Uncircumcised Boys

The common problem of UTIs in uncircumcised boys, although suspected in the 1970s, was first documented in the 1980s by Ginsburg and McCracken. The strongest evidence of a causal link between an intact foreskin and a UTI comes from several studies conducted by Wiswell and colleagues. In their series, an overall 10-fold increased incidence of UTI was found in uncircumcised compared with circumcised male infants (1.12% vs. 0.11%; P < .001). Wiswell and other investigators have continued to document this problem. In the recent meta-analysis by Shaikh and associates, among febrile male infants younger than 3 months of age, 2.4% (confidence interval [CI], 1.4–3.5) of circumcised males and 20.1% (CI, 16.8–23.4) of uncircumcised males had a UTI. Where and when rates of circumcision have decreased, the frequency of UTIs in boys has increased. The presence of preputial folds in uncircumcised boys encourages a high density of bacterial growth and contamination of the urethral opening. Circumcision reduces meatal contamination, decreasing the ascent of bacteria into the bladder. The high risk for acquiring UTIs in uncircumcised boys diminishes with age (as the foreskin becomes more retractable) but is still present in the toddler age group.

Dysfunctional Voiding

Dysfunctional voiding is a risk factor for the development of a UTI and an occasional consequence of UTI. Dysfunctional voiding refers to a lack of coordination between the two functions that are essential for normal voiding to occur—relaxation of the urethral sphincter and contraction of the detrusor muscle of the bladder. Ordinarily the sphincter must relax as the detrusor contracts. The failure of the sphincter to relax causes an obstruction to the outflow of urine. Consequently, voiding pressures and intravesicular pressure are high, the bladder becomes overdistended, dribbling instead of a good flow occurs, and residual urine remains in the bladder after the void. This dyscoordination is termed dyssynergia.

Clinical manifestations typically appear after toilet training and include incontinence, enuresis, urinary urgency, and UTI. Constipation is a common occurrence because of the inability to relax the musculature of the pelvic floor. The presence of dysfunctional voiding also may promote the persistence of vesicoureteral reflux (VUR) and lead to recurrence or contralateral reflux after attempts are made at surgical correction of reflux.

Constipation

The distended rectum in constipated children has been suggested to press on the bladder wall and produce an obstruction to bladder outflow that may cause dysfunctional voiding and a large residual volume. Urodynamic studies have shown instability of the detrusor muscle in patients with functional constipation and associated enuresis or UTI. Loening-Baucke studied a group of children referred with encopresis and constipation. The history indicated that many were incontinent of urine, and 11% had histories of UTIs. When a vigorous regimen to alleviate the constipation was prescribed, a dramatic improvement occurred in the enuresis and the frequency of recurrent UTI.

Kasirga and coworkers studied 38 children with chronic functional constipation and 31 children as the control group. A detailed past and present history of UTIs or symptoms pointing to this diagnosis, enuresis, encopresis, urgency, and urge incontinence was obtained from both groups. Frequency of UTI and urgency was significantly higher in the group with constipation.

Sexual Activity

The well-recognized association in women of acute cystitis with sexual intercourse is reflected in the popular, now perhaps outdated, term honeymoon cystitis. This phenomenon is often related to the new onset of sexual activity or a recent change in sexual partners. A novel study of 15 patients with a history of recurrent UTIs involved daily monitoring for the presence of UTI with dipslides and calendars that recorded episodes of intercourse, menses, and the occurrence of symptoms. Eleven patients experienced 16 infections; 12 infections occurred within 24 hours of engaging in intercourse. In 12 control subjects, three infections occurred, all within 24 hours of having intercourse. The authors concluded that in sexually active women, most UTIs are related to intercourse.

These results were reinforced by a large prospective study from Seattle, Washington, which confirmed that the incidence of symptomatic UTI is high in sexually active young women and that a strong and independent association exists between UTI and recent sexual intercourse, recent use of a diaphragm with spermicide, and a history of recurrent UTIs. Most of these same risk factors, including frequency of sexual intercourse and use of spermicide, were documented as risk factors associated with development of APN in healthy women.

