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Acute infectious cystitis: Management and prognosis in children older than two years and adolescents

Acute infectious cystitis: Management and prognosis in children older than two years and adolescents
Authors:
Debra L Palazzi, MD, MEd
Judith R Campbell, MD
Section Editors:
Tej K Mattoo, MD, DCH, FRCP
Sheldon L Kaplan, MD
Deputy Editor:
Mary M Torchia, MD
Literature review current through: Dec 2022. | This topic last updated: Oct 27, 2022.

INTRODUCTION — Cystitis is inflammation of the urinary bladder, usually caused by infection, which can occur alone or in conjunction with pyelonephritis.

The management and prognosis of acute infectious cystitis in children older than two years and adolescents will be reviewed here. The clinical features and diagnosis of acute infectious cystitis in children older than two years and adolescents is discussed separately. (See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents".)

Urinary tract infection in newborns and children younger than two years (in whom it is difficult to distinguish cystitis from pyelonephritis on clinical grounds) also is discussed separately.

(See "Urinary tract infections in neonates".)

(See "Urinary tract infections in children: Epidemiology and risk factors".)

(See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis".)

(See "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis".)

BACTERIAL CYSTITIS — Management of acute bacterial cystitis in children ≥2 years and adolescents depends upon clinical features, age, and antimicrobial resistance patterns in the community.

When to initiate antimicrobial therapy — Decisions regarding the initiation of empiric antimicrobial therapy for urinary tract infection (UTI) are best made on a case-by-case basis based upon the probability of UTI, which is determined by demographic and clinical factors, including results of the urinalysis (table 1). (See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents", section on 'Epidemiology' and "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents", section on 'Risk factors'.)

We typically initiate antimicrobial therapy for acute infectious cystitis pending culture results for:

Children who are febrile, immunocompromised, ill-appearing, or have an indwelling bladder catheter, underlying genitourinary abnormalities, or previous history of UTI

Children who are afebrile, immunocompetent, well-appearing, and without indwelling bladder catheter, underlying genitourinary abnormalities, or history of UTI if they have evidence of bacteriuria (with or without pyuria) on dipstick or microscopic analysis

We typically initiate antimicrobial therapy only if the urine culture is positive in afebrile, immunocompetent, well-appearing children without indwelling bladder catheter, underlying genitourinary abnormalities, or history of UTI who have evidence of pyuria but not bacteriuria on dipstick or microscopic analysis. Although children with pyuria without bacteriuria may have fungal or viral cystitis, such infections that require treatment generally occur in immunocompromised children or children with indwelling catheters. Other conditions that cause pyuria (eg, infections outside the urinary tract) should be considered. (See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents", section on 'Differential diagnosis'.)

In a systematic review, the probability of culture-proven UTI in verbal children ≥2 years with urinary or abdominal symptoms was approximately 90 percent if the urine dipstick was positive for both nitrite and leukocyte esterase and only 4 to 8 percent if the urine dipstick was negative for both nitrite and leukocyte esterase [1].

Choice of agent — The choice of empiric antibiotic therapy is guided by clinical features, age, local resistance patterns [2], and urine Gram stain, if performed. When urine culture results are available, antibiotic therapy can be tailored according to susceptibilities of the identified uropathogen.

Factors that increase the likelihood of a resistant isolate include immunocompromise, underlying medical problems (eg, neurogenic bladder), and antibiotic prophylaxis (for urinary tract or other medical problems). (See "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Antibiotic therapy'.)

A 2012 meta-analysis of 16 randomized and quasi-randomized trials evaluating antibiotic therapy for symptomatic acute bacterial cystitis in children concluded that antibiotic treatment was effective in clearing bacteriuria, but the data were insufficient to determine which antibiotic or duration of therapy is most effective [3].

Uncomplicated cystitis — Uncomplicated cystitis is limited to the lower urinary tract and typically occurs in children older than two years with no underlying medical problems or anatomic or physiologic abnormalities. Although uncomplicated cystitis may occur in children younger than two years, it is difficult to differentiate upper from lower UTI in such children and they are usually assumed to have upper UTI. Uncomplicated cystitis usually is caused by pathogens that are susceptible to commonly used antimicrobial agents.

