THE CIRCUMCISION REFERENCE LIBRARY


THE PEDIATRICS INFECTIOUS DISEASE JOURNAL, Volume 8, Number 8: Pages 552-555,
August 1989.


Options in antimicrobial management of urinary
tract infections in infants and children

GEORGE H. MCCRACKEN, JR, MD

The diagnosis and management of urinary tract infections (UTI) in infants and children are usually routine and outcome is generally good. Assuming those premises to be correct, why is it necessary to prepare a review of the subject?

Although the bladder and upper urinary tract are usually sterile, urine obtained per urethra can easily be contaminated especially in infants and young children, by bacteria that colonize the urethral meatus, periurethral sites (e.g. prepuce of uncircumcised males) and perineum. Collection of sterile urine from young patients poses a potential problem if a plastic receptacle is used, and percutaneous suprapubic bladder aspiration or bladder catheterization is usually performed only in very young infants who require immediate antimicrobial therapy or in those in whom sterile collection of urine by bag technique is thought to be unlikely.

Management of pediatric patients with UTI is confounded by inadequate follow-up to establish the structural integrity of the urinary system by radiographic techniques, to document recurrence of infection and to prevent renal damage. The ultimate goal of managing children with UTI occur most commonly in adolescence or young adult life, the pediatrician can mistakenly believe that the long term outcome of infants and children with UTI is uniformly excellent and that rigorous attention to details of diagnosis and follow-up is unnecessary.

INCIDENCE RATES

The exact rates of UTI are unknown because as many as 40% of infections in infants and children are asymptomatic (Table 1). It has been estimated that approximately 3% of Swedish girls and 1% of Swedish boys have symptomatic UTI before the age of 11 years.1

===========================================================
Table 1. Estimated rates of asymptomatic bacteriuria in
infants and children.
-----------------------------------------------------------
Age           Factor        Incidence(%)
-----------------------------------------------------------
Newborns             Term                 1
                     Preterm              2-3
Preschool            Males                0.2
                     Females              0.8
School               Males                0.03
                     Females              1-2
15-24 year olds      Females              2
========================================================

Studies conducted at Parkland Memorial Hospital in Dallas demonstrated that the incidence rate of UTI in infants 6 months of age and younger was 1.65 cases/1000 live births in 1972 to 1975 and 2.04 cases/1000 live births in 1977 to 1980.2 The male:female ratios were 2.7:1 and 5:1, in the two time periods. We documented that 95% of the male infants with UTI were uncircumcised, even during the period when greater than 90% of newborn infants were circumcised.2,3 Wiswell and Roscelli4 corraborated these findings in a review of UTI in infants hospitalized in United States Army Hospitals worldwide for a 10-year period. The uncircumcised male had the highest rate of UTI (1.12%) compared with female infants (0.57%) and circumcised males (0.11%). Because long term outcome of UTI in uncircumcised males is unknown, it is inappropriate at this time to recommend circumcision as a routine medically indicated procedure.5

DIAGNOSIS

The first and most critical step in establishing the diagnosis of UTI in infants and young children is the method by which urine is collected. In the young patient care must be taken to prepare carefully the perineum and periurethral area for placement of the sterile plastic receptacle for collection of urine. In the infant the quickest and surest way to obtain urine for culture aseptically is by urethral percutaneous supra-pubic bladder aspiration or by catherization. These procedures avoid the potential problem of contaminated urine cultures that often result from bag specimens. Older children and adolescents can be instructed to collect a midstream urine specimen after proper cleansing of the urethral area.

Demonstration of bacteria microscopically in the most reliable and fastest means to establish the diagnosis of UTI before results of urine cultures are available. The presence of 105 organisms or more per mil of urine is diagnostic of UTI. As few as 5 X 102 to 104 organisms/ml have been etiomologically associated with the frequency/dysuria syndrome in women.6 It is unknown whether these observations in adults apply to school girls. If 5 X 10(to the third power to 10(to the fifth power) colony forming units of a single genus and species per ml are recovered from two succesive urine cultures of a child, a diagnosis of UTI should be made and the patient managed accordingly. Cultures from urine obtained by percutaneous bladder aspiration or by catherization may contain fewer than 10(to the fifth power) organisms/ml because the bacteria have not had sufficient time to multiply before removal of urine from the bladder.

