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Recurrent Urinary Tract Infections

From The Child's Doctor, Fall 2011

Jennifer Schreiber, CPNP
Bladder Function Improvement Training (BFIT) Program, Urology, Children's Memorial Hospital
Disclosure: Ms. Schreiber has no industry relationships to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.
Elizabeth B. Yerkes, MD
Attending Physician, Urology, Ann & Robert H. Lurie Children's Hospital of Chicago; Assistant Professor of Urology, Northwestern University Feinberg School of Medicine
Disclosure: Dr. Yerkes has no industry relationships to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.

Other Disclosure Information


Educational objectives

At the conclusion of this activity, participants will be able to:

  • Troubleshoot positive urine cultures in the setting of negative urinalysis or insignificant cultures in the setting of positive urinalysis
  • Identify indications for imaging the urinary tract in recurrent urinary tract infections (UTIs)
  • Initiate behavioral management in children with recurrent UTIs

CME credit

Credit statement


Urinary tract infections (UTIs) are one of the most common medical diagnoses treated by Pediatric Urology providers. Recurrent UTIs, formally defined as 2 or more infections within a 6 month period, are frustrating to the child, the parents, and the providers. Although recurrent non-febrile UTIs are uncommonly associated with renal involvement and new cortical scarring, severe bladder symptoms associated with UTI may result in missed school days or activities. Any child with UTI deserves some evaluation of elimination habits to minimize the risk of recurrent symptoms. This article addresses the evaluation and management of recurrent UTIs in children, with the focus primarily on recurrent non-febrile UTIs. 

The management principles to minimize recurrence are similar in non-febrile and febrile UTIs, but fever associated with a UTI implies renal involvement with its attendant risk of acute pyelonephritis and renal scarring. In the case of febrile UTI, an anatomic host factor that facilitates ascending infection is assumed to be present until proven otherwise. Radiological evaluation is indicated in the setting of a first febrile UTI and need not be repeated, in most cases, if negative. This article will primarily address toilet-trained children, as they are best able to participate in behavior modification programs, but some healthy elimination patterns can be encouraged even in the pre-toilet-trained child. 

Another UTI?! Is it a UTI or not? 

Accurately determining whether a child actually has a UTI is an important factor in addressing recurrent infections. 

Clinical scenario: An 8-year-old girl presents with recurrent UTIs. Urinalysis is often positive, but the cultures are at times surprisingly equivocal. Symptoms and complaints improve quickly with antibiotics. Mother notes that the primary complaint of strong odor often returns quickly after antibiotics are complete. She did have 1 possible infection with fever at 18 months of age; no radiographic evaluation was completed at that time and no subsequent complaints have been associated with fever or back or abdominal pain. 

The last 4 urinalyses and cultures are listed below. Which of these needs to be treated? If it is not a UTI, why are there symptoms? 

a. Leukocyte esterase: moderate; nitrite: negative; WBC: 10-20; epithelial cells: 3-5; culture: 10-50K mixed flora 

b. Leukocyte esterase: large; nitrite: positive; WBC: 10-20; epithelial cells: 0-3; culture: >10K gram negative rod 

c. Leukocyte esterase: moderate; nitrite: negative; WBC: 20-40; epithelial cells: 5-10; culture: no growth 

d. Leukocyte esterase: trace; nitrite: negative; WBC: 0-3; epithelial cells: 3-5; culture: >100K gram negative rods 

Answer: B is the only specimen that is clearly a UTI. 

Urinary symptoms and the urinalysis, particularly a dipstick analysis on a suboptimally collected or processed specimen, can be misleading. It is important to know what we are treating to minimize the emergence of antibiotic-resistant strains. 

Many girls present with recurrent UTI-type complaints (dysuria, frequency, urgency, odor), but do not actually have a UTI each time that symptoms occur. Recommended testing includes both a urinalysis with microscopy and a urine culture with speciation and sensitivities. See Table 1 on sorting out urinalyses and UTI-type symptoms. 

