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Fever without a source in children younger than 36 months [A]

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  1. Fever is commonly defined as a rectal temperature >38°C (100.4 ºF), which usually corresponds to an axillary temperature of 37.5 °C (99.5 ºF). Tympanic thermometers offer a quick but less reliable reading, with an average temperature of 0.3 ºC above the rectal one. Forehead chemical thermometers are unreliable and should not be used 1 .
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  1. Feverish illness in children. Assesment and initial management in children younger than 5 years. NICE guideline 2013. Available from: http://guidance.nice.org.uk/CG160/Guidance/pdf/English. (Last accessed 20 March 2017)
Asses body temperature, immunization status, history and thorough physical examination [B]
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  1. It is often called fever without a source (FWS) when the history and physical examination cannot identify a specific source in an acutely ill, nontoxic-appearing child between 3 months and 3 years of age, with fever of less than 7 days duration 2 . The presence of isolated pharyngeal or tympanic hyperemia or mild rhinorrhea does not exclude the criterion of FWS 3
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  1. Allen CH. Fever without a source in children 3 to 36 months of age. UpToDate 2014. Available from: http://www.uptodate.com/contents/fever-without-a-source-in-children-3-to-36-months-of-age?source=search_result&search=fever+children&selectedTitle=2%7E150 (Last accessed 20 March 2017)
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  1. Rodrigo C, Méndez M. Fiebre sin foco. Protocolos diagnósticos y terapéuticos de la AEP 2011. Available from: http://www.aeped.es/sites/default/files/documentos/fiebresinfoco.pdf . (Last accessed 20 March 2017)
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  1. Age is the first factor to consider in a child with fever. The probability of presenting a serious bacterial infection is greater in children younger than 3 months (2-3 %) and especially in children under 1 month (1 in 8) 3 . The risk decreases between 3 and 36 months and from that age it is very uncommon for a serious bacterial infection to manifest without focal symptoms. All children with fever without a focus and toxic aspect or age <3 months should be referred to hospital for urinalysis, blood count, blood culture, C-reactive protein (CRP) and according to results, assess chest X-ray and lumbar puncture.
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  1. Rodrigo C, Méndez M. Fiebre sin foco. Protocolos diagnósticos y terapéuticos de la AEP 2011. Available from: http://www.aeped.es/sites/default/files/documentos/fiebresinfoco.pdf (Last accessed 20 March 2017)
Age < 3 months [C]
Age 3 – 36 months
Low
Risk of serious illness [D]
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  1. There are several clinical scales to assess the risk of a serious bacterial infection. However they are not easily available, they need time to be assessed and also children frequently present with a fever of few hours of evolution and little disruption of general state despite having an underlying bacterial infection, so they do not replace the "clinical eye" and the parents' impression must always be taken into account.
    The most used scales in children under 3 months are the YIOS (Young Infant Observation Scale) scale ) ( Table 2 ) and the Rochester criteria, which include the of laboratory tests to identify infants younger than 3 months with low risk of bacterial infection ( Table 3 ).
    The Yale observational scale (YOS) is used for children aged 3 months to 3 years ( Table 4 ). Patients with a score < 10 have only a 3% probability of serious bacterial infection; between 10 and 15 it rises to 26% and with a score > 16, 92% of patients have a serious illness.
    The National Institute for Clinical Excellence (NICE) 1 proposes a clinical practice guide with a traffic light system to identify the risk of serious illness in children under five years with fever ( Tables 5 and 6 ). Children with fever and any of the symptoms or signs in the red column should be recognized as being at high risk. Similarly, children with fever and any of the symptoms or signs in the amber column and none in the red column should be recognized as being at intermediate risk. Children with symptoms and signs in the green column and none in the amber or red columns are at low risk. Children with any “red” feature should be referred urgently to hospital.
    To detect signs of a potentially serious infection, the mnemonic rule ABCD may be used: "A": decreased alert or activity, "B" ("breath"): signs of respiratory distress, such as nasal flaring and tachypnea, "C" (circulation or color): tachycardia, pallor, poor perfusion, petechiae, "D": (decrease in urine output or dehydration) 4 . The presence of any of these signs indicates the need for immediate referral to a hospital emergency department. The risk of occult bacteremia and severe bacterial infection correlates inversely with age (increased risk at lower age) and is influenced by general condition and, in a lesser extent, the magnitude of fever. Response to antipyretics does not correlate with severity of infection (strength of recommendation: A).
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  1. Feverish illness in children. Assesment and initial management in children younger than 5 years. NICE guideline 2013. Available from: http://guidance.nice.org.uk/CG160/Guidance/pdf/English. (Last accessed 20 March 2017)
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  1. Basic Clinical Practice Guidelines for the acute treatment of infants and children with fever. Policy Directive. NSW Government Health. 2010. Disponible en: http://www0.health.nsw.gov.au/policies/pd/2010/pdf/PD2010_063.pdf (Last accessed 20 March 2017)
High
No

 Age < 24 m
Yes
Intermediate (includes Tª > 39 °C (102.2 ºF) if age 3-6 m and fever > 5 days) [E]
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  1. Severe bacterial infections such as urinary tract infection (UTI) and occult bacteremia are more frequent with temperatures above 39 ° C (102.2 ºF). Thus, in children over 3 months a high grade fever is considered a risk factor. However, many viral infections also occur at temperatures between 39 °C and 40 °C. Temperature greater than 40 0C (104.0 ºF) and especially 40.5 °C (104.9 ºF) is more typical of bacterial infections.
No
Tª > 39 °C (102.2 ºF). or fever > 24 h
Measure heart and respiratory rates and body temperature and refer to the hospital
( Table 1 )
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Table 1. Heart and respiratory rates for age

Tachycardia Tachypnea
Age Heart rate (bpm) Age Respiratory rate (breaths/minute)
< 12 months >160 0 - 5 months > 60
12-24 months >150 6 – 12 months > 50
2 – 5 years >140 > 12 months > 40

Full blood count [F] , blood culture, procalcitonin (PCT)/ C-reactive protein (CPR) [G]

Urinalysis, and urine culture collected by catheterization or suprapubic aspiration [H, I]

Chest radiograph if respiratory signs are present: tachypnea (>60 rpm), crackles, retractions, cyanosis or oxygen saturation < 95 % [J]

Stool culture if diarrhea is present

Lumbar puncture for children younger than 1 month, ill appearing or WBC less than 5 × 109 or greater than 15 × 109/liter

