Chein-Wei Lin, Yee-Hsuan Chiou, Ying-Yao Chen, Yung-Feng Huang,. Kai-Sheng Hsieh, Ping-Kuang Sung*. The symptoms and ..... Wiswell TE, Roselli, JD.
Urinary Tract Infection in Neonates Chein-Wei Lin, Yee-Hsuan Chiou, Ying-Yao Chen, Yung-Feng Huang, Kai-Sheng Hsieh, Ping-Kuang Sung*
The symptoms and signs of urinary tract infection (UTI) in the newborn are non-specific. We carried out a retrospective investigation of 30 neonates in whom urinary tract infections were diagnosed by urinary culture. In our study, UTI was a little more common in boys (56%). Eight babies (27%) had low birth weights (less then 2,500 gm). In addition to fever, gastrointestinal tract symptoms and jaundice were also frequently associated with UTI. Escherichia coli was the most common causative pathogen, 85% of which was sensitive to gentamicin. Thirteen patients (43%) had congenital genitourinary (GU) tract anomalies. Of these, five cases were diagnosed via prenatal ultrasonography. Ureteropelvic junction stenosis was the most common malformation. Recurrent UTI occurred in 3 babies who had major congenital GU tract anomalies. Resistant strains were found in cases of recurrent UTI. Pyuria was seen in 21 cases (75%) and bacteremia in two. Key words: neonate, urinary tract infection, congenital genitourinary tract anomaly, chemoprophylaxis Urinary tract infection (UTI) is an important cause of fever in the neonates [1]. But the diagnosis of UTI can be overlooked because the symptoms are often non-specific and the sterile samples may be difficult to obtain. The medical management and radiological evaluation of UTI in neonates are quite different from that of older children and adults. Early detection of UTI and resolving the underlying congenital genitourinary (GU) tract anomalies can prevent recurrent renal damage leading to end stage renal disease [2]. To better understand of urinary tract infection in this age group, we retrospectively reviewed 30 neonates diagnosed with UTI by positive urine cultures. The clinical manifestations, laboratory findings, underlying congenital GU tract anomalies and clinical course were reviewed.
colonies from a suprapubic bladder aspiration. The specimens were collected from urinary bags in 11 patients, from catheterization in 4 patients and from suprapubic puncture in 15 patients. Blood, cerebrospinal fluid (CSF) and stool cultures were also done in 25, 14 and 6 cases respectively. Ancillary studies for urinary tract evaluation were performed including renal sonography (28/30), intravenous pyelogram (IVP) (5/30), radiographic or nuclear voiding cystourethrography (VCUG) (11/30), 99mTc dimercaptosuccinic acid (DMSA) scintigraphy (12/30), diuretic renogram (5/30) and computed tomography (1/30). The renal sonography and DMSA scintigraphy were performed as soon as possible after diagnosis. VCUG was done at least one week after antibiotic therapy begun. The results were determined by the radiologists and nuclear medicine physicians.
