Stream 2

Urinary and skin-and-soft-tissue infections (UTIs, SSTIs): generating and synthesising the evidence about antibiotic benefits and harms for these conditions and developing interventions to reduce antibiotic use

The problem: The evidence quantifying the benefits of antibiotics for uncomplicated UTIs (eg in young women) provides little evidence in comparison with that for ARIs (which shows that the empirical benefits are much smaller than most patients or their clinicians expect). Nevertheless, for UTIs we are aware of 3 randomised controlled trials (RCTs) comparing antibiotics with non-steroidal anti-inflammatory drugs (NSAIDs) (with another Norwegian trial in progress) but only two RCTS comparing antibiotics against placebo.26, 27 For most SSTIs, the evidence similarly appears to be weak. This makes it difficult to a) create safe guidelines and b) to design interventions that recommend less use of antibiotics for these largely self-limiting infections. However, the extent and quality of evidence in this area is not accurately known as no formