Approach

The decision to start empirical antibiotic therapy is informed by the child’s likelihood of having a urinary tract infection and their overall clinical condition. Infection may involve the upper or lower urinary tract; be complicated or uncomplicated; severe or non-severe; recurrent, breakthrough, or a re-infection; atypical, asymptomatic, or symptomatic. See Classification for more information.

Diagnosis and treatment are often concurrent processes. Empirical therapy may be commenced before diagnostic assessment is completed if there is a high risk of serious illness.

Children who are systemically unwell (toxic-looking, haemodynamically unstable, immunocompromised, unable to tolerate oral medication, or not responding to oral medication), and most children aged ≤2 months, should receive urgent empirical parenteral treatment.[54][62]

Treat children with febrile UTIs as soon as possible (within 48-72 hours) to avoid subsequent renal scarring.[1][26] 

Children who have a positive urinalysis but are not systemically unwell may be monitored closely until urine culture results are available.[1][4]​​

The goal of treatment is the eradication of bacteria. Choice of antimicrobial agents and route of administration (oral versus parenteral) should be based on:

  • Severity of illness

  • Patient factors (e.g., age, underlying renal disease, immunocompromised, recent antibiotic exposure)

  • Most likely pathogen: target initial therapy at Escherichia coli and other Enterobacterales, including Klebsiella and Enterobacter species

  • Local antimicrobial resistance patterns: antimicrobial resistance among uropathogens is a significant concern: more than 40% of E coli isolates from children with UTIs are resistant to ampicillin, and >20% are resistant to trimethoprim/sulfamethoxazole, which limits their use as initial therapy.[63] Consult local guidelines and formularies.

Adjust therapy to the nearest spectrum antibiotic following complete identification of the pathogen and susceptibility data.

Cure rates with antibiotics exceed 95%.[64]

Renal function and aminoglycoside blood levels should be monitored in patients treated with aminoglycosides (e.g., gentamicin) for >48 hours.[40]

Uncomplicated UTI

An uncomplicated UTI is one that occurs in a patient who has a structurally and functionally normal urinary tract, normal renal function, and a competent immune system. Uncomplicated UTIs generally involve the lower urinary tract (cystitis) rather than the upper urinary tract.[1]

Children may have mild pyrexia and mild dehydration, but do not have vomiting or any signs of sepsis, dehydration, or haemodynamic instability.

Choice of empirical therapy is guided by local antimicrobial resistance patterns. Therapy should be reviewed when the organism and its antimicrobial sensitivities are confirmed by culture, and changed to a narrower-spectrum agent if appropriate.

Oral therapy is usually appropriate for children with uncomplicated UTI. Options include a second- or third-generation cephalosporin (e.g., cefixime), amoxicillin/clavulanate, trimethoprim, trimethoprim/sulfamethoxazole, or nitrofurantoin.[1][5]​​[65][66]​​​ Cefalexin or amoxicillin may be used second-line if culture results confirm susceptibility.[65] Trimethoprim/sulfamethoxazole is active against multiple antibiotic-resistant bacteria, including extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales such as E coli and AmpC-beta-lactamase-producing Enterobacterales such as Klebsiella species.[66] Nitrofurantoin is active against cystitis caused by ESBL-producing Enterobacterales and AmpC-beta-lactamase-producing Enterobacterales.[66]

Treatment for penicillin-allergic patients depends on the age of the patient, history of drug allergy, and severity of illness. Consult a specialist for guidance on antibiotic selection in these patients. Allergy to penicillin is generally not a concern in neonates and young infants because they have not been challenged with penicillin before.

Typical treatment course is 7-14 days.[1] The American Academy of Pediatrics (AAP) recommends that oral antibiotic therapy for 7 to 10 days is adequate for uncomplicated febrile UTI that responds well to treatment.[5]​ One systematic review found that a 2- to 4-day course of antibiotics was as effective as a 7- to 14-day course at eradicating lower UTI in children.[67] A 3- to 5-day course may be considered.[1]

Complicated UTI

A complicated UTI is one that occurs in a child who has a structural or functional abnormality of the urinary tract. Complicated UTIs generally involve the upper urinary tract (pyelonephritis) rather than the lower urinary tract.[1]

Children ≤2 months

Neonates and infants aged ≤2 months are at high risk for serious bacterial infection and sepsis.[1][40] Symptoms are non-specific in this age group, making it difficult to distinguish UTI from other causes of serious bacterial infection at initial evaluation.[41][54] These children should be admitted to hospital for evaluation and most should receive empirical parenteral antibiotic therapy. See Sepsis in children for more information.