We recommend that empiric therapy for uncomplicated acute bacterial cystitis in children and adolescents provide coverage for Escherichia coli. E. coli and other enteric gram-negative organisms are responsible for nearly 90 percent of UTI in children. Coverage for Staphylococcus saprophyticus in addition to E. coli coverage also may be warranted for sexually active female adolescents or if the urine Gram stain (if performed) or culture demonstrates gram-positive organisms. Coverage for Enterococcus rather than E. coli may be warranted if the urine Gram stain (if performed) or culture demonstrates gram-positive organisms. However, Enterococcus is more commonly isolated in cases of complicated cystitis. (See "Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents", section on 'Microbiology' and 'Complicated cystitis' below.)

E. coli coverage – For E. coli coverage, we suggest a second-generation (eg, cefuroxime, cefprozil) or third-generation cephalosporin (eg, cefdinir, cefixime, cefpodoxime, ceftibuten) for empiric therapy (table 2) because of increasing rates of E. coli and other pediatric uropathogen resistance to trimethoprim-sulfamethoxazole (TMP-SMX), amoxicillin-clavulanate, and first-generation cephalosporins [4-9]. However, depending upon local resistance rates, these agents may be acceptable alternatives to second- or third-generation cephalosporins [2].

Second- and third-generation cephalosporins have excellent activity against E. coli and most other gram-negative uropathogens [4]. However, they are not effective in treating gram-positive uropathogens (eg, Enterococcus or S. Saprophyticus).

S. saprophyticus coverage – TMP-SMX or nitrofurantoin can be used to treat S. saprophyticus. In a review of 524 S. saprophyticus isolates recovered from the urinary tracts of female outpatients, 3 percent were resistant to TMP-SMX and none to nitrofurantoin [10].

S. saprophyticus is also usually susceptible to fluoroquinolones. However, the safety of quinolones in children is still under study, and fluoroquinolones are not recommended for uncomplicated UTI [11-13]. (See "Fluoroquinolones", section on 'Children'.)

Enterococcus coverage – For most isolates of community-acquired Enterococcus, amoxicillin provides appropriate coverage. Nitrofurantoin is an alternative for children with penicillin allergy. (See "Penicillin allergy: Immediate reactions".)

Complicated cystitis — Complicated cystitis is defined by coexisting upper UTI, multiple-drug resistant uropathogens, or hosts with special considerations (eg, anatomic or physiologic abnormality of the urinary tract, indwelling bladder catheter, malignancy, diabetes). (See "Etiology and clinical features of bladder dysfunction in children" and "Evaluation and diagnosis of bladder dysfunction in children".)

Empiric therapy for children and adolescents with complicated cystitis is individualized according to clinical status, underlying problem(s), and previous culture results and susceptibilities. Parenteral therapy may be necessary. (See 'Indications for parenteral therapy' below.)

Empiric therapy for upper UTI in children is discussed separately. (See "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Empiric therapy'.)

When urine culture results are available, antibiotic therapy can be tailored according to susceptibilities of the identified uropathogen.

Indications for parenteral therapy — Parenteral therapy occasionally is indicated for:

Patients with complicated cystitis caused by multiple drug-resistant uropathogens; parenteral therapy can be switched to oral therapy after clinical improvement (eg, resolution of fever, decreased symptoms) if appropriate oral agents are available

Patients who are allergic or intolerant to available and appropriate oral agents

Duration of therapy — The duration of therapy depends upon the age of the child and the clinical scenario. The duration of therapy is generally shorter for uncomplicated than complicated cystitis.

We usually treat the first episode of uncomplicated, afebrile cystitis in females ≥2 years and males between 2 and 13 years for five days.

We usually treat children ≥2 years with recurrent, febrile, or complicated cystitis and males ≥13 years of age with uncomplicated cystitis for 7 to 10 days.

The duration of antibiotic therapy for afebrile children with presumed cystitis has been the subject of several meta-analyses of randomized trials [3,14-16], the most recent of which concluded that the data were insufficient to determine which duration of therapy is most effective [3]. In general, children treated with a single day or single dose of antibiotics have decreased cure rates (resolution of bacteriuria and lack of recurrence) compared with those treated for at least 7 days. Excluding trials in which the short course was one day or less, the cure rate was similar among children treated with antibiotics for 2 to 4 days and children treated for longer (7 to 14 days). However, a number of the primary studies included in these analyses had limitations (eg, inclusion of an unspecified number of children with asymptomatic bacteriuria or recurrent UTI) [16], and the results should be applied with caution.

