Pediatric urinary tract infections in a tertiary care center from north India.
Abstract: Background & objectives: Paediatric urinary tract infections (UTI) are associated with high morbidity and long term complications like renal scarring, hypertension, and chronic renal failure. A cause of occult febrile illness, they often remain undiagnosed. We studied the clinical and microbiologic profile and antibiotic resistance profile of such infections in paediatric UTI patients at our center.

Methods: Clean catch mid-stream urine samples for culture were received from 1974 children aged < 12 yr over a period of 6 months. Quantitative wet mount microscopy and semiquantitative culture on cysteine lactose electrolyte deficient medium were done to diagnose UTI. Isolates were identified by standard biochemical tests and antimicrobial sensitivity was determined. Clinical details including risk factors and underlying illness were noted.

Results: Significant bacteriuria was found in 558 children (28.3%). Male gender (25.6%), age < 1 yr (77.5%), vesicoureteric reflux disease (VUR) (19.9%) and posterior urethral valve (PUV) (27.6%) were common risk factors in children suffering from UTI. Pyuria was detected in 53.6 per cent of infections. Common uropathogens isolated were Escherichia coli (47.1%), Klebsiella spp. (15.6%), Enterococcus fecalis (8.7%), members of tribe Proteae (5.9%), Pseudomonas aeruginosa (5.9%) and Candida spp. (5.5%). Against lactose fermenting Enterobacteriaceae, in-vitro resistance was least against amikacin (32.5%), nitrofurantoin (26.7%) and imipenem (3.7%). Among enterococci, vancomycin resistant enterococci constituted 12 per cent of the strains. 93.4 per cent of the UTI detected was nosocomial.

Interpretation & conclusion: Paediatric UTI was common in children with male gender, age < 1 yr, and in children suffering from VUR and PUV. Spectrum of pathogens causing paediatric UTI in our center had a preponderance of nosocomial multi-drug resistant pathogens.

Key words Escherichia coli--Klebsiella spp.--paediatric--uropathogens--UTI
Article Type: Report
Subject: Urinary tract infections (Risk factors)
Urinary tract infections (Diagnosis)
Urinary tract infections (Care and treatment)
Urinary tract infections (Demographic aspects)
Urinary tract infections (Research)
Urinary tract infections in children (Risk factors)
Urinary tract infections in children (Diagnosis)
Urinary tract infections in children (Care and treatment)
Urinary tract infections in children (Demographic aspects)
Urinary tract infections in children (Research)
Children (Diseases)
Children (Risk factors)
Children (Diagnosis)
Children (Care and treatment)
Children (Demographic aspects)
Children (Research)
Authors: Taneja, Neelam
Chatterjee, Shiv Sekhar
Singh, Meenakshi
Singh, Surjit
Sharma, Meera
Pub Date: 01/01/2010
Publication: Name: Indian Journal of Medical Research Publisher: Indian Council of Medical Research Audience: Academic Format: Magazine/Journal Subject: Biological sciences; Health Copyright: COPYRIGHT 2010 Indian Council of Medical Research ISSN: 0971-5916
Issue: Date: Jan, 2010 Source Volume: 131 Source Issue: 1
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: India Geographic Code: 9INDI India
Accession Number: 229526980
Full Text: Paediatric urinary tract infections (UTI) are associated with high morbidity and long term complications like renal scarring, hypertension, and chronic renal failure. A cause of occult febrile illness in up to 5 per cent of young children often remains undiagnosed (1), documented in cases associated with vesicoureteral reflux (VUR) (2). Gram negative enteric bacilli, especially Escherichia coli and Klebsiella spp. are the leading pathogens1 though Enterococcus spp., yeasts and Staphylococcus aureus have emerged as prominent agents in recent years (3-5), many of them resistant to multiple antibiotics (3-5). Therapy for these children requires urine culture and appropriate antimicrobial sensitivity testing. Recent studies on paediatric UTI in India are limited. In a retrospective analysis, of the 52 children treated for posterior urethral valves (PUV), 34 had renal scarring (3). A significant correlation was seen between the occurrence of renal scarring and breakthrough UTI (3). UTI in children with symptomatic unilateral pelvi-ureteric junction obstruction (PUJO) was shown to be associated with poor somatic growth in another study from India (5). In the present study, we report the clinical, microbiological, and antimicrobial resistance profile of all consecutive paediatric UTI patients, presented at 304 bed advanced paediatric centre at Postgraduate Institute of Medical Education & Research, Chandigarh, from July to December 2006.