Catheters

In the hospital, urinary catheters are major risk factors for acquisition of health care–associated infection. In adults, the risk for developing an infection is approximately 5% per day of catheterization. The usual infecting strains include Escherichia coli, Proteus, Pseudomonas, Klebsiella, and Serratia. Many strains of bacteria that cause infection display antibiotic susceptibilities that are more resistant than usual. The route of infection may be either intraluminal or periurethral. Bacteremia is an unusual complication of nosocomial UTI. In a study of nosocomial UTIs in a pediatric intensive care unit, catheter-associated UTI occurred at a rate of 0.95 per 100 admissions. Nosocomial UTIs were associated with previous cardiovascular surgery and with urinary tract catheterization of at least 3 days. Major efforts to reduce the occurrence of catheter-associated urinary tract infections are nearly universal in both pediatric and adult care units.

Bacteriology

Most uncomplicated UTIs are caused by members of a large family of gram-negative bacteria known as Enterobacteriaceae. In most instances, the urinary tract becomes infected by the ascending route. Bacteria derived from the fecal flora colonize the periurethral area and gain access to the urethra. The most common bacterial species in primary and recurrent infections is E. coli. Other gram-negative species that commonly cause UTI are Klebsiella, Proteus, Enterobacter, and Citrobacter, although virtually any enteric organism can be the cause of these infections. Gram-positive bacterial species account for approximately 5% of UTIs and primarily include Staphylococcus saprophyticus and enterococcal species. After E. coli, S. saprophyticus is the most common cause of uncomplicated UTIs in teenagers and young adults of both sexes.

Rarely the urinary tract may become infected hematogenously in the course of a bacteremic infection. This mechanism is thought to account for at least some cases of neonatal UTIs. Increasing evidence indicates that, even in neonates, most infections occur by the ascending route.

Virulence Factors

The key virulence factor for isolates of E. coli is the mechanism by which they attach or adhere to the uroepithelial cell. Bacterial adherence is an essential initiating step in all infections. So-called uropathogenic bacteria, derived from the numerous species found in the fecal flora, can attach to specific receptor sites on the uroepithelium and can bind in a nonspecific manner by electrostatic and hydrophobic bonds. The primary adherence factors encoded by uropathogenic E. coli and many other microbes are supramolecular, filamentous adhesive organelles known as pili or fimbriae. Some of these pili are referred to as P fimbriae because they can recognize and agglutinate erythrocytes of the P1 blood group; this P blood group antigen also is present on human uroepithelial cells. Other common adhesive organelles elaborated by E. coli are types 1, 5, and F1C pili encoded by the fim, sfa, and foc operons, respectively.

Evidence to support the notion of the increased pathogenicity or virulence of the P fimbriae comes from studies of E. coli recovered from children with infection at different levels of the urinary tract. When E. coli strains recovered from patients with pyelonephritis are examined, 76% to 94% are P fimbriated; in contrast, strains of E. coli recovered from patients with cystitis or asymptomatic bacteriuria are 19% to 23% and 14% to 18% P fimbriated, respectively. Although P-fimbriated strains of E. coli are common findings in patients with pyelonephritis whose urinary tracts are completely normal, their frequency decreases considerably when strains of E. coli are examined from patients with pyelonephritis associated with VUR. Apparently this virulence characteristic (and others described later) is unnecessary when reflux is present.

The principal adhesin on the tip of the P fimbriae that fosters adherence to the uroepithelial cell is known as the PapG adhesin. More recently, 153 E. coli organisms recovered from the urinary tracts of infants and children with pyelonephritis were analyzed by polymerase chain reaction for class I, II, and III alleles of the pyelonephritis-associated adhesin gene papG. Strains with any class II papG alleles were found significantly more often in infants with normal anatomy and function or in infants with clinically insignificant abnormalities than in infants with significant abnormalities (90 of 119 vs. 14 of 34 infants; P < .001). This virulence factor is more important when the urinary tract is structurally normal than when anatomic features predispose the individual to infection.

