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doi:10.1111/jpc.12070
COCHRANE COMMENTARIES
Edited by Katrina Williams (katrina.williams@rch.org.au)
Written by Katrina Williams (katrina.williams@rch.org.au) and
Mike South (mike.south@rch.org.au)
Pros and cons of antibiotics for preventing
recurrent urinary tract infection
Williams G, Craig J. Long-term antibiotics for preventing recurrent
urinary tract infection in children.
http://www.onlinelibrary.wiley.com/doi/10.1002/14651858.
CD001534.pub3/abstract
What is this review about? studies were at low risk of bias and involved a more balanced
gender ratio, with 30–40% of participants having vesico-
This review is about the use of antibiotics to prevent recurrent ureteric reflux (VUR). Information about antibiotic resistance is
urinary tract infection (UTI). likely of more current relevance, too.
Table 1 shows the 12 studies and comparisons included. Six
What are the findings? studies examined antibiotics versus placebo/no treatment,
with two of these including more than one antibiotic treat-
Long-term antibiotics reduce the risk of repeat symptomatic ment arm. Five trials assessed the effectiveness for different
UTI in susceptible children, but the benefit is small and must antibiotics, and one trial compared everyday versus alternate-
be considered together with the increased risk of microbial day therapy with the same antibiotic. The duration of long-
resistance. term antibiotic treatment varied from 10 weeks to 12 months.
Outcomes of interest were recurrent UTI, urine culture posi-
tive, adverse events and resistance to antibiotics for subse-
What are the findings based on? quent UTIs.
Although there were 12 studies included, two were crossover
studies, and the findings were difficult to interpret in the same Implications for practice
way as the other included studies. Also, earlier published studies
were at higher risk of bias and more likely to include girls with • A small benefit of low-dose antibiotics to prevent repeat
previous frequent recurrent UTI and normal renal tracts. As a symptomatic UTI in children, with a greater benefit seen in
result, most of the findings about the comparison between studies with low risk of bias (Fig. 2)
placebo and antibiotics are based on two studies completed in • Benefit for children with VUR appears more consistent, but
the last decade: one from Australia (PRIVENT) and one from this information is not presented here, as it will be the topic
Italy (Figs 1,2). The study from Italy was not blinded. These for a future commentary
Review: Long-term antibiotic for preventing recurrent urinary tract infection in children
Comparison: 1 Antibiotic treatment versus placebo/no treatment
Outcome: 1 Recurrence of symptomatic UTI
Study or subgroup Antibiotic Placebo/no treatment Risk Ratio Weight Risk Ratio
n/N n/N M-H, random, 95% CI M-H, random, 95% CI
1 All studies
Smellie 1978 0/25 10/22 5.9 % 0.04 [0.00, 0.68]
Savage 1975 7/29 4/34 21.8 % 2.05 [0.67, 6.31]
Montini 2008 15/211 12/127 31.5 % 0.75 [0.36, 1.56]
PRIVENT Study 2009 36/288 55/288 40.9 % 0.65 [0.44, 0.96]
Subtotal (95% CI) 553 471 100.0% 0.75 [0.36, 1.53]
Total events: 58 (Antibiotic), 81 (Placebo/no treatment)
Heterogeneity: Tau2 = 0.29; χ2 = 7.87, df = 3 (P = 0.05); I2 = 62%
Test for overall effect: Z = 0.79 (P = 0.43)
0.002 0.1 1 10 500
Favours antibiotic Favours placebo/no treatment
Fig. 1 Antibiotic treatment versus placebo/no treatment for the recurrence of symptomatic UTI (from the Cochrane systematic review).
Journal of Paediatrics and Child Health 49 (2013) 75–77 75
© 2013 The Authors
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

2. Cochrane Commentaries
Review: Long-term antibiotic for preventing recurrent urinary tract infection in children
Comparison: 1 Antibiotic treatment versus placebo/no treatment
Outcome: 3 Recurrence of symptomatic UTI: risk of bias fields
Study or subgroup Antibiotic Placebo/no treatment Risk Ratio Weight Risk Ratio
n/N n/N M-H, random, 95% CI M-H, random, 95% CI
1 Adequate allocation concealment studies
PRIVENT Study 2009 36/288 55/288 77.9 % 0.65 [0.44, 0.96]
Montini 2008 15/211 12/127 22.1 % 0.75 [0.36, 1.56]
Subtotal (95% CI) 499 415 100.0% 0.68 [0.48, 0.95]
Total events: 51 (Antibiotic), 67 (Placebo/no treatment)
Heterogeneity: Tau2 = 0.0; χ2 = 0.11, df = 1 (P = 0.74); I2 = 0.0%
Tens for overall effect: Z = 2.25 (P = 0.024)
2 Unclear allocation concealment studies
Smellie 1978 0/25 10/22 45.8 % 0.04 [0.00, 0.68]
Savage 1975 7/29 4/34 54.2 % 2.05 [0.67, 6.31]
Subtotal (95% CI) 54 56 100.0% 0.35 [0.00, 27.93]
Total events: 7 (Antibiotic), 14 (Placebo/no treatment)
Heterogeneity: Tau = 8.94; χ = 8.64, df = 1 (P = 0.003); I = 88%
2 2 2
Tens for overall effect: Z = 0.47 (P = 0.64)
3 Double-blinded studies
PRIVENT Study 2009 36/288 55/288 100.0 % 0.65 [0.44, 0.96]
Subtotal (95% CI) 288 288 100.0% 0.65 [0.44, 0.96]
Total events: 36 (Antibiotic), 55 (Placebo/no treatment)
Heterogeneity: not applicable
Tens for overall effect: Z = 2.15 (P = 0.032)
4 Open label, unblinded studies
Smellie 1978 0/25 10/22 18.0 % 0.04 [0.00, 0.68]
Montini 2008 15/211 12/127 43.8 % 0.75 [0.36, 1.56]
Savage 1975 7/29 4/34 38.2 % 2.05 [0.67, 6.31]
Subtotal (95% CI) 265 183 100.0% 0.66 [0.15, 2.90]
Total events: 22 (Antibiotic), 26 (Placebo/no treatment)
Heterogeneity: Tau2 = 1.17; χ2 = 7.92, df = 2 (P = 0.02); I2 = 75%
Tens for overall effect: Z = 0.56 (P = 0.58)
0.002 0.1 1 10 500
Favours antibiotic Favours placebo/no treatment
Fig. 2 Antibiotic treatment versus placebo/no treatment for the recurrence of symptomatic UTI for risk of bias (from the Cochrane systematic review).