Escherichia coli is the most frequent etiologic agent of acute uncomplicated UTI in infants and children, accounting for 85 to 90% of all pathogens recovered from urine cultures. Other organisms include Group B streptococci, Klebsiella-Enterobacter species and occasionally enterococci. Staphylococcus saphrophyticus can cause UTI in adolescent girls.

Chronic infections of UTI that occur in those who are receiving antimicrobial prophylaxis are frequently caused by enterococci, Proteus species, Pseudomonas aeruginosa or Candida species.

TREATMENT

As with other infectious diseases in pediatric patients, management of UTI in newborn and young infants is considerably different from that of older infants and children.

Newborn and young infants; UTI in infants younger than 3 or 4 months are best managed in the hospital. In the Dallas experience approximately one-fifth of such infants have positive blood cultures, the incidence being largest in neonates; as many as one-third have positive blood and urine cultures.3,7 Initial therapy is provided with parenterally admininistered ampicillin and gentamycin or another of the aminoglycosides (Table 2). Parenteral therapy is continued until repeat urine cultures at 24 to 48 hours after start of therapy and blood cultures are sterile and the infant has improved and is able to take medication orally. If the infants has delayed improvement, of pyelonephritis is suspected clinically or radiographically or if there is obstruction of the urinary tract parenteral therapy should be continued for 7 days or longer.

===========================================================
Table 2. Antimicrobial therapy of urinary tract infections
in infants younger than 3 or 4 months of age.
-----------------------------------------------------------
Initial Therapy
       Ampicilliin, 75-100 mg/kg daily in 3 or 4 doses, iv
       or im, and gentamicin(a), 7.5 mg/kd daily in 3 doses,
       iv or im.
       Parenteral therapy is continued until there is
       evidence of clinical improvement and blood and urine
       cultures are stable.
Subsequent therapy
       Amoxicillin, 50 mg/kg daily in 2 or 3 doses, po, or
       Augmentin(a,b) 50mg/kg daily in 2 or three doses, po,
       or cephalexin, 50 mg/kg daily in 2 or 3 doses, po, or
       sulfasoxazole(c), 120 mg/kg daily in 3 or 4 doses.
Total therapy
       Therapy should be given for 10 days.  In those with
       pyelonephritis, parenteral antimicrobial therapy
       should be given for the entire 10 days.
-----------------------------------------------------------
a. Tobramycin, 4 to 6 mg/kg daily in 3 doses, or amikacin,
   15 to 22.5 mg/kg daily in 3 doses is a suitable
   alternative.
b. Amoxicillin plus clavulate potassium.
c. A sulfomide should not be administered to infants
   younger than 6 weeks or to infants with jaundice.
============================================================

Orally administered aminopenicillins, cephalosporins, and in the older infants, sulfonamides can be given when the above caveats are heeded and when the child is able to tolerate oral medication and compliance by the parents is assured. Selection of the most appropriate antibiotic is dependent on the susceptibility of the pathogen. Ampicillin-resistant strains of E. coli. will usually be susceptible to an orally administered cephalosporin or to Augmentin (amoxicillin plus clavulanate potassium. If a sulfonamide is to be administered sulfisoxazole or trisulfapyrimides are preferred.

Older infants and children. Positive blood cultures occur infrequently in older infants and children with UTI unless infection involves the renal parenchyma. The principal variable in determining selection of an antimicrobial agent, the route of administration and duration of therapy is the presence clinically or radiologically of pyelonephritis. Most symptomatic children with pyelonephritis should be hospitalized and treated initially with parenterally administered antibiotics (Table 3). Once there is evidence of clinical improvement and urine and blood cultures are sterile, therapy can be given orally. The preferred drug for oral administration is trimethoprim/sulfamethoxazole (TMP/SMX) because of its excellent absorption and tissue penetration and because most urinary pathogens are highly susceptible to this combination of drugs. Exceptions include enterococci and Pseudomonas species. Children with upper UTI are best treated for a minimum of ten days; shorter courses of therapy can result in relapse of infection.

