Acute infectious cystitis: Clinical features and diagnosis in children older than two years and adolescents

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

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

TERMINOLOGY

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. Uncomplicated cystitis usually is caused by pathogens that are susceptible to commonly used antimicrobial agents.

Complicated cystitis — Complicated cystitis is defined by coexisting upper urinary tract infections, 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".)

PATHOGENESIS — In the normal host, most uropathogens originate in the gastrointestinal tract, migrate to the periurethral area and the urethra, and ascend to the bladder, where they stimulate a host response. Bacterial adhesins (pili) and other virulence factors, such as hemolysin and flagellae, provide a selective advantage. (See "Bacterial adherence and other virulence factors for urinary tract infection".)

Patients who have urodynamic dysfunction, neurogenic bladder, or incomplete bladder emptying may harbor pathogens in residual urine, creating a source for persistent or recurrent infection.

The pathogenesis of catheter-associated urinary tract infections involves ascension of organisms along a biofilm on intraluminal or extraluminal surface of the catheter. Failure to maintain the integrity of a closed urinary catheter system provides access for organisms to enter the bladder.

EPIDEMIOLOGY — The prevalence of acute infectious cystitis in children is difficult to determine because most epidemiologic studies include children with both lower and upper urinary tract infection (UTI). In pooled analysis of four studies that included children younger than 19 years (most of whom were older than two years) and had urinary symptoms and/or fever, the prevalence of UTI was 7.8 percent (95% CI 6.6-8.9) [1]; no distinction was made between upper and lower tract disease, and sexual activity was not assessed.

RISK FACTORS — Risk factors for acute infectious cystitis in children and adolescents include:

●Female sex – Urinary tract infections (UTI), including acute infectious cystitis, are more common among females than males [2]. The combination of virulence factors and the propensity of bacteria to adhere to the female periurethral mucosa may explain the increased incidence of acute infectious cystitis in females compared with males [3]. Other factors that may contribute to the lower incidence of acute infectious cystitis in males include the antibacterial properties of prostatic fluid, drier periurethral environment, and longer urethra.

●Lack of circumcision is a risk factor for UTI in males, but is most important in infants. (See "Urinary tract infections in children: Epidemiology and risk factors" and "Urinary tract infections in children: Epidemiology and risk factors", section on 'Lack of circumcision'.)

●Sexual activity – Sexual intercourse is one of the most important risk factors for acute infectious cystitis in females. Sexually active young females have approximately 0.5 episodes of acute infectious cystitis per person-year [4].

Unprotected insertive anal intercourse also may increase the risk of acute infectious cystitis in males [5].

●Abnormalities of the urinary system, including [6]:

•Bladder stones (see "Kidney stones in children: Clinical features and diagnosis", section on 'Dysuria and urgency')

•Bowel and bladder dysfunction (see "Etiology and clinical features of bladder dysfunction in children", section on 'Urinary tract infection')

•Neurogenic bladder (prolonged stasis of urine in the bladder predisposes to infection) [7,8] (see 'Pathogenesis' above)

•Anatomic abnormalities (eg, bladder outlet obstruction [posterior urethral valves], which also lead to prolonged stasis; vesicoureteral reflux) (see "Clinical presentation and diagnosis of posterior urethral valves" and "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux")

●Indwelling bladder catheter or recent instrumentation of the urinary system [9-12]; the risk of catheter-associated UTI increases with duration of urinary catheter use, female sex, severity of illness, cardiovascular surgery, multiple trauma, diabetes, and multiple organ failure [10,13].

●Sickle cell disease. (See "Sickle cell disease effects on the kidney", section on 'UTI and pyelonephritis'.)

●Diabetes mellitus. (See "Susceptibility to infections in persons with diabetes mellitus" and "Emphysematous urinary tract infections".)

●Immunodeficiency.

MICROBIOLOGY — Most cases of cystitis in children and adolescents are caused by enteric bacteria. However, cystitis may be caused by any pathogen that colonizes the periurethral area and urinary tract, including nonenteric bacteria, fungi, viruses, and parasites (table 1) [14,15].