Materials and Methods From January 1992 to December 1997, 628 patients were admitted to the Veterans General Hospital-Kaohsiung with a diagnosis of urinary tract infction with positive urine cultures. Thirty were neonates, ranging from 1 day to 28 days old. Positive urine cultures were defined as more than 105/mL bacterial colonies in a specimen collected with a clean-catch urinary bag, more than 104/mL from intermittent catheterization and any number of Department of Pediatrics, Department of Pediatric Surgery*, Veterans General Hospital, Kaohsiung, Taiwan, ROC Received: April 12, 1999 Accepted: October 11, 1999
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Results Prenatal Factors and Prenatal Sonography Eight of the 30 patients had low birth weights (< 2,500 gm). Their mean gestational age was 35 and 5/7 weeks. Only one of these patients also had congenital GU tract malformation. In prenatal sonography, congenital urinary tract malReprint requests to: Dr. Ying-Yao Chen, Department of Pediatrics, Veterans General Hospital-Kaohsiung, 386, Ta-chung 1st Road, Kaohsiung, Taiwan, ROC
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CW Lin, YH Chiou, YY Chen, et al formations were seen in 5 patients. These included ureteropelvic junction (UPJ) stenosis, ureterocele and hydronephrosis. Sex Distribution and Clinical Manifestations Seventeen patients were boys. The sex ratio of infants with UTI was male : female : 1.3 : 1. The most common complaint was fever (83%), followed by gastrointestinal tract problems (40%). These manifestations were poor appetite, diarrhea, blood tinged stool, vomiting and abdominal distention. Four patients had elevated conjugated and unconjugated bilirubin values. The values were 22.2/1.6 mg/dL in a 3 day-old patient, 17.2/1.7 mg/dL in a 5 day-old patient, 16.3/1.5 mg/dL in a 12 dayold patient and 15.8/1.5 mg/dL in a 15 day-old patient. Abdominal mass was found in one patient with severe hydronephrosis due to UPJ stenosis. One patient with right side UPJ stenosis and left side multiple cystic dysplastic kidney (MCDK) had oliguria. Table 1 summarizes these manifestations. Table 1. Clinical Findings of Neonatal Urinary Tract Infection Symptoms & signs Fever Gastrointestinal problems Poor appetite Vomiting Diarrhea Blood tinged stool Abdominal distention Hyperbilirubinemia Abdominal mass Oliguria Irritability
Number of patients (%) 25(83) 12(40) 10(33) 5(16) 3(10) 1(3) 3(10) 4(13) 1(3) 1(3) 2(7)
Laboratory Findings C reactive protein (CRP) was determined in 22 patients. Six patients had values less than 0.1 mg/dL, 9 patients’ values were between 0.1-1 mg/dL and 7 patients’ values were greater than 1 mg/dL. The highest value was 14.7 mg/dL. The total white blood cell (WBC) count was less than 5,000/μL in 3 patients, between 5,000-10,000/ μL in 5 patients, between 10,000-15,000/μL in 11 patients, between 15,000-20,000/ μ L in 8 patients and greater than 20,000/μL in 3 patients. Urinary analysis was done in 28 cases. For the other two cases, only urinary cultures were done because the specimens were obtained via suprapubic pucture and were too small for urinary analysis. Pyuria of at least 10 WBC/ HPF urine were found in 20 cases (71%). Es-
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cherichia coli was the most common organism, found in 20 cases (20/30), followed by Klebsiella pneumoniae (3/30), Enterococcus (2/30) and Enterobacter cloacae (2/30). Blood bacterial cultures were done in 25 cases. Bacteremia was found in 2 cases and the causative organisms were E coli and Enterococcus faecalis. The urinary culture results in these two patients were the same as those of the blood cultures. CSF and stool cultures were performed in 14 and 6 cases but there was no bacterial growth. Genitourinary Tract Anomalies Thirteen of 28 patients evaluated for GU tract anomalies and kidney function had congenital GU tract anomalies. Nine were boys. Hydronephrosis was found in 12 cases. Seven patients had UPJ stenosis, 5 cases on the left side, 1 case on the right side and 1 case had bilateral involvement. Radiographic or nuclear voiding cystourethrography was performed in only 11 cases. One case had grade 2 vesicoureteral reflux (VUR), according to international criteria grading the VUR. IVP was done in 4 patients with UPJ stenosis and in one patient with right ureterocele, double right ureters and grade 2 VUR. Inguinal hernia was found in 4 patients. Table 2 summarizes these findings. Table 2. Congenital Genitourinary Tract Anomalies in 30 Neonates with Urinary Tract Infection Urinary tract status
Number of Patients No.