When it is likely that the patient has cystitis, orally administered sulfonamides, aminopenicillins or cephalosporins are satisfactory (Table 3). In general those antimicrobial agents do not need to be administered more often than two or three times daily. The duration of therapy for lower UTI can be as brief as one dose or several days or to can be for the conventional period of 7 to 10 days. In adult women with cystitis localized by bladder washout technique, single dose aminoglycoside therapy was shown to be effective in eradicating the pathogen.8 By contrast most of those who had pyelonephitis had immediate relapse of infection after single dose treatment. The efficacy of single dose antibiotic therapy for cystitis in women has been documented by others.9 The evidence is not as clear for short term therapy in children. The principle problem of a one dose regimen in children is the uncertainty regarding localization of infection. There is no simple laboratory technique, such as the antibody coated bacteria test used successfully in women, that is uniformly effective in localizing the site of UTI in children and clinical features can be misleading.

==========================================================
Table 3. Antimicrobial therapy of urinary tract infections
in older infants and children
----------------------------------------------------------
Pyelonephritis
       Most children with clinical and/or
          radiologic evidence of pyelonephritis should be
          treated initially with parenterally administered
          antibiotics.
       Ampicillin, 100 mg/kg daily in 3-4 doses, iv or im
          and gentamycin,(a) 7.5 mg/kg. daily in 3 doses iv
          or im.
       Ampicillin,(as above) and cefotaxime, 100-150 mg/kg
          daily in 3 doses.  For oral therapy, TMP/SMX is
          preferred in a dosage of 6-8 mg of TMP/30-40 mg
          per kg in 2 doses,
Cystitis
       Sulfisoxazole or trisulfapyrimidines, 120-150 mg per
          kg daily in 4 doses, po or amoxicillin, 50 mg/kg
          daily in 2 or 3 doses, po, or TMP/SMX(as above) or
          cephalexin, 50 mg/daily in 2 or 3 doses, po.
Duration of therapy
       Therapy is conventionally provided for 7-10 days.  In
       children with uncomplicated UTI, therapy for 3-7 days
       is usually satisfactory.
------------------------------------------------------------
a. Tobramycin or amikacin treatment is a suitable
   alternative.
============================================================

A methodologic review of the 14 published studies of short course antibiotic therapy for UTI in children was recently presented (Table 4).10 There were no significant diferences in cure rates of UTI for short course vs. conventional regimens of 7 to 10 days of treatment. Because of differences in study designs and of insufficient numbers of patients in most studies, the authors of that review concluded there was not enough evidence to warrant routine use of short course antibiotic therapy in children. Subsequently Madrigal et al.11 published results of short course therapy in 82 children who received treatment for 1 dose or 3 days and compared results with those children who received a conventional 7-day course of antibiotic therapy (Table 5). The conclusion was that therapy for 3 or 7 days is satisfactory for most children with uncomplicated UTI.

We recommend that antibiotic therapy for 3 to 7 days be used in children with uncomplicated UTI. Shorter courses of treatment can result in higher rates of recurrent infection.10 Children who had complicated infections, including all those who had pyelonephitis, should receive therapy for at least 10 days. The critical feature of management of all children with UTI is adequate follow-up to identify those patients with structural abnormalities of the urinary system and to document recurrence of infection, which occurs in approximately one-third of patients.

RADIOLOGIC STUDIES

Because structural abnormalities of the urinary system are present in 20 to 30% of infants and children with UTI, roentgentographic evaluation should be performed on all males up to the age of 3 to 5 years after treatment of the infection. Although the criteria for choosing who should be studied and which procedures should be use differ among experts, most agree that renal sonography or intravenous pyelography (IVP) and a voiding cystourethrogram should be performed. A recent study from Haifa, Israel, concluded that an IVP is not necessary if ultrasonography is normal and the voiding cystourethrogram shows only low grade vesicoureteral reflux.12

