern for clinicians evaluating febrile fants and young children. This text is a with vesicoureteral reflux (VUR). Theinfants who have no recognizable summary of the analysis. The data on latter was based on the new and grow-source of infection. With the introduc- which the recommendations are ing body of evidence questioning thetion of effective conjugate vaccines based are included in a companion effectiveness of antimicrobial prophy-against Haemophilus influenzae type technical report.4 laxis to prevent recurrent febrile UTI inb and Streptococcus pneumoniae Like the 1999 practice parameter, this children with VUR. To explore this par-(which have resulted in dramatic de- revision focuses on the diagnosis and ticular issue, the literature search wascreases in bacteremia and meningi- management of initial urinary tract in- expanded to include trials publishedtis), there has been increasing appre- fections (UTIs) in febrile infants and since 1993 in which antimicrobial pro-ciation of the urinary tract as the most young children (2–24 months of age) phylaxis was compared with no treat-frequent site of occult and serious bac- who have no obvious neurologic or an- ment or placebo treatment for chil-terial infections. Because the clinical atomic abnormalities known to be as- dren with VUR. Because all except 1 ofpresentation tends to be nonspecific in sociated with recurrent UTI or renal the recent randomized controlled tri-infants and reliable urine specimens damage. (For simplicity, in the remain- als (RCTs) of the effectiveness of pro-for culture cannot be obtained without der of this guideline the phrase “fe- phylaxis included children more thaninvasive methods (urethral cathe- brile infants” is used to indicate febrile 24 months of age and some did notterization or suprapubic aspiration infants and young children 2–24 provide specific data according to[SPA]), diagnosis and treatment may months of age.) The lower and upper grade of VUR, the authors of the 6 RCTsbe delayed. Most experimental and age limits were selected because stud- were contacted; all provided raw dataclinical data support the concept that ies on infants with unexplained fever from their studies specifically ad-delays in the institution of appropriate generally have used these age limits dressing infants 2 to 24 months of age,treatment of pyelonephritis increase and have documented that the preva- according to grade of VUR. Meta-the risk of renal damage.1,2 lence of UTI is high (ϳ5%) in this age analysis of these data was performed.This clinical practice guideline is a re- group. In those studies, fever was de- Results from the literature searchesvision of the practice parameter pub- fined as temperature of at least 38.0°C and meta-analyses were provided tolished by the American Academy of (Ն100.4°F); accordingly, this definition committee members. Issues werePediatrics (AAP) in 1999.3 It was devel- of fever is used in this guideline. Ne- raised and discussed until consensusoped by a subcommittee of the Steer- onates and infants less than 2 was reached regarding recommenda-ing Committee on Quality Improvement months of age are excluded, because tions. The quality of evidence support-and Management that included physi- there are special considerations in ing each recommendation and thecians with expertise in the fields of ac- this age group that may limit the ap- strength of the recommendation wereademic general pediatrics, epidemiol- plication of evidence derived from assessed by the committee memberogy and informatics, pediatric the studies of 2- to 24-month-old chil- most experienced in informatics andinfectious diseases, pediatric nephrol- dren. Data are insufficient to deter- epidemiology and were graded ac-ogy, pediatric practice, pediatric radi- mine whether the evidence gener- cording to AAP policy5 (Fig 1).ology, and pediatric urology. The AAP ated from studies of infants 2 to 24 The subcommittee formulated 7 rec-funded the development of this guide- months of age applies to children ommendations, which are presentedline; none of the participants had any more than 24 months of age. in the text in the order in which a clini-financial conflicts of interest. The cian would use them when evaluatingguideline was reviewed by multiple METHODS and treating a febrile infant, as well asgroups within the AAP (7 committees, 1 To provide evidence for the guideline, 2 in algorithm form in the Appendix. Thiscouncil, and 9 sections) and 5 external literature searches were conducted, clinical practice guideline is not in-organizations in the United States and that is, a surveillance of Medline-listed tended to be a sole source of guidanceCanada. The guideline will be reviewed literature over the past 10 years for for the treatment of febrile infants withand/or revised in 5 years, unless new significant changes since the guideline UTIs. Rather, it is intended to assist clini-evidence emerges that warrants revi- was published and a systematic re- cians in decision-making. It is not in-sion sooner. The guideline is intended view of the literature on the effective- tended to replace clinical judgment or to596 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 4. FROM THE AMERICAN ACADEMY OF PEDIATRICS tainer, because they may be contami- nated by bacteria in the distal urethra. Cultures of urine specimens collected in a bag applied to the perineum have an unacceptably high false-positive rate and are valid only when they yield negative results.6,14–16 With a preva- lence of UTI of 5% and a high rate of false-positive results (specificity: ϳ63%), a “positive” culture result forFIGURE 1 urine collected in a bag would be aAAP evidence strengths. false-positive result 88% of the time. For febrile boys, with a prevalence of UTI of 2%, the rate of false-positive re-establish an exclusive protocol for the administered, because the antimicro- sults is 95%; for circumcised boys,care of all children with this condition. bial agents commonly prescribed in with a prevalence of UTI of 0.2%, the such situations would almost certainly rate of false-positive results is 99%.DIAGNOSIS obscure the diagnosis of UTI. Therefore, in cases in which antimicro-Action Statement 1 SPA has been considered the standard bial therapy will be initiated, catheter-If a clinician decides that a febrile method for obtaining urine that is un- ization or SPA is required to establishinfant with no apparent source for contaminated by perineal flora. Vari- the diagnosis of UTI.the fever requires antimicrobial able success rates for obtaining urine ● Aggregate quality of evidence: A (diag-therapy to be administered be- have been reported (23%–90%).6–8 nostic studies on relevant populations).cause of ill appearance or another When ultrasonographic guidance ispressing reason, the clinician used, success rates improve.9,10 The ● Benefits: A missed diagnosis of UTIshould ensure that a urine speci- technique has limited risks, but tech- can lead to renal scarring if left un-men is obtained for both culture nical expertise and experience are treated; overdiagnosis of UTI canand urinalysis before an antimicro- required, and many parents and phy- lead to overtreatment and unneces-bial agent is administered; the sicians perceive the procedure as sary and expensive imaging. Once an-specimen needs to be obtained unacceptably invasive, compared timicrobial therapy is initiated, the op-through catheterization or SPA, be- with catheterization. However, there portunity to make a definitivecause the diagnosis of UTI cannot may be no acceptable alternative to diagnosis is lost; multiple studies ofbe established reliably through cul- SPA for boys with moderate or se- antimicrobial therapy have shownture of urine collected in a bag vere phimosis or girls with tight la- that the urine may be