Other virulence factors related to the bacterial species causing UTIs are the K antigen, lipopolysaccharides, hemolysins, colicins, resistance to the bactericidal action of serum, and increased iron-binding capacity. In addition to the immunogenic activity of lipopolysaccharides (activating an intense host response), they have been shown to have direct toxic effects on renal cells via their biologically active component lipid A. The K antigen is a capsular polysaccharide that constitutes an outer surface of the E. coli organism. The capsule has the capacity to impede phagocytosis and to shield the bacteria from lysis induced by complement. Hemolysins are cytotoxic proteins that can damage renal tubular cells in vitro.

Approximately 50% of the types of E. coli isolated from the urine of patients with APN produce a pore-forming toxin, α-hemolysin. α-Hemolysin damages the cell membrane and may activate apoptosis in renal tubular cells. Colicins, elaborated by “uropathogenic” strains of E. coli, kill other bacteria that are in their vicinity. In the presence of human serum, many bacteria are killed after activation of complement. Virulent E. coli organisms have the capacity to resist this bactericidal effect of serum. Another virulence factor found in bacteria is their ability to acquire and bind iron. Most bacteria require iron for optimal growth and metabolism and have developed mechanisms to acquire iron when the supply is limited. One strategy to acquire iron is the use of siderophores to scavenge iron from the environment and subsequently concentrate it in the bacterial cytosol. Siderophores such as enterobactin or aerobactin are secreted low-molecular-weight molecules that have a high affinity for ferric (Fe ³⁺ ) iron. Bacteria retrieve iron bound to siderophores through receptors that facilitate the transport of iron through the bacterial membrane.

Additional insights into the pathogenesis of E. coli UTI have emerged during the past decade. Models in mice and humans (including children) have shown intracellular bacterial communities in the bladder epithelium. These intracellular organisms can result in more extensive infection and, because of their protected location, escape from the immune response and lead to recurrent infections.

After reaching the bladder, P-fimbriated E. coli organisms can colonize the ureter even in the absence of VUR. Bacterial colonization of the ureter affects ureteral peristalsis, leading to dilation and a physiologic obstruction. This dilation of the ureter and calyces favors a change in the shape of the renal papillae, which facilitates intrarenal reflux of colonizing bacteria at low pressure. APN develops because the receptors for the P-fimbriated E. coli are present in the collecting duct and proximal tubules.

Experimental studies conducted by Roberts have led to a theory of the chain of events involved in the process that ultimately leads to renal scarring. The initial event is the inoculation of the renal parenchyma with bacteria, which leads to an intense inflammatory response. Liberation of proinflammatory cytokines (interleukin-1 [IL-1], IL-6, and IL-8) is followed by recruitment of inflammatory cells and a second cytokine burst. This inflammation results in the release of toxic enzymes within the granulocytes and tubular lumen. Superoxide is released simultaneously, generating oxygen radicals that are toxic to the bacteria and to the tubular cells. The resultant death of the tubules intensifies and extends the inflammatory process into the interstitium. At the same time, focal ischemia results from the intravascular aggregation of granulocytes and edema. The tissue damage that results from the toxic enzymes, oxygen radicals, inflammatory response, and ischemia culminates in the creation of renal scars.

Cystitis

Most children older than 5 years of age with cystitis have urgency, frequency, or dysuria. Children who have the urge to urinate may have a history of difficulty in initiating the urinary stream. Occasionally children may complain of abdominal or suprapubic pain. If fever is present, it is low grade. Suprapubic tenderness may be present on palpation. The urine may be foul smelling and cloudy.

Pyelonephritis

Many children who have APN have impressive chills, spiking fevers, and complaints of back pain. They may have associated gastrointestinal complaints of vomiting and diarrhea, especially vomiting. Lower urinary tract symptoms, such as frequency, urgency, dysuria, and suprapubic discomfort, may or may not be present.