The potential pathogens vary according to host characteristics (table 2):

●Normal host – Escherichia coli and other gram-negative organisms account for nearly 90 percent of cases of uncomplicated cystitis in older children, adolescents, and young adults. In a 2009 national surveillance study, E. coli accounted for 79 percent of outpatient urinary isolates obtained from children younger than 18 years [2]. E. coli was more frequently isolated from females than males (83 versus 50 percent). Other pathogens were more frequently isolated from males than females: Enterococcus (17 versus 5 percent), Proteus mirabilis (11 versus 4 percent), Pseudomonas aeruginosa (7 versus 2 percent), and Enterobacter (5 versus 1 percent).

Adenovirus is an uncommon cause of acute infectious cystitis (usually hemorrhagic) in children without underlying medical problems. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Genitourinary tract'.)

In Africa and the Middle East, hematuria and cystitis in otherwise healthy children may be due to Schistosoma haematobium [16]. (See "Schistosomiasis: Epidemiology and clinical manifestations", section on 'Genitourinary schistosomiasis'.)

●Recent or prolonged antibiotic exposure – Recent or prolonged antibiotic exposure (eg, prophylactic antibiotics for children with vesicoureteral reflux) increases the risk of resistant E. coli and non-E. coli uropathogens.

●Underlying genitourinary abnormality

•Bladder dysfunction – Among children with bladder dysfunction, E. coli is the most frequently isolated organism, unless there is a history of recent infection, recent antibiotic exposure, or colonization with a gram-negative rod other than E. coli or another pathogen.

•Other genitourinary abnormalities – Enteric pathogens that are increasingly isolated from children with other underlying genitourinary abnormalities include Klebsiella spp, Enterobacter spp, and P. aeruginosa [15].

●Indwelling bladder catheter – P. aeruginosa and Candida albicans are the most common pathogens in catheter-associated cystitis. Cystitis caused by coagulase-negative staphylococcal species, such as Staphylococcus epidermidis, also almost exclusively occurs in patients with indwelling devices. Funguria is particularly common in patients with indwelling urinary catheters who are taking antibiotics or are immunocompromised [17].

●Sexually active females – In addition to E. coli and other gram-negative organisms, uropathogens that must be considered in sexually active female adolescents and young adults include Staphylococcus saprophyticus [18] and Trichomonas vaginalis. (See "Bacterial adherence and other virulence factors for urinary tract infection", section on 'Staphylococcus saprophyticus' and "Trichomoniasis: Clinical manifestations and diagnosis", section on 'Clinical features and consequences'.)

●Immunocompromised child – During prolonged hospitalization or urinary catheterization, immunocompromised patients are susceptible to health care-associated infection, including cystitis caused by enteric pathogens, gram-positive organisms (eg, Enterococcus), viruses, and yeast (table 1).

Patients with impaired T cell immune function can develop primary or reactivated adenoviral infection, which often presents as hemorrhagic cystitis. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Genitourinary tract'.)

Hematopoietic cell transplant and solid organ transplant recipients are at risk of developing hemorrhagic cystitis due to reactivation of latent adenovirus or polyomaviruses (BK and JC) [19-22]. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Genitourinary tract' and "Overview and virology of JC polyomavirus, BK polyomavirus, and other polyomavirus infections".)

CLINICAL PRESENTATION — Patients with acute infectious cystitis usually present with lower urinary tract symptoms (eg, dysuria, frequency, urgency, new onset incontinence [in toilet-trained child], abdominal or suprapubic pain), and/or hematuria [23]. However, lower urinary tract symptoms are not always caused by acute infectious cystitis. (See 'Differential diagnosis' below.)

Children with acute uncomplicated cystitis usually do not have fever or systemic complaints. Fever >38°C (100.4°F), chills, or flank pain suggest upper tract infection rather than acute infectious cystitis [24] but cannot reliably make this distinction. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Clinical presentation'.)

The clinical manifestations of hemorrhagic cystitis range from microscopic hematuria to extensive bladder hemorrhage with clot formation and obstruction. Adenovirus cystitis is characterized by the acute onset of dysuria and frequency followed by hematuria 12 to 24 hours later [25]; upper respiratory tract infection may precede urinary symptoms. (See "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Clinical presentation'.)

Symptoms of dysuria or frequency often are absent in patients with neurogenic bladder. In patients with bladder dysfunction and urinary stasis, cloudiness of urine, a change in the urinary sediment and/or odor, and pathogen colony count ≥100,000 colony forming units (CFU)/mL may help to differentiate between acute infectious cystitis and chronic bacteriuria due to colonization. (See 'Diagnosis' below.)