rapidly(evidence quality: A; strong bial adhesions. sterilized.recommendation). Urine obtained through catheteriza- ● Harms/risks/costs: CatheterizationWhen evaluating febrile infants, clini- tion for culture has a sensitivity of 95% is invasive.cians make a subjective assessment of and a specificity of 99%, compared ● Benefit-harms assessment: Prepon-the degree of illness or toxicity, in ad- with that obtained through SPA.7,11,12 derance of benefit over harm.dition to seeking an explanation for the The techniques required for catheter- ● Value judgments: Once antimicro-fever. This clinical assessment deter- ization and SPA are well described.13 bial therapy has begun, the opportu-mines whether antimicrobial therapy When catheterization or SPA is being attempted, the clinician should have a nity to make a definitive diagnosis isshould be initiated promptly and af- sterile container ready to collect a lost. Therefore, it is important tofects the diagnostic process regardingUTI. If the clinician determines that the urine specimen, because the prepara- have the most-accurate test for UTIdegree of illness warrants immediate tion for the procedure may stimulate performed initially.antimicrobial therapy, then a urine the child to void. Whether the urine is ● Role of patient preferences: There isspecimen suitable for culture should obtained through catheterization or is no evidence regarding patient pref-be obtained through catheterization or voided, the first few drops should be erences for bag versus catheterizedSPA before antimicrobial agents are allowed to fall outside the sterile con- urine. However, bladder tap hasPEDIATRICS Volume 128, Number 3, September 2011 597 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 5. been shown to be more painful than urethral catheterization.● Exclusions: None.● Intentional vagueness: The basis of the determination that antimicro- bial therapy is needed urgently is not specified, because variability in clinical judgment is expected; con- siderations for individual patients, such as availability of follow-up care, may enter into the decision, FIGURE 2 and the literature provides only gen- Probability of UTI Among Febrile Infant Girls28 and Infant Boys30 According to Number of Findings Present. aProbability of UTI exceeds 1% even with no risk factors other than being uncircumcised. eral guidance.● Policy level: Strong recommendation. be obtained through catheteriza- than 1% for 10.4% of academicians andAction Statement 2 tion or SPA and cultured; if urinaly- 11.7% for practitioners26; when theIf a clinician assesses a febrile infant sis of fresh (<1 hour since void) threshold was increased to 1% to 3%,with no apparent source for the fever urine yields negative leukocyte es- 67.5% of academicians and 45.7% ofas not being so ill as to require imme- terase and nitrite test results, then practitioners considered the yield suf-diate antimicrobial therapy, then the it is reasonable to monitor the clin- ficiently high to warrant urine culture.clinician should assess the likelihood of ical course without initiating anti- Therefore, attempting to operational-UTI (see below for how to assess microbial therapy, recognizing that ize “low likelihood” (ie, below a thresh-likelihood). negative urinalysis results do not old that warrants a urine culture) does rule out a UTI with certainty. not produce an absolute percentage;Action Statement 2a If the clinician determines that the de- clinicians will choose a threshold de-If the clinician determines the febrile gree of illness does not require imme- pending on factors such as their confi-infant to have a low likelihood of UTI diate antimicrobial therapy, then the dence that contact will be maintained(see text), then clinical follow-up likelihood of UTI should be assessed. through the illness (so that a specimenmonitoring without testing is suffi- As noted previously, the overall preva- can be obtained at a later time) and com-cient (evidence quality: A; strong lence of UTI in febrile infants who have fort with diagnostic uncertainty. Fig 2 in-recommendation). no source for their fever evident on the dicates the number of risk factors as- basis of history or physical examina- sociated with threshold probabilitiesAction Statement 2b tion results is approximately 5%,17,18 of UTI of at least 1% and at least 2%.If the clinician determines that the but it is possible to identify groups In a series of studies, Gorelick, Shaw,febrile infant is not in a low-risk with higher-than-average likelihood and colleagues27–29 derived and vali-group (see below), then there are 2 and some with lower-than-average dated a prediction rule for febrile in-choices (evidence quality: A; strong likelihood. The prevalence of UTI fant girls on the basis of 5 risk factors,recommendation). Option 1 is to ob- among febrile infant girls is more than namely, white race, age less than 12tain a urine specimen through cath- twice that among febrile infant boys months, temperature of at least 39°C,eterization or SPA for culture and (relative risk: 2.27). The rate for uncir- fever for at least 2 days, and absenceurinalysis. Option 2 is to obtain a cumcised boys is 4 to 20 times higher of another source of infection. Thisurine specimen through the most than that for circumcised boys, whose prediction rule, with sensitivity ofconvenient means and to perform a rate of UTI is only 0.2% to 0.4%.19–24 The 88% and specificity of 30%, permitsurinalysis. If the urinalysis results presence of another, clinically obvious some infant girls to be considered insuggest a UTI (positive leukocyte source of infection reduces the likeli- a low-likelihood group (Fig 2). For ex-esterase test results or nitrite test hood of UTI by one-half.25 ample, of girls with no identifiableor microscopic analysis results In a survey asking, “What yield is re- source of infection, those who are non-positive for leukocytes or bacte- quired to warrant urine culture in fe- white and more than 12 months of ageria), then a urine specimen should brile infants?,” the threshold was less with a recent onset (Ͻ2 days) of low-598 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 6. FROM THE AMERICAN ACADEMY OF PEDIATRICSgrade fever (Ͻ39°C) have less than a TABLE 1 Sensitivity and Specificity of Components of Urinalysis, Alone and in Combination1% probability of UTI; each additional Test Sensitivity (Range), % Specificity (Range), %risk factor increases the probability. It Leukocyte esterase test 83 (67–94) 78 (64–92) Nitrite test 53 (15–82) 98 (90–100)should be noted, however, that some Leukocyte esterase or 93 (90–100) 72 (58–91)of the factors (eg, duration of fever) nitrite test positivemay change during the course of the Microscopy, WBCs 73 (32–100) 81 (45–98) Microscopy, bacteria 81 (16–99) 83 (11–100)illness, excluding the infant from a Leukocyte esterase test, 99.8 (99–100) 70 (60–92)low-likelihood designation and nitrite test, orprompting testing as described in microscopy positiveaction statement 2a.As demonstrated in Fig 2, the major definitive urine specimen through Action Statement 3risk factor for febrile infant boys is catheterization initially.whether they are circumcised. The prob- To establish the diagnosis of UTI, ● Aggregate quality of evidence: A (diag- clinicians should require both uri-ability of UTI can be estimated on the ba- nostic studies on relevant populations). nalysis results that suggest infec-sis of 4 risk factors, namely, nonblackrace, temperature of at least 39°C, fever ● Benefits: Accurate diagnosis of UTI tion (pyuria and/or bacteriuria) can prevent the spread of infection and the presence of at least 50 000for more than 24 hours, and absence of and renal scarring; avoiding overdi- colony-forming units (CFUs) per mLanother source of infection.4,30 agnosis of UTI can