Other findings, such as irritability, poor feeding, vomiting, decreased urinary output, and clinical evidence of dehydration, vary. The youngest children with APN usually have high fever without other localizing features.

Physical Examination

Features of the physical examination that should be emphasized include (1) an accurate measurement of blood pressure (hypertension may be present in patients who have chronic renal disease), (2) general growth and development (failure to thrive may be a sign of more chronic or recurrent UTI), and (3) a careful abdominal examination (which might reveal tenderness or a mass caused by either an enlarged bladder or an obstructed urinary tract). An effort should be made to elicit the finding of costovertebral angle tenderness in children of all ages. The perineum should be inspected carefully to search for signs of irritation, scars, tears, signs of trauma, labial adhesions, or evidence of vulvovaginitis. In uncircumcised infants, the foreskin may not be retractable, leading to phimosis. A rectal examination should be considered to detect masses or poor sphincter tone, which might be associated with a neurogenic bladder. The lower back should be observed for any lipoma, sinus, pigmentation, or tufts of hair that may be signs of an occult myelodysplasia.

Neurologic examination of the lower extremities and evaluation of the bulbocavernosal reflex often reflect the neurologic integrity of the lower motor neuron reflex arcs. The bulbocavernosus reflex is elicited by squeezing the glans penis or clitoris and observing or feeling a reflex contraction at the external anal sphincter. Absence of this reflex suggests a possible sacral lesion.

Asymptomatic Bacteriuria

A large body of work has been produced dealing with the issue of asymptomatic bacteriuria. Data were accumulated during a long-term study by Kunin of the natural history of recurrent bacteriuria among school-aged girls in a well-defined community in central Virginia. Girls were identified in the first grade and were observed prospectively for 10 years. Each year, approximately 0.5% of school-aged girls developed asymptomatic bacteriuria. The cumulative prevalence was 5% for the years between entrance to grade school and graduation from high school. Although it was billed as asymptomatic bacteriuria, approximately one-third of the girls did have symptoms, and some were known to have had infection or, rarely, abnormalities of the urinary tract before the first screening.

Just a few years after Kunin began his investigations, a similar study was conducted in Göteborg, Sweden. Beginning in 1970, 19,000 girls a year were screened routinely for bacteriuria in Göteborg schools at ages 7, 11, 14, and 16 years. A significant minority had a history of previous infection or symptoms that were referable to the urinary tract.

Savage and colleagues also studied covert bacteriuria in school-aged girls. In their three studies, the point prevalence of bacteriuria ranged from 0.7% to 1.1% to 1.6%. The risks associated with asymptomatic bacteriuria are difficult to assess from these studies because patients who were truly asymptomatic were difficult to separate from patients with symptoms.

Several prospective studies of infants and school-aged girls from Scandinavia have provided important information regarding the natural history of asymptomatic bacteriuria. Most children identified as having asymptomatic bacteriuria among a large cohort of infants ( n = 3581) spontaneously cleared the bacteriuria within months. Only 2 of 45 went on to develop symptomatic bacteriuria. In contrast, none of 42 infants who developed symptomatic UTIs had been identified previously as having asymptomatic bacteriuria, suggesting that asymptomatic bacteriuria rarely is a precursor to symptomatic UTI. In addition, prophylactic antibiotics used to treat children with asymptomatic bacteriuria seemed to predispose them to the development of pyelonephritis, usually with microorganisms that had not been present at the outset.

Currently physicians have little enthusiasm for screening children of any age to discover the presence of asymptomatic bacteriuria. The absence of pyuria in these specimens of urine provides additional evidence that the host is not perturbed by the presence of asymptomatic bacteriuria. The presence of bacteria of low virulence in the urine in asymptomatic patients seems to be protective. These strains apparently prevent invasion by other bacteria and provide a kind of biologic prophylaxis.