No evaluation Normal Hydronephrosis Ureteropelvic junction stenosis Left side Right side Bilateral Vesicoureteral reflux Right ureterocele Double right ureter Multiple cystic dysplastic kidney
2 15 12 7 5 1 1 1 1 1 1
Clinical Course and Prognosis The duration of parenteral antibiotic therapy varied. Most patients had treatment for 10 days. Generally, ampicillin and gentamicin were started until the culture and sensitivity results were available. Four had surgery for major congenital GU tract anomalies. Two of these patients had UPJ stenosis, obstructive type, one patient had left side UPJ stenosis combined with right side multiple cystic dysplastic kidney and one patient had right
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Neonates with Urinary Tract Infection ureterocele with a double right ureters and grade 2 VUR. After discharge, the oral antibiotics including amoxicillin and cephalexin were prescribed for chemoprophylaxis. However, three patients had recurrent UTI. The first recurrence bagan at 12th day, 14th day and 59th day after the initial infection. The causative organisms were E coli, E cloacae, Proteus mirabilis, K pneumoniae and Pseudomonas aeruginosa. These pathogens were resistant to prophylactic oral antibiotics and multiple parenteral antibiotics.
Discussion The prevalence of UTI varies with age and gender. During early infancy, UTI is more common in males than in females. Ratios of 10.5: 1 to 1:1 of males to females have been reported [3-6]. In our study, the male : female ratio was 1.3 : 1. Prenatal sonography offers information on congenital GU tract anomalies which could lead to UTI. Antibiotic prophylaxis has been suggested for patients with an abnormal renal sonography on a prenatal examination [7]. Only 5 of 13 cases of congenital GU tract anomaly were diagnosed by prenatal sonography. This may be because prenatal sonography was not done or because of limitations in prenatal sonography. One patient had major congenital GU tract anomalies including right side UPJ stenosis and left side multiple cystic dysplastic kidney which were not found until oliguria occurred after birth. The symptoms of UTI in early infancy are nonspecific [8, 9]. The most common presenting symptoms in our series were fever, gastrointestinal tract problems and hyperbilirubinemia. The total bilirubin level increased to 22.2 mg/dL and the direct bilirubin level was 1.6 mg/dL in one case. Abdominal mass, hypertension, oliguria, urosepsis, hyperchloremic acidosis and oligohydramnios are important manifestations of urinary tract obstruction, which is often followed by repeated UTI [2]. Physicians need to be alert to these important signs. CRP and WBC results showed individualized inflammatory response in different patients. Two patients had bacteremia and their CRP levels were less than 0.1 mg/dL and 1.2 mg/dL and total white blood cell counts were 16,250/μL and 9,740/μL. No left shift was found in their differential counts. Pyuria was found in only 71% of our patients. Urinary cultures should be done in any sick baby with a possibility of UTI, even in the absence of pyuria. The association of childhood UTI and concomitant bacteremia ranges from 6% to 31% according to different age patients. In two reports, almost 30% of neonates with UTI had positive blood cultures [5, 10]. In our series, most did
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not receive any antibiotic treatment before blood cultures were done, but positive blood cultures were found in only 2 cases. The organisms were identical in the blood and urine cultures. Thus a septic workup is indicated if sepsis or meningitis is suspected. Because of the possibility of sepsis, all neonates with UTI should be treated with parenteral antibiotics for 10 to 14 days. We recommend using ampicillin and an aminoglycoside for the initial treatment of neonatal UTI until the culture and sensitivity results are available. The incidence of GU tract anomalies is reported to be 20% to 60% in infants less 2 months old with UTI [5, 10, 11]. VUR is the most prevalent GU tract abnormality and has been reported in 33% to 57% of neonatal UTI cases [5, 9]. But in our study, UPJ stenosis was most common. VUR was found in only one