prevent over- of a uropathogen cultured from aIf the clinician determines that the in- treatment and unnecessary and ex- urine specimen obtained throughfant does not require immediate anti- pensive imaging. catheterization or SPA (evidencemicrobial therapy and a urine speci- quality: C; recommendation). ● Harms/risks/costs: A small propor-men is desired, then often a urine tion of febrile infants, considered atcollection bag affixed to the perineum Urinalysis low likelihood of UTI, will not receiveis used. Many clinicians think that this timely identification and treatment General Considerationscollection technique has a low contam- of their UTIs.ination rate under the following cir- Urinalysis cannot substitute for urine ● Benefit-harms assessment: Prepon- culture to document the presence ofcumstances: the patient’s perineum is derance of benefit over harm. UTI but needs to be used in conjunctionproperly cleansed and rinsed beforeapplication of the collection bag, the ● Value judgments: There is a risk of with culture. Because urine culture re- UTI sufficiently low to forestall fur- sults are not available for at least 24urine bag is removed promptly after ther evaluation. hours, there is considerable interesturine is voided into the bag, and the ● Role of patient preferences: The in tests that may predict the results ofspecimen is refrigerated or processed choice of option 1 or option 2 and the urine culture and enable presump-immediately. Even if contamination the threshold risk of UTI warranting tive therapy to be initiated at the firstfrom the perineal skin is minimized, obtaining a urine specimen may be encounter. Urinalysis can be per-however, there may be significant con- formed on any specimen, includingtamination from the vagina in girls or influenced by parents’ preference to avoid urethral catheterization (if one collected from a bag applied to thethe prepuce in uncircumcised boys, perineum. However, the specimenthe 2 groups at highest risk of UTI. A a bag urine sample yields negative urinalysis results) versus timely must be fresh (Ͻ1 hour after voiding“positive” culture result from a speci- with maintenance at room tempera- evaluation (obtaining a definitivemen collected in a bag cannot be used ture or Ͻ4 hours after voiding with re- specimen through catheterization).to document a UTI; confirmation re- frigeration), to ensure sensitivity andquires culture of a specimen collected ● Exclusions: Because it depends on a specificity of the urinalysis. The teststhrough catheterization or SPA. Be- range of patient- and physician- that have received the most atten-cause there may be substantial delay specific considerations, the precise tion are biochemical analyses of leu-waiting for the infant to void and a sec- threshold risk of UTI warranting ob- kocyte esterase and nitrite through aond specimen, obtained through cath- taining a urine specimen is left to rapid dipstick method and urineeterization, may be necessary if the the clinician but is below 3%. microscopic examination for whiteurinalysis suggests the possibility of ● Intentional vagueness: None. blood cells (WBCs) and bacteriaUTI, many clinicians prefer to obtain a ● Policy level: Strong recommendation. (Table 1).PEDIATRICS Volume 128, Number 3, September 2011 599 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 7. Urine dipsticks are appealing, because 64%–92%]) generally is not as good as during infancy. In a study of infants 2 tothey provide rapid results, do not re- the sensitivity, which reflects the non- 24 months of age, 0.7% of afebrile girlsquire microscopy, and are eligible for specificity of pyuria in general. Accord- had 3 successive urine cultures witha waiver under the Clinical Laboratory ingly, positive leukocyte esterase test 105 CFUs per mL of a single uropatho-Improvement Amendments. They indi- results should be interpreted with cau- gen.26 Asymptomatic bacteriuria cancate the presence of leukocyte es- tion, because false-positive results are be easily confused with true UTI in aterase (as a surrogate marker for common. With numerous conditions febrile infant but needs to be distin-pyuria) and urinary nitrite (which is other than UTI, including fever result- guished, because studies suggest thatconverted from dietary nitrates in the ing from other conditions (eg, strepto- antimicrobial treatment may do morepresence of most Gram-negative enteric coccal infections or Kawasaki dis- harm than good.36 The key to distin-bacteria in the urine). The conversion of ease), and after vigorous exercise, guishing true UTI from asymptomaticdietary nitrates to nitrites by bacteria re- WBCs may be found in the urine. There- bacteriuria is the presence of pyuria.quires approximately 4 hours in the fore, a finding of pyuria by no meansbladder.31 The performance characteris- Microscopic Analysis for Bacteriuria confirms that an infection of the uri-tics of both leukocyte esterase and ni- nary tract is present. The presence of bacteria in a fresh,trite tests vary according to the defini- Gram-stained specimen of uncentri- The absence of pyuria in children withtion used for positive urine culture fuged urine correlates with 105 CFUs true UTIs is rare, however. It is theoret-results, the age and symptoms of the per mL in culture.37 An “enhanced uri- ically possible if a febrile child is as-population being studied, and the nalysis,” combining the counting sessed before the inflammatory re-method of urine collection. chamber assessment of pyuria noted sponse has developed, but the previously with Gram staining of dropsNitrite Test inflammatory response to a UTI pro- of uncentrifuged urine, with a thresh- duces both fever and pyuria; therefore,A nitrite test is not a sensitive marker old of at least 1 Gram-negative rod infor children, particularly infants, who children who are being evaluated be- 10 oil immersion fields, has greater sen-empty their bladders frequently. cause of fever should already have sitivity, specificity, and positive predic-Therefore, negative nitrite test results WBCs in their urine. More likely expla- tive value than does the standard urinal-have little value in ruling out UTI. More- nations for significant bacteriuria in ysis33 and is the preferred method ofover, not all urinary pathogens reduce culture in the absence of pyuria in- urinalysis when appropriate equipmentnitrate to nitrite. The test is helpful clude contaminated specimens, insen- and personnel are available.when the result is positive, however, sitive criteria for pyuria, and asymp-because it is highly specific (ie, there tomatic bacteriuria. In most cases, Automated Urinalysisare few false-positive results).32 when true UTI has been reported to oc- Automated methods to perform uri- cur in the absence of pyuria, the defi- nalysis are now being used in manyLeukocyte Esterase Test nition of pyuria has been at fault. The hospitals and laboratories. Image-The sensitivity of the leukocyte es- standard method of assessing pyuria based systems use flow imagingterase test is 94% when it used in the has been centrifugation of the urine analysis technology and software tocontext of clinically suspected UTI. and microscopic analysis, with a classify particles in uncentrifugedOverall, the reported sensitivity in var- threshold of 5 WBCs per high-power urine specimens rapidly.38 Resultsious studies is lower (83%), because field (ϳ25 WBCs per ␮L). If a counting correlate well with manual methods,the results of leukocyte esterase tests chamber is used, however, the finding especially for red blood cells, WBCs,were related to culture results without of at least 10 WBCs per ␮L in uncentri- and squamous epithelial cells. In theexclusion of individuals with asymp- fuged urine has been demonstrated to future, this may be the most commontomatic