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  1. White blood cell count (WBC) is generally not very useful for detecting or ruling out a serious bacterial infection. It has different characteristics depending on whether the infection is due to a Gram positive (pneumococcus) or a Gram negative pathogen (salmonella or meningococcus). In the last case there may be no leukocytosis but leftward deviation. WBC greater than 15,000 or less than 5,000/mm3 or an absolute neutrophil count (ANC) above 10,000/mm3 are considered risk factors for occult bacteremia. A total leukocyte count above 20,000/mm3 suggests an increased risk of occult pneumonia 1 .
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  1. Feverish illness in children. Assesment and initial management in children younger than 5 years. NICE guideline 2013. Available from: http://guidance.nice.org.uk/CG160/Guidance/pdf/English. (Last accessed 20 March 2017)
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  1. Elevations in levels of inflammatory mediators (i.e. C-reactive protein [CRP]and procalcitonin[PCT[]) may be better markers of severe bacterial infection (SBI) than white blood cell count (WBC) and absolute neutrophil count (ANC) in children at significant risk for bacterial infection. A CRP level > 150 mg/l is useful as a marker of bacterial infection, but CRP concentrations generally do not increase until 12 hours after the onset of fever. CRP values <20 mg/l are typical of viral infections
    PCT levels rise in response to bacterial infections more rapidly than those of CRP (3 h). PCT levels are usually < 1 ng/ml in viral infections whereas a value > 20 ng/ml is indicative of SBI. Some data suggest that PCT levels may be more sensitive and specific markers for severe invasive bacterial infection in infants and children than WBC, ANC, and CRP. However, those trials included febrile children with urinary tract infection (UTI) or other focal symptoms of infection, so their value in the diagnosis of children with fever without a source (FWS) and good general condition is still unknown. 5 .
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  1. Benito Fernández J. Aportación de los reactantes de fase aguda y los test de diagnóstico rápido en la orientación del niño con fiebre sin focalidad aparente. En: AEPap ed. Curso de Actualización Pediatría 2009. Madrid: Exlibris Ediciones; 2009. p. 81-6. Available from: http://www.aepap.org/sites/default/files/reactantes_fase_aguda.pdf (Last accessed 20 March 2017)
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  1. Urine dipstick is very useful in the outpatient setting to guide the need to collect a urine culture and asses the indication of an empirical treatment until its result. Urinary nitrite can indirectly reflect the presence of bacteriuria, because dietary nitrates are converted to nitrites in the presence of the most Gram-negative enteric bacteria in urine. This conversion requires urine to remain in the bladder for at least 4 hours, which often does not occur in infants, who empty their bladders frequently. Nitrite test has a high specificity (i.e. there are few false-positive results) but a low sensitivity, so it´s helpful when the result is positive but has a little value when negative in ruling out urinary tract infection (UTI)
    The presence of leukocyte esterase in the urine dipstick is a surrogate marker for pyuria. The overall sensitivity of leukocyte esterase test ranges from 85-95 % but specificity of the test is not as good, and therefore false-positive results are common. The absence of pyuria in children with true UTI is rare 6 and leucocyte esterase is also negative in asymptomatic bacteriuria.
    The probability of UTI with dipstick negative for leukocytes and nitrites is 2-6%, raises to 40-65% with positive nitrites or leukocytes and to 75-90 % with both positive nitrites and leukocytes 7 . Therefore, for non-toxic, febrile children >3 months, dipstick urinalysis is an appropriate screening test 4 . However, some guidelines recommend to perform urine culture with sterile technique in children without sphincter control (see UTI pathway). With dipstick positive for nitrites, UTI is very reliable and it would be indicated to start an empiric antibiotic after collecting an appropriate urine sample for culture. If negative for nitrites and positive for leukocytes, a urine culture should be collected and individualize the decision between initiating antibiotic treatment or waiting for results (see UTI pathway).
  2. Urinary tract infection (UTI) is the most common serious bacterial infection in children with fever without focus (FWS). The overall prevalence of UTI in febrile infants between 2 months and 2 years with FWS is 3-7%. 6 . In the first 6 months of life it is more prevalent in males, frequently associated with structural abnormalities of the urinary tract and from this age on it´s more prevalent in girls. Risk factors of UTI are Tª> 390C and previous UTI.
    It is necessary to ensure that a urine specimen for both culture and urinalysis is obtained before If it is decided to start antimicrobial therapy. The specimen needs to be obtained through catheterization or suprapubic aspiration (SPA) 6 because the diagnosis of UTI cannot be reliably established through an urine culture collected in a bag because it has a high percentage of false positives (30%). So, a “positive” culture result from a specimen collected in a bag cannot be used to document an UTI, although it is valid to discard it if negative. It could be an acceptable technique If immediate antimicrobial therapy is not required.
    Urine obtained through catheterization for culture has a sensitivity and specificity similar to that obtained through SPA 1 and is less painful.
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  1. Shaikh M, Hoberman A. Urinary tract infections in infants and children older than one month: Clinical features and diagnosis. UpToDate 2014. Available from: http://www.uptodate.com/contents/urinary-tract-infections-in-infants-and-children-older-than-one-month-clinical-features-and-diagnosis?source=search_result&search=urine+infection+children&selectedTitle=2%7E150 (Last accessed 20 March 2017)
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  1. Basic Clinical Practice Guidelines for the acute treatment of infants and children with fever. Policy Directive. NSW Government Health. 2010. Disponible en: http://www0.health.nsw.gov.au/policies/pd/2010/pdf/PD2010_063.pdf (Last accessed 20 March 2017)
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  1. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management from the American Academy of Pediatrics. Clinical Practice Guideline . Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months. Pediatrics 2011: 128: 595-610
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  1. Feverish illness in children. Assesment and initial management in children younger than 5 years. NICE guideline 2013. Available from: http://guidance.nice.org.uk/CG160/Guidance/pdf/English. (Last accessed 20 March 2017)
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  1. Most children with fever and pneumonia have some signs on physical examination: usually tachypnea, abnormal auscultation, low pulse oximetry, retractions, or nasal flaring, suggesting respiratory tract disease. The absence of cough or respiratory signs (tachypnea, retractions, nasal flaring, pulse oximetry <95% or abnormal auscultation) makes the diagnosis of occult pneumonia very unlikely 3 . Chest x-ray is indicated in infants under 3 months of age only if respiratory signs are present (Recommendation: B). There is insufficient evidence to determine when an Rx should be performed in children older than 3 years, but a chest x-ray should be considered in highly febrile children (temperature >39°C [>102.2°F]) with leukocytosis (WBC count >20,000/mm3) (Recommendation C) because of the strong association between leukocytosis and pneumonia 8 . The lack of signs or symptoms of lower respiratory tract infection obviates the need for a chest x-ray in children with Tª < 39ºC (>102.2°F) with no features of serious illness 9 .
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  1. Rodrigo C, Méndez M. Fiebre sin foco. Protocolos diagnósticos y terapéuticos de la AEP 2011. Available from: http://www.aeped.es/sites/default/files/documentos/fiebresinfoco.pdf (Last accessed 20 March 2017)
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  1. Rutman MS, Bachur R, Harper MB. Radiographic pneumonia in young, highly febrile children with leukocytosis before and after universal conjugate pneumococcal vaccination. Pediatr Emerg Care 2009;25:1
