URINARY TRACT INFECTIONS IN NEWBORNS
Moslehi Mohammad Ashkan
Department of Pediatrics, Nemazee Hospital , Shiraz University of Medical Sciences, Iran
Address for Correspondence
Moslehi Mohammad Ashkan, MD, Department of Pediatrics, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz , Iran.
Email
moslehim@sums.ac.ir
INTRODUCTION

Urinary tract infection (UTI) in newborns is one of most clinical problem that frequently is associated with bacteremia and may produce long-term complications. Newborns that label as have UTI should be admitted in hospital and further workup for evaluation for associated systemic infection and anatomic or functional abnormalities of the urinary tract must be done. The epidemiology, pathogenesis, clinical features, diagnosis, and management of UTIs in newborns are reviewed here.

EPIDEMIOLOGY

In normal term newborns, the incidence of bacteriuria determined by prospective bladder urine collection (suprapubic aspiration) is 0.1 to 1 percent.(2-9) The risk of significant bacteriuria may be higher in high-risk newborns. (3) In premature infants, the incidence of bacteriuria is 2 to 6 percent. (3, 4, 7, 8) UTI occurs in 1.5 to 5 times as many males as females in the neonatal period and is higher in uncircumcised than circumcised males .(3, 6, 10, 11) The incidence decreases in boys and increases in girls during the first six months after birth.(12) It is approximately three times more common in females than males by one year of age. The higher incidence in neonatal males also appears to occur in preterm infants .(4, 9, 13) UTI typically presents in the second week after birth in term infants and somewhat later in preterm infants .(3, 9, 11) This infection is an unusual occurrence during the first three days after birth.(14, 15)

Escherichia coli is the most common organism isolated in the newborn period, accounting for up to 80 percent of infections in most large series.(3,6,16,17) This pathogen also is the most frequent cause of UTI at all ages. Other Enterobacteriaceae, which can produce UTI, include: Klebsiella, Enterobacter, Citrobacter, Proteus, Providencia, Morganella, Serratia, and Salmonella species.

Fungal infections (predominantly Candida species) occur commonly in premature infants. Gestational and postnatal ages were lower in infants with Candida compared to bacterial infections .(18)

Several virulence factors in E. coli account for the propensity of this organism to cause UTI, especially when the urinary tract is anatomically normal.(17)

Factors that affect the virulence of E. coli include:

  • Bacterial fimbriae

  • Bacterial flagella

  • Production of a hemolysin (induces formation of pores in the cell membrane), aerobactin, siderophore (necessary for iron acquisition in the iron-poor environment of the urinary tract).

  • Most UTIs in newborns affects upper tract infection rather than lower parts (simple cystitis). Approximately one-third of infants with UTI have bacteremia with the same organism.(18-20) This may be more common in preterm infants. Associated bacteremia becomes less important with increasing postnatal age. As an example, in a review of 100 infants with UTI, sepsis occurred in 31, 21, and 5 percent of infants less than one, one to three, and more than three months of age, respectively.(16)

    Hematogenous spread of infection has been thought to be responsible for neonatal UTI because upper tract infection with associated bacteremia is common. However, the microbiology of these infections and the high incidence of urinary tract abnormalities raise the question of whether neonatal UTI truly arises from hematogenous spread from a remote source (e.g., intravascular catheter) or, in the majority of cases, actually represents an ascending urinary tract infection with an associated bacteremia.

  • Urinary tract abnormalities: Approximately 30 to 50 percent of newborns with UTI have urinary tract abnormalities, of which vesicoureteric reflux (VUR) is most common.(4, 8, 16-20) This incidence was illustrated in one report of 45 males younger than eight weeks old with UTI; urinary tract abnormalities were observed in 22 of which 19 had VUR, two had VUR and another problem (double collecting system and posterior urethral valves), and one had ureteropelvic junction stricture.(20)

    The risk of acute pyelonephritis and subsequent renal scarring is related to the severity of VUR, which is graded according to whether the reflux reaches the kidney and by the degree of dilatation of the collecting system.(21) Children with high-grade VUR are four to six times more likely to have renal scarring than are those with low-grade VUR and 8 to 10 times more likely than are those without VUR.(22-24) Other lesions found in infants with UTI include obstructive abnormalities (ureteropelvic junction or ureterovesical junction obstruction; posterior urethral valves), malformations (ectopic ureter), or renal conditions (polycystic diseases, renal dysplasia).