 

In toilet-trained children, a voided specimen is sufficient. Parents should be instructed on proper techniques for obtaining a specimen, specifically adequate cleansing of the perineal area and collection of a midstream urine sample. Positive dipsticks performed in the office should be sent for confirmatory laboratory microscopic analysis and urine culture. Urine dipsticks are designed as a screening tool and, unfortunately, may yield false positive results. A negative dipstick, however, is reliable for absence of infection.[1] 

For accurate results in children not yet toilet-trained, a catheterized specimen is the most direct and most accurate approach. Catheterization is strongly recommended for first-line testing in young children when the child is ill and would receive immediate therapy. Bagged urine specimens with positive results require confirmation with catheterization as they may become contaminated by coliform bacteria colonizing the urethra, perineum or prepuce. 

A positive urinalysis and culture on a voided specimen is presumed to be a UTI in the setting of urinary complaints. Recurrent positive specimens without symptoms, when obtained per routine protocol at well child visits or obtained as spot checks in children with a history of prior infections, should be viewed with suspicion. In girls with recurrent positive cultures, with or without symptoms, a perineal examination is indicated to assess for evidence of vaginitis, chronic irritation, or anatomic features that would make a clean catch specimen difficult to obtain. Consideration may be given to a catheterized specimen to clarify the situation in these challenging cases. 

A voided specimen with a negative urinalysis and microscopy but a positive culture does not indicate a true UTI. Some children may be colonized externally with bacteria, which can lead to a false positive result on a urine culture. This commonly occurs in girls with vaginal reflux of urine during voiding. It could also suggest contamination from improper collection or processing of the specimen. 

A positive urinalysis but negative culture is also not a UTI and may be seen in girls with vulvar irritation or nonspecific vaginitis or in cases of preputial inflammation. 

Also, it is important to differentiate between recurrent infections and infections that have not responded to treatment. When a child finishes treatment for a UTI, a repeat urinalysis and urine culture should be completed within 24-48 hours to confirm that the infection has cleared. 

Common causes of UTIs in children at different ages 

Whether UTIs are limited to the bladder  (cystitis) or involve renal parenchymal inflammation (pyelonephritis), the source of the bacteria is nearly always the fecal stream via colonization of the perineal, perivaginal or periurethral skin. Before the age of 1 year, boys are more likely than girls to develop a UTI, with this disparity further increased by the presence of intact prepuce. After the age of 1 year, girls are at an increased risk largely due to the shorter female urethra and close proximity to fecal bacteria. Since boys and girls suffer from UTIs, the decision to test or treat should not be based upon gender. 

Some children have anatomical or functional abnormalities that impede efficient emptying of the bladder. Anatomic abnormalities are more commonly picked up in younger children, but new diagnosis of congenital reflux can occur in children of any age. Presence of anatomic abnormalities will become clear as the work-up and management proceed. Functional abnormalities, such as different forms of neurogenic bladder dysfunction, may require special intervention. Unless the history and examination suggest a neurological disturbance, the management strategies discussed in this article represent the first-line approach. 

Children who begin having non-febrile UTIs around or after 5 years of age are unlikely to have an anatomic abnormality that predisposes to bacteriuria and UTI. Behavioral factors are far more common than anatomic factors in the toilet-trained child. 

Several behavioral factors increase a toilet-trained child’s risk of developing UTIs, and these same factors can have a detrimental effect on the acquisition of healthy elimination and continence. Some of these factors can affect pre-toilet-trained children as well. Dysfunctional elimination habits, including voiding postponement and constipation, are common causes of UTIs in these children.[2] 

As a child achieves voluntary control of urination, she/he may feel the need to void 1 or more times per hour. If the child does not initiate these trips, a good rule of thumb is to take the child to the restroom every 1.5 to 2 hours. Adequate intake of fluids to help the child become successful with this schedule will create a good foundation for healthy elimination habits. 