========================================================
Table 4. Review of 14 published studies of short course
antibiotic therapy for UTI in Children10
--------------------------------------------------------
Treatment     No of     No           No with       %
Regimens      Studies   Cured after  Recurrent   Cured
                        Treatment    UTI
--------------------------------------------------------
 1 dose vs      7       101               76       75
 CR                     128               87       68
 1-3 days vs    4       112               91       81
 CR                     108               98       91
--------------------------------------------------------
CR, conventional regimens of 7 to 10 days.
========================================================

========================================================
Table 5. Duration of treatment and outcome from urinary
tract infections in children.11
---------------------------------------------------------
TMX/SMX9(a)     No.           No.           No. with
 Regimen       Studied     Cured after      Recurrent
                           Treatment          UTI
---------------------------------------------------------
 A. 1 dose       42          39(93(b)       8(20.5)(d)
 B. 3 days       40          36(90)         2(5.6)
 C. 7 days       50          50(100)        4(8)
---------------------------------------------------------
a. TMP/SMX (6 mg of TMP-30 mg of SMX per day in two divided
   doses except for those receiving regimen A).
b. Numbers in parentheses, percentages.
c. A vs B or C, P=0.679
d. A vs B or C, P=0.033
=========================================================

Renal sonography is preferred to IVP because the former is noninvasive and avoids the risk of radiation. Sonography should be performed only by radiologists who are experienced with the procedure in infants and children.

LONG TERM MANAGEMENT.

Recurrent UTIs occur in approximately 30% of children after an initial acute infection. The risk of recurrence increases to as high as 75% in children who have had three or more previous UTIs. Vesicouterual reflux has been reported in 29 to 50% of children with vesicouteral reflux and in approximately 5% of those with recurrent UTI. The principal goals of management are to identify in infancy or early childhood those patients with recurrent UTI who have reflux with or without renal scars and to prevent further renal damage and the complications associated with chronic renal insufficiency. The optimal means to accomplish these goals are controversial. In this review only antimicrobial prophylaxis for prevention of recurrent UTI in such patients will be addressed.

Antibiotics with proved efficacy and safety in preventing UTI in infants and young children include sulfonamides (e.g. sulfisoxanole and the trisulfapyrimidines), nitrofurantoin, nalidixic acid and TMP/SMX. Because emergence of resistant strains of Enterobacteriaceae occurs commonly during long term prophylaxis with the sulfonamides, these agents are not routinely recommended for that purpose.

For many years nitrofuratoin has been successfully and safely used for prevention of recurrent UTI in infants and children. The agent is active against many of the organisms causing infection but is ineffective against Pseudomonas species, enterococci, and some strains of Klebsiella-Enterobacter and Proteus. Maximum bactericidal activity of nitrofurantoin occurs in acidic urine. Large concentrations occur in urine after oral administration of 1- to 2- mg/kg doses. It has been suggested that use of this drug be limited because of the relative high frequency of adverse reactions especially pulmonary, that occur in adolescent and adult females.13 Corragio et al.14 reviewed recently the serious adverse reaction reports submitted to the Food and Drug Administration since 1953. There were 26 cases of adverse cases of serious reactions to nitrofuratoin in United States children and adolescents who were less than 20 years of age. Neurologic and hepatic reactions occurred in 7 and 9 patients, respectively, which equated to 0.8 and 1.0 cases/million uses, respectively. The total rate of serious adverse reactions was 3.0/million users.14 On the bases of these data and of clinical experience it appears that nitrofurantoin is a safe and effective antibiotic for prophylaxis in infants and children with recurrent UTI.

The new fluoroquinolones (e.g. ciprofloxacin and norfloxacin) are broad spectrum antibiotics that have been used effectively in adults with a variety of infectious diseases, including UTI. They have not been approved by the Food and Drug Administration because of concern about possible toxicity to cartilage of weight-bearing joints that had been observed in animals with incomplete skeletal growth.15 Naxidixic acid, the first quinolone antibiotic, has been used frequently in children with UTI without apparent adverse effect.16 Until there is additional information the new fluoroquinolones should not be used routinely in children and adolescents.

TMP/SMX has been used for many years for prophylaxis of recurrent UTI. When used in a dosage of 1 to 2 mg of TMP-5 to 10 mg of SMX per kg daily in one dose the agent has been well tolerated, safe and effective.