EVALUATION

History

●Acute illness – The history of the acute illness should include:

•Fever (temperature ≥38°C [100.4°F]) – Suggests upper urinary tract infection (UTI) rather than acute infectious cystitis but cannot reliably make this distinction (see "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Clinical presentation')

•Vomiting – Suggestive of upper UTI

•Recent illness – May suggest adenovirus infection or acute poststreptococcal glomerulonephritis, both of which may be associated with hematuria (see "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Clinical presentation' and "Poststreptococcal glomerulonephritis")

•Recent antibiotics – May be associated with pathogens other than E.coli and resistant pathogens [26]

•Urethral discharge – May be associated with urethritis and in males, possibly epididymitis

•Vaginal discharge – May be associated with vaginitis or cervicitis

•Sexual activity – Increases the risk of acute infectious cystitis and expands the list of pathogens to be considered (eg, S. saprophyticus, T. vaginalis)

-Use of barrier contraception with spermicidal agents in sexually active females – Predisposes to UTI by altering the normal vaginal flora [27] and may contribute to chemical cystitis [28] (see 'Microbiology' above)

●Past medical history – Information from the past medical history should include (see "Urinary tract infections in children: Epidemiology and risk factors", section on 'Host factors'):

•Chronic urinary symptoms (eg, incontinence, poor stream, frequency, urgency, withholding maneuvers) – May be associated with anatomic or physiologic abnormalities of the urinary tract (eg, bladder dysfunction, posterior urethral valves), increasing the risk of resistant pathogens or recurrent UTI (see "Evaluation and diagnosis of bladder dysfunction in children", section on 'When to suspect bladder dysfunction' and "Clinical presentation and diagnosis of posterior urethral valves", section on 'Presentation')

•Chronic constipation – May be associated with bladder and bowel dysfunction (eg, overactive bladder, dysfunctional voiding) (see "Constipation in infants and children: Evaluation", section on 'Constipation and bladder dysfunction' and "Etiology and clinical features of bladder dysfunction in children", section on 'Bowel and bladder dysfunction')

•Previous UTI or undiagnosed febrile illnesses (which may have been UTI) – Associated with progression of renal scarring (see "Urinary tract infections in children: Long-term management and prevention", section on 'Monitor for recurrent symptoms')

•Vesicoureteral reflux (VUR) – Associated with increased risk of recurrent infection and possibly loss of renal parenchyma (see "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Loss of renal parenchyma')

•Medications – May be associated with interstitial nephritis or urinary retention (see 'Differential diagnosis' below)

•Family history of frequent UTI, VUR, and other genitourinary abnormalities – May be associated with undiagnosed anatomic or physiologic abnormalities of the urinary tract in the patient (see "Clinical presentation, diagnosis, and course of primary vesicoureteral reflux", section on 'Genetics' and "Overview of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Epidemiology')

Physical examination — Important aspects of the physical examination in the child with suspected UTI include [14,23,29]:

●Temperature – Fever (temperature ≥38°C [100.4°F]) suggests upper UTI rather than acute infectious cystitis but cannot reliably make this distinction (see "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Clinical presentation')

●Blood pressure – Hypertension may be an early sign of chronic kidney disease (see "Chronic kidney disease in children: Complications", section on 'Hypertension')

●Growth parameters – Poor weight gain may be an indication of chronic or recurrent UTI (see "Chronic kidney disease in children: Complications", section on 'Malnutrition and poor growth')

●Abdominal palpation for mass (eg, enlarged bladder or enlarged kidney, suggestive of anatomic abnormality)

●Assessment of suprapubic and costovertebral angle tenderness (suprapubic tenderness is suggestive of lower UTI, whereas costovertebral angle tenderness suggests upper UTI)

●Evaluation of the lower back for signs of occult myelodysplasia (eg, midline pigmentation, lipoma, vascular lesion, sinus, tuft of hair), which may be associated with a neurogenic bladder (see "Myelomeningocele (spina bifida): Anatomy, clinical manifestations, and complications")

●Examination of the external genitalia for anatomic abnormalities that may predispose to UTI (eg, phimosis or labial adhesions) and signs of considerations in the differential diagnosis (eg, vulvovaginitis, vaginal foreign body, sexually transmitted diseases) (see "Vulvovaginitis in the prepubertal child: Clinical manifestations, diagnosis, and treatment" and "Overview of vulvovaginal conditions in the prepubertal child" and "Sexually transmitted infections: Issues specific to adolescents", section on 'STI clinical patterns' and "Care and complications of the uncircumcised penis in infants and children", section on 'Phimosis')

Laboratory evaluation — The laboratory evaluation of the child or adolescent with possible cystitis typically includes a urinalysis (dipstick and microscopic examination) and urine culture. (See 'Diagnosis' below.)