Rather than screening asymptomatic populations of children, an appropriate approach is vigorous evaluation for the presence of UTIs in febrile children without an obvious focus of infection. In addition, health maintenance examinations should be used as an opportunity to screen for historical information that might suggest the need to collect a urine specimen for culture ( Box 39.1 ). Important items include frequent episodes of unexplained fever, dribbling when urinating, enuresis, encopresis, constipation, urgency, frequency, and dysuria. In addition, it is valuable to know when toilet training was accomplished; frequency of voiding; frequency of stooling; and any apparent difficulties associated with voiding, such as in initiating the urinary stream. The practitioner also should inquire about so-called avoidance maneuvers (e.g., repetitive habitual squirming, crossing of legs, or sitting on heels) and family history of UTI.

Infectious

E. coli is the most common cause of infection in the urinary tract for primary infections (in which E. coli causes 85% to 90% of infections) and recurrent infections (in which E. coli causes approximately 75% of infections). Virtually any other gram-negative enteric bacteria may cause infection. Common etiologic agents include Klebsiella, Proteus, Enterobacter, Serratia, and Pseudomonas. Proteus mirabilis is a common cause of UTIs in some series of boys and in health care–associated UTIs associated with catheterization. Enterococcus and Pseudomonas were the most common cause of nosocomial UTI after E. coli in a large series of cases reported from Austria. In young women, S. saprophyticus is second only to E. coli as a cause of cystitis. Rarely Staphylococcus epidermidis has been reported as a cause of pyelonephritis in young boys with anatomic abnormalities of the urinary tract.

Acute lobar nephronia is a localized nonliquefactive inflammatory infection of the kidney that has also been called acute focal bacterial nephritis. It represents the midpoint in the spectrum of acute uncomplicated pyelonephritis and renal abscess. From a clinical perspective, it may be signaled by protracted fever before and after diagnosis and may warrant a longer duration of antimicrobial treatment than uncomplicated APN. The diagnosis depends on the performance of an enhanced computed tomographic (CT) scan. The bacterial etiology is the same as for other cases of APN. Occasionally the urinalysis may be misleading because of absent or diminished pyuria.

Xanthogranulomatous pyelonephritis is a rare, chronic, suppurative renal infection. Although it can occur at any age, it typically involves middle-aged women. Cases in children have been reported across all age groups, including infants. The patient usually presents with what appears to be an acute UTI, caused most often by E . coli or Proteus spp. Evaluation of the patient usually reveals a unilateral enlargement of the kidney, often accompanied by urolithiasis and sometimes a staghorn calculus. The differential diagnosis of the mass lesion includes neuroblastoma, Wilms tumor, tuberculosis, and renal carcinoma. The lesion is characterized histologically by granulomas, abscesses, and lipid-laden foam cells. Nephrectomy is the usual means of management.

In the context of bacteremia or septicemia, occasionally the blood culture and the urine culture are positive for the same bacterial species. In these instances, the kidney has been seeded as part of a hematogenous dissemination. Any organism that is responsible for sepsis, such as Haemophilus influenzae type B, Neisseria meningitidis, Neisseria gonorrhoeae, Staphylococcus aureus, Streptococcus pneumoniae, or Streptococcus pyogenes, may be found in the urine.

Anaerobic infections of the urinary tract are rare occurrences in children despite the high density of gram-positive and gram-negative anaerobes in the fecal flora; this fact relates to the probable lack of adherence of these bacterial species to the uroepithelium. Anaerobic infections of the urinary tract should be suspected when organisms are seen on Gram stain but do not grow in conventional culture or when the urine of symptomatic children shows no bacterial growth. Another unusual infecting agent that should be suspected in instances in which the Gram stain of the urine shows gram-negative rods but the urine culture is negative is H. influenzae.

Fungal infections of the urinary tract usually are caused by Candida spp., but they also may be caused by Cryptococcus neoformans, Aspergillus spp., and the endemic mycoses. Candiduria is an increasingly common form of health care–associated infection that may involve any level of the urinary tract. It often occurs in immunosuppressed patients, especially patients who are receiving broad-spectrum antibiotics for treatment of documented or undocumented systemic infections. In many immunosuppressed patients, the infection is complicated by the presence of an indwelling urinary catheter.

Viruses also may cause infection of the urinary tract. For the most part, these infections involve the bladder rather than the kidney, although infection of any part of the urinary tract may occur. The principal etiologic agents are adenoviruses, enteroviruses, coxsackieviruses, and echoviruses. Mumps virus and hepatitis viruses occasionally have been implicated. Type 11 adenovirus has been the most common cause of acute hemorrhagic cystitis in school-aged boys; type 21 also has been documented to be a cause of infection in this age group. In immunosuppressed patients, especially children who have undergone bone marrow transplantation or are recipients of kidney transplants, BK polyomavirus and adenovirus may cause hemorrhagic cystitis.

Granulomatous cystitis is the histopathologic description of cystitis caused by Mycobacterium tuberculosis and by schistosomiasis and other parasitic infections. Granulomas formed in response to certain parasites, such as Toxocara and microfilariae, also may contain numerous eosinophils . Enterobius vermicularis infection occasionally leads to signs and symptoms of cystitis and inflammatory changes of the bladder wall.

Infectious urethritis caused by N. gonorrhoeae or Chlamydia trachomatis is a common cause of symptoms suggestive of UTI. In addition, any etiologic agents of vulvovaginitis may cause inflammation of the distal urethra, with urgency, frequency, or dysuria; they include Candida spp., Gardnerella vaginalis, Trichomonas vaginalis, S. pyogenes, S. pneumoniae, H. influenzae, C. trachomatis, Shigella spp., and Yersinia enterocolitica.

Noninfectious

Urethral symptoms such as urgency, frequency, and dysuria may be caused by any factor or process that gives rise to inflammation in the lower urinary tract. Examples include mechanical irritation (which might result from insertion of foreign bodies, migration of pinworms, or masturbation) and chemical irritation (which might arise from bubble baths or shampoos). Chemical cystitis has been reported from the inadvertent insertion of a vaginal contraceptive suppository (nonoxynol 9) into the bladder. Pharmacologic causes of urethral symptoms include cyclophosphamide and methenamine mandelate, both of which can lead to inflammatory changes in the urinary bladder. Several other agents used in the topical treatment of bladder cancer have been noted to cause cystitis.

Collection of a Urine Specimen

Proper collection of a urine specimen is crucial to facilitate interpretation of the culture. In toilet-trained children, a midstream clean-catch specimen is appropriate for evaluation. When this specimen is used, the definition of significant bacteriuria is 10 ⁵ colony-forming units (CFU)/mL or more. The child is asked to void into the toilet. Straddling the commode in a reverse position creates a natural separation between the urethra and the vulva. Cleansing of the perineum does not result in less contamination of the specimen and is no longer encouraged. The child is asked to begin voiding. A second or two after the void has been initiated, a sterile cup is passed into the stream. The hope is that the initial void succeeds in washing out the distal urethra, the site from which the urine specimen is most likely to be contaminated.

If the child is not toilet trained, a specimen may be collected by urethral catheterization or suprapubic aspiration. When the urine is collected by urethral catheterization, the perineum is cleaned with 1% iodine. A properly sized catheter (10 or 12 Fr) or a size 5 feeding tube may be used. The catheter is lubricated and inserted into the urethra and threaded a short distance. The first few drops of urine should be collected outside the sterile container. This part of the specimen is the most likely to be contaminated with fecal flora from the distal urethra; these bacteria are not eliminated by the process of perineal cleansing. The remaining urine is collected in a sterile container and sent to the laboratory. When a urine specimen is collected by urethral catheterization, significant bacteriuria is defined as 50,000 CFU/mL or more. This method is preferred when a small volume of urine in the bladder is anticipated and collecting a specimen of urine is necessary so that antibiotic therapy can be initiated. Unfortunately there is a high likelihood that even a urine sample obtained by catheter will be contaminated (14%), especially in infants younger than 6 months of age, when the catheterization is difficult, and in uncircumcised boys. Use of bladder ultrasonography increases the success of the procedure.