Breakthrough urinary infections occur commonly in children who are receiving chemoprophylaxis. These infections are usually caused by enterococci, Proteus species of P. aeruginosa although Candida species can also cause UTI in this setting. Ampicillin or amoxicillin therapy is effective for enterococcal UTI and an aminoglycoside given intramuscularly once daily is usually curative for Proteus or Pseudomonas infection. A fluoroquinolone could be used in the latter situation especially in adolescent girls. With Candida infection it usually suffices to stop antimicrobial prophylaxis until the infection clears.

CONCLUSION

Management of infants and children with acute UTI must be undertaken with four major goals in mind: (1) the diagnosis should be properly documented to avoid unnecessary radiologic studies and follow-up; (2) the structural status of the urinary tract must be delineated by radiologic techniques in infancy or early childhood as a basis for formulating long term management; (3) children with structural abnormalities of the urinary system must be followed up for many years; (4) antibiotic therapy should be given for a minimum of 3 to 7 days in children with uncomplicated UTI and for 10 days or longer in those with suspected or proved pyelonephritis.

REFERENCES:

  1. Winberg J. Epidemiology of symptomatic urinary tract infections in childhood. Acta Paediatr Scand Suppl 1974:252.
  2. Nelson J, McCracken GH. Circumcision and UTI. Pediatr Infect Dis Newslett 1984; 10:6.
  3. Ginsburg CM, McCracken GH. Urinary tract infections in young infants. Pediatrics 1982; 69:409-12.
  4. Wiswell TF, Roscelli JD. Corroborative evidence for the decreased incidence of urinary tract infections in circumcised infants. Pediatrics 1986; 78:96-9.
  5. Lohr LA. The foreskin and urinary tract infections. J Pediatr 1988; 114:502-3.
  6. Stamm WE, Counts GW, Running KR, et al. Diagnosis of coliform infection in acutely dysuric women. N Engl J Med 1982; 307:463-8.
  7. Israeli V, Darabi A, McCracken GH. The role of bacterial virulence factors and Tamm-Horsfell protein in the pathogenesis of Escherichia coli urinary tract infection in infants. Am J Dis Child 1987; 141:1230-4. [Abstract]
  8. Ronald AB, Boutros B, Mourtader H. Bacteriuria localization and response to single-dose therapy in women. JAMA 1976; 235:1854-6.
  9. Fang LST, Tolkoff-Rubin NE, Rubin NH. Efficacy of single-dose and conventional amoxicillin therapy in urinary tract infection localized by the antibody coated technique. N Engl J Med 1978; 198:413-6.
  10. Moffat M, Embree J, Grimm P, Law B. Short-course antibiotic therapy for urinary tract infections in children. Am J Dis Child 1988; 142:57-61.
  11. Madrigal G, Odio CM, Mohs E, Guevara J, McCracken GH. Single dose antibiotic therapy is not as effective as conventional regimens for management of acute urinary tract infections in children. Pediatr Infec Dis J 1988; 7:316-9.
  12. Alon U, Berant M, Pery M, Intravenous pyelography in children with urinary tract infection and vesicoureteral reflux. Pediatrics 1989; 83:332-6.
  13. Holmberg L, Bowman G, Bottiger LE, et al. Adverse reactions to nitrofuratoin: analysis of 921 reports. Am J Med 1980; 69:733-8.
  14. Corraggio MJ, Gross TP, Roscelli, JD. Nitrofuratoin toxicity in children. Pediatr Infect Dis J 1989; 8:163-5.
  15. Schluter G. Toxicology of ciprofloxacin. In: Neu HN, Wenta H, eds., 1st International Ciprofloxacin Workshop, Proceedings Excerpta Medica. Amsterdam, 1986:61-70.
  16. Schaad VB, Wedgwood-Krucko J. Nalidixic acid in children: retrospective matched controlled study for cartilage toxicity. Infection 1987; 15:165-8.

Accepted for publication April 24, 1989.
From the Department of Pediatrics, University of Texas South-
Western Medical Center
at Dallas, TX
Reprints not available.


Citation:
(File revised 15 September 2006)

Return to CIRP library

http://www.cirp.org/library/disease/UTI/mccracken/