    Urinary tract abnormalities may contribute to UTI by several mechanisms, including inadequate urine flow, incomplete emptying of the bladder and incompetent anatomic junctions that permit reflux of contaminated urine. As a result, infection can occur with organisms lacking virulence factors. In a study of children with UTI, for example, infections caused by P-fimbriated stains of E. coli were less common with than without VUR (36 versus 71 percent).(25)

  • Uncircumcised males: The incidence of UTI is increased in uncircumcised males. In one report of approximately 136,000 boys in United States Army hospitals, the frequency of UTI during the first month after birth was significantly higher in uncircumcised than circumcised infants (0.19 versus 0.02 percent).(19) The increased incidence in uncircumcised males persists during the first year after birth.(26) The higher incidence of UTI in uncircumcised males is related to an increased rate of bacterial colonization and enhanced bacterial adherence.(27-29) In one study, E. coli and other Gram negative uropathogenic organisms were cultured more frequently from the urethras of uncircumcised than from those of circumcised boys, and bacterial colony counts were higher .(27) In another report, uropathogenic organisms preferentially adhered to the mucosal inner surface of the foreskin rather than the keratinized external surface, increasing the likelihood of ascending infection.(29)


CLINICAL FEATURES

The signs and symptoms of UTI in newborns are nonspecific. Infants can have lethargy, irritability, tachypnea, or cyanosis, and may appear acutely ill. Preterm infants frequently present with apnea.(9)

The most common clinical findings are:

  • Fever (20 to 40 percent)>

  • Failure to thrive (15 to 43 percent)

  • Jaundice (3 to 41 percent)

  • Vomiting (9 to 41 percent)

  • Loose stools (3 to 5 percent)

  • Poor feeding (3 to 5 percent)

The hyperbilirubinemia that occurs with UTI typically is conjugated and related to cholestasis, although it may be unconjugated. Jaundice may be the first sign of UTI in some infants. In one report, UTI was diagnosed in 12 (7.5 percent) of 160 asymptomatic jaundiced infants less than eight weeks of age who presented to an emergency department.30 Onset of jaundice after eight days was more common in infants with positive compared to negative cultures (50 versus 10 percent). Other findings that occur less commonly include abdominal distension resulting from ileus or enlarged kidneys caused by hydronephrosis.

DIAGNOSIS

Diagnosis of UTI is based upon culture of an organism from an appropriately collected specimen of urine. An abnormal urinalysis must be confirmed by a positive urine culture.

Urinalysis
A urinalysis typically includes microscopic assessment of the number of white blood cells (WBC) per high powered field (hpf) of a centrifuged specimen of urine. However, the sensitivity, specificity and positive predictive value of pyuria, defined as 5 WBC per hpf, to correlate with a positive urine culture are low.(34,35) Prediction of UTI is improved when hemocytometer WBC counts are performed on uncentrifuged specimens, as recommended in adults.(36) In a study of febrile (rectal temperature >38º C) infants younger than eight weeks of age in which UTI occurred in 13.6 percent, hemocytometer WBC 10/µL had a higher sensitivity (82 versus 59 percent) compared to standard urinalysis.(35) Dipsticks that detect the presence of leukocyte esterase and nitrite are available commercially; the former corresponds to significant pyuria and the latter to Enterobacteriaceae, which convert urinary nitrate to nitrite. In adults, the dipstick has a sensitivity and specificity of 95 and 75 percent, respectively.(37) The positive predictive value is 30 to 40 percent (when tested in patients suspected of possible UTI), and the negative predictive value is 99 percent. Dipsticks may be used for rapid and easy screening. However, urine culture must always be performed in an infant in whom UTI is suspected. The presence of organisms on a Gram stain of 0.01 mL of unspun urine correlates with subsequent growth in a urine culture of >10(5) CFU in adults. This density of bacteria rarely is recovered in a urine culture from neonates. Even if urine Gram staining were readily available, it rarely would be performed in infants for this reason.
  • Urine collection
    Specimens should be obtained by suprapubic bladder aspiration or catheterization. Collections in a bag frequently are contaminated, and a midstream clean catch specimen is impractical in newborns.

  • Suprapubic aspiration
    Suprapubic aspiration of the bladder urine is the most reliable technique to identify bacteriuria.(31)The technique is simple, relatively safe, and causes minimum discomfort. The procedure should be performed in infants who have a palpable bladder and who have not voided recently. After cleaning the suprapubic area with an antiseptic solution, a 23- or 25-gauge needle is inserted perpendicular to the baby, approximately one centimeter above the pubic symphysis. In one report, ultrasound guidance improved the yield of urine compared to unguided aspiration (96 versus 60 percent).(32) Any growth of urinary pathogens is significant.