Material & Methods

For all cases of suspected UTI, urine culture was done by semi-quantitative technique on cysteine lactose electrolyte deficient medium (CLED agar--(Hi-Media, Mumbai)6 and quantitative unspun wet mount microscopy done to detect pyuria (> lpus cell/7 high power fields of well mixed uncentrifuged urine samples) (6), bacteriuria, haematuria or candiduria. One (il urine was cultured using a calibrated bacteriological loop on CLED agar, and colonies were counted after overnight incubation at 370C. Number of colonies obtained was multiplied by 1000 to obtain the colony forming units (cfu) / ml. For boys and girls, 104 and 105 cfu/ml of bacterial growth of a single type was taken as threshold (significant bacteriuria) respectively (7-9). In case of girls with mid-stream urine showing 104-105 cfu/ml, repeat samples were asked for (8,9). Any number of colonies from a suprapubic sample were considered significant (8,9). Guidelines by Hellerstein et al (8) were strictly adhered to for diagnosis of paediatric UTI. Isolates were identified by Gram stain, motility test and routine biochemical reactions. Antibiotic sensitivity was put up by the Kirby Bauer method following the clinical laboratory standards institute (CLSI) guidelines (10). All Enterobacteriaceae and Acinetobacter spp. were tested against first line agents: gentamicin(10[micro]g),amikacin(30[micro]g),cefoperazone(75([micro]g), cefotaxime (30([micro]g), nitrofurantoin (300([micro]g), trimethoprimsulphamethoxazole (1.25-23.75([micro]g), nalidixic acid (30([micro]g), norfloxacin(10([micro]g) and ciprofloxacin (5([micro]g); Enterococcus spp. against amoxycillin (10(g), vancomycin(30(g), nitrofurantoin (300([micro]g), ciprofloxacin (5([micro]g) and high level aminoglycoside resistance gentamicin (HLAR-G, 120([micro]g); Pseudomonas aeruginosa against amikacin (30(g), cefoperazone (75(g), gentamicin (10(g), ceftazidime (30(g) and ciprofloxacin (5(g). Second line antibiotics were tested only for organisms in those isolates resistant to all 1st line antimicrobials or specifically requested for by the attending physician. These included; imipenem (10(g), cefoperazone-sulbactam (75(g) and piperacillintazobactam (100/10(g) for all Enterobacteriaceae, Acinetobacter spp. and Pseudomonas isolates. E. coli ATCC 25922, E. coli ATCC 35218 and P. aeruginosa ATCC 27853 were used as controls. Apart from demographic data, risk factors and underlying illness were recorded in 428 cases of UTI. Symptomatic UTI was defined and further characterized as community acquired or hospital acquired as per CDC case definition (11). Cases (n=203) with PUV and VUR were followed up during the study period to determine the frequency of repeat infections. Statistical analysis was done using Microsoft Excel software version 2003 and Students t test done to check the significance of proportions.

Results & Discussion

A total of 1974 children (age < 12 yr) with suspected UTI (Ward: OPD ratio--5.8:4.2) were evaluated in the study, of whom 558 (28.3%) children [434 male (77.8%), and 124 female (22.2%)] had culture proven UTI [538 due to a single uropathogen (508 bacterial, and 30 due to yeasts) and 20 bi-microbial infections (18 bacterial co-infections and 2 mixed bacterial and yeast infection)]. Of them, 143 (25.6%, 116 male, and 27 female) were infants, 216 (38.7%, 155 male, and 61 female) between 1-5 yr age, and 199 (35.7%, 163 male, and 36 female) between 5-12 yr age. These children presented to the paediatric surgery (234, 41.9%), paediatric medicine (238, 42.7%), paediatric intensive care unit (PICU) (45, 8.1%), and paediatric emergency (41, 7.3%) departments. A significantly greater proportion of surgical patients were below one year age (P<0.05). There was an overall male preponderance in cases of UTI (77.8%). The incidence of UTIs in the PICU during this period was 20 episodes / 1000 patient days while none were recorded from the neonatal ICU.

