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.

What is this review about?

This review is about the use of antibiotics to prevent recurrent urinary tract infection (UTI).

What are the findings?

Long-term antibiotics reduce the risk of repeat symptomatic UTI in susceptible children, but the benefit is small and must be considered together with the increased risk of microbial resistance.

What are the findings based on?

Although there were 12 studies included, two were crossover studies, and the findings were difficult to interpret in the same way as the other included studies. Also, earlier published studies were at higher risk of bias and more likely to include girls with previous frequent recurrent UTI and normal renal tracts. As a result, most of the findings about the comparison between placebo and antibiotics are based on two studies completed in the last decade: one from Australia (PRIVENT) and one from Italy (Figs 1, 2). The study from Italy was not blinded. These studies were at low risk of bias and involved a more balanced gender ratio, with 30–40% of participants having vesico-ureteric reflux (VUR). Information about antibiotic resistance is likely of more current relevance, too.

Figure 1.

Antibiotic treatment versus placebo/no treatment for the recurrence of symptomatic UTI (from the Cochrane systematic review).

Figure 2.

Antibiotic treatment versus placebo/no treatment for the recurrence of symptomatic UTI for risk of bias (from the Cochrane systematic review).

Table 1 shows the 12 studies and comparisons included. Six studies examined antibiotics versus placebo/no treatment, with two of these including more than one antibiotic treatment arm. Five trials assessed the effectiveness for different antibiotics, and one trial compared everyday versus alternate-day therapy with the same antibiotic. The duration of long-term antibiotic treatment varied from 10 weeks to 12 months. Outcomes of interest were recurrent UTI, urine culture positive, adverse events and resistance to antibiotics for subsequent UTIs.

Table 1. Trials included in the Cochrane systematic review
 StudyIntervention armsAntibioticControl
  1. aCrossover trial.
Antibiotic versus controlPRIVENT Study 20092Trimethoprim + sulphamethoxazoleYes
Lohr 1977a2NitrofurantoinYes
Savage 19752Cotrimoxazole or nitrofurantoinYes
Stansfeld 19752CotrimoxazoleYes
Two or more antibiotics and controlMontini 20083Cotrimoxazole versus amoxycillin and clavulanic acidYes
Smellie 19783Trimethoprim + sulphamethoxazole versus nitrofurantoinYes
Between antibiotic comparison onlyFalakaflaki 20072Trimethoprim + sulphamethoxazole versus nitrofurantoinNo
Belet 20043Cefadroxil versus cefprozil versus trimethoprim + sulphamethoxazoleNo
Lettgen 20022Cefixime versus nitrofurantoinNo
Brendstrup 19902Trimethoprim versus nitrofurantoinNo
Carlsen 1985a2Pivmecillinam versus nitrofurantoinNo
Dosage frequencyBaciulis 20032Cefadroxil every night versus alternate daysNo

Implications for practice

  • A small benefit of low-dose antibiotics to prevent repeat symptomatic UTI in children, with a greater benefit seen in studies with low risk of bias (Fig. 2)
  • Benefit for children with VUR appears more consistent, but this information is not presented here, as it will be the topic for a future commentary
  • Sixteen children with VUR would need to be treated to prevent one recurrent UTI
  • Nitrofurantoin was the most effective treatment but led to considerable adverse events; for other antibiotics, there were few adverse effects
  • There is a non-significant increased risk of bacterial resistance to the treatment drug in subsequent infections for those taking antibiotics, with cotrimoxazole significantly more likely to be associated with resistance than nitrofurantoin
  • The greatest risk of repeat symptomatic infection occurs in the 3–6 months following initial UTI

Clinical perspective

The role of long-term antibiotics to prevent recurrent UTI has long been controversial. Early studies suggested a useful role, but on the basis of more recent and better quality data, it appears the effect size was greatly overestimated in those old studies.

The benefit of long-term antibiotics in preventing UTI is small and has to be weighed against cost, inconvenience, selection pressure for more resistant organisms and adverse effects. While paediatricians may be interested in preventing recurrent UTI, they are more concerned with reducing the risk of long-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 need to treat 16 patients to prevent one UTI, we would probably need to treat many hundreds of children to avoid one significantly damaged kidney.

The benefit of long-term antibiotics is probably greater for children with significant VUR, but the strong trend away from voiding cystography after uncomplicated UTI means we do not readily identify these children.

There is a very strong trend away from the routine use of prophylactic antibiotics after UTI in Australia, the United Kingdom, some US centres and elsewhere. In one US study, the rate of antibiotic use for this indication fell from 97% to 5% in a 2-year period.[1] It will be interesting to see the benefits or harms of this change over time.

Many paediatricians now reserve long-term antibiotics for very young infants, those with significantly symptomatic recurrent UTI or those with abnormalities demonstrated on renal ultrasound. When antibiotics are used, it is often for much shorter periods than previously.