An alternative to urethral catheterization is suprapubic aspiration. Some physicians contend that catheterization is less traumatic than suprapubic aspiration. There is modest evidence that when suprapubic aspiration is performed in very young infants it may be associated with greater discomfort than catheterization of the urine. The procedure can be done in children of any age; it has been used to obtain specimens of urine in pregnancy. Urine culture specimens obtained by suprapubic aspiration are easy to interpret because the usual source of contamination, the distal urethra, has been bypassed. The presence of any bacteria in a specimen collected by suprapubic aspiration is significant, although most samples obtained from patients with infection contain 10 ⁵ CFU/mL or more.

To perform a suprapubic aspiration, the patient is placed in a supine position with the lower extremities flexed ( Fig. 39.1 and Table 39.1 ). Iodine and alcohol are used to clean the suprapubic area. The symphysis pubis is located with the index finger. A 3-mL syringe is attached to a 1.5-inch, 22-gauge needle. A spinal needle (2.5- or 3-inch, 21-gauge) can be used in older patients. The needle is passed in the midline about 1.5 cm above the symphysis pubis. It is angled 10 to 20 degrees from the vertical, pointing in a slightly cephalad direction ( Fig. 39.2 ). Negative pressure is applied while the needle is inserted. The procedure is most likely to be successful when the infant can be encouraged to drink and the diaper has been dry for at least 60 minutes before the procedure is done. The success rate of suprapubic aspiration can be improved with the use of a portable ultrasound device. If the suprapubic aspiration is unsuccessful, a catheterized specimen should be obtained. Complications of suprapubic aspiration are rare and include formation of a hematoma, perforation of the bowel, and formation of a suprapubic abscess. Suprapubic aspiration is contraindicated if the patient has a bleeding diathesis.

Suprapubic aspiration technique, position of patient.

Suprapubic aspiration technique, position of needle.

The last method of urine collection is the bag technique. The perineum is washed with soap and water and allowed to dry. A sterile plastic bag is attached. The bag is removed as soon as the patient voids. If the patient has not voided in 20 minutes, the bag is removed, the perineum is cleaned again, and a new bag is attached. If this procedure is followed meticulously, a reasonable specimen can be collected. This specimen is susceptible to contamination from periurethral flora, however, and the technique is not recommended if the patient appears ill and antibiotic therapy needs to be started immediately after the specimen of urine is collected. The results of the culture of a bagged specimen are useful only if they are negative. If the culture is positive, a second specimen must be collected by a more reliable method.

A new noninvasive bladder stimulation technique has been described to obtain clean-catch urine in infants younger than 30 days old. After cleaning the genital and perineal area, one clinician dangles the infant by holding under the arms, then taps the suprapubic area rapidly to provide stimulation to the bladder. Another clinician also gently massages the lumbar paravertebral area. A sterile container catches the urine. Most infants void in less than 1 minute. Although this method is labor intensive (at least three attendants are required), it is quick and effective.

Diagnosis of Urinary Tract Infection

The diagnosis of UTI hinges on the results of culture of a properly collected urine specimen. Disagreement within the literature is substantial regarding the definition of significant bacteriuria. As indicated in the previous section, the definition of UTI varies according to the method by which the urine is collected. This variability in definition acknowledges that although the bladder urine is regarded as a sterile body fluid, contamination of the urine specimen may occur as it passes through the urethra. The distal urethra frequently is colonized with coliforms derived from the gastrointestinal tract. The only urine specimen that bypasses the urethra and is free of contamination is obtained by suprapubic aspiration. When a specimen is collected by this technique, any colony count of coliforms is significant.

In urine that is collected by a midstream clean-catch method, significant bacteriuria is defined, most stringently, by the recovery of 100,000 CFU/mL or more ( Table 39.2 ). For specimens of urine obtained by catheter, significant bacteriuria is defined as 50,000 CFU/mL or more. In each of these instances, physicians recognize that although urine specimens containing lower colony counts rarely may represent true infection, for the most part lower colony counts usually are the result of contamination of the specimen.