In a school-age child, the voiding interval should not exceed 3 hours. Older children should void at least 2 times during a typical school day. Infrequent urination and poor recognition of bladder cues are very common in the busy world of the school-age child. 

Voiding postponement behaviors include infrequent urination, “last minute warning” urinary urgency, and dribbling in the underwear prior to voiding. The child will often exhibit “posturing” that suggest he/she is attempting to prevent involuntary loss of urine. Squatting on a heel (Vincent’s curtsy), doing the “potty dance” and other means of twisting and squeezing to compress the external sphincter complex can be quite effective at aborting bladder contractions. Habitually postponing urination leads to bladder over-distension, and the child may lose the normal sensation of the need to urinate. 

With repeated postponement posturing behaviors, the child no longer relaxes the sphincter appropriately during voluntary evacuation. Incomplete pelvic floor relaxation is a risk factor for poor bladder emptying and recurrent UTI. 

Children who postpone voiding and have difficulty relaxing the pelvic floor also tend to retain stool. The role of constipation or fecal retention in UTIs is twofold. A chronically distended rectum reduces sensation and alters contractility of the bladder,  impairing bladder emptying and increasing the risk of bacteriuria. Additionally, large volumes of retained stool, even soft stool awaiting daily evacuation, may increase perineal or periurethral colonization with typical urinary pathogens, thereby increasing the risk of bacteria in the urine and development of UTI.[3,4] (See Figures 1 and 2.) 

 

Role of imaging in recurrent UTI 

If a child has recurrent non-febrile infections, an ultrasound of the kidneys and bladder provides reassurance that the kidneys are structurally sound, and perhaps more importantly, allows assessment of residual urine after voiding. A VCUG is only obtained when there have been febrile UTIs, or if there is an abnormality of the kidneys on ultrasound. A plain film of the abdomen may be requested to assess the fecal load when fecal retention is strongly suspected but refuted by parental history. 

Management of recurrent UTIs 

Once a UTI is confirmed, culture-specific antibiotics should be prescribed. Five to 7 days of therapy is sufficient to eradicate the bacteria in an uncomplicated UTI, but 10 to 14 days is recommended for febrile infections, confirmed pyelonephritis and complicated anatomy. Re-testing 1 to 2 days after treatment completion is recommended. 

A multi-modal approach is utilized in the management of children with recurrent UTIs, including children with a structural abnormality such as vesicoureteral reflux. This treatment plan includes behavior modification, timed voiding, improved hydration, techniques for pelvic floor relaxation and management of fecal retention. Specialized teaching with biofeedback may be recommended to address more challenging pelvic floor dysfunction. 

Management of patients with recurrent UTIs is time-intensive, and therefore it is often helpful to both the family and pediatrician to begin treatment in a program that specifically addresses all factors related to elimination of urine and stool.

Behavior modification programs can take as long as 6 to 12 months to achieve results and it is imperative that the family understand this at the outset. Many Urology practices in large academic medical centers offer successful programs that are physician-supervised and run by nurse practitioners who specialize in treating children with recurrent UTIs. These programs provide the unique comprehensive support that these patients and families need. Behavior modification is a key element in the treatment of recurrent UTIs. These modifications involve the parent and the child, since this personal health issue for the child has often become a frustration and an emotionally-charged family affair. Embracing the prescribed treatment plan is the responsibility of the parent and child. All should realize that new healthy elimination habits are not established quickly, and these behaviors need to become an ongoing part of life, not just for a few weeks. 

Given that typically the parent is no longer directly involved in the child’s toilet routine and given that children have a poor recall of specifics, the parent and child should complete an elimination diary. The diary should include oral intake, time and volume of voids, characterization of bowel movements and any other relevant elimination data. This is a simple but excellent tool to help everyone understand what is occurring. 

