Original Article Vol. 24 No. 1 Urinary Tract Infections in Newborns in Beheshti Hospital:- Movahedian AH, et al. 7 Urinary Tract Infections in Hospitalized Newborns in Beheshti Hospital, Iran: A Retrospective Study Amir Hossein Movahedian, M.D.*, Ziba Mosayebi, M.D.**, Rezvan Moniri, D.V.M., Ph.D.*** ABSTRACT Early diagnosis and proper treatment including long-term follow-up are crucial in management of neonatal urinary tract infections (UTIs). To determine the pathogens responsible for UTI in newborns and the antibiotic susceptibility of these organisms, all medical records of 3,623 hospitalized newborns in the neonatal unit of Beheshti Hospital, Kashan, Iran, during a five-year period from April 2000 to March 2005 who developed UTIs were retrospectively reviewed. Urine specimen was obtained by a suprapubic bladder aspiration. Our results showed that 38 of 3,623 (1.04%) newborns had UTI. The mean age of these newborns was 8.1 days (range: 1-28 days), and 15 of them (39.5%) were less than 7 days old. UTI associated with septicemia was observed in 10.5 percent of them. Seven of 38 (18.4%) newborns were preterm, and 27 of them were boys. The most common clinical findings was jaundice which occurred in 68.4 percent of these newborns. Escherichia coli were the most common isolated organism. E. coli isolates were most susceptible to amikacin and gentamicin (5.2%), but were most resistant to cephalexin (78.9%). Cephalexin-resistant Gram-negative bacteria were the most common cause of UTI in infants of less than 29 days old. Our findings would impact clinicians in choosing appropriate empirical antibiotic for the treatment of UTI before obtaining the microbiologic results based on local surveillance of causative pathogens of UTIs and antibiotic susceptibility patterns. (J Infect Dis Antimicrob Agents 2007;24:7-11.) INTRODUCTION Urinary tract infections (UTIs) occur with the prevalence between 5 percent and 11 percent among febrile newborns younger than 8 weeks olds. 1 The incidence of bacteremia and sepsis in an infant with UTI has been reported to be between 6 percent and 36 percent. 1 UTI in newborns is frequently associated with bacteremia, and may result in long-term *Department of Pediatrics, Kashan University of Medical Sciences and Health Services, Kashan, Iran. ** Department of Neonatology, Kashan University of Medical Sciences and Health Services, Kashan, Iran. *** Department of Microbiology, Kashan University of Medical Sciences and Health Services, Kashan, Iran. Received for publication: November 9, 2006. Reprint request: Rezvan Moniri, D.V.M., Ph.D., Associate Professor of Microbiology, Kashan University of Medical Sciences, P.O. Box: 87155.111, Kashan, Iran. E-mail: moniri_re@yahoo.com Keywords: Urinary tract infections, newborn, drug resistance 7
8 J INFECT DIS ANTIMICROB AGENTS Jan.-Apr. 2007 complications. 2,3 In normal and full-term newborns, the incidence of bacteriuria obtained by a suprapubic bladder aspiration ranges from 0.1 to 1 percent. 2-7 UTI occurs more commonly in male than in female newborns. 2-5,8 Most UTIs in newborns are caused by Gram-negative aerobic bacilli. Escherichia coli is the most commonly isolated organism in the newborn period, accounting for up to 80 percent of UTIs in most large series. 2-5 Signs and symptoms of UTI in newborns are nonspecific. They may show lethargy, irritability, tachypnea, and may appear acutely ill. Approximately one-third of these newborns developed secondary bacteremia. 