Antibiotic Resistance in Children with Recurrent or Complicated Urinary Tract Infection

Introduction: Urinary tract infection is certainly one of the most common childhood infections. Emerging resistance to the antibiotics is not unusual. Current hospitalization for children with urinary tract infection is reserved for severe or complicated cases. The aim of the present study was to determine the antibiotic resistance pattern among children with recurrent or complicated urinary tract infection.


IntRODUctIOn
2][3] The true incidence of UTI in children is difficult to estimate, particularly because young children with UTI may only have fever and no specific urinary tract symptoms or signs. 1 The prognosis is usually favorable, but it relies on timely administration of appropriate antimicrobial treatment. 1,25][6] However, 30-40% of these patients have another episode within 2 years, particularly in girls.Also, recurrent infections may be complicated. 4,7Treatment for recurrences or complicated UTI is difficult and serious sequel may be seen. 7 patients with suspected UTI, antibiotic treatment is usually started empirically.To insure appropriate treatment, knowledge of the organisms that cause UTI and their antibiotic susceptibility is mandatory to eliminate the symptoms, eradicate the infection, prevent urosepsis and to reduce the likelihood of renal damage. 2,5,8,9e aim of this study was to delineate the uropathogens recovered in children with recurrent or complicated urinary tract infection, to study the pattern of antibiotic susceptibility and to recommend initial empiric antibiotic prescription before the result of urine culture become available.

MetHODs
A retrospective study carried out at Pediatric department, Prince Hashem general hospital, located in Zarqa city at eastern part of Jordan, and involved 121 patients with recurrent UTI, who were treated as either inpatients or at outpatient's clinics during the period between April  1, 2004 and December 31, 2006.Patients with recurrent UTI were separated into 2 groups: Group 1 for patients with renal anomaly and group 2 for those without renal anomaly.All these patients received antimicrobial prophylaxis against UTI.
Cultures were obtained by suprapubic aspiration, transurethral bladder catheterization or midstreamcollected urine; bag-collected urine cultures were not included.Identification of microbial growth and determination of antimicrobial susceptibility done by the disk diffusion technique, with the recommended media and standard control strains. 10Susceptibility was routinely tested for the following antimicrobial agents: Ampicillin, Ceftriaxone, Cephalexin, Ciprofloxacillin, Gentamicin, Meropenam, Nalidixic acid, Nitrofurantoin, Norfloxacin and Trimethoprim-Sulfamethoxazole.UTI was defined according to the AAP guidelines. 8ultures were considered positive when there was growth of a single pathogen of >10 5 colony forming units/ml in a urine specimen collected by midstream catch; of >10 4 colony forming units/ml in urine collected by bladder catheterization; and any growth in urine obtained by a suprapubic aspiration.Mixed pathogen growth results were considered unreliable and been excluded.
Recurrent UTI was defined as a single further infection by a new organism. 7The UTI occurring in the presence of catheterization, functional or anatomical abnormalities of the of the urinary tract, host with altered defenses, chronic renal failure, renal transplantation, and those receiving peritoneal and hemodialysis were defined as complicated UTI. 11dominal ultrasound, technetium 99m dimercaptosuccinic acid (DMSA) scan and voiding cystourethrogram were performed in all cases.Diethylene traimine pentaacetic acid (DTPA) was performed in children with the obstructive anomaly.The DMSA scan was routinely done at the time of diagnosis and at the follow up after six months in patients with renal scars.
Patients were divided into two groups: Group 1 for patients with renal anomaly, and group 2 for those without renal anomaly.All these patients received antimicrobial prophylaxis against UTI.Both groups were compared for gender deference and antimicrobial susceptibility.
Statistical Package for Social Sciences for windows, version 10 was used for statistical analysis.The Chi-Square as well as Fisher's exact test were used to compare categoric variables.P value <0.05 was considered significant.
Escherichia coli (E.coli) was determined to be the predominant microorganism in both groups; it was seen in 104 patients (71%) with recurrent UTI, and in 91 patients (47%) with complicated UTI.Proteus,