Treatment of complicated cystitis for 7 to 10 days is supported by a multicenter retrospective comparative effectiveness study of 791 children with pyelonephritis, in which rates of treatment failure (approximately 10 percent) were similar whether antibiotics were prescribed for 6 to 9 days or ≥10 days [17].

Response to therapy — Patients receiving treatment with an antimicrobial agent to which the infecting pathogen is susceptible should have clear signs of improvement (eg, resolution or decrease in lower urinary symptoms) within 24 to 48 hours.

In patients who improve as expected, "test of cure" urine cultures are not necessary. For patients who worsen or fail to demonstrate the expected clinical response during the first 48 hours of therapy, urine culture should be repeated to assess persistence of bacteriuria.

In addition, imaging of the urinary tract may be necessary to evaluate potential complications including:

Upper tract infection (see "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Renal scintigraphy')

Renal abscess (see "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Ultrasonography')

Urinary calculi (see "Kidney stones in children: Clinical features and diagnosis", section on 'Imaging')

Surgically correctable anatomic abnormalities or obstruction (see "Urinary tract infections in infants older than one month and young children: Acute management, imaging, and prognosis", section on 'Ultrasonography')

Management of bladder catheters — In patients with an indwelling bladder catheter, removal of the catheter may help to eradicate bacteriuria; if the patient requires an indwelling catheter, placement of a new catheter may be beneficial. The new catheter should be changed if signs of colonization recur (eg, isolation of bacteria from the urine without symptoms).

FUNGAL CYSTITIS — The majority of fungal infections of the bladder are caused by Candida spp, and most patients with candiduria have asymptomatic colonization rather than infection. Treatment of symptomatic and asymptomatic candiduria is discussed in detail separately. (See "Candida infections of the bladder and kidneys", section on 'Treatment'.)

In patients with an indwelling bladder catheter, removal of the catheter may help to eradicate funguria; if the patient requires an indwelling catheter, placement of a new catheter may be beneficial. The new catheter should be changed if signs of colonization recur (eg, isolation of Candida spp from the urine without symptoms).

If antifungal therapy is indicated, the choices include intravenous (IV) amphotericin B, oral or IV fluconazole, or bladder irrigation with amphotericin B [18]. There are few controlled trials that compare different antifungal regimens, and almost all therapeutic management decisions are based on past experience.

Our general approach to treating patients with catheter-associated funguria is to remove or replace the indwelling catheter and initiate treatment with oral/enteral fluconazole for 7 to 10 days. Patients who cannot tolerate enteral medications are treated with IV fluconazole. Those patients with contraindications to azole therapy (eg, allergy, medication interactions, azole-resistant pathogens) or those with systemic candidiasis are treated with IV amphotericin B. Bladder irrigation with amphotericin B deoxycholate for five days may be warranted for patients with fluconazole-resistant organisms (eg, Candida krusei and Candida glabrata).

VIRAL CYSTITIS — The treatment of adenovirus and polyomavirus cystitis usually is supportive. Reduction of immunosuppressive medications, if feasible, may be helpful for patients on immunosuppressive therapy. Decisions regarding management of immunosuppressive therapy should be made in consultation with the prescribing specialist.

We make decisions regarding antiviral therapy on a case-by-case basis based on several variables (eg, degree of immunosuppression). Controlled trials of the treatment of viral hemorrhagic cystitis are lacking; in anecdotal reports, antiviral therapy (ribavirin or cidofovir) has been tried with variable outcomes [19-24]. (See "Diagnosis, treatment, and prevention of adenovirus infection", section on 'Treatment'.)

PROGNOSIS — Most children and adolescents with acute uncomplicated bacterial cystitis have no long-term sequelae and little risk of recurrence.

Children and adolescents with anatomic, functional, or immunologic abnormalities may develop chronic bacteriuria, recurrent cystitis, or progression to upper urinary tract disease. Recurrent upper urinary tract infection may lead to chronic renal scarring and impaired renal function. (See "Urinary tract infections in children: Epidemiology and risk factors", section on 'Risk factors for renal scarring'.)