Sexually active adolescents with history or examination findings of possible urethritis (urethral discharge); vaginitis or cervicitis (eg, vaginal discharge, intermenstrual or postcoital bleeding, dyspareunia); or epididymitis (urethral discharge, painful or swollen epididymis) should be tested for sexually transmitted infections (with nucleic acid amplification or nucleic acid hybridization tests or culture). (See "Sexually transmitted infections: Issues specific to adolescents", section on 'STI clinical patterns' and "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents" and "Clinical manifestations and diagnosis of Chlamydia trachomatis infections", section on 'Nucleic acid amplification testing (test of choice)'.)

DIAGNOSIS — Acute bacterial cystitis is defined as significant bacteriuria (ie, ≥100,000 colony forming units [CFU]/mL of a uropathogen from a clean catch urine sample or ≥50,000 CFU/mL of a uropathogen from a catheterized urine sample) in a patient with an inflammatory response and lower urinary tract symptoms (eg, dysuria, frequency, etc). Quantitative urine culture is the standard test for significant bacteriuria. Pyuria on dipstick or microscopic urinalysis confirms the inflammatory response. The criterion for pyuria is less likely to be met if the uropathogen is an Enterococcus species, Klebsiella species, or P. aeruginosa than for E. coli [30].

Clinical suspicion — Acute infectious cystitis should be suspected in children ≥2 years and adolescents with lower urinary tract symptoms (eg, dysuria, frequency, urgency, new onset incontinence, abdominal or suprapubic pain) and/or hematuria [31].

Whether or not they have lower urinary tract symptoms, urinary tract infection (UTI; including complicated cystitis) also should be suspected in children who are febrile (≥38°C [100.4°F]) if they:

●Have an indwelling bladder catheter or had bladder catheterization in the previous 48 hours

●Are immunocompromised and an alternative source of fever (eg, bacteremia) has not been identified

●Have abnormalities of the urinary tract

●Have a history of previous UTI

●Have a family history of urinary tract disease

Urinalysis — Urinalysis is necessary to assess the inflammatory response (ie, pyuria). Pyuria can be established on dipstick or microscopic urinalysis. Dipstick and microscopic urinalysis also can suggest bacteriuria before the results of the urine culture are available. However, quantitative urine culture is necessary to confirm the diagnosis. (See 'Bacterial culture' below.)

A clean-voided specimen is the preferred method of collection for toilet-trained children. For children who are not toilet trained, we prefer catheterized urine samples to suprapubic aspiration samples given that providers may not be proficient in obtaining suprapubic samples. (See "Urine collection techniques in infants and children with suspected urinary tract infection".)

●Pyuria – Pyuria is established by any of the following:

•Positive leukocyte esterase on dipstick analysis

•≥5 white blood cells (WBC)/high power field (hpf) with standard microscopy (centrifuged and unstained)

•≥10 WBC/mm3 on a hemocytometer with an enhanced urinalysis (which is performed at some centers on catheterized urine samples that are Gram stained but not centrifuged) [32]

Pyuria may be less likely with certain pathogens (eg, Enterococcus species, Klebsiella species, P. aeruginosa) [30].

●Bacteriuria – Bacteriuria is suggested by any of the following:

•Positive nitrites on dipstick analysis; nitrites are produced by Enterobacteriaceae (eg, E. coli, Klebsiella, and Proteus); a negative dipstick nitrite does not exclude bacteriuria because urine must remain in the bladder for at least four hours to accumulate a detectable amount of nitrite (see "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Rapidly available tests')

•Any bacteria per hpf on standard microscopic analysis (centrifuged and unstained)

•Any bacteria per 10 oil immersion fields on a Gram-stained smear on enhanced urinalysis (which is performed at some centers on catheterized urine samples) [32]

In studies correlating urinalysis results with urine culture, positive leukocyte esterase and/or nitrites on dipstick analysis or WBC or bacteria on microscopic examination are highly suggestive of UTI (table 3) [33,34]. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Rapidly available tests'.)