DIscUssIOn
The UTI has a tendency to recur in children with renal anomaly or preexisting renal disease, and its importance, as a cause of renal insufficiency is well known.There are multiple risk factors for the UTI in pediatric patients, including age, gender, periurethral or colonization factors, native immunity, genitourinary abnormalities, genetic, and iatrogenic factors. 12Patients with recurrent UTI who have such risk factors, are at increased risk of pyelonephritis and subsequent risk of renal scaring with progressive renal disease in adulthood. 13e incidence of VUR is 1-3% among children, and 20-75% of them have UTI. 8,14In our study the prevalence rate was 58.9% (Table 3), and VUR was found to be the most common anatomic malformation in patients with complicated UTI.Renal scaring was clamed to be related to the presence of anatomic malformation. 15ur data support this theory; renal scars were seen in 79.1% of patients with VUR, while it was 24.3% of patients without VUR (P<0.05).As well, the prevalence rate of renal scare was also high in patients with other anomalies (43.3%).
According to demographic data, females are affected more often than males, but the prevalence of resistant microorganisms was less among females than males for all agents under study.This trend is explained by the tendency of males to present more often with complicated UTIs (75%), which may be associated with more antimicrobial resistant pathogens.Similar results were reported by Prais 3 and Howard. 16terobacteriaceae are the most common organisms isolated from patients with UTI.Of these, E. coli account for 65-90% of all urinary infections in children. 1,3,5In our study, the overall prevalence rate for E-coli was 58%, but among patients with recurrent UTI, it was 71.7%.While among patients with complicated UTI; Proteus, Pseudomonas, and Candida spp.were significantly more prevalent (P<0.001), and this results might be explained by the misuse or the abuse of broad spectrum antibiotics, as well as, the frequent hospitalization of patients with complicated UTI (Table 4).
The most common empiric oral antibiotics prescribed in our practice for treatment and for secondary prophylaxis of UTI are first generation Cephalosporins (Cephlexin), and Trimethoprim-Sulfamethoxazole (TMP-SMX).Our study shows an increase bacterial resistance to commonly used oral antibiotics in children with UTI and particularly to the above mentioned drugs; it was 41% and 59% respectively.Raz in his study on children with UTI aged 1-15 years reported even a higher percentage of uropathogen resistant to Ampicillin and Cephalexin with slightly less resistance to Trimethoprim-Sulfamethoxazole (TMP-SMX). 17They were 88%, 44% and 52% respectively.
In 1999, Hoberman and colleagues recommended oral Cefixime for the treatment of young children with fever and UTI.Cefixime was not tested in our study, but the published data support the efficacy of this third generation cephalosporin to be used empirically. 6ong bacterial isolates from children with UTI in our study, resistance to Meropenem and Ciprofloxacin were the least.It was 1.7% and 3.8% respectively.This might be due to the limited usage of these antibiotics in our practice.The other two oral antimicrobials which still have relatively low resistance are Nitrofurantoin and Nalidexic acid.Nitrofurantoin is considered one of the oldest urinary anti-infective drugs in use, surprisingly; resistance to this drug remains minimal.As seen in (Table 5), the overall resistance was 13.3%, but among patients with recurrent UTI, the percentage was even less 5.5%.The lack of resistance may be related to the fact that Nitrofurantoin has multiple mechanisms of action, requiring organisms to develop more than a single mutation in order to develop resistance.In addition, limited usage of Nitrofurantoin for treating uncomplicated cystitis, may also be a contributing factor to the lack of development of widespread resistance to this drug. 18,19The other oral antimicrobial agent who maintains to a less degree a high efficacy against urinary pathogens is Nalidixic acid.The overall resistance in our study was 29.3%, while among patients with recurrent UTI, it was 21.3%.Even more encouraging results regarding these antimicrobials were reported by Prais 3 which makes these drugs a good option for initial empirical treatment of UTI in children.

table 1 . Demographic data of the study population
Younis et al.Antibiotic Resistance in Children with Recurrent or Complicated Urinary Tract Infection