Background Epidemiology and resistance patterns of bacterial pathogens in paediatric urinary tract infections (UTIs) show large inter-regional variability, and rates of bacterial resistance are changing due to different antibiotic treatment. Empiric therapy to treat UTI should be tailored to the surveillance data on the epidemiology and resistance patterns of common uropathogens to reduce treatment failures and emergence of bacterial resistance within the community.
Objective A retrospective data review was carried out to evaluate the resistance patterns to commonly used antibiotics in children with culture proven UTIs.
Methods All infants and children with culture proven UTI from 2002 to 2008 were included. Urine culture was deemed positive with a pure growth >105 (single organism).
Results A total of 547 UTIs were confirmed on urine cultures in 337 patients. An average of 78 cases were diagnosed each year. E coli was the most commonly grown pathogen (92%). From 2002 to 2008, rising resistance patterns were noted for trimethoprim (p≤0.05) and Augmentin (p≤0.001). In contrast, resistance to cefalexin and nitrofurantoin remained relatively low (11% and 7%, respectively, in 2008).
Conclusion Our data suggest that there has been an increasing resistance trend to the first-line antibiotics like trimethoprim and Augmentin against E coli. In accordance with NICE (National Institute for Health and Clinical Excellence) guidance, each region should monitor resistance patterns to urinary pathogens on a regular basis and use antibiotics with a low resistance pattern. Further studies are required from other centres in the UK to look at similar data.
- Urinary tract infection
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Urinary tract infection (UTI) is a common paediatric problem and remains one of the common infections diagnosed in outpatients as well as hospitalised patients, with 2% of all children experiencing one by the age of 10 years.1 Early diagnosis and prompt antimicrobial treatment are required to minimise renal scarring and progressive kidney damage.2 The confirmatory diagnosis in children is based on positive results of microbiological tests. In patients with suspected UTI, antibiotic treatment is usually started empirically, before urine culture results are available. The selection of an antimicrobial drug for empirical treatment and prophylaxis of UTI is determined by the susceptibility of bacterial strains isolated from urine cultures. Trimethoprim is usually the first-line antibiotic used in this setting.
Regular use of antibiotics is a platform for the emergence of resistant strains.3 The changing pattern of antimicrobial resistance to the causative microorganisms of UTI in childhood is a mounting problem. There is growing concern regarding antimicrobial resistance worldwide, particularly of Escherichia coli. Epidemiology and resistance patterns of bacterial pathogens in paediatric UTI show large interregional variability, and rates of bacterial resistances are changing due to different antibiotic treatment.4
Empirical antibiotic treatment in UTI in children must rely on surveillance data on the epidemiology and resistance patterns of common uropathogens. This has been endorsed by the recently published guidelines by the National Institute for Health and Clinical Excellence (NICE) in the UK which advises laboratories to monitor resistance patterns to urinary pathogens and use antibiotics with a low resistance pattern.5 Therefore, current knowledge on antimicrobial susceptibility pattern is essential for appropriate therapy. Retrospective data were analysed to evaluate the resistance patterns to commonly used antibiotics in children with culture proven UTI in a hospital setting.
Materials and methods
Data analysis was carried out retrospectively on all infants and children (up to the age of 16 years) with culture proven UTI over a period of 7 years (2002–08). Patients were identified and data were extracted using the Hospital Information and Support System. Urine culture was deemed positive with a pure growth >105 of a single organism.
A total of 547 UTIs were confirmed on urine cultures in 337 patients. Figure 1 shows year-wise distribution of all cases of UTIs from 2002 to 2008. An average of 78 cases were diagnosed each year. Figure 2 illustrates age distribution of all children with culture proven UTI. More than 50% of the patients were <3 years of age. Overall, there was a male to female ratio of 1:3.
Of the 547 UTIs, E coli was the most commonly grown pathogen and was confirmed as the causative organism in 92% of cases (table 1). Other organisms included Pseudomonas, Proteus, group B streptococcus, Staphylococcus aureus and Haemophilus influenzae. Routinely used antibiotics included trimethoprim, cefalexin, augmentin and nitrofurantoin. Figure 3 shows the overall resistance to antibiotics against E coli (from 2002 to 2008); table 2 illustrates the probability of antibiotic resistance.