In patients with asymptomatic funguria, progression to candidemia is uncommon (1.3 percent in a large series of adult patients) [25]. (See "Candida infections of the bladder and kidneys".)

Immunocompromised patients with hemorrhagic cystitis due to either adenovirus or BK virus are at increased risk of developing persistent infection and hematuria that may require surgical intervention (eg, diverting nephrostomy, bladder fulguration cystoscopy, removal of bladder clots). (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Infections in immunocompromised hosts'.)

The risk for dissemination and multiorgan system infection, which are associated with increased mortality, is greatest in patients with marked immune dysfunction.

PREVENTION — Prevention of recurrent urinary tract infection in children and female adolescents is discussed separately. (See "Urinary tract infections in children: Long-term management and prevention", section on 'Antimicrobial prophylaxis' and "Management of vesicoureteral reflux" and "Recurrent simple cystitis in women", section on 'Initial approach to prevention'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Urinary tract infections in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topic (see "Patient education: Urinary tract infections in children (Beyond the Basics)")

Beyond the Basics topic (see "Patient education: Urinary tract infections in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

When to initiate antimicrobial therapy – Decisions regarding the initiation of empiric antimicrobial therapy for urinary tract infection (UTI) are best made on a case-by-case basis based upon the probability of UTI, which is determined by demographic and clinical factors (table 1). (See 'When to initiate antimicrobial therapy' above.)

We typically initiate antimicrobial therapy pending culture results for children who are:

Febrile, immunocompromised, ill-appearing, have underlying genitourinary abnormalities or previous history of UTI

Afebrile, immunocompetent, well-appearing, and without underlying genitourinary abnormalities or history of UTI if they have bacteriuria (with or without pyuria) on dipstick or microscopic analysis

We typically initiate antimicrobial therapy only if the urine culture is positive in afebrile, immunocompetent, well-appearing children without underlying genitourinary abnormalities or history of UTI who have pyuria without bacteriuria (on dipstick or microscopic analysis).

Choice of agent – The choice of antibiotic therapy for acute bacterial cystitis should be guided by local resistance patterns, urine Gram stain (if performed), and, ultimately, urine culture and susceptibility results. (See 'Choice of agent' above.)

We recommend that empiric therapy for uncomplicated acute bacterial cystitis in children and adolescents include coverage for Escherichia coli (Grade 1B). We suggest a second- or third-generation cephalosporin rather than amoxicillin-clavulanate, trimethoprim-sulfamethoxazole (TMP-SMX), or a first-generation cephalosporin as the first-line agent for these patients (table 2) (Grade 2B). However, depending upon local resistance rates, TMP-SMX or a first generation cephalosporin may be an acceptable alternative to a second- or third-generation cephalosporin. (See 'Uncomplicated cystitis' above.)

Coverage for Staphylococcus saprophyticus (in addition to E. coli) also may be warranted for sexually active female adolescents or if the urine Gram stain or culture demonstrates gram-positive organisms. We suggest trimethoprim-sulfamethoxazole (TMP-SMX) or nitrofurantoin for S. saprophyticus coverage (table 2) (Grade 2B). The most appropriate first-line therapy is suggested by local susceptibility patterns. (See 'Uncomplicated cystitis' above.)

Duration of therapy – The duration of therapy depends upon the age of the child and the clinical scenario. We usually treat the first episode of uncomplicated, afebrile cystitis in females ≥2 years and males between 2 and 13 years for at least five days. We usually treat children ≥2 years with recurrent, febrile, or complicated cystitis and males ≥13 years of age with uncomplicated cystitis for 7 to 10 days. (See 'Duration of therapy' above.)

Response to therapy – Patients being treated for acute bacterial cystitis with an antimicrobial agent to which the infecting pathogen is susceptible should have clear signs of improvement (eg, resolution or decrease in lower urinary symptoms) within 24 to 48 hours. (See 'Response to therapy' above.)

Prognosis – Most children and adolescents with uncomplicated cystitis have no long-term sequelae and little risk of recurrence. (See 'Prognosis' above.)

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