Table 1 Trials included in the Cochrane systematic review
Study Intervention Antibiotic Control
arms
Antibiotic versus control PRIVENT Study 2009 2 Trimethoprim + sulphamethoxazole Yes
Lohr 1977† 2 Nitrofurantoin Yes
Savage 1975 2 Cotrimoxazole or nitrofurantoin Yes
Stansfeld 1975 2 Cotrimoxazole Yes
Two or more antibiotics Montini 2008 3 Cotrimoxazole versus amoxycillin and clavulanic acid Yes
and control Smellie 1978 3 Trimethoprim + sulphamethoxazole versus nitrofurantoin Yes
Between antibiotic Falakaflaki 2007 2 Trimethoprim + sulphamethoxazole versus nitrofurantoin No
comparison only Belet 2004 3 Cefadroxil versus cefprozil versus trimethoprim + sulphamethoxazole No
Lettgen 2002 2 Cefixime versus nitrofurantoin No
Brendstrup 1990 2 Trimethoprim versus nitrofurantoin No
Carlsen 1985† 2 Pivmecillinam versus nitrofurantoin No
Dosage frequency Baciulis 2003 2 Cefadroxil every night versus alternate days No
†Crossover trial.
• Sixteen children with VUR would need to be treated to • There is a non-significant increased risk of bacterial
prevent one recurrent UTI resistance to the treatment drug in subsequent infections
• Nitrofurantoin was the most effective treatment but led to for those taking antibiotics, with cotrimoxazole signifi-
considerable adverse events; for other antibiotics, there were cantly more likely to be associated with resistance than
few adverse effects nitrofurantoin
76 Journal of Paediatrics and Child Health 49 (2013) 75–77
© 2013 The Authors
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)

3. Cochrane Commentaries
• The greatest risk of repeat symptomatic infection occurs in The benefit of long-term antibiotics is probably greater for
the 3–6 months following initial UTI children with significant VUR, but the strong trend away from
voiding cystography after uncomplicated UTI means we do not
readily identify these children.
Clinical perspective There is a very strong trend away from the routine use of
prophylactic antibiotics after UTI in Australia, the United
The role of long-term antibiotics to prevent recurrent UTI has Kingdom, some US centres and elsewhere. In one US study, the
long been controversial. Early studies suggested a useful role, but rate of antibiotic use for this indication fell from 97% to 5% in
on the basis of more recent and better quality data, it appears the a 2-year period.1 It will be interesting to see the benefits or
effect size was greatly overestimated in those old studies. harms of this change over time.
The benefit of long-term antibiotics in preventing UTI is small Many paediatricians now reserve long-term antibiotics for
and has to be weighed against cost, inconvenience, selection very young infants, those with significantly symptomatic recur-
pressure for more resistant organisms and adverse effects. rent UTI or those with abnormalities demonstrated on renal
While paediatricians may be interested in preventing recurrent ultrasound. When antibiotics are used, it is often for much
UTI, they are more concerned with reducing the risk of long- shorter periods than previously.
term renal damage from upper tract infections. More recent
understanding of the very limited role of recurrent UTI in the
causal pathway of long-term kidney damage tells us that if we
Reference
need to treat 16 patients to prevent one UTI, we would prob- 1 Schroeder AR, Abidari JM, Kirpekar R et al. Impact of a more restrictive
ably need to treat many hundreds of children to avoid one approach to urinary tract imaging after febrile urinary tract infection.
significantly damaged kidney. Arch. Pediatr. Adolesc. Med. 2011; 165: 1027–32.
Journal of Paediatrics and Child Health 49 (2013) 75–77 77
© 2013 The Authors
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)