Oral antibiotics may be appropriate for well-appearing, febrile, term infants aged 29-60 days who have positive urinalysis result and normal inflammatory markers.[54]

Choice of empirical therapy is guided by past infections and associated antibiotic susceptibility data from the past 6 months, antibiotic exposures within the past 30 days, and local antimicrobial resistance patterns.[66] Suitable regimens include ampicillin plus gentamicin or ampicillin plus a third-generation cephalosporin (e.g., cefotaxime, cefepime, ceftriaxone).[62][68] The UK National Institute for Health and Care Excellence (NICE) recommends a third-generation cephalosporin plus an antibiotic active against listeria (e.g., ampicillin) for infants aged <3 months admitted to hospital with fever.[69] Gentamicin is active against multiple antibiotic-resistant bacteria, including ESBL-producing Enterobacterales such as E coli, AmpC-beta-lactamase-producing Enterobacterales such as Klebsiella species, and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR).[66] Cefepime is active against AmpC-beta-lactamase-producing Enterobacterales.[66]

Adjust therapy to the nearest spectrum antibiotic treatment following complete identification of the pathogen and determination of susceptibility data. Treatment is usually given for 7-14 days.[40]

Children >2 months with no structural renal disease

The choice between oral and intravenous therapy depends on patient age, suspicion of sepsis, illness severity, hydration status, tolerance for oral medication, and whether there are complications of infection.[1] NICE recommends intravenous antibiotics for children with pyelonephritis who are vomiting, unable to take oral antibiotics, or severely unwell.[70]

Choice of empirical therapy is guided by past infections and associated antibiotic susceptibility data from the past 6 months, antibiotic exposures within the past 30 days, and local antimicrobial resistance patterns.[66] Therapy should be reviewed when the organism and its antimicrobial sensitivities are confirmed by culture, and changed to a narrower-spectrum agent if appropriate.

Examples of suitable oral antibiotics include cefalexin, cefixime, and amoxicillin/clavulanate (if cultures confirm sensitivity).[1][70] Cefuroxime, ceftriaxone, gentamicin (with or without ampicillin), amikacin, or tobramycin may be used if intravenous treatment is required.[1][70] Ampicillin is added to cover Enterococci.[62] Amikacin is active against ESBL-producing Enterobacterales such as E coli.[66] Similarly to gentamicin, tobramycin is active against multiple antibiotic-resistant bacteria, including ESBL-producing Enterobacterales, AmpC-beta-lactamase-producing Enterobacterales such as Klebsiella species, and Pseudomonas aeruginosa with DTR.[66]

Treatment course is 7-14 days.[1] Switching from parenteral to oral antibiotic treatment in a stepwise manner for hospitalised patients should be considered whenever possible.[66] One systematic review reported no significant difference in microbiological eradication, renal scarring, clinical cure, re-infection, persistence of acute pyelonephritis, or re-infection in children who were switched to oral antibiotics after 5-10 days, compared with children who received intravenous antibiotics for 14 days.[71]

Children >2 months with structural renal disease

Choice of empirical therapy is guided by past infections and associated antibiotic susceptibility data from the past 6 months, antibiotic exposures within the past 30 days, and local antimicrobial resistance patterns.[66]

Cefalexin or amoxicillin/clavulanate may be used as first-line oral antibiotics (if culture results are available and bacteria are susceptible).​​[70]​

In patients with an underlying renal disorder who require broader gram-negative and Pseudomonas coverage and who are systemically stable at presentation, consider a fluoroquinolone such as oral ciprofloxacin.[72][73] Ciprofloxacin is active against ESBL-producing Enterobacterales such as E coli and AmpC-beta-lactamase-producing Enterobacterales such as Klebsiella species.[66]

Systemic fluoroquinolone antibiotics, such as ciprofloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[74]

  • Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability)

  • Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Consider second-line parenteral ampicillin plus gentamicin for patients with pre-existing structural renal disease and normal renal function. Alternative options include cefotaxime or ceftriaxone.[1] Both oral and intravenous formulations of cephalosporins have been demonstrated to be effective.[75]

Special patient populations

Consult a specialist for guidance on antibiotic selection in patients with penicillin allergy and those who are immunosuppressed, have renal impairment, or do not respond adequately to initial treatment. Therapy is individualised depending on patient factors, severity of illness, likely causative organisms, and local antimicrobial susceptibility patterns.

