• 
• 

Three Part Question

In [young children (<2y) with a first uncomplicated UTI], is [single-dose antibiotic therapy] as effective as the [standard duration therapy] in [clearing UTI]?

Clinical Scenario

An unwell infant presents with high intermittent fever and irritability. She has had no previous illnesses. A urine sample showed >100 white blood cells and >100,000 E.coli/ml, confirming a diagnosis of urinary tract infection (UTI). The mother asks whether she could be treated with just one dose of antibiotic as she herself was treated this way for a recent urinary tract infection, instead of the standard 5-7 days of antibiotics currently recommended.

Search Strategy

Using Cochrane Database of Systematic Review, Issue 3, 2006 – [Search date : 1950 – present]
PubMed [Search date : 1950 – present]
Cochrane: "urinary tract infection" AND "children" AND "antibiotics"
Pubmed:"urinary tract infection" AND "antibiotics" AND "single dose" LIMIT to "humans" AND "Child : 0-18 years" –

Search Outcome

Cochrane:two systematic reviews identified but irrelevant (one investigating recurrent UTI and one investigating short-course duration of antibiotics).
Pubmed:2 relevant meta-analysis paper identified, 10 relevant primary trials identified (of which 9 RCTs have been reviewed by both meta-analysis with some RCTs overlapping between the two, 1 RCT excluded due to insufficient quality).

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Tran et al, July 2001, USA	22 RCTs, 1279 children aged 0-18 years, with uncomplicated cystitis, comparing short course (single-dose to 4 days) therapy with conventional therapy (>5 days)	Meta-analysis (level 1a)	Cure rates (1-[number of treatment failures/number of patients completing protocol]) of short course and conventional therapy of antibiotics	Absolute difference in cure rate of 6.38% (95% CI : 1.88 to 10.89) in favour of longer treatment. NNT was 16 (95% CI : 9 to 53)	Significant heterogeneity between the studies (P=0.01) in antibiotics used and length of treatment for short course therapy Meta-analysis of the subset included 1 RCT with 4 days of amoxicillin therapy. No significant heterogeneity (P=0.6)
			Cure rates of a subset comparing single-dose with longer (10 days) course of amoxicillin	Longer course of amoxicillin increased cure rate (5 RCTs : difference in cure rate 13% (95% CI : 4 to 24)
Keren R, Chan E, May 2002, USA	17 RCTs, 1126 children aged 0-18 years, comparing short course (<3 days) and long course (7-14 days) antibiotics	Meta-analysis (level 1a)	Relative risk of treatment failure and re-infection for short course antibiotics	Pooled estimate for RR of treatment failure with short-course antibiotic was 1.94 (95% CI : 1.19-3.15) and of re-infection was 0.76 (95% CI : 0.39-1.47)	No statistical data on heterogeneity was given Most RCTs did not have RR for re-infection as the results of the original study were not presented in a form amenable to extraction
			Relative risk of treatment failure and re-infection of a subgroup comparing single-dose or 1-day therapy with long-course therapy	Pooled RR of treatment failure was 2.73 (95% CI : 1.38-5.40) and of re-infection was 0.37 (95% CI : 0.12-1.18)

Comment(s)

The current standard of care for treatment of acute UTI in adult women ranges from a single dose to 3 days. As well as being effective, a shorter course of antibiotics have added benefits of being less expensive, improve adherence, have fewer side effects and may prevent reinfections with resistant organisms. However, both meta-analysis demonstrated that in children presenting for the first time with acute UTI, courses of antibiotic therapy 5 days in length or longer were associated with better outcomes than shorter courses. This is consistent with the the recommendation by The American Academy of Pediatrics 1999 that infants and young children 2 months to 2 years of age receive a 7- to 14-day antimicrobial course for management of acute UTI. In answering the original question regarding the effectiveness of a single dose antibiotic regimen, the subset of amoxicillin trials in Tran et al was analyzed. The cure rate for short courses of amoxicillin was significantly less than that of a conventional length course. 4 of the 5 studies compared a single-dose with a 10-day course, with the remaining study comparing a short 4-day course with a 10-day course. Inclusion of the 4-day course study may bias the cure rates for single-dose studies towards a higher cure rate. Thus, the cure rate for single-dose treatment may actually be lower than that estimated in the subset meta-analysis, concluding that a single dose of amoxicillin is not effective in the treatment of acute UTI. This finding was supported by the subgroup analyses in Keren et al, which did a restricted meta-analysis for 11 studies comparing single-dose or 1-day therapy with long course therapy for different antibiotic agents. Again, the inclusion of 1-day therapy may bias the relative risk of treatment failure and re-infection albeit only slightly. In some of the studies, the antibiotic used in the single-dose was different to that in the long course therapy, resulting in potential sources of heterogeneity. As such, it is difficult to determine for certain that the fewer treatment failures associated with long-course therapy is due to the length of the therapy rather than the type of antibiotics used.

Clinical Bottom Line

The standard conventional antibiotic therapy (5- to 7-day course) should be given in children presenting with acute UTI for the first time as single dose of amoxicillin is not as effective. However, it might be worth looking at the efficacy of other and newer antibiotic agents in a single-dose, which maybe as effective with reduced side-effects.

References

1. Tran D, Muchant DG, Aronoff SC. Short-course versus conventional length antimicrobial therapy for uncomplicated lower urinary tract infections in children : A meta-analysis of 1279 patients. The Journal Of Pediatrics 2001; 139:93-9.
2. Keren R, Chan E. A meta-analysis of randomized, controlled trials comparing short- and long-course antibiotic therapy for urinary tract infections in children. Pediatrics 2002; 109(5):E70-0.
3. American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics. 1999;103:843–852.