Over the years, rising resistance patterns were noted for trimethoprim and augmentin. In 2002, 25% and 0% of E coli UTIs were resistant to trimethoprim and augmentin, respectively. In contrast, the resistance pattern changed in 2008, with 34% and 48% of E coli UTIs being resistant to trimethoprim (p≤0.05) and augmentin (p≤0.001), respectively. In comparison, resistance to cefalexin and nitrofurantoin remained relatively low (3% and 11% in 2002 vs 11% and 7% in 2008, respectively).
This comprehensive data analysis in children with UTIs in a district general hospital setting in the United Kingdom suggests significantly increasing resistance trends to the first-line antibiotics like trimethoprim and augmentin in our region. Although the resistance to cefalexin has increased from 3% to 11% in 7 years, it remains significantly lower compared to trimethoprim and augmentin. Similar data depicting resistance to ampicillin and co-trimoxazole has also emerged in other regions of the world in recent years.7 8 E coli remains the predominant organism causing UTIs in the majority of our patients. This is in keeping with the pattern of bacterial strains isolated from patients with community acquired UTIs reported in the literature.9 This is also in accordance with the data from a UK based multicentre study on organisms isolated from patients with UTI.10
Antibiotic resistance has become an important factor to be considered in the treatment of infections. In vitro antimicrobial resistance is an evolving and growing problem in UTI.11 The trend of increasing resistance of urinary pathogens has been published in the recent years.12–14 As the antibiotic resistance is an important factor, we would like to reinforce that urine culture and sensitivity should be routinely performed in paediatric patients with UTI. Depending on the antibiotic susceptibility, therapy should ideally be tailored to an antibacterial agent with the narrowest spectrum, least cost, and few adverse effects.
Clear guidance and decisions about antibiotic prophylaxis in patients with anatomic lesions or recurrent UTIs are even more difficult. With increasing antibiotic resistance, paediatricians are often faced with the dilemma of whether to use a logical starter antibiotic (eg, trimethoprim, as has been the case historically) with a risk of failure, or a broad spectrum antibiotic that may, in the long term, contribute to treatment failures and increasing antibiotic resistance. A recently published randomised controlled trial on 576 children showed that long-term low dose co-trimoxazole was associated with a decreased number of UTIs in predisposed children.15 The authors would not recommend using cephalosporins for prophylaxis in children with recurrent UTIs as children receiving cephalosporin prophylaxis are more likely to have extended spectrum β-lactamase-producing bacteria or multidrug-resistant uropathogens (including cephalosporins) following breakthrough UTIs.16 17
Our cohort appears to have low resistance to cefalexin and nitrofurantoin. Although this could be due to inter-regional variability, we feel this is likely to be a true reflection. Most large studies on antimicrobial resistance in community acquired UTI seldom have data on the paediatric population. Bean et al reported a cefalexin resistance of ∼8% in patients less than 16 years of age, which we feel might be a true reflection in the paediatric age group.18
Hospitalisation of children with UTIs is reserved for severe and complicated cases, for example pyelonephritis. In such cases, intravenous antibiotics are often used for the first few days of treatment. There may also be a difference (in vivo and in vitro) in the resistance pattern in this group of children. Moreover, the defined risk factors associated with non-E coli UTI and its antimicrobial resistance patterns should also be considered, in order to improve empiric parenteral antibiotic therapy for these infections.19
Large-scale prospective studies are urgently required from other centres in the UK to look at the similar data in order to investigate this matter further and to identify predisposing factors for urinary pathogens with antibiotic resistance. If consistent results are found, cefalexin should be considered as a suitable alternative first-line oral antibiotic to treat uncomplicated UTI in children. Continuous surveillance of the resistance pattern will, however, still be required to monitor against the emergence of resistance against broad spectrum cephalosporin antibiotics. We also believe that the local/regional policies for the choice of first-line oral antibiotic treatment for uncomplicated UTI in children should be reviewed every 3 years or so according to local resistance rates.
Urinary tract infection (UTI) remains one of the common infections diagnosed in the paediatric population.
Trimethoprim is usually the first-line antibiotic used to treat UTIs.
Empirical antibiotic treatment in UTIs in children should rely on surveillance data on the epidemiology and emerging resistance patterns to common uropathogens.
E coli remains the predominant organism causing UTIs in the majority of paediatric patients.
In recent years, there have been increasing resistance trends to first-line antibiotics such as trimethoprim and augmentin.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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