Allergy to penicillin is generally not a concern in neonates and young infants because they have not been challenged with penicillin before.

Nitrofurantoin should be avoided in children with renal impairment.

Antifungal therapy may be required in immunosuppressed patients.

Supportive care

Some patients may require supportive care with intravenous fluids and/or an antipyretic (e.g., paracetamol).

Lack of response to initial treatment

Lack of response to initial therapy may indicate that the organism is not susceptible to the antimicrobial agent used, or indicate the development of pyonephrosis, renal abscess, or obstructed urine drainage. Culture results should be reviewed and urgent ultrasound performed.

Recurrent UTI

A recurrent UTI is defined as:[4]

  • ≥2 episodes of acute pyelonephritis, or

  • 1 episode of acute pyelonephritis plus ≥1 episode of cystitis, or

  • ≥3 episodes of cystitis.

Recurrent UTIs may be due to unresolved infection (initial treatment is inadequate for elimination of bacteria in the urinary tract) or persistent infection (caused by re-emergence of bacteria in the urinary tract due to a site of persistent infection that cannot be eradicated [e.g., infected stones or fistulas]). The same pathogen is implicated in each recurrent infection.[1]

The American Urological Association recommends antibiotic prophylaxis for children aged <1 year with vesicoureteral reflux (VUR) and a history of febrile UTI, or grade 3 to 5 VUR identified through screening. Antibiotic prophylaxis may be considered for children with grade 1 to 2 VUR identified through screening without a history of febrile UTI.[37] The use of antibiotic prophylaxis for children aged ≥1 year with VUR is determined on a case-by-case basis. Clinical context, including the presence of bladder bowel dysfunction (BBD), patient age, VUR grade, the presence of scarring, and parental preferences, should be taken into account. Prophylaxis is recommended for children with both VUR and BBD.[37] BBD increases the risk of recurrent UTI twofold, and increases the risk of breakthrough UTI in children who also have vesicoureteral reflux.[25][27]

A short course of prophylactic antibiotics may be considered for toilet-trained children with BBD and recurrent UTIs, while optimising bladder and bowel management.[19] Children and carers should be educated about adequate hydration and ready access to toilets, to prevent delayed voiding.[4] Constipation should be treated to prevent further infections. Maintenance therapy may be required for months or years.  See Constipation in children for more information.

Antibiotic prophylaxis may also be considered in children with a significant urological anomaly.[37][38]

Prophylactic antibiotics have not been conclusively shown to reduce the risk of recurrent infection or renal scarring in children with or without VUR.[76][77][78][79] [ Cochrane Clinical Answers logo ]  

Suitable choices for prophylaxis include a first- or second-generation cephalosporin, trimethoprim, trimethoprim/sulfamethoxazole, or nitrofurantoin.[1][80] Nitrofurantoin and trimethoprim are preferred where available.[1]

Where possible, choice of prophylactic antibiotic should be guided by recent culture and sensitivity results. Rotating the prophylactic antibiotic used may increase the risk of antibiotic resistance. One meta-analysis calculated that one multidrug-resistant infection occurs for every 21 patients with VUR treated with antibiotic prophylaxis.[81] If a child develops acute UTI while taking prophylaxis, a different antibiotic should be used to treat the acute infection.[80]

The risk of resistance increases with the duration of antibiotic therapy. A course of prophylactic antibiotics usually lasts 3-6 months, after which it should be reassessed.[37][38]

Surgical management of high-grade VUR has also generally been recommended for children with recurrent UTI, but the added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone is unclear.[79][82] [ Cochrane Clinical Answers logo ] Refer patients with grade 4/5 VUR or a significant urological anomaly to a urologist.[38]

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