Wet mount microscopy for presence of bacteria/ yeast or pus cells in significant amount per field was positive in 459 patients with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 82.3, 58.3, 43.4 and 89.3 per cent respectively in detecting infections. Significant pyuria alone was found in 299 patients with sensitivity, specificity, PPV and NPV of 53.6, 62.6, 36.1, and 77.4 per cent respectively. Of the 428 patients in whom information about underlying disease was available, commonest underlying illnesses were PUV (118, 27.6%), VUR (85, 19.9%), neurogenic bladder (22, 5.1%), PUJO (15, 3.5%), hydronephrosis (10, 2.3%), percutaneous nephrostomy (10, 2.3%), other congenital anomalies of the urinary tract (14, 3.3%), stricture urethra (9, 2.1%), recurrent UTI (7, 1.6%), urinary tract trauma (5, 1.2%), renal stone disease (4, 0.9%), and post surgical patients (on systems other than genitourinary tract) (11, 2.6%). The remaining 118 (27.6%) children had no predisposing conditions known to cause UTI. According to CDC case definitions, 28 of these 428 UTI cases were community acquired (6.6%) while the remaining were nosocomial infections (400, 93.4%). When the 203 UTI cases with PUV and VUR were followed up, 152 (74.9%) showed complete cure and no relapse; 9 (4.4%) reported reinfection with same microbe with same antibiogram; 19 (9.4%) reinfection with same species but more resistant antibiogram; and lastly 23 (11.3%) with infections due to a different pathogen.

Commonest uropathogens isolated included E. coli (47.1%), and Klebsiella pneumoniae (14.5%) (Table). In the PICU, Candida spp. were isolated significantly more commonly (P<0.001) and E. coli significantly less commonly (P<0.05) compared to other units. In vitro resistance (R) and intermediate susceptibility (IS) in lactose fermenting and late lactose fermenting (LF and LLF) Enterobacteriaceae (including E. coli, Klebsiella, Enterobacter spp., and Citrobacter spp., n=392) was as follows: (cefotaxime-75.5%,0.8%), (cefoperazone-72.7%,1.3%), (gentamicin-74.2%, 1.3%), (amoxycillin-32.7%,9.2%), (nalidixic acid-94.4%,0.3%), (norfloxacin-86%,2%), (ciprofloxacin-79.6%,0.5%), (trimethoprim-sulphamethoxazole-89%,0.8%), and (nitrofurantoin26.8%,7.4%). In vitro R and IS in P. aeruginosa (n=34) were as follows: (cefoperazone-70.6%,2.9%), (gentamicin-32.4%,0%), (amikacin-58.8%,0%), (ciprofloxacin-52.9%,2.9%), (ceftazidime-64.7%,2.9%). In vitro R and IS in Enterococcus fecalis (n=50) were as follows: (ciprofloxacin-88%,4%), (nitrofurantoin-32%,12%), (amoxicillin-72%,12%), (vancomycin-12%,0%); and HLAR-G in 86 per cent isolates. In vitro R and IS in Acinetobacter (n=16) were as follows: (cefotaxime-93.8%,0%), (cefoperazone-81.3%,0%), (gentamicin-87.5%,0%), (amikacin-93.8%,0%), (nalidixic acid-68.8%,0%), (norfloxacin-68.8%,0%), (ciprofloxacin-62.5%,0%), (trimethoprim-sulpha methoxazole-87.5%,6.3%), (ceftazidime-68.8%,0%). Among 108, 8, and 5 isolates of Enterobacteriaceae, Acinetobacter, and P. aeruginosa tested for second line antibiotics in vitro susceptibility to Imipenem, piperacillin, cefoperazone-sulbactam was found in 96.3, 50.9, and 58.3 per cent; 62.5, 50, and 50 per cent; 40, 40, and 80 per cent isolates respectively. There was no statistically significant difference in the susceptibility profiles of the isolates from various categories (surgical, medical, emergency and ICUs). LF Enterobacteriaceae with two different antibiograms (R to cefoperazone, gentamicin, co-trimoxazole, nalidixic acid, norfloxacin, ciprofloxacin, cefotaxime, amikacin; and R to cefoperazone, gentamicin, cotrimoxazole, nalidixic acid, norfloxacin, ciprofloxacin, cefotaxime but susceptible to amikacin) constituted 28 and 22 per cent of the isolates.