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  1. Clinical policy for children younger than three years presenting to the emergency department with fever. American College of Emergency Physicians Clinical Policies Committee; American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric Fever. Ann Emerg Med. 2003;4:530-45
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  1. Around 15% of cases of invasive meningococcal disease may present as fever without focus (FWS), basically in children aged 3 months to 3 years. There are no clinical nor analytical predictive factors of meningococcal bacteremia in the febrile child. Left shift with band cells > 10% is characteristic of meningococcal bacteremia, but it has a very low positive predictive value. Lumbar puncture is indicated in infants younger than 1 month, all infants aged 1–3 months who appear unwell or with a white blood cell count (WBC) less than 5 × 109/liter or greater than 15 × 109/liter, children with “red” features (NICE´s traffic light scale of all ages and also should be considered for children younger than 1 year who have 1 or more “amber” features.
    Physical examination may lead to suspicion of meningitis in patients older than 3 months and therefore lumbar puncture is not systematically indicated in this age group 3 .
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  1. Rodrigo C, Méndez M. Fiebre sin foco. Protocolos diagnósticos y terapéuticos de la AEP 2011. Available from: http://www.aeped.es/sites/default/files/documentos/fiebresinfoco.pdf (Last accessed 20 March 2017)
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  1. Paracetamol is given at doses of 10-15 mg / kg / dose every 4-6 h (max 75 mg / kg / day or 90 mg / kg / day for less than 3 consecutive days). The onset of action occurs at 30-60 minutes, with peak at 3-4 h, duration of 4-6 h and a reduction of the temperature of 1-2 °C. Ibuprofen, at 10 mg / kg / dose every 6 hours, has a similar onset, peak and temperature reductions, but a somewhat longer effect (6-8 h). Magnesium metamizole at doses of 10 mg / kg / dose every 6 hours orally or rectally or at 0.05 - 0.1 ml / kg / dose i.v. has also an antipyretic effect but presents the potential risk of agranulocytosis, and therefore is less commonly used.
    Paracetamol and ibuprofen have a similar safety profile and antipyretic efficacy, perhaps with a somewhat longer duration of antipyretic effect for ibuprofen. Although hepatotoxicity with acetaminophen at recommended doses has been rarely reported, hepatoxicity is most commonly seen in the setting of an acute overdose. In addition, there is significant concern over the possibility of acetaminophen-related hepatitis in the setting of a chronic overdose. The most commonly reported scenarios are those of children receiving multiple supratherapeutic doses (i.e. > 15mg/kg per dose) or frequent administration of appropriate single doses at intervals of less than 4 hours, which have resulted in doses of more than 90 mg/kg per day for several days. Ibuprofen can potentially cause gastritis, although no data suggest that this is a common occurrence when used on an acute basis, such as during a febrile illness10. Ibuprofen does not seem to worsen asthma symptoms 10 . A special mention should be made of the possibility of nephrotoxicity after the administration of an adequate dose of non-steroidal anti-inflammatory drugs (NSAID) 11 . In children with dehydration, prostaglandin synthesis is an important mechanism for maintaining an adequate renal flow, which could be interfered by the use of ibuprofen or other NSAIDs. However, the actual incidence of renal failure secondary to the use of ibuprofen over a short period of time is not known. Children at highest risk of ibuprofen-related renal toxicity are those with dehydration, cardiovascular disease, underlying nephropathy, or concomitant use of other nephrotoxic drugs. Another potential group at risk are infants younger than 6 months because of the possibility of differences in ibuprofen pharmacokinetics and developmental differences in renal function 3
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  1. Sullivan JE, Farrar HC. Clinical Report. Fever and Antipyretic Use in Children. Pediatrics 2011; 127: 580-587
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  1. Misurac JM, Knoderer CA, Leiser JD, Nailescu C, Wilson AC, Andreoli SP. Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children. J Ped 2013, 162: 1153-1159.e1 http://www.sciencedirect.com/science/article/pii/S0022347612014035 (Last accessed 20 March 2017)
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  1. Rodrigo C, Méndez M. Fiebre sin foco. Protocolos diagnósticos y terapéuticos de la AEP 2011. Available from: http://www.aeped.es/sites/default/files/documentos/fiebresinfoco.pdf (Last accessed 20 March 2017)
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  1. The mere presence of fever does not always require treatment. Fever may produce child's discomfort and increase insensible fluid losses, but with the exception of children with chronic or those critically ill who may not tolerate the increase in fever-induced metabolic demand, there is no evidence that the reduction of fever could reduce the morbimortality of the process. There is also no evidence that antipyretic therapy decreases the recurrence of febrile seizures. Therefore, the main goal of treating a febrile child should be to improve the child’s overall comfort rather than to achieve normothermia
    Adequate hydration should be ensured and avoid excessive draping to prevent dehydration. Application of alcohol, which can cause intoxication by inhalation, and cold water baths, which could even raise the central temperature by provoking skin vasoconstriction, are formally contraindicated. According to a limited number of studies, bath with warm water associated with antipyretic could contribute to reduction of temperature, but this effect is transient and is associated with discomfort. For all of the above, the use of physical measures to treat fever is not recommended 12, 13 .
    Alternation or combination of antipyretic drugs is a widespread practice, even favored or allowed by doctors. However, there is little evidence on the benefit of combined treatment compared with the use of each drug alone 14, . In addition, there are doubts about the safety of this practice, since Ibuprofen blocks renal prostaglandins and inhibits the production of glutathione (essential for the excretion of the toxic metabolite of paracetamol), and can lead to dosage errors and promote "feverfobia". Therefore, this practice is not recommended. 1, 4, 12
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  1. Feverish illness in children. Assesment and initial management in children younger than 5 years. NICE guideline 2013. Available from: http://guidance.nice.org.uk/CG160/Guidance/pdf/English. (Last accessed 20 March 2017)
X
  1. Basic Clinical Practice Guidelines for the acute treatment of infants and children with fever. Policy Directive. NSW Government Health. 2010. Disponible en: http://www0.health.nsw.gov.au/policies/pd/2010/pdf/PD2010_063.pdf (Last accessed 20 March 2017)
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  1. Richardson M, Lakhanpaul M, Guideline Development G, the Technical T. Assessment and initial management of feverish illness in children younger than 5 years: summary of NICE guidance. BMJ 2007;334:1163-4.
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  1. Meremikwu MM, Oyo-Ita A. Physical methods versus drug placebo or no treatment for managing fever in children. Cochrane Database of Systematic Reviews 2003, Issue 2. Available from: http://summaries.cochrane.org/CD004264/physical-methods-for-treating-fever-in-children (Last accessed 20 March 2017)
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  1. Systematic review of studies comparing combined treatment with paracetamol and ibuprofen, with either drug alone. Purssell E. Arch Dis Child. 2011;96:1175-9
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  1. Prescription of oral antibiotics to children with fever without apparent source is discouraged. However, with suspected meningococcal disease it is recommended to give parenteral antibiotics to children at the earliest opportunity (either benzylpenicillin or a third-generation cephalosporin). 1, 12
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  1. Feverish illness in children. Assesment and initial management in children younger than 5 years. NICE guideline 2013. Available from: http://guidance.nice.org.uk/CG160/Guidance/pdf/English. (Last accessed 20 March 2017)
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  1. Richardson M, Lakhanpaul M, Guideline Development G, the Technical T. Assessment and initial management of feverish illness in children younger than 5 years: summary of NICE guidance. BMJ 2007;334:1163-4.