Specimens of urine usually are inoculated onto two different kinds of solid media—one that supports the growth of only gram-negative enteric bacteria (e.g., MacConkey agar) and another that supports gram-positive and gram-negative bacteria (e.g., 5% sheep blood agar), with use of a 0.001 calibrated loop. Colonies are counted the next day (18 hours later), and the total is multiplied by 1000 to determine the colony count. The results of the urine culture are unavailable during the practitioner’s first encounter with the ill child. Consequently, there is great interest in the development of a method that would predict the results of the urine culture so that appropriate antimicrobial therapy could be initiated presumptively at the time of the initial encounter. Microscopic methods (to evaluate pyuria and bacteriuria) and biochemical tests (which can be evaluated with a dipstick) have been evaluated and will be discussed. However, the performance of urine culture is mandatory because no rapid urine test is sufficiently sensitive to identify all children with UTI.

Determining the Site of Infection

Urinalysis is useful for detecting infection but not for determining the location of the infection within the urinary tract (i.e., upper tract vs. lower tract). To determine the site of infection (i.e., kidney vs. bladder), many investigations of the discriminatory ability of C-reactive protein, erythrocyte sedimentation rate, and total peripheral WBCs have been performed. Several studies have evaluated the accuracy of procalcitonin levels compared with C-reactive protein levels to predict renal involvement among children with febrile UTIs. These studies showed that serum procalcitonin concentrations, measured with either an immunoluminetric quantitative test or a rapid semiquantitative test, diagnosed APN with a sensitivity of 70.3% to 94.1% and a specificity of 82.6% to 93.6%.

In a meta-analysis published in 2011, 12 studies representing 526 patients with UTI (10% with VUR of grade III or higher) were included. The sensitivity of procalcitonin greater than or equal to 0.5 mg/mL as an indicator of VUR of grade III or higher was 83% (95% CI, 71–91) with a 43% specificity rate (95% CI, 38–47). In the subgroup of children with positive results on dimercaptosuccinic acid (DMSA) scan, procalcitonin greater than or equal to 0.5 mg/mL was also associated with high-grade VUR (adjusted odds ratio, 4.8; 95% CI, 1.3–17.6).

A systematic review published in 2015 set out to determine whether procalcitonin (≥0.5 ng/mL), C-reactive protein (20 mg/L), or erythrocyte sedimentation rate (≥30 mm Hg) could replace DMSA scans in the diagnostic evaluation of UTI in children (i.e., distinguish between cystitis and APN). Six studies (434 children) included data on procalcitonin, 13 studies (1638 children) included data on CRP, and 6 studies (1737 children) included data on ESR. The summary sensitivity estimates (95% CI) for procalcitonin, CRP, and ESR were 0.86 (0.72–0.93), 0.94 (0.85–0.97), and 0.87 (0.77–0.93), respectively. The summary specificity values for procalcitonin, CRP, and ESR were 0.74 (0.55–0.87), 0.39 (0.23–0.58), and 0.48 (0.33–0.64), respectively. Although the procalcitonin looked promising, the small number of studies and marked heterogeneity does not provide enough evidence to recommend its use.

Imaging

The recommendations for performing imaging procedures on children with a diagnosis of UTI have changed and remain somewhat controversial. The imaging studies that usually are considered are renal ultrasonography, contrast voiding cystourethrography (VCUG) to detect VUR, renal cortical scintigraphy, and magnetic resonance imaging (MRI) ( Box 39.2 ).

Renal Scintigraphy

In patients with presumed APN, renal scintigraphy with technetium-99m DMSA or technetium-99m glucoheptonate has been shown to be the most practical and reliable method for detecting APN. DMSA and glucoheptonate are amino acids that are cleared by the renal tubules. When these amino acids are labeled with technetium and injected intravenously, they can be used to create an image of the kidney, which reflects vascular flow and tubular function ( Fig. 39.3 ). In experimentally induced APN in piglets, the DMSA scan had a sensitivity of 87% and a specificity of 100% in showing lesions consistent with APN compared with histology as the gold standard.

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