Urine culture

Bacterial culture — Urine culture should be obtained in children in whom acute infectious cystitis is suspected. Urine culture is necessary to determine if the bacteriuria is significant, whether the isolate is a uropathogen, and for susceptibility testing to guide therapy. (See "Acute infectious cystitis: Management and prognosis in children older than two years and adolescents", section on 'Bacterial cystitis'.)

The definition of significant bacteriuria depends upon the method of collection and the identification of the isolated organism (see "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Diagnostic criteria'):

●With midstream (clean catch) samples, significant bacteriuria usually is defined by the growth of ≥100,000 CFU/mL of a single pathogenic organism [35]. However, we suggest using a threshold of 10,000 CFU/mL for males ≥15 years of age in whom there is an association between UTI and underlying urologic abnormalities (which increases the potential benefit of antibiotic therapy). (See "Acute simple cystitis in adult and adolescent males", section on 'Urine culture'.)

●With catheterized samples, significant bacteriuria usually is defined by growth of at least 50,000 CFU/mL of a single pathogenic organism [36,37].

●Uropathogens in children and adolescents include organisms such as E. coli, Klebsiella spp, Enterobacter spp, and P. aeruginosa (table 1).

Lactobacillus spp, coagulase-negative staphylococci other than S. saprophyticus, and Corynebacterium spp are not considered clinically relevant uropathogens in immune-competent children without indwelling bladder catheters.

Viral culture

●Immunocompromised children – Viral cultures should be obtained in immunocompromised children and adolescents with hematuria (gross or microscopic) if a bacterial pathogen has not been isolated and if another explanation for hematuria (eg, vulvovaginitis) has not been identified.

Adenovirus, cytomegalovirus, and polyomaviruses (BK, JC) may cause cystitis in children with impaired T cell function and children who have undergone hematopoietic cell or solid organ transplant. (See 'Microbiology' above and "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection", section on 'Genitourinary tract' and "Evaluation of gross hematuria in children", section on 'Symptomatic hematuria'.)

Viral culture and polymerase chain reaction assays are highly sensitive and specific methods for detecting cytomegalovirus and most adenoviruses. (See "Diagnosis, treatment, and prevention of adenovirus infection".)

The diagnosis of polyomavirus cystitis is discussed separately. (See "Overview and virology of JC polyomavirus, BK polyomavirus, and other polyomavirus infections".)

●Immune-competent children – In immune-competent children, viral cultures generally do not identify the cause of urinary tract signs and symptoms and we do not obtain them routinely [38].

Adenovirus is a rare cause of symptomatic acute infectious cystitis in immune-competent children and adolescents without abnormalities of the urinary tract. Most immune-competent children with adenoviral infection present with incidental microscopic hematuria associated with respiratory symptoms [38]. Those with hemorrhagic cystitis usually present with fever. Therefore, if a bacterial pathogen has not been isolated and if another explanation for hematuria (eg, severe thrombocytopenia, vulvovaginitis) has not been identified, noninfectious causes of hematuria (eg, autoimmune disease such as systemic lupus erythematosus) should be considered. (See "Evaluation of microscopic hematuria in children" and "Evaluation of gross hematuria in children".)

Fungal culture — The vast majority of fungal UTIs are caused by Candida spp, which are easily isolated on routine bacterial media. Specific fungal cultures rarely are warranted in pediatric patients.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of urinary symptoms (dysuria, frequency, urgency, new onset incontinence, abdominal or suprapubic pain) and/or hematuria in children ≥2 years and adolescents includes the conditions listed below (table 4). Detailed approaches to children with dysuria, hematuria, and abdominal pain are provided separately. (See "Etiology and evaluation of dysuria in children and adolescents" and "Evaluation of gross hematuria in children" and "Causes of acute abdominal pain in children and adolescents" and "Emergency evaluation of the child with acute abdominal pain".)

Negative urine culture usually distinguishes the conditions listed below from acute infectious cystitis in otherwise healthy children. However, in immunocompromised children, viral and/or fungal cultures may be warranted before excluding infectious cystitis.

●Bladder dysfunction – Frequency, urgency, and incontinence may be symptoms of bladder dysfunction, a diagnosis that is frequently overlooked in children with urinary symptoms and a negative urine culture. (See "Etiology and clinical features of bladder dysfunction in children".)

●Vulvovaginitis vaginal foreign body – Females with nonspecific vulvovaginitis or vaginal foreign body may complain of dysuria and/or bleeding and may have white blood cells (WBC) in their urine. (See "Vulvovaginitis in the prepubertal child: Clinical manifestations, diagnosis, and treatment" and "Overview of vulvovaginal conditions in the prepubertal child".)