Full blood count [F] , blood culture, PCT/CPR [G]

Urinalysis, and urine culture collected by catheterization or suprapubic aspiration [H, I]

Chest radiograph if WBC ≥20,000 and Tª > 39 °C (102.2 ºF). [J]

Consider lumbar puncture for children younger than 1 year [K]

Full blood count [F] , blood culture, PCT/CPR [G]

Urinalysis, and urine culture collected by catheterization or suprapubic aspiration [H, I]

Chest X-ray irrespective of body temperature and WBC

Lumbar puncture

Serum electrolytes and blood gases.

Positive nitrite test
Collect urine culture by catheterization or suprapubic aspiration and initiate antimicrobial treatment until culture result is available [H, I]
Urine dipstick
Negative nitrite test and positive leukocyte esterase
Collect urine culture and invidualize need for empiric treatment [H, I]
Negative leukocyte esterase and nitrite tests
Observation at home, antipyretics [L] if discomfort [M] and reevaluation in 24 h, or before if alert signs appear [N] . Some guidelines also recommend to collect a urine sample for culture if age <3 years (see UTI algorithm).

La traducción de esta publicación ha sido financiada por la Fundación para la Investigación e Innovación Biomédica de Atención Primaria de la Comunidad de Madrid (FIIBAP) mediante la convocatoria de ayudas para traducciones/publicaciones 2016

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