Our tertiary centre caters to a group of children at very high risk of UTI as can be estimated from the 28.3 per cent culture positivity. Similar situations exist in other parts of India, albeit the load has not been studied in children (12). Important facts emanating from the present study include (i) infants (25.6%) and toddlers (38.7%) represent the group most vulnerable to UTI, (ii) Male gender is clearly a risk factor towards acquiring UTI in infancy, (iii) not surprisingly, majority of culture positive cases were diagnosed in patients attending paediatric surgery OPDs, as a complication of PUV, VUR, other congenital abnormalities, neurogenic bladder and obstructive uropathy. Preexisting congenital anomalies and physiological voiding disturbances contribute to the high burden of disease as seen in other studies (1,2) (iv) E. coli (47.1%) was the leading aetiology of paediatric UTI at our center, multidrug resistant microbes (Enterococcus spp., K. pneumoniae, P. aeruginosa and Candida spp.) were responsible for a substantial proportion of infections, however, staphylococci were not found to play a major role in UTI at our center (<2%) unlike reports from elsewhere (13), (v) incidence of UTI in our PICU was high compared to that reported from the western world (14,15), and Candida spp., E. fecalis and Pseudomonas aeruginosa complex were the major pathogens, (vi) 2nd generation cephalosporins, cotrimoxazole and fluoroquinolones, once the mainstay in treatment of UTIs, were no longer useful at our centre. Previous work from our laboratory has shown very high rates of extended spectrum beta-lactamase and Amp-C beta-lactamase production (16) in these isolates, (vii) carbapenem resistance has spread to E. coli and K. pneumoniae and an increase is seen in the isolation of VRE (from 5.8% in 2003 (17) to 12% in 2006), (viii) presence of antibiotype clones of bacteria suggests that resistance to currently useful agents (imipenem and amikacin) may increase with great rapidity in future, (xi) most of the infections were acquired due to nosocomial transmission. Surgical intervention and long term indwelling catheters were recognized risk factors towards UTI acquisition in these patients. Infection control and catheter and bag care practices have a major role in prevention of such infections (18). While a majority of our patients with PUV and VUR showed complete cure, a substantial proportion showed relapsed infections. Re-infection due to a more resistant antibiotype (9.4% of these patients) points towards the need for better infection control practices.

Acknowledgment

Authors thank Shri LP Singh, Shrimati Ritu, and Shri Govind for technical assistance.

Received January 1, 2009

References

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16. Taneja N, Rao P, Arora J, Dogra A. Occurrence of ESBL & Amp-C P-lactamases & susceptibility to newer antimicrobials in complicated UTI. Indian J Med Res 2008; 127 : 85-8.

17. Taneja N, Rani P, Emmanuel R, Sharma M. Significance of vancomycin resistant enterococci from urinary specimens at a tertiary care centre in northern India. Indian J Med Res 2004; 119 : 72-4.

18. Gould CV, Umscheid, CA, Agarwal RK, Kuntz G, Pegues DA and the Healthcare Infection Control Practices Advisory Committee (HICPAC). Guideline for prevention of catheter-associated urinary tract infections 2009. Department of Health and Human Services, USA and Center for Disease Control and Prevention (CDC&P). Available from: http://www.cdc.gov/ncidod/dhqp/gl_catheter_assoc.html/, accessed on December 10, 2009.