●Chemical/mechanical cystitis or urethritis – Children with chemical/mechanical cystitis or urethritis (eg, related to bath products, migration of pinworms, masturbation) may complain of dysuria and/or bleeding and may have WBC in their urine.

●Epididymo-orchitis – Clinical manifestations of epididymo-orchitis may include scrotal swelling, pain, and tenderness with erythema and shininess of the overlying skin, as well as dysuria [39]. Mumps is the most common viral etiology. (See "Causes of scrotal pain in children and adolescents", section on 'Orchitis' and "Mumps", section on 'Orchitis or oophoritis'.)

●Nephrolithiasis – Most children with symptomatic nephrolithiasis have flank pain/renal colic in addition to gross or microscopic hematuria. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis".)

●Urethral strictures – Symptoms and signs of urethral stricture may include difficulty urinating and an abnormal urine stream in addition to lower urinary tract symptoms.

●Systemic diseases – Systemic diseases that may be associated with urinary symptoms and sterile pyuria and/or hematuria include:

•Kawasaki disease – Additional manifestations of Kawasaki disease may include conjunctivitis, cervical lymphadenopathy, rash, oral lesions (injected or fissured lips, injected pharynx, strawberry tongue), extremity changes (erythema or edema of the hands and feet, periungual desquamation) (see "Kawasaki disease: Clinical features and diagnosis", section on 'Clinical manifestations')

•Autoimmune diseases (eg, systemic lupus erythematosus, Sjögren's disease) with interstitial nephritis [40] – Urinalysis may demonstrate proteinuria and hematuria in addition to pyuria (see "Lupus nephritis: Diagnosis and classification", section on 'Tubulointerstitial lesions' and "Kidney disease in primary Sjögren's disease")

•Behçet syndrome, a multisystem disorder that may include urogenital involvement (eg, aphthous ulcers, epididymitis, urethritis, recurrent cystitis); recurrent oral ulcers are the cardinal feature (see "Clinical manifestations and diagnosis of Behçet syndrome")

•Poststreptococcal glomerulonephritis – The clinical presentation of poststreptococcal glomerulonephritis ranges from asymptomatic, microscopic hematuria to full-blown acute nephritic syndrome (see "Poststreptococcal glomerulonephritis")

●Drugs – Drugs, such as nonsteroidal anti-inflammatory agents (eg, ibuprofen), antibiotics (eg, penicillins, cephalosporins, trimethoprim-sulfamethoxazole), and various chemotherapeutic agents (eg, cyclophosphamide, doxorubicin, methotrexate) may cause interstitial nephritis, which may be associated with hematuria. (See "Clinical manifestations and diagnosis of acute interstitial nephritis", section on 'Drugs'.)

●Neoplasms – Neoplasms, such as neuroblastoma, pelvic teratoma, or Wilms tumor may cause urinary symptoms secondary to bladder compression. Additional findings in patients with these tumors commonly include a palpable mass on abdominal/pelvic examination, hypertension, and/or neurologic symptoms or signs. (See "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma", section on 'Clinical presentation' and "Presentation, diagnosis, and staging of Wilms tumor", section on 'Clinical presentation'.)

Additional considerations in sexually active patients include:

●Chemical cystitis (eg, related to spermicides) [28].

●Vaginitis – Vaginal odor, discharge, pruritus, or dyspareunia suggests vaginitis. Causes of vaginitis include yeast infection, trichomoniasis, and bacterial vaginosis. (See "Vaginitis in adults: Initial evaluation".)

●Cervicitis – Signs and symptoms of cervicitis may include purulent or mucopurulent discharge from the endocervix, intermenstrual or postcoital bleeding, pruritus, dyspareunia, vulvovaginal irritation, cervical motion tenderness, cervical friability, and cervical edema. (See "Acute cervicitis", section on 'Diagnosis'.)

●Pelvic inflammatory disease – In addition to dysuria and abdominal pain, female adolescents with pelvic inflammatory disease may have vaginal discharge, pain with coitus, and constitutional symptoms. (See "Pelvic inflammatory disease: Clinical manifestations and diagnosis", section on 'Clinical features'.)