bacteriuria. The absence of be more sensitive33 and performs well method by which urinalysis is per-leukocyte esterase in the urine of indi- in clinical situations in which the stan- formed in laboratories.viduals with asymptomatic bacteriuria dard method does not, such as withis an advantage of the test, rather than very young infants.34 Culturea limitation, because it distinguishes An important cause of bacteriuria in The diagnosis of UTI is made on the ba-individuals with asymptomatic bacte- the absence of pyuria is asymptomatic sis of quantitative urine culture re-riuria from those with true UTI. bacteriuria. Asymptomatic bacteriuria sults in addition to evidence of pyuriaThe specificity of the leukocyte es- often is associated with school-aged and/or bacteriuria. Urine specimensterase test (average: 72% [range: and older girls,35 but it can be present should be processed as expediently as600 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 8. FROM THE AMERICAN ACADEMY OF PEDIATRICSpossible. If the specimen is not pro- spp are not considered clinically rele- ● Harms/risks/costs: Stringent diag-cessed promptly, then it should be re- vant urine isolates for otherwise nostic criteria may miss a smallfrigerated to prevent the growth of or- healthy, 2- to 24-month-old children.) number of UTIs.ganisms that can occur in urine at Reducing the threshold from 100 000 ● Benefit-harms assessment: Prepon-room temperature; for the same rea- CFUs per mL to 50 000 CFUs per mL derance of benefit over harm.son, specimens that require transpor- would seem to increase the sensitivity ● Value judgments: Treatment oftation to another site for processing of culture at the expense of decreased asymptomatic bacteriuria may beshould be transported on ice. A prop- specificity; however, because the pro- harmful.erly collected urine specimen should posed criteria for UTI now include evi- dence of pyuria in addition to positive ● Role of patient preferences: We as-be inoculated on culture medium that culture results, infants with “positive” sume that parents prefer no actionwill allow identification of urinary tract culture results alone will be recog- in the absence of a UTI (avoidingpathogens. nized as having asymptomatic bacteri- false-positive results) over a veryUrine culture results are considered small chance of missing a UTI. uria rather than a true UTI. Some labo-positive or negative on the basis of the ratories report growth only in the ● Exclusions: None.number of CFUs that grow on the cul-ture medium.36 Definition of significant following categories: 0 to 1000, 1000 to ● Intentional vagueness: None. 10 000, 10 000 to 100 000, and more ● Policy level: Recommendation.colony counts with regard to the than 100 000 CFUs per mL. In suchmethod of collection considers that cases, results in the 10 000 to 100 000 MANAGEMENTthe distal urethra and periurethral CFUs per mL range need to be evalu-area are commonly colonized by the Action Statement 4 ated in context, such as whether thesame bacteria that may cause UTI; urinalysis findings support the diagno- Action Statement 4atherefore, a low colony count may be sis of UTI and whether the organism ispresent in a specimen obtained When initiating treatment, the clini- a recognized uropathogen.through voiding or catheterization cian should base the choice ofwhen bacteria are not present in blad- Alternative culture methods, such as route of administration on practi-der urine. Definitions of positive and dipslides, may have a place in the of- cal considerations. Initiating treat-negative culture results are opera- fice setting; sensitivity is reported to ment orally or parenterally istional and not absolute. The time the be in the range of 87% to 100%, and equally efficacious. The clinicianurine resides in the bladder (bladder specificity is reported to be 92% to should base the choice of agent onincubation time) is an important deter- 98%, but dipslides cannot specify the local antimicrobial sensitivity pat-minant of the magnitude of the colony organism or antimicrobial sensitivi- terns (if available) and should ad- ties.41 Practices that use dipslides just the choice according to sensi-count. The concept that more than should do so in collaboration with a tivity testing of the isolated100 000 CFUs per mL indicates a UTI certified laboratory for identification uropathogen (evidence quality: A;was based on morning collections of and sensitivity testing or, in the ab- strong recommendation).urine from adult women, with compar- sence of such results, may need to per-ison of specimens from women with- form “test of cure” cultures after 24 Action Statement 4bout symptoms and women considered hours of treatment. The clinician should choose 7 to 14clinically to have pyelonephritis; thetransition range, in which the propor- ● Aggregate quality of evidence: C (ob- days as the duration of antimicrobialtion of women with pyelonephritis ex- servational studies). therapy (evidence quality: B;ceeded the proportion of women with- ● Benefits: Accurate diagnosis of UTI recommendation).out symptoms, was 10 000 to 100 000 can prevent the spread of infection The goals of treatment of acute UTI areCFUs per mL.39 In most instances, an and renal scarring; avoiding overdi- to eliminate the acute infection, to pre-appropriate threshold to consider agnosis of UTI can prevent over- vent complications, and to reduce thebacteriuria “significant” in infants and treatment and unnecessary and ex- likelihood of renal damage. Most chil-children is the presence of at least pensive imaging. These criteria dren can be treated orally.42–44 Patients50 000 CFUs per mL of a single urinary reduce the likelihood of overdiagno- whom clinicians judge to be “toxic” orpathogen.40 (Organisms such as sis of UTI in infants with asymptom- who are unable to retain oral intakeLactobacillus spp, coagulase-negative atic bacteriuria or contaminated (including medications) should re-staphylococci, and Corynebacterium specimens. ceive an antimicrobial agent parenter-PEDIATRICS Volume 128, Number 3, September 2011 601 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 9. TABLE 2 Some Empiric Antimicrobial Agents TABLE 3 Some Empiric Antimicrobial Agents for Oral Treatment of UTI for Parenteral Treatment of UTI Antimicrobial Agent DosageAntimicrobial Dosage Amoxicillin-clavulanate 20–40 mg/kg per d in 3 doses Agent SulfonamideCeftriaxone 75 mg/kg, every 24 h Trimethoprim-sulfamethoxazole 6–12 mg/kg trimethoprim and 30-60 mg/kg sulfamethoxazoleCefotaxime 150 mg/kg per d, per d in 2 doses divided every 6–8 h Sulfisoxazole 120–150 mg/kg per d in 4 dosesCeftazidime 100–150 mg/kg per d, Cephalosporin divided every 8 h Cefixime 8 mg/kg per d in 1 dose Gentamicin 7.5 mg/kg per d, Cefpodoxime 10 mg/kg per d in 2 doses divided every 8 h Cefprozil 30 mg/kg per d in 2 dosesTobramycin 5 mg/kg per d, Cefuroxime axetil 20–30 mg/kg per d in 2 doses divided every 8 h Cephalexin 50–100 mg/kg per d in 4 doses Piperacillin 300 mg/kg per d, divided every 6–8 h the total course of therapy should be 7 distinguishes the benefit of treatingally (Table 2) until they exhibit clinical to 14 days. The committee attempted to 7 vs 10 vs 14 days, and the range isimprovement, generally within 24 to 48 identify a single, preferred, evidence- allowable.hours, and are able to retain orally ad- based duration, rather than a range, but ● Policy level: Strong recommendation/ministered fluids and medications. In a data comparing 7, 10, and 14 days di-study of 309 febrile infants with UTIs, recommendation. rectly were not found. There is evidenceonly 3 (1%) were deemed too ill to be that 1- to 3-day courses for febrile UTIs Action Statement 5assigned randomly to either paren- are inferior to courses in the recom-teral or oral treatment.42 Parenteral Febrile infants