  • Bladder catheterization
    Bladder catheterization is an alternative to suprapubic collection. Bacterial contamination resulting from incomplete cleansing of the perineal area or prepuce renders this technique less reliable than suprapubic aspiration. In a study comparing catheterization to bladder aspiration in febrile infants younger than one year of age, catheterization cultures with >1000 CFU/mL had a sensitivity and specificity of 95 and 99 percent, respectively.(33)

Sepsis evaluation As noted above, approximately one-third of newborns with UTI have an accompanying bacteremia, and some have meningitis. Thus, a blood culture should be obtained in all infants in whom UTI is suspected, and culture of the cerebrospinal fluid (CSF) should be considered. Infants at increased risk for fungal infection should be evaluated for disseminated disease.

TREATMENT

Treatment with intravenous broad-spectrum antimicrobial agents should be initiated as soon as cultures of urine, blood, and CSF (if indicated) have been obtained. Ampicillin and gentamicin provide coverage for the most common bacterial pathogens. Experts vary in their dosing recommendations. In term infants younger than seven days old, the American Academy of Pediatrics Red Book recommends ampicillin (25 to 50 mg/kg per dose Q8 hour IV) and gentamicin (2.5 mg/kg per dose Q12 hour IV).(38) Other experts use once-daily gentamicin dosing (4 mg/kg per dose Q24 hour IV).(39) Vancomycin (10 to15 mg/kg per dose Q12 hour IV for infants < 7 days and Q8 hours thereafter) usually is substituted for ampicillin in infants with later onset infections to provide empiric coverage for hospital-associated infections, including coagulase-negative staphylococci, Staphylococcus aureus, and Enterococcus species. If meningitis is suspected, the higher doses of antibiotics must be used, pending the results of cultures .(38) Antibiotics should be tailored when the results of the cultures and the antimicrobial susceptibilities become available. Sterilization of the urine should occur within 48 hours of treatment with the appropriate antimicrobial agent. Optimally, it should be confirmed by repeating the urine culture at that time. If bacteriuria persists despite appropriate therapy, the urinary tract and other sites should be investigated to determine a potential reservoir of infection.

The duration of antibiotic therapy is 10 to 14 days for newborns with uncomplicated bacterial UTI. We complete the treatment course in newborns with intravenous antibiotics, although older infants often are switched to oral antibiotics after clinical improvement. Longer treatment is needed for fungal infections.

Conventional teaching holds that the urine culture should be repeated two to three days following the completion of treatment. However, because suprapubic aspiration or repeat catheterization would be required, it often is omitted if the patient is clinically stable. Antibiotic prophylaxis with low-dose amoxicillin (15 to 20 mg/kg per day PO) is started until a radiographic evaluation has been performed to detect urinary tract abnormalities. Continuation of this prophylaxis depends upon the results of imaging studies.

RADIOGRAPHIC EVALUATION

Radiographic evaluation must be performed in all newborns with UTI. This evaluation includes ultrasonography and voiding cystourethrogram (VCUG). A renal ultrasound should be obtained after antibiotic treatment is initiated and the infant's clinical condition has stabilized. This examination will demonstrate the presence, position, and size of the kidney; the size and thickness of the bladder; dilation of the collecting system; and any structural abnormalities. A normal ultrasound examination does not exclude VUR or renal scarring.
  • Voiding cystourethrogram A VCUG is performed to detect VUR. Performing VCUG should not be delayed in infants who have abnormalities detected on ultrasonography. Earlier examination also may be indicated in infants with abnormalities detected on antenatal ultrasound examination.

  • Radionuclide cystography (RNC) is used by some physicians as an alternative to VCUG in children. VCUG with fluoroscopy characterizes reflux better than does RNC. VCUG also detects intrarenal reflux and provides functional and anatomic information about the bladder and urethra that cannot be obtained by RNC. For these reasons, VCUG is the preferred technique. Alternative procedures that avoid radiation exposure, such as contrast-enhanced sonography, remain under investigation.40

  • Other imaging Renal cortical scintigraphy (with 99 m Tc-DMSA or 99 m Tc-glucoheptonate) and enhanced computed tomography may be used to identify renal scarring and acute changes due to pyelonephritis. Cortical scintigraphy is more sensitive than is ultrasonography to detect renal changes.1It may be considered if renal damage is suggested by ultrasonography or as part of follow-up evaluation.

    OUTCOME

    Many children with UTI develop renal scarring, and newborns also are likely at risk for this complication. Renal scarring may result in hypertension and chronic renal disease. In one study, renal scars were documented by follow-up scintigraphy in 40 percent of infants with UTI at less than one year of age.(42)

    In another report by the same authors; few infants in this age group with renal scarring had VUR.43 Nephropathy also can be present at birth in infants with severe reflux seen on prenatal ultrasonography even without UTI.(44, 45)

    Neonatal UTI may impair renal growth. In one study, 22 children who had UTI before reaching one month of age were followed for 12 to 21 years.46 Renal growth was decreased in patients with and without reflux at approximately four years after the UTI, although renal size tended to become normal later.
Funding
None
Conflict of Interest
None
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