Pediatr Nephrol (2005) 20:1583–1586 DOI 10.1007/s00467-005-1976-8
ORIGINAL ARTICLE
Maria Bitsori · Sofia Maraki · Maria Raissaki · Anna Bakantaki · Emmanouil Galanakis
Community-acquired enterococcal urinary tract infections
Received: 17 March 2005 / Revised: 5 April 2005 / Accepted: 5 April 2005 / Published online: 22 June 2005 IPNA 2005
Abstract Enterococcal urinary tract infection (UTI) is usually hospital-acquired and affects individuals with predisposing conditions. The aim of this study was to evaluate the community-acquired enterococcal UTIs in otherwise well children. We reviewed all the 257 first UTI episodes in children hospitalized in a General Hospital during a 5-year period. Enterococcus faecalis was isolated in 13 episodes, accounting for 5.1% of the total UTIs. All strains were susceptible to ampicillin, vancomycin and nitrofurantoin. Imaging studies revealed major urinary tract abnormalities in 9 and parenchymal defects in 8 children. During a follow-up period from 2 to 6 years, 4 children suffered break-through infections despite antibiotic prophylaxis, 3 developed renal scarring and 4 underwent corrective surgical procedures. Children with enterococcal UTIs presented with significantly higher rates of anatomical abnormalities and worse prognosis in terms of renal scarring, recurrences and corrective surgery compared with the total cohort of children with Gramnegative UTIs. However children with enterococcal UTIs did not present with a worse prognosis when compared with a group of children with Gram-negative UTIs matched for age and degree of reflux. Enterococcal infection is not an independent risk factor for poor outcome, nevertheless positive urine culture including enterococci is M. Bitsori · E. Galanakis ()) Department of Pediatrics, Infectious Diseases Unit, University Hospital of Heraklion, University of Crete, POB 2208, 71003 Heraklion, Greece e-mail:
[email protected] Fax: +30-2810-392827 S. Maraki Department of Clinical Bacteriology-Parasitology-Zoonoses and Geographical Medicine, University Hospital of Heraklion, Greece M. Raissaki · A. Bakantaki Department of Radiology, University Hospital of Heraklion, Greece
highly indicative for underlying urinary tract abnormalities, recurrences, renal scarring, and need for surgical intervention. Keywords Enterococci · Enterococcus faecalis · Renal scarring · Urinary tract abnormalities
Introduction Urinary tract infections (UTIs) are mainly caused by Gram-negative microorganisms of the intestinal flora, whereas Gram-positive cocci are unusual pathogens. Enterococcus species have recently emerged as a major cause of nosocomial infections with alarming rates of multi-drug resistance [1, 3]. Underlying conditions predisposing to enterococcal UTI include urinary tract malformations, urinary catheters or prolonged antibiotic treatment [4]. Enterococci as childhood uropathogens have been mostly studied in nosocomial UTIs, in children with urinary tract malformations, and in children on prophylaxis [5, 6, 7, 8], but not in the general population. In this study we investigated the frequency, clinical characteristics, susceptibility patterns, imaging findings and long-term outcome of children with community-acquired enterococcal UTI.
Patients and methods All children with culture-proven first UTI episode, hospitalized in the Department of Pediatrics, University General Hospital of Heraklion, Greece, during the 5-year period 1998–2002 were included in the study and their records were reviewed. In the study area, hospitalization for febrile UTI is a common practice, especially for first episodes and at the younger ages. UTI was defined as any bacterial growth in specimens obtained by suprapubic aspiration, the growth of >104 colony-forming units (CFUs)/ml in specimens obtained by transurethral catheterization, or the growth of >105 CFUs/ml in two consecutive mid-stream specimens. Enterococci were identified by standard microbiological methods, including colony morphology, Gram stain, catalase testing,
1584 growth in 6.5% sodium chloride broth, esculin hydrolysis and by the API 20STREP system (Biomrieux, Marcy L’ Etoile, France). Antimicrobial susceptibility was tested by the disc diffusion technique according to the National Committee for Clinical Laboratory Standards [9]. High-level resistance to aminoglycosides was determined by the agar dilution method. Strains with intermediate susceptibility were considered resistant. According to the UTI imaging protocols in the Department of Pediatrics, renal ultrasonography (US) is performed during acute infection in all children with their first UTI episode. All infants regardless of sonographic findings and children younger than 5 years with an abnormal US undergo a voiding cystourethrogram (VCUG) 2–4 weeks after acute infection. 99m Tc-dimercaptosuccinic acid (DMSA) scan is routinely performed for all children younger than 5 years, 3–6 months after acute infection and exceptionally during acute phase. Reflux was graded 0–V according to the International Reflux Study Committee [10]. DMSA scan images were recorded in the posterior-anterior projection using a gamma camera, 2–3 h after injection of 99m Tc-DMSA. Renal parenchymal damage was defined as perfusion defects or as split renal uptake of less than 45%. Cortical scarring was defined as a defect in the normal kidney outline [11]. The clinical course of the study population over time was evaluated in terms of urinary tract abnormalities, recurrences of infection, surgical intervention and renal scarring. To test the hypothesis that enterococcal infection could be an independent risk factor for poor outcome, the group of the children with enterococcal UTIs was compared with both the total Gram-negative UTI cohort and a group of children matched for age and degree of reflux or urinary tract abnormalities.