8 In most of developing countries, these organisms have developed increased drug resistance over the last two decades, and the management of these patients is becoming a major problem. The objective of our study was to investigate the causative organisms of neonatal UTI, emphasizing on Gram-negative bacilli. MATERIALS AND METHODS Beheshti Hospital is a 400-bed, tertiary-care, teaching hospital with a 20-bed neonatal ward, which is capable of ventilating up to three neonates at once. The catchments population is 385,000 persons, and there are about 5,500 deliveries annually. We conducted a retrospective study in the neonatal ward of Beheshti Hospital, Kashan, Iran, from April 2000 to March 2005. All newborns with positive urine culture obtained from urine bag were included in our study. Urine specimen was sent for culture based on clinical data including fever, weight loss of more than 10 percent of birth weight, or nonspecific symptoms including (feeding intolerance, lethargy, irritability, tachypnea, and jaundice). In these cases, another urine culture was collected by a suprapubic bladder aspiration to confirm the diagnosis. UTI was defined by the presence of 100,000 colony-forming units (CFUs)/ml of the organism isolated from a urine bag collection, or the presence of any CFU/ml of the organism isolated from a suprapubic bladder aspiration. A technique of urine bag specimen collection included using of antiseptics and a sterile plastic bag, fitted on the genitalia. If diuresis did not occur within 30 minutes, the procedure was repeated until obtaining a urine specimen. The overlying skin was cleaned by antiseptics and punctured the suprapubic area with a 25-gauge needle on a syringe, and about 2 ml of urine was aspirated. All urine specimens were promptly transported to the microbiology laboratory. Urine specimen was cultured on blood and MacConkey agars. The identification of Gram-negative bacteria was based on Gram staining, indole, methyl red, Vogesproskaur, citrate (IMViC), oxidase, and -glucoronidase test results. An antimicrobial susceptibility test was performed on all urinary isolates using the disk diffusion method against antimicrobials commonly used for treatment of UTIs in Iran. The susceptibility of these isolates was carried out and interpreted according to the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. 13 The antibiotic concentration per disk was as follows: amikacin (30 g), gentamicin (10 g), ampicillin (10 g), cephalexin (30 g), and trimethoprim-sulfamethoxazole (1.25/23.75 g), manufactured by the Padtan-Teb Company, Iran. The study was carried out with the permission of the Kashan University of Medical Sciences. We used the SPSS program for Windows (version 11) to perform the analysis of all clinical data. RESULTS In our study, the incidence of UTI in newborns, determined by suprapubic urine collection was 1.04 percent (38 of 3,623 patients). Characteristics of sex and age of all newborns with UTI are shown in Table 1, and the clinical manifestations are shown in Table 2.
Vol. 24 No. 1 Urinary Tract Infections in Newborns in Beheshti Hospital:- Movahedian AH, et al. 9 Thirty-one (81.6%) newborns with UTI were fullterm, and seven of them (18.4%) were preterm. The most common clinical finding was jaundice (68.4%), followed by lethargy (36.8%), fever (34.2%), poor feeding (13.2%), vomiting (10.5%), loose stools (10.5%), and restlessness (10.5%). Positive blood cultures occurred in 18.4 percent (7 of 38 patients) of newborns. Of all urinary isolates, there were 36 (94.7%) Gramnegative and 2 (5.3%) Gram-positive bacteria. Of these 38 bacteria, there were 19 (50%) E. coli, 3 (7.9%) Proteus spp., 11 (29%) Klebsiella pneumoniae, 2 (5.2%) Pseudomonas aeruginosa, 2 (5.2%) Staphylococcus epidermidis, and 1 (2.6%) Enterobacter cloacae. These results are shown in Table 3. Of E. coli isolates, the lowest resistance rates were observed in amikacin and gentamicin (5.2%), Table 1. Demographic characteristics of 38 newborns with urinary tract infection in Beheshti Hospital, Iran. Characteristics Number (%) Male Female Total Age (days) 1-7 14 (93.3) 1 (6.7) 15 (39.5) 8-14 5 (41.7) 7 (58.3) 12 (31.6) 15-21 3 (75) 1 (25) 4 (10.5) 22-28 5 (71.4) 2 (28.6) 7 (18.4) Gestational age Term 23 (60.5) 8 (21.1) 31 (81.6) Preterm 4 (10.5) 3 (7.9) 7 (18.4) Method of parturition Natural delivery 20 (52.6) 8 (21.1) 28 (73.7) Cesarean section 7 (18.4) 3 (7.9) 10 (26.3) Blood culture Positive 3 (7.9) 4 (10.5) 7 (18.4) Negative 24 (63.2) 7 (18.4) 31 (81.6) 9 Table 2. Clinical manifestations of 38 newborns with urinary tract infection in Beheshti Hospital, Iran. Clinical manifestation Percent Jaundice 68.4 Lethargy 36.8 Fever 34.2 Poor feeding 13.2 Vomiting 10.5 Loose stools 10.5 Restlessness 10.5 Table 3. Bacterial pathogens isolated from 38 newborns with urinary tract infection in Beheshti Hospital, Iran. Pathogen Number (%) Escherichia coli 19 (50) Klebsiella pneumoniae 11 (29) Proteus spp. 3 (7.9) Pseudomonas aeruginosa 2 (5.25) Staphylococcus epidermidis 2 (5.25) Enterobacter cloacae 1 (2.6) Total 38 (100) followed by trimethoprim-sulfamethoxazole (26.3%), ampicillin (64.7%), and cephalexin (78.9%) (Table 4). Of K. pneumonia isolates, the lowest resistance rates were observed in amikacin (9.1%), followed by gentamicin (54.5%), cotrimoxazole (54.5%), cephalexin (72.7%), and ampicillin (100%). DISCUSSION In our study, the rate of UTI was 1.04 percent. Thirty-one (81.6%) newborns with UTI were full-term. In contrast to a study by Tamim and colleagues which showed the rate of UTI in preterm newborns was higher
10 J INFECT DIS ANTIMICROB AGENTS Jan.-Apr. 2007 Table 4. Antimicrobial resistance rates of E. coli and K. pneumoniae isolated from 38 newborns with urinary tract infection in Beheshti Hospital, Iran. Antimicrobial agents Resistance rate (%) E. coli K. pneumonia Amikacin 5.25 9.1 Gentamicin 5.25 54.5 Trimethoprim-sulfamethoxazole 26.3 54.5 Ampicillin 64.7 100 Cephalexin 78.9 72.7 than full-term newborns. 4 UTI usually occurs in the second week after birth in full-term newborns and somewhat later in preterm newborns. 2,8 In our study, UTIs were more common in males than females. UTI occurs in 1.5 to 5 times as many males as females in the neonatal period. 2-5,8 The higher incidence in neonatal males also appears to occur in preterm newborns, although the data are limited. 9 In our study, Gram-negative bacteria were the most common cause of UTIs in 94.7 percent of newborns. E. coli and K. pneumoniae were the most commonly isolated Gram-negative bacteria, accounting for 78.9 percent of patients. Our results were consistent with other studies which showed that E. coli was the most frequent cause of UTIs at all ages. 2-5,12 Other Enterobacteriaceae, which can cause UTIs, include Klebsiella, Enterobacter, Citrobacter, Proteus, Providencia, Morganella, Serratia, and Salmonella. Staphylococcus and Enterococcus are the most common isolated Gram-positive bacteria, but they occur distinctly less frequently than do Gram-negative bacteria. 12 In our study 18.4 percent of patients had also positive blood cultures. Approximately one-third of newborns with UTIs have secondary bacteremia. 8,12 We suggest that sampling for blood cultures should be obtained in all newborns in whom UTI is suspected. The most common clinical findings of UTI in newborns included fever (20-40%), failure to thrive (15-43%), jaundice (3-41%), vomiting (9-41 %), loose stools (3-5%), and poor feeding (3-5%). 2-5,8 In our study, the most common clinical finding was jaundice. Previous studies have indicated that jaundice may be one of the first signs in UTI. Several studies have described patients with other bacterial infections, whom developed jaundice during the course of their illnesses. 1 Of 19 E. coli isolates in our study, 15 (78.9%) were resistant to cephalexin. Musa-Aisien and colleagues showed that E. coli, K. pneumonia, and S. aureus were the most commonly isolated bacteria, and they all showed high susceptibility rate, to amoxicillinclavulanate, gentamicin, and ceftriaxone, but poorly susceptible to trimethoprim-sulfamethoxazole. 14 Adeyemo and colleagues also described that all urinary isolates were poorly susceptible to trimethoprimsulfamethoxazole, and ampicillin, but exhibited good susceptibility to nalidixic acid, nitrofurantoin, and ofloxacin. 15 A study of Das and colleagues showed the susceptibility rate of urinary isolates was highest for amikacin (87.2%), followed by ciprofloxacin (74.8%), ceftazidime (71.5%), gentamicin (70.4%), nitrofurantoin (35%), cephalexin (49.7%), and ampicillin