case. Since only 11 patients had a VCUG and 5 of them had a radiographic VCUG, the sensitivity for detecting low grade VUR was lower than that for nuclear VCUG. So, the actual prevalence of VUR may have been underestimated in our series. UPJ stenosis more frequently involved the left side (left: right: 5:1), which is compatible with report from the literature [12, 13]. In previous reports, low birth weight babies were significantly more often affected than those of normal weight [11]. In our patients, 8 cases had low birth weights (27%). Most had no GU tract malformations. Immunologic impairment in these patients may have from been the causative factor. Repeated UTI increases the incidence of renal scarring. Effective prophylaxis is recommended in patients with GU tract anomalies which cause recurrent UTI [14,15]. Oral antibiotics were prescribed to our patients with UPJ stenosis and the patient with ureterocele, double ureter and VUR. For 3 patients with frequent UTI, prophylactic failure may have been due to resistant strains and poor compliance of patients and families. Urinary tract infection is responsible for approximately 20% of end stage renal disease in European children [16]. The importance of prompt diagnosis of UTI in early infancy becomes more clear, as three-fifths of all UTI and underlying GU tract anomalies are diagnosed in early infancy [10]. Untreated high grade VUR results in renal scarring [17]. Congenital urinary tract obstruction results in renal vasoconstriction, parenchymal loss and renal dysfunction [2, 18]. Any newborn with a urinary tract infection, regardless of sex, should be presumed to have urinary obstruction or reflux and should have image studies to rule out these conditions. Further prophylactic management, either medical or surgical, is necessary to reduce the formation of renal scars and to preserve renal function.
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References 1. Crain EF, Gershel JC. Urinary tract infections in febrile infants younger than 8 weeks of age. Pedatrics 1990; 86: 363-7. 2. Samir SE, John EL.Urinary tract obstruction and infection in the neonate. Clin perinatol 1992; 19: 213221. 3. Ginsburg CM, McCracken GH. Urinary tract infections in young infants. Pediatrics 1982; 69: 409-12. 4. Wiswell TE, Roselli, JD. Corroborative evidence for the decreased incidence of urinary tract infections in circumcised male infants. Pediatrics 1986; 78-96. 5. Wang SF, Huang FY, Chiu NC, et al. Urinary tract infection in infants less than 2 months of age. Acta Paed Sin 1994; 35: 294-300. 6. Donald B. Pediatric urinary tract infections. Pediatr Ann 1996; 25 : 266-76. 7. Dacher JN, Mandell J, Lebowitz RL. Urinary tract infection in infants in spite of prenatal diagnosis of hydronephrosis. Pediatr Radiol 1992; 22: 401-5. 8. Chiu NC, Huang FY,Tsai TC. Urinary tract infections in children. Acta Paed Sin 1989; 30: 225-32. 9. Burns MW, Burns JL, Krieger JN. Pediatric urinary tract infection. Pediatr Clin North Am 1987; 34: 1349-64.
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10. Ring E, Zobel G.Urinary tract infection and malformations of urinary tract in infancy. Arch Dis Child 1988; 63: 818-20. 11. Airede AI. Urinary tract infections in African neonates. J Infect 1992; 25:55-62. 12. Clark WR, Malek RS. Ureteropelvic junction obstruction : Observations on the classic type in adults. J Urol 1987; 138: 276-81. 13. Murphy JP. Holder TM, Ashcraft KW, et al. Ureteropelvic junction in the newborn. J Pediatr Surg 1984; 19: 642-7. 14. Hanson E, Hansson S, Jodal U. TrimethoprimSulphadiazine prophylaxis in children with vesicoureteric reflux. Scan J Infect Dis 1989; 21: 201-4. 15. Jones KU. Antimicrobial treatment for urinary tract infections. Arch Dis Child 1990; 65: 327-30. 16. Broyer M, Rizzoni G, Brunner FP,et al. Combined report on regular dialysis and transplantation of children in Europe, XIV. Proc Eur Dial Transplant Assoc 1984; 5: 55-79. 17. Belman AB. A perspective on vesicoureteral reflux. Urol Clin North Am 1995; 22: 139-50. 18. Chevalier RL, Gonmez RA, Jones CA. Developmental determinants of recovery after relief of partial ureteral obstruction. Kidndy Int 1988; 33: 775-9.
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