with UTIs should mended range; therefore, the minimaladministration of an antimicrobial undergo renal and bladder ultra- duration selected should be 7 days.agent also should be considered when sonography (RBUS) (evidence ● Aggregate quality of evidence: A/B quality: C; recommendation).compliance with obtaining an antimi-crobial agent and/or administering it (RCTs). The purpose of RBUS is to detect ana-orally is uncertain. The usual choices ● Benefits: Adequate treatment of UTI tomic abnormalities that require fur-for oral treatment of UTIs include can prevent the spread of infection ther evaluation, such as additional im-a cephalosporin, amoxicillin plus and renal scarring. Outcomes of aging or urologic consultation. RBUSclavulanic acid, or trimethoprim- short courses (1–3 d) are inferior to also provides an evaluation of the re-sulfamethoxazole (Table 3). It is essen- those of 7- to 14-d courses. nal parenchyma and an assessment oftial to know local patterns of suscepti- ● Harms/risks/costs: There are mini- renal size that can be used to monitorbility of coliforms to antimicrobial mal harm and minor cost effects of renal growth. The yield of actionableagents, particularly trimethoprim- antimicrobial choice and duration findings is relatively low.45,46 Wide-sulfamethoxazole and cephalexin, be- of therapy. spread application of prenatal ultra-cause there is substantial geographic ● Benefit-harms assessment: Prepon- sonography clearly has reduced thevariability that needs to be taken into derance of benefit over harm. prevalence of previously unsuspectedaccount during selection of an antimi- obstructive uropathy in infants, but the ● Value judgments: Adjusting antimi-crobial agent before sensitivity results consequences of prenatal screening crobial choice on the basis of avail-are available. Agents that are excreted with respect to the risk of renal abnor- able data and treating according toin the urine but do not achieve thera- malities in infants with UTIs have not best evidence will minimize cost andpeutic concentrations in the blood- yet been well defined. There is consid- consequences of failed or unneces-stream, such as nitrofurantoin, should erable variability in the timing and sary treatment.not be used to treat febrile infants with quality of prenatal ultrasonograms,UTIs, because parenchymal and serum ● Role of patient preferences: It is as- and the report of “normal” ultrasono-antimicrobial concentrations may be sumed that parents prefer the graphic results cannot necessarily beinsufficient to treat pyelonephritis or most-effective treatment and the relied on to dismiss completely theurosepsis. least amount of medication that en- possibility of a structural abnormality sures effective treatment.Whether the initial route of administra- unless the study was a detailed ana-tion of the antimicrobial agent is oral ● Exclusions: None. tomic survey (with measurements),or parenteral (then changed to oral), ● Intentional vagueness: No evidence was performed during the third tri-602 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 10. FROM THE AMERICAN ACADEMY OF PEDIATRICSmester, and was performed and inter- children with reduced renal function. Action Statement 6preted by qualified individuals.47 The radiation dose from dimercapto- Action Statement 6aThe timing of RBUS depends on the succinic acid is additive with that of VCUG should not be performedclinical situation. RBUS is recom- VCUG when both studies are per- routinely after the first febrilemended during the first 2 days of treat- formed.50 The radiation dose from UTI; VCUG is indicated if RBUS re-ment to identify serious complications, VCUG depends on the equipment that veals hydronephrosis, scarring,such as renal or perirenal abscesses is used (conventional versus pulsed or other findings that would sug-or pyonephrosis associated with ob- digital fluoroscopy) and is related di- gest either high-grade VUR or ob-structive uropathy when the clinical ill- rectly to the total fluoroscopy time. structive uropathy, as well as inness is unusually severe or substantial Moreover, the total exposure for the other atypical or complex clinicalclinical improvement is not occurring. child will be increased when both circumstances (evidence qualityFor febrile infants with UTIs who dem- acute and follow-up studies are ob- B; recommendation).onstrate substantial clinical improve- tained. The lack of exposure to radi-ment, however, imaging does not need ation is a major advantage of RBUS, Action Statement 6bto occur early during the acute infec- even with recognition of the limita- Further evaluation should be con-tion and can even be misleading; ani- tions of this modality that were de- ducted if there is a recurrence of fe-mal studies demonstrate that Esche- scribed previously. brile UTI (evidence quality: X;richia coli endotoxin can produce recommendation). ● Aggregate quality of evidence: C (ob-dilation during acute infection, which servational studies). For the past 4 decades, the strategy tocould be confused with hydronephro- ● Benefits: RBUS in this population protect the kidneys from further dam-sis, pyonephrosis, or obstruction.48 age after an initial UTI has been to de-Changes in the size and shape of the will yield abnormal results in ϳ15% tect childhood genitourinary abnor-kidneys and the echogenicity of renal of cases, and 1% to 2% will have ab- malities in which recurrent UTI couldparenchyma attributable to edema normalities that would lead to ac- increase renal damage. The most com-also are common during acute infec- tion (eg, additional evaluation, re- mon of these is VUR, and VCUG is usedtion. The presence of these abnormal- ferral, or surgery). to detect this. Management includedities makes it inappropriate to con- ● Harms/risks/costs: Between 2% continuous antimicrobial administra-sider RBUS performed early during and 3% will be false-positive results, tion as prophylaxis and surgical inter-acute infection to be a true baseline leading to unnecessary and invasive vention if VUR was persistent or recur-study for later comparisons in the as- evaluations. rences of infection were not preventedsessment of renal growth. with an antimicrobial prophylaxis reg- ● Benefit-harms assessment: Prepon-Nuclear scanning with technetium- derance of benefit over harm. imen; some have advocated surgicallabeled dimercaptosuccinic acid has intervention to correct high-grade re- ● Value judgments: The seriousnessgreater sensitivity for detection of flux even when infection has not re-acute pyelonephritis and later scar- of the potentially correctable abnor- curred. However, it is clear that therering than does either RBUS or voiding malities in 1% to 2%, coupled with are a significant number of infantscystourethrography (VCUG). The scan- the absence of physical harm, was who develop pyelonephritis in whomning is useful in research, because it judged sufficiently important to tip VUR cannot be demonstrated, and theensures that all subjects in a study the scales in favor of testing. effectiveness of antimicrobial prophy-have pyelonephritis to start with and it ● Role of patient preferences: Be- laxis for patients who have VUR haspermits assessment of later renal cause ultrasonography is noninva- been challenged in the past decade.scarring as an outcome measure. The sive and poses minimal risk, we as- Several studies have suggested thatfindings on nuclear scans rarely affect sume that parents will prefer RBUS prophylaxis does not confer the de-acute clinical management, however, over taking even a small risk of sired benefit of preventing recurrentand are not recommended as part of missing a serious and correctable febrile UTI.51–55 If prophylaxis is, in fact,routine evaluation of infants with their condition. not beneficial and VUR is not