●Urethritis – Urethritis is a consideration in sexually active patients with dysuria, particularly those with pyuria and no bacteriuria. Causes of urethritis include Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, or T. vaginalis as well as routine uropathogens, such as E. coli. Symptoms of urethritis caused by N. gonorrhoeae or C. trachomatis typically develop gradually over several weeks in an adolescent whose sexual partner may or may not have urethral symptoms. (See "Sexually transmitted infections: Issues specific to adolescents", section on 'Discharge syndromes'.)

EVALUATION FOR UNDERLYING ABNORMALITIES — Radiologic evaluation (eg, renal ultrasonography, renal scan, voiding cystourethrogram) for underlying abnormalities is not routinely necessary in children and adolescents with uncomplicated cystitis.

The imaging indications and modalities for children with complicated cystitis vary depending upon the clinical scenario; imaging may be indicated for patients with:

●Suspected or confirmed recurrent cystitis

●Cystitis caused by an unusual pathogen

●Family history of renal or urologic disease

●Poor growth

●Hypertension

●Failure to respond as expected to antimicrobial therapy (in children with confirmed bacterial infection)

These clinical features may indicate an underlying anatomic or functional abnormality (eg, renal calculus, cyst, abscess, foreign body, bladder dysfunction) that may require additional intervention.

Guidelines for imaging the urinary tract after urinary tract infection in young children and children with upper tract infections are discussed separately. (See "Urinary tract infections in infants older than one month and children less than two years: Acute management, imaging, and prognosis", section on 'Imaging'.)

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 5^th to 6^th 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 10^th to 12^th 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

●Risk factors – Risk factors for acute infectious cystitis in children ≥2 years and adolescents include (see 'Risk factors' above):

•Female sex

•Sexual activity

•Abnormalities of the urinary system (eg, vesicoureteral reflux, bowel and bladder dysfunction, neurogenic bladder)

•Indwelling bladder catheter

•Recent instrumentation of the urinary system

•Certain chronic diseases (eg, sickle cell disease, diabetes mellitus)

•Immunodeficiency

●Microbiology – Acute infectious cystitis is usually caused by Escherichia coli but may be caused by any pathogen that colonizes the periurethral area and urinary tract (table 1), particularly in children with underlying genitourinary abnormalities, or immune-compromise (table 2). (See 'Microbiology' above.)

●Clinical presentation – Children with acute infectious cystitis typically present with dysuria, frequency, urgency, new onset incontinence (in toilet trained child), abdominal or suprapubic pain, and/or hematuria. Fever >38°C (100.4°F), chills, or flank pain suggest upper tract infection rather than acute infectious cystitis but cannot reliably make this distinction. (See 'Clinical presentation' above.)

●Evaluation – The history (table 5) and examination (table 6) of children with suspected acute infectious cystitis focus on risk factors for urinary tract infection and evaluation of other conditions in the differential diagnosis. (See 'Evaluation' above and 'Risk factors' above and 'Differential diagnosis' above.)

●Clinical suspicion – Acute infectious cystitis should be suspected in children ≥2 years and adolescents with lower urinary tract symptoms (eg, dysuria, frequency, urgency, new onset incontinence, abdominal or suprapubic pain) and/or hematuria. (See 'Clinical suspicion' above.)

Whether or not they have lower urinary tract symptoms, urinary tract infection (UTI; including complicated cystitis) also should be suspected in children who are febrile (≥38°C [100.4°F]) if they:

•Have an indwelling bladder catheter or had bladder catheterization in the previous 48 hours

•Are immunocompromised and an alternative source of fever (eg, bacteremia) has not been identified

•Have abnormalities of the urinary tract

•Have a history of previous UTI

•Have a family history of urinary tract disease

●Diagnosis – The diagnosis of acute bacterial cystitis requires isolation of ≥100,000 colony forming units (CFU)/mL of a single uropathogen from a clean catch urine sample or ≥50,000 CFU/mL of a single uropathogen from a catheterized urine sample in a patient with urinary symptoms and pyuria on dipstick or microscopic urinalysis. The criterion for pyuria is less likely to be met if the uropathogen is an Enterococcus species, Klebsiella species, or Pseudomonas aeruginosa. (See 'Diagnosis' above and 'Urinalysis' above and 'Bacterial culture' above.)

●Differential diagnosis – The results of the urine culture differentiate acute infectious cystitis from other causes of lower urinary tract symptoms, hematuria, and/or lower abdominal pain in children and adolescents (table 4). (See 'Differential diagnosis' above.)