Reprint requests: Dr Neelam Taneja, Associate Professor, Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012, India e-mail: drneelampgi@yahoo.com

Neelam Taneja, Shiv Sekhar Chatterjee, Meenakshi Singh, Surjit Singh * & Meera Sharma

Departments of Medical Microbiology & * Paediatrics, Postgraduate Institute of Medical Education & Research Chandigarh, India
Table. Microbiological profile and percentage distribution of isolates

Organism                           Surgical (%)   Medical (%)

Escherichia coli                    118 (48.4)    118 (47.8)
Klebsiella spp.    K. pneumoniae     35 (14.9)     36 (14.6)
                   K. oxytoca               --       4 (1.6)
Tribe Proteae      P. mirabilis       10 (4.3)       6 (2.4)
                   P. vulgaris         1 (0.4)       1 (0.4)
                   M. morganii         5 (2.1)       9 (3.6)
Staphylococcus aureus                  6 (2.6)       4 (1.6)
Pseudomonas aeruginosa                19 (7.8)        10 (4)
Enterococcus fecalis                  15 (6.4)       25 (10)
Acinetobacter calcoaceticus-             7 (3)       6 (2.4)
baumanii complex
Enterobacter aerogenes                10 (4.3)       9 (3.6)
Citrobacter spp.   C. freundii         1 (0.4)       1 (0.4)
                   C. diversus         1 (0.4)       4 (1.6)
Streptococcus spp. (alpha              5 (2.1)       4 (1.6)
haemolytic streptococci)
Candida spp.       C. albicans           7 (3)       6 (2.4)
                   C. glabrata         4 (1.7)       4 (1.6)
Total isolates                             244           247

Organism                             PICU (%)    Emergency (%)

Escherichia coli                    13 (28.3) *     23 (56.1)
Klebsiella spp.    K. pneumoniae      4 (8.7)          9 (22)
                   K. oxytoca         1 (2.2)         1 (2.4)
Tribe Proteae      P. mirabilis       1 (2.2)         1 (2.4)
                   P. vulgaris             --              --
                   M. morganii             --              --
Staphylococcus aureus                      --              --
Pseudomonas aeruginosa               5 (10.9)              --
Enterococcus fecalis                 6 (13.2)         4 (9.8)
Acinetobacter calcoaceticus-          3 (6.6)              --
baumanii complex
Enterobacter aerogenes                3 (6.6)              --
Citrobacter spp.   C. freundii             --         1 (2.4)
                   C. diversus             --              --
Streptococcus spp. (alpha              1(2.2)              --
haemolytic streptococci)
Candida spp.       C. albicans     6 (13.2) **        2 (4.9)
                   C. glabrata      3(6.6) **              --
Total isolates                             46              41

Organism                                  Overall (%)

Escherichia coli                   272 (47.1)
Klebsiella spp.    K. pneumoniae    84 (14.5) 90 (15.6)
                   K. oxytoca        6 (1.0)
Tribe Proteae      P. mirabilis     18 (3.1)   34 (5.9)
                   P. vulgaris       2 (0.3)
                   M. morganii      14 (2.4)
Staphylococcus aureus               10 (1.7)
Pseudomonas aeruginosa              34 (5.9)
Enterococcus fecalis                50 (8.7)
Acinetobacter calcoaceticus-        16 (2.8)
baumanii complex
Enterobacter aerogenes              22 (3.8)
Citrobacter spp.   C. freundii       3 (0.5)   8 (1.4)
                   C. diversus       5 (0.8)
Streptococcus spp. (alpha           10 (1.7)
haemolytic streptococci)
Candida spp.       C. albicans      21 (3.6)  32 (5.5)
                   C. glabrata      11 (19)
Total isolates                                     578

PICU=Paediatric intensive care unit

P * <0.05 ** <0.001 compared to other units
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