requiredfirst febrile UTI. The radiation dose to for development of pyelonephritis, ● Exclusions: None.the patient during dimercaptosuccinic then the rationale for performingacid scanning is generally low (ϳ1 ● Intentional vagueness: None. VCUG routinely after an initial febrilemSv),49 although it may be increased in ● Policy level: Recommendation. UTI must be questioned.PEDIATRICS Volume 128, Number 3, September 2011 603 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 11. RCTs of the effectiveness of prophy- TABLE 4 Recurrences of Febrile UTI/Pyelonephritis in Infants 2 to 24 Months of Age With and Without Antimicrobial Prophylaxis, According to Grade of VURlaxis performed to date generally in- Reflux Prophylaxis No Prophylaxis Pcluded children more than 24 months Gradeof age, and some did not provide com- No. of Total N No. of Total N Recurrences Recurrencesplete data according to grade of VUR. None 7 210 11 163 .15These 2 factors have compromised I 2 37 2 35 1.00meta-analyses. To ensure direct com- II 11 133 10 124 .95parisons, the committee contacted the III 31 140 40 145 .29 IV 16 55 21 49 .146 researchers who had conducted themost recent RCTs and requested rawdata from their studies.51–56 All com- the initial UTI, those who have the ● Benefits: This avoids, for the vastplied, which permitted the creation of greatest likelihood of having high- majority of febrile infants with UTIs,a data set with data for 1091 infants 2 grade VUR. Unfortunately, there are no radiation exposure (of particularto 24 months of age according to grade clinical or laboratory indicators that concern near the ovaries in girls),of VUR. A ␹2 analysis (2-tailed) and a have been demonstrated to identify in- expense, and discomfort.formal meta-analysis did not detect a fants with high-grade VUR. Indications ● Harms/risks/costs: Detection of astatistically significant benefit of pro- for VCUG have been proposed on the small number of cases of high-phylaxis in preventing recurrence of basis of consensus in the absence of grade reflux and correctable abnor-febrile UTI/pyelonephritis in infants data57; the predictive value of any of the malities is delayed.without reflux or those with grades I, II, indications for VCUG proposed in this manner is not known. ● Benefit-harms assessment: Prepon-III, or IV VUR (Table 4 and Fig 3). Only 5 derance of benefit over harm.infants with grade V VUR were in- The level of evidence supporting rou- tine imaging with VCUG was deemed ● Value judgments: The risks associ-cluded in the RCTs; therefore, data for insufficient at the time of the 1999 ated with radiation (plus the ex-those infants are not included in Table practice parameter to receive a rec- pense and discomfort of the proce-4 or Fig 3. ommendation, but the consensus of dure) for the vast majority of infantsThe proportion of infants with high- outweigh the risk of delaying the de- the subcommittee was to “strongly en-grade VUR among all infants with fe- tection of the few with correctable courage” imaging studies. The positionbrile UTIs is small. Data adapted from abnormalities until their second UTI. of the current subcommittee reflectscurrent studies (Table 5) indicate that, the new evidence demonstrating anti- ● Role of patient preferences: Theof a hypothetical cohort of 100 infants microbial prophylaxis not to be effec- judgment of parents may come intowith febrile UTIs, only 1 has grade V tive as presumed previously. More- play, because VCUG is an uncomfort-VUR; 99 do not. With a practice of wait- over, prompt diagnosis and effective able procedure involving radiationing for a second UTI to perform VCUG, treatment of a febrile UTI recurrence exposure. In some cases, parentsonly 10 of the 100 would need to un- may be of greater importance regard-dergo the procedure and the 1 with may prefer to subject their children less of whether VUR is present or the to the procedure even when thegrade V VUR would be identified. (It child is receiving antimicrobial pro-also is possible that the 1 infant with chance of benefit is both small and phylaxis. A national study (the Ran- uncertain. Antimicrobial prophy-grade V VUR might have been identified domized Intervention for Children Withafter the first UTI on the basis of abnor- laxis seems to be ineffective in pre- Vesicoureteral Reflux study) is cur- venting recurrence of febrile UTI/py-mal RBUS results that prompted VCUG rently in progress to identify the ef-to be performed.) Data to quantify ad- elonephritis for the vast majority of fects of a prophylactic antimicrobialditional potential harm to an infant infants. Some parents may want to regimen for children 2 months to 6who is not revealed to have high-grade avoid VCUG even after the second years of age who have experienced aVUR until a second UTI are not precise UTI. Because the benefit of identify- UTI, and it is anticipated to provide ad-but suggest that the increment is in- ing high-grade reflux is still in some ditional important data58 (see Areassufficient to justify routinely subject- doubt, these preferences should be for Research).ing all infants with an initial febrile UTI considered. It is the judgment of theto VCUG (Fig 4). To minimize any harm Action Statement 6a committee that VCUG is indicated af-incurred by that infant, attempts have ● Aggregate quality of evidence: B ter the second UTI.been made to identify, at the time of (RCTs). ● Exclusions: None.604 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 12. FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 5 Rates of VUR According to Grade in Hypothetical Cohort of Infants After First UTI and After Recurrence Rate, % After First After UTI Recurrence (N ϭ 100) (N ϭ 10) No VUR 65 26 Grades I–III VUR 29 56 Grade IV VUR 5 12 Grade V VUR 1 6 FIGURE 4 Relationship between renal scarring and num- ber of bouts of pyelonephritis. Adapted from Jodal.59 ● Intentional vagueness: None. ● Policy level: Recommendation. Action Statement 6b ● Aggregate quality of evidence: X (ex- ceptional situation). ● Benefits: VCUG after a second UTI should identify infants with very high-grade reflux. ● Harms/risks/costs: VCUG is an un- comfortable, costly procedure that involves radiation, including to the ovaries of girls. ● Benefit-harms assessment: Prepon-FIGURE 3 derance of benefit over harm.A, Recurrences of febrile UTI/pyelonephritis in 373 infants 2 to 24 months of age without VUR, with andwithout antimicrobial prophylaxis (based on 3 studies; data provided by Drs Craig, Garin, and Mon- ● Value judgments: The committeetini). B, Recurrences of febrile UTI/pyelonephritis in 72 infants 2 to 24 months of age with grade I VUR, judged that patients with high-with and without antimicrobial prophylaxis (based on 4 studies; data provided by Drs Craig, Garin,Montini, and Roussey-Kesler). C, Recurrences of febrile UTI/pyelonephritis in 257 infants 2 to 24 grade reflux and other abnormali-months of age with grade II VUR, with and without antimicrobial prophylaxis (based on 5 studies; data ties may benefit from interventionsprovided by Drs Craig, Garin, Montini, Pennesi, and Roussey-Kesler). D, Recurrences of febrile UTI/ to prevent further scarring. Furtherpyelonephritis in 285 infants 2 to 24 months of age with grade III VUR, with and without antimicrobialprophylaxis (based on 6 studies; data provided by Drs Brandström, Craig, Garin, Montini, Pennesi, and studies of treatment for grade VRoussey-Kesler). E, Recurrences of febrile UTI/pyelonephritis in 104 infants 2 to 24 months of age with VUR are not underway and are un-grade IV VUR, with and without antimicrobial prophylaxis (based on 3 studies; data provided by Drs likely in the near future, because theBrandström, Craig, and Pennesi). M-H indicates Mantel-Haenszel; CI, confidence interval. condition is uncommon and ran- domization