A child who chronically postpones voiding may not receive clear messages telling him/her when the bladder is full. Voiding by the clock, rather than by urge, helps to prevent chronic bladder distention and poor bladder emptying. Adequate hydration offers dual benefits of improving compliance with the timed voiding schedule and flushing out bacteria from the urinary tract before a UTI can develop.

Children and families can evaluate hydration status by the color of the urine. Dark yellow or amber colored urine implies that the child is not drinking enough fluids. Pale-yellow urine indicates adequate hydration. Children who habitually hold their urine are not aware that they are incompletely relaxing the pelvic floor muscles or voiding abnormally. Therefore, relaxation techniques and repositioning on the toilet to relax the pelvic floor with voiding are essential in the management of recurrent UTIs. These include sitting with the feet supported and knees slightly apart and breathing techniques. 

Bowel management is an integral part of recurrent UTI management and a thorough elimination history is imperative. Once the parent is no longer involved in the child’s bathroom hygiene, the child is the best source of information. A visual aid, such as the Bristol Stool Scale,[5] can provide a frame of reference and yield more accurate information. Children who have a daily bowel movement may still be retaining a significant amount of stool due to inefficient emptying of the bowel. 

A bowel management program consists of hydration, medications such as polyethylene glycol to improve texture and transit, fiber supplements, and timed toileting. Timed toileting in conjunction with a gentle laxative or fiber helps to promote regular evacuation and decreases over-distension of the rectum. If a child is retaining a large amount of stool, a bowel cleanout will be recommended prior to beginning the bowel program. 

Recurrent UTIs, particularly when associated with missed time from school and activities, urinary incontinence or disruption of the family dynamics, can result in behavioral issues or family conflict. Participation in an elimination dysfunction program can help redirect these behaviors and conflicts as the child establishes a relationship with the provider and experiences pride and self-confidence with clinical improvement. Multiple visits for repetition and encouragement are required to establish this healthy rapport. Although this relationship can at times be almost magically effective, Urology providers are not certified psychologists or behavioral therapists. Consultation and collaboration with these specialists are essential in cases with severe behavioral issues, psychiatric diagnoses, or concerning family dynamics. 

The role of antibiotic prophylaxis in recurrent UTI 

While research on the use of prophylactic antibiotics in children with recurrent UTIs is conflicting, current evidence suggests that a low-dose daily antibiotic may be beneficial in the prevention of UTIs in certain cases.6 It is difficult to rehabilitate the bladder if the child continues to have UTIs while initiating a bowel and bladder management program. In these cases, several months of prophylactic antibiotics may be beneficial as they often help to break the cycle of UTIs and allow for improved adherence to the program without the setback of recurrent UTI symptoms. 

What to do when the program fails to prevent infections 

Most children progress well with the principles of a bowel and bladder management program. That does not mean that the child will never have another UTI. Periodic lapses in hydration or elimination habits may be the culprit, or there may be other nonbehavioralhost factors. As suggested above, forming new habits is a challenge. After a long symptom-free period, good habits may become less of a priority and the principles of the program need to be re-emphasized. If the child is clearly sticking to the bladder and bowel program and does not have a correctable anatomic issue, we have to look for other reasons for recurrent infections. 

If inefficient bladder emptying persists despite behavioral modification and biofeedback, specialized testing of bladder function, such as urodynamics or cystometrogram, may be recommended. Additional medications may be offered by the Urology provider, or in very rare cases, intermittent catheterization may be required to assist with emptying and to reduce symptomatic infections. 

Some adults and children have a genetic predisposition to UTIs. Their mucosal and epithelial cells are “programmed” for bacterial adherence, ascent, and invasion. In these cases, bacteria are better able to ascend the urethra to the bladder and are less likely to be successfully cleared with good elimination habits. Genetic testing is not warranted, as it will not yield useful information. Research is ongoing into this mechanism for susceptibility to UTIs and new options for therapy may become available. As with all individuals with recurrent UTIs, meticulous elimination habits remain important. Long-term low-dose prophylactic antibiotics may be necessary to keep infections to a minimum, but many families are dissatisfied with long-term pharmaceuticals and there are long-term risks in a small proportion of individuals on long-term prophylaxis. 