Vol. 24 No. 1 Urinary Tract Infections in Newborns in Beheshti Hospital:- Movahedian AH, et al. 11 (50.5%). 16 A continuous monitoring of bacterial epidemiology and antibiotic susceptibility is crucial for clinicians in choosing appropriate empirical antibiotic for the treatment of UTI before obtaining the microbiologic results. Initial antibiotic selection must be constantly refined until final bacterial identification and antibiotic susceptibilities are known. In cases of UTI caused by Enterobacteriaceae, the clinicians must be aware of the potential for treatment failure with first-generation cephalosporin treatment. Additional research is needed to identify risk factors for acquisition of antibiotic-resistant bacteria and strategies to help control of transmission of these urinary pathogens. ACKNOWLEDGEMENT We gratefully acknowledge Kashan University of Medical Sciences for their financial support of our study. We thank Dr. Kamran Dastehgoli and Mr. Hossein Akbari for their assistance with the preparation of this manuscript. References 1. Garcia FJ, Nager AL. Jaundice as an early diagnostic sign of urinary tract infection in infancy. Pediatrics 2002;109:846-51. 2. Maherzi M, Guignard JP, Torrado A. Urinary tract infection in high-risk newborn infants. Pediatrics 1978;62:521-3. 3. Abbott GD. Neonatal bacteriuria: a prospective study in 1,460 infants. Br Med J 1972;1:267-9. 4. Tamim MM, Alesseh H, Aziz H. Analysis of the efficacy of urine culture as part of sepsis evaluation in the premature infant. Pediatr Infect Dis J 2003;22:805-8. 5. Bergstrom T, Larson H, Lincoln K, Winberg J. Studies of urinary tract infections in infancy and childhood. XII. Eighty consecutive patients with neonatal infection. J Pediatr 1972;80:858-66. 6. Zies L, Ramirez J, Jannach JR. Incidence of bacteriuria in the premature infant as determined by suprapubic aspiration. J Fla Med Assoc 1968;55:452-4. 7. Moncrieff M, Bamford M, Benson J, Bodden J. Asymptomatic bacteriuria in healthy preterm babies. Arch Dis Child 1980;55:723-5. 8. Littlewood JM. 66 infants with urinary tract infection in first month of life. Arch Dis Child 1972;47:218-26. 9. Airede AI. Urinary-tract infections in African neonates. J Infect 1992;25:55-62. 10. DiGeronimo RJ. Lack of efficacy of the urine culture as part of the initial workup of suspected neonatal sepsis. Pediatr Infect Dis J 1992;11:764-6. 11. Visser VE, Hall RT. Urine culture in the evaluation of suspected neonatal sepsis. J Pediatr 1979;94:635-8. 12. Ginsburg CM, McCracken GH, Jr. Urinary tract infections in young infants. Pediatrics 1982;69:409-12. 13. National Committee for Clinical Laboratory Standards (NCCLS). Performance standards for antimicrobial susceptibility testing. Ninth informational supplement. NCCLS document M100-S9. Wayne, PA: NCCLS, 1999. 14. Musa-Aisien AS, Ibadin OM, Ukoh G, Akpede GO. Prevalence and antimicrobial sensitivity pattern in urinary tract infection in febrile under-5s at a children s emergency unit in Nigeria. Ann Trop Paediatr 2003;23:39-45. 15. Adeyemo AA, Gbadegesin RA, Onyemenem TN, Ekweozor CC. Urinary tract pathogens and antimicrobial sensitivity patterns in children in Ibadan, Nigeria. Ann Trop Paediatr 1994;14:271-4. 16. Das RN, Chandrashekhar TS, Joshi HS, Gurung M, Shrestha N, Shivananda PG. Frequency and susceptibility profile of pathogens causing urinary tract infections at a tertiary care hospital in western Nepal. Singapore Med J 2006;47:281-5. 11