of treatment in this group generally has been consid- ered unethical.PEDIATRICS Volume 128, Number 3, September 2011 605 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 13. ● Role of patient preferences: As men- ● Aggregate quality of evidence: C (ob- first UTI is not recommended; VCUG is tioned previously, the judgment of servational studies). indicated if RBUS reveals hydrone- parents may come into play, be- ● Benefits: Studies suggest that early phrosis, scarring, or other findings cause VCUG is an uncomfortable treatment of UTI reduces the risk of that would suggest either high-grade procedure involving radiation expo- renal scarring. VUR or obstructive uropathy, as well as sure. In some cases, parents may in other atypical or complex clinical ● Harms/risks/costs: There may be prefer to subject their children to circumstances. VCUG also should be additional costs and inconvenience the procedure even when the performed if there is a recurrence of to parents with more-frequent visits chance of benefit is both small and febrile UTI. to the clinician for evaluation of uncertain. The benefits of treatment fever. of VUR remain unproven, but the AREAS FOR RESEARCH point estimates suggest a small po- ● Benefit-harms assessment: Prepon- derance of benefit over harm. One of the major values of a compre- tential benefit. Similarly, parents hensive literature review is the identi- may want to avoid VCUG even after ● Value judgments: None. fication of areas in which evidence is the second UTI. Because the benefit ● Role of patient preferences: Parents lacking. The following 8 areas are pre- of identifying high-grade reflux is will ultimately make the judgment to sented in an order that parallels the still in some doubt, these prefer- seek medical care. previous discussion. ences should be considered. It is the ● Exclusions: None. 1. The relationship between UTIs in in- judgment of the committee that ● Intentional vagueness: None. fants and young children and re- VCUG is indicated after the second ● Policy level: Recommendation. duced renal function in adults has UTI. been established but is not● Exclusions: None. CONCLUSIONS well characterized in quantitative● Intentional vagueness: Further eval- terms. The ideal prospective cohort The committee formulated 7 key action uation will likely start with VCUG but study from birth to 40 to 50 years of statements for the diagnosis and may entail additional studies de- age has not been conducted and is treatment of infants and young chil- pending on the findings. The details unlikely to be conducted. There- dren 2 to 24 months of age with UTI and of further evaluation are beyond the fore, estimates of undesirable unexplained fever. Strategies for diag- scope of this guideline. outcomes in adulthood, such as nosis and treatment depend on● Policy level: Recommendation. whether the clinician determines that hypertension and end-stage renal antimicrobial therapy is warranted im- disease, are based on the mathe-Action Statement 7 matical product of probabilities mediately or can be delayed safely un-After confirmation of UTI, the cli- til urine culture and urinalysis results at several steps, each of which isnician should instruct parents or are available. Diagnosis is based on subject to bias and error. Otherguardians to seek prompt medical the presence of pyuria and at least attempts at decision analysis andevaluation (ideally within 48 50 000 CFUs per mL of a single uro- thoughtful literature review havehours) for future febrile ill- pathogen in an appropriately collected recognized the same limitations.nesses, to ensure that recurrent specimen of urine; urinalysis alone Until recently, imaging tools avail-infections can be detected and does not provide a definitive diagnosis. able for assessment of the effectstreated promptly (evidence qual- After 7 to 14 days of antimicrobial of UTIs have been insensitive. Withity: C; recommendation). treatment, close clinical follow-up the imaging techniques now avail-Early treatment limits renal damage monitoring should be maintained, with able, it may be possible to identifybetter than late treatment,1,2 and the evaluation of the urine during subse- the relationship of scarring to re-risk of renal scarring increases as the quent febrile episodes to permit nal impairment and hypertension.number of recurrences increase (Fig prompt diagnosis and treatment of re- 2. The development of techniques that4).59 For these reasons, all infants who current infections. Ultrasonography of would permit an alternative to inva-have sustained a febrile UTI should the kidneys and bladder should be per- sive sampling and culture would behave a urine specimen obtained at the formed to detect anatomic abnormali- valuable for general use. Special at-onset of subsequent febrile illnesses, ties that require further evaluation tention should be given to infantso that a UTI can be diagnosed and (eg, additional imaging or urologic girls and uncircumcised boys, be-treated promptly. consultation). Routine VCUG after the cause urethral catheterization may606 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 14. FROM THE AMERICAN ACADEMY OF PEDIATRICS be difficult and can produce con- microbial resistance. To overcome the infants will have recurrent UTIs; taminated specimens and SPA now these issues, evidence of effective- some will be identified as having VUR is not commonly performed. Incu- ness with a well-tolerated, safe or other abnormalities. Further re- bation time, which is inherent in the product would be required, and search addressing the optimal culture process, results in delayed parents would need sufficient edu- course of management in specific sit- treatment or presumptive treat- cation to understand the value and uations would be valuable. ment on the basis of tests that lack importance of adherence. A urinary 8. The optimal duration of antimicro- the desired sensitivity and specific- antiseptic, rather than an antimi- bial treatment has not been deter- ity to replace culture. crobial agent, would be particularly mined. RCTs of head-to-head com-3. The role of VUR (and therefore of desirable, because it could be taken parisons of various duration would VCUG) is incompletely understood. indefinitely without concern that be valuable, enabling clinicians to It is recognized that pyelonephritis bacteria would develop resistance. limit antimicrobial exposure to (defined through cortical scintigra- Another possible strategy might be what is needed to eradicate the of- phy) can occur in the absence of the use of probiotics. fending uropathogen. VUR (defined through VCUG) and 5. Better understanding of the ge- that progressive renal scarring nome (human and bacterial) may LEAD AUTHOR provide insight into risk factors Kenneth B. Roberts, MD (defined through cortical scintigra- phy) can occur in the absence of (VUR and others) that lead to in- SUBCOMMITTEE ON URINARY TRACT demonstrated VUR.52,53 The pre- creased scarring. Blood specimens INFECTION, 2009 –2011 sumption that antimicrobial pro- will be retained from children en- Kenneth B. Roberts, MD, Chair Stephen M. Downs, MD, MS phylaxis is of benefit for individuals rolled in the Randomized Interven- S. Maria E. Finnell, MD, MS with VUR to prevent recurrences of tion for Children With Vesi- Stanley Hellerstein, MD UTI or the development of renal scars coureteral Reflux study, for future Linda D. Shortliffe, MD examination of genetic determinants Ellen R. Wald, MD is not supported by the aggregate of J. Michael Zerin, MD data from recent studies and cur- of VUR, recurrent UTI, and renal scar- rently is the subject of the Random- ring.58 VUR is recognized to “run in OVERSIGHT BY THE STEERING ized Intervention for Children With families,”60,61 and multiple investiga- COMMITTEE ON QUALITY