Dietary supplements may be a promising natural alternative to antibiotics. The FDA does not regulate efficacy of nutritional supplements and there is no guarantee that any supplement will be beneficial. While clinical evidence is limited and what does exist is contradictory, energetic testimonials support the basic science theories. 

Probiotics may be beneficial to restore the normal flora, particularly after a course of antibiotics for a UTI. Different probiotic preparations may be useful for maintaining intestinal and urogenital health. A few strains in particular seem to have utility in prevention of recurrent UTIs.[7-9] Families may be referred to www.usprobiotics.org for more information regarding regulation of probiotics. 

Cranberry juice has been touted for years as beneficial in prevention of UTI, although the mechanism is not entirely clear. Acidification of the urine was the proposed mechanism, but that does not bear out in clinical studies. Newer evidence suggests protective benefits of proanthocyanidin in cranberries and blueberries, as well as presence of mannose, a non-digestible sugar that repels bacteria.[10,11] If elected, pure cranberry juice, rather than juice cocktail, is the better choice, as the beneficial elements are more concentrated and fewer calories are consumed. Combination therapy with both natural compounds as a commercially available dietary supplement is another option we consider in the most refractory and frustrating cases. As with other supplements, there is little formal evidence but popular support. We have seen very favorable results in challenging situations. We do not recommend a specific brand or dose for children, although starting with a fraction of the adult dose is reasonable. While the internet contains a wealth of information, caution is warranted when considering natural but alternative remedies. Families who wish to order these supplements are encouraged to use a reputable online outlet where they can read feedback from other consumers prior to purchasing. 

Summary 

Recurrent UTIs can be adequately managed in most cases with adherence to good bladder and bowel elimination habits. The principles of a bladder and bowel management program will point children in the right direction. Follow-up visits help to reinforce good habits to minimize the risk of relapse. 

References 

[1.] Deville WWLJM, Yzermans JC, Van Duijn NP, et al. The urine dipstick test useful to rule out infections. A mega-analysis of the accuracy. BMC Urology 2004;4:4. 

[2.] Wan J, Kaplinsky R, Greenfield S. Toilet habits of children evaluated for urinary tract infection. The Journal of Urology 1995;154(2 Pt 2):797-799. 

[3.] Loening-Baucke V. Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood. Pediatrics 1997 Aug;100(2 Pt 1):228-232. 

[4.] Giramonti KM, Kogan BA, Agboola OO, et al. The association of constipation with childhood urinary tract infections. J Pediatric Urology 2005;1:273-278. 

[5.] Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32(9):920–924. 

[6.] Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. New England Journal of Medicine 2009;361:1748-1759. 

[7.] Falagas ME, Betsi GI, Tokas T, Athanasiou S. Probiotics for prevention of recurrent urinary tract infections in women: a review of the evidence from microbiological and clinical studies. Drugs 2006:66(9):1253-1261. 

[8.] Marelli G. Papaleo E, Ferrari A. Lactobacilli for prevention of urogenital infections: a review. Eur Rev Med Pharmacol Sci 2004;8:87-95. 

[9.] Reid G. Probiotic agents protect the urogenital tract against infection. Am J Clin Nutr 2001;73:437S-43S. 

[10.] DiMartino P, Agniel R, David K, et al. Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial. World J Urol 2006;24:21-27. 

[11.] Howell AB, Botto H, Combescure C, et al. Dosage effect on uropathogenic E. coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study. BMC Infect Dis 2010;10:94.


Accreditation Statement

The Northwestern University Feinberg School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Credit Designation Statement

The Northwestern University Feinberg School of Medicine designates this live activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.