Results During the study period, 257 first UTI episodes were confirmed. The more common uropathogens were Escherichia coli (79%), Klebsiella spp. (5.8%), Enterococcus faecalis (5.4%) and Proteus mirabilis (4.7%). A total of 13 episodes of enterococcal UTI were identified, all of them due to E. faecalis. All 13 episodes were community acquired. The patients were 7 boys and 6 girls, aged from 15 days to 5 years (mean, 1.3 years; median, 0.5 year) (Table 1). All cases presented with fever, except for 2 neonates who were referred for antenatal hydronephrosis and vomiting. First-line laboratory investigation revealed leukocytosis (mean white cell count 16,559/mm3; range 5,470–24,700), neutrophilia (mean neutrophil count 10,191/mm3; range 2,407– 18,723), elevated erythrocyte sedimentation rate (mean 50 mm/h; range 15–100) and elevated c-reactive protein (mean 9.2 mg/dl; range 2.1–53.9). Urine specimens were obtained by suprapubic aspiration, by transurethral catheterization and by midstream collection (6, 4 and 3 cases, respectively). E. faecalis was the single pathogen isolated in 9 cultures, whereas E. coli was isolated as a second pathogen in the remaining 4. All 4 cultures with mixed growth were obtained either by suprapubic aspiration or by transurethral catheterization and in all growth was >105 CFUs/ml. None of the children was on preceding antibiotic prophylaxis and only 2 of them (patients 7 and 12) had received in the past multiple antibiotic regimens. Both children had had febrile episodes since infancy, which were treated with various broad-spectrum antibiotics. Further details were
Table 1 Patient characteristics and imaging findings in 13 episodes of community acquired E. faecalis urinary tract infection (VUR vesicoureteral reflux) Patient
Gender, age (in years)
Imaging results
1
F, 2.0
2
M, 3.0
3
M, 0.5
4 5
M, 0.1 F, 0.2
6 7
F, 2.5 F, 5.0
Right: 3rd grade VUR. Left: duplicated collecting system, UPJ obstruction. Bilateral parenchymal defects. Posterior urethral valves. Parenchymal defect on left kidney. Right: 3rd grade VUR. Left: 5th grade VUR, parenchymal defect. Right: 1st grade VUR, bladder diverticulum. Right: 5th grade VUR, parenchymal defect. Left: 2nd grade VUR. Left: 3rd grade VUR, parenchymal defect. Bilateral 4th grade VUR, bilateral defects, scarring. Right: parenchymal defect. Bilateral 3rd grade VUR. Left: mild pelvic dilatation. Normal ultrasound. Imaging not completed. Left: 3rd grade VUR, parenchymal defect. Phimosis, no urinary tract abnormalities.
8 9 10 11 12 13
F, 0.1 M, 0.05 M, 0.05 F, 1.5 M, 2.1 M, 0.2
not available; however, none of the children had been on antibiotics for at least 3 months prior to diagnosis of UTI. All E. faecalis strains were susceptible to ampicillin, amoxicillin-clavulanate, nitrofurantoin, and vancomycin and all were resistant to second and third generation cephalosporins. All strains exhibited intrinsic, low-level aminoglycoside resistance and 3/13 were high-level aminoglycoside resistant as well. Almost all strains (12/ 13) were resistant to trimethoprim-sulfamethoxazole, 8/13 to chloramphenicol and 7/13 to tetracycline. Antibiotics were administered for 7–14 (mean, 9.5) days. Urine cultures obtained under treatment were sterile in all cases. A complete imaging investigation was performed in 12/13 children and revealed urinary tract abnormalities in 9, including vesicoureteral reflux (8), duplicated collecting system (1), ureteropelvic junction obstruction (1), posterior urethral valves (1) and bladder diverticulum (one). One child did not complete the recommended imaging and was lost to follow-up. All the remaining patients underwent an acute-phase DMSA scan within 1 week from acute infection because of complicated presentation with toxic appearance and dehydration and/or abnormal US findings, including pelvic and ureter dilatations, duplications, abnormal kidney size or position, solitary kidney, and diffuse or focal increased echogenicity. DMSA scan revealed parenchymal defects in 8/ 12 children, including an infant without urinary tract abnormalities. Three children progressed to renal scarring. Follow-up information was available for 11 children for a period of 24–76 (mean 50) months. Four children suffered recurrences, due to E. faecalis (patient 13) or Gram-negative organisms (patients 1, 3 and 4). Four children (patients 1, 2, 3, and 13) underwent corrective surgery. Two children (patients 2 and 3), both operated for reflux and posterior urethral valves, have been free of
1585 Table 2 Anatomical abnormalities, renal scarring, recurrences and corrective surgery in children with urinary tract infections caused by E. faecalis and by Gram-negative uropathogens
E. faecalis Number of patients Complete imaging and follow-up Corrective surgery Anatomical abnormalities Recurrences Renal scarring
13 12
Gram-negative uropathogens 243 227
4 (33%) 9 (75%)
6 (2.6%) 44 (19%)
4 (33%) 3 (25%)
11 (4.8%) 14 (6.2%)
UTIs for more than 3 years. All children received antibiotic prophylaxis for a period of 6 months to 6 years, depending on age and recurrences. The 13 children with enterococcal UTIs were compared with 227 children with Gram-negative UTIs, aged 0.01–13 years (mean 1.16, median 0.45 years), who had available imaging and follow-up information. As shown in Table 2, the enterococcal group had significantly higher rates of anatomical abnormalities, renal scarring, recurrences and corrective surgery. The 13 children with enterococcal UTIs were further compared with 34 children with Gram-negative infections, matched for age and degree of reflux/urinary tract abnormalities. The enterococcal group did not present with significantly higher relative risks (RR) for renal scarring [RR=1.42, 95% confidence interval (CI)=0.418–4.80, P=0.581], recurrences (RR=1.62, 95% CI=0.574–4.57, P=0.373) and corrective surgery (RR=2.27, 95% CI=0.726–7.07, P=0.162).
Discussion Enterococcal UTI in children is more often of nosocomial origin than community acquired, with frequencies of 12– 15% and 4.4–5.6% of the total UTI episodes, respectively [5,6,12,13]. E. faecalis is the predominant species (14), and was the single Enterococcus species isolated in this study. Enterococcal UTI has been reported to affect predominantly boys and younger ages [13]. In our study the gender distribution was almost equal; however, boys were younger than girls (median ages 0.2 and 1.75 years, respectively). Enterococcal UTI is an important source of bacteremia in adults [2], but none of the children in this study presented with E. faecalis -positive blood cultures. Enterococci are intrinsically resistant to many antimicrobials, including aminoglycosides, cephalosporins and cotrimoxazole, which are common empirical drugs of choice for the treatment of UTIs [4]. High-level aminoglycoside resistance was found to be relatively uncommon compared with studies with adult patients [14]. Vancomycin-resistant enterococci are mostly responsible for colonization of the urinary tract or asymptomatic bacteriuria and only exceptionally cause true UTIs in patients with underlying diseases [15]. Repeated episodes of antibiotic treatment or prophylaxis induce enterococcal colonization, hence enterococcal UTIs are considered to be the consequence of a preceding antibiotic treatment for UTI or other infections.
Relative risk (95% CI); P by chi-square
11.4 (4.13–31.7); P