tors are currently engaged in re- IMPROVEMENT AND MANAGEMENT, Vesicoureteral Reflux study.58 search to identify a genetic basis for 2009 –20114. Although the effectiveness of anti- microbial prophylaxis for the pre- VUR. Studies may also be able to dis- STAFF tinguish the contribution of congeni- Caryn Davidson, MA vention of UTI has not been demon- tal dysplasia from acquired scarring strated, the concept has biological ACKNOWLEDGMENTS attributable to UTI. plausibility. Virtually all antimicro- The committee gratefully acknowl- bial agents used to treat or to pre- 6. One of the factors used to assess edges the generosity of the research- vent infections of the urinary tract the likelihood of UTI in febrile in- ers who graciously shared their data are excreted in the urine in high fants is race. Data regarding rates to permit the data set with data for concentrations. Barriers to the ef- among Hispanic individuals are lim- 1091 infants aged 2 to 24 months ac- fectiveness of antimicrobial pro- ited and would be useful for predic- cording to grade of VUR to be com- phylaxis are adherence to a daily tion rules. piled, that is, Drs Per Brandström, regimen, adverse effects associ- 7. This guideline is limited to the initial Jonathan Craig, Eduardo Garin, Gio- ated with the various agents, and management of the first UTI in febrile vanni Montini, Marco Pennesi, and the potential for emergence of anti- infants 2 to 24 months of age. Some of Gwenaelle Roussey-Kesler.REFERENCES 1. Winter AL, Hardy BE, Alton DJ, Arbus GS, 3. American Academy of Pediatrics, Commit- 4. Finnell SM, Carroll AE, Downs SM, et al. Technical Churchill BM. Acquired renal scars in chil- tee on Quality Improvement, Subcommittee report: diagnosis and management of an initial dren. J Urol. 1983;129(6):1190 –1194 on Urinary Tract Infection. Practice urinary tract infection in febrile infants and 2. Smellie JM, Poulton A, Prescod NP. Retro- parameter: the diagnosis, treatment, and young children. Pediatrics. 2011;128(3):e749 spective study of children with renal scar- evaluation of the initial urinary tract infec- 5. American Academy of Pediatrics, Steering ring associated with reflux and urinary in- tion in febrile infants and young children. Committee on Quality Improvement and fection. BMJ. 1994;308(6938):1193–1196 Pediatrics. 1999;103(4):843– 852 Management. Classifying recommenda-PEDIATRICS Volume 128, Number 3, September 2011 607 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 15. tions for clinical practice guidelines. Pedi- 21. Wiswell TE, Hachey WE. Urinary tract infec- 35. Kunin C. A ten-year study of bacteriuria in atrics. 2004;114(3):874 – 877 tions and the uncircumcised state: an up- schoolgirls: final report of bacteriologic, 6. Leong YY, Tan KW. Bladder aspiration for date. Clin Pediatr (Phila). 1993;32(3): urologic, and epidemiologic findings. J In- diagnosis of urinary tract infection in in- 130 –134 fect Dis. 1970;122(5):382–393 fants and young children. J Singapore Pae- 22. Wiswell TE, Smith FR, Bass JW. Decreased 36. Kemper K, Avner E. The case against screen- diatr Soc. 1976;18(1):43– 47 incidence of urinary tract infections in cir- ing urinalyses for asymptomatic bacteri- 7. Pryles CV, Atkin MD, Morse TS, Welch KJ. cumcised male infants. Pediatrics. 1985; uria in children. Am J Dis Child. 1992;146(3): Comparative bacteriologic study of urine 75(5):901–903 343–346 obtained from children by percutaneous 23. 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Prenat Diagn. 1994; study on circumcision of newborn boys and of febrile infants ages 60 days and younger 14(3):177–180 subsequent risk of urinary-tract infection. at low risk for serious bacterial illness. Pe- 48. Roberts J. Experimental pyelonephritis in Lancet. 1998;352(9143):1813–1816 diatrics. 2001;108(4):866 – 871 the monkey, part III: pathophysiology of ure-608 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 16. FROM THE AMERICAN ACADEMY OF PEDIATRICS teral malfunction induced by bacteria. In- 53. Montini G, Rigon L, Zucchetta P, et al. Pro- Management: NICE Clinical Guideline 54. vest Urol. 1975;13(2):117–120 phylaxis after first febrile urinary tract in- London, England: National Institute for49. Smith T, Evans K, Lythgoe MF, Anderson PJ, fection in children? A multicenter, random- Health and Clinical Excellence; 2007. Avail- Gordon I. Radiation dosimetry of ized, controlled, noninferiority trial. able at: technetium-99m-DMSA in children. J Nucl Pediatrics. 2008;122(5):1064 –1071 11819/36032/36032.pdf. Accessed March Med. 1996;37(8):1336 –1342 54. Roussey-Kesler G, Gadjos V, Idres N, et al. 14, 201150. Ward VL. Patient dose reduction during Antibiotic prophylaxis for the prevention of 58. Keren R, Carpenter MA, Hoberman A, et al. voiding cystourethrography. Pediatr Radiol. recurrent urinary tract infection in children Rationale and design issues of the Random- 2006;36(suppl 2):168 –172 with low grade vesicoureteral reflux: re- ized Intervention for Children With Vesi-51. Pennesi M, Travan L, Peratoner L, et al. Is sults from a prospective randomized study. coureteral Reflux (RIVUR) study. Pediatrics. antibiotic prophylaxis in children with vesi- J Urol. 2008;179(2):674 – 679 2008;122(suppl 5):S240 –S250 coureteral reflux effective in preventing py- 55. Craig J, Simpson J, Williams G. Antibiotic 59. Jodal U. The natural history of bacteriuria in elonephritis and renal scars? A random- prophylaxis and recurrent urinary tract in- childhood. Infect Dis Clin North Am. 1987; ized, controlled trial. Pediatrics. 2008; fection in children. N Engl J Med. 2009; 1(4):713–729 121(6). Available at: 361(18):1748 –1759 cgi/content/full/121/6/e1489 60. Eccles MR, Bailey RR, Abbott GD, Sullivan MJ. 56. Brandström P, Esbjorner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Unravelling the genetics of vesicoureteric52. Garin EH, Olavarria F, Garcia Nieto V, Valen- Swedish Reflux Trial in Children, part III: uri- reflux: a common familial disorder. Hum ciano B, Campos A, Young L. Clinical signifi- nary tract infection pattern. J Urol. 2010; Mol Genet. 1996;5(Spec No.):1425–1429 cance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute 184(1):286 –291 61. Scott JE, Swallow V, Coulthard MG, Lambert pyelonephritis: a multicenter, randomized, 57. National Institute for Health and Clinical Ex- HJ, Lee RE. Screening of newborn babies for controlled study. Pediatrics. 2006;117(3): cellence. Urinary Tract Infection in Children: familial ureteric reflux. Lancet. 1997; 626 – 632 Diagnosis, Treatment, and Long-term 350(9075):396 – 400PEDIATRICS Volume 128, Number 3, September 2011 609 Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 17. APPENDIXClinical practice guideline algorithm.610 FROM THE AMERICAN ACADEMY OF PEDIATRICS Downloaded from at Southern Peru Copper Corp on September 2, 2011
  • 18. Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis andManagement of the Initial UTI in Febrile Infants and Children 2 to 24 Months SUBCOMMITTEE ON URINARY TRACT INFECTION and STEERING COMMITTEE ON QUALITY IMPROVEMENT AND MANAGEMENT Pediatrics; originally published online August 28, 2011; DOI: 10.1542/peds.2011-1330Updated Information & including high resolution figures, can be found at:Services /peds.2011-1330Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: mlReprints Information about ordering reprints can be found online: is the official journal of the American Academy of Pediatrics. A monthlypublication, it has been published continuously since 1948. PEDIATRICS is owned, published,and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, ElkGrove Village, Illinois, 60007. Copyright © 2011 by the American Academy of Pediatrics. Allrights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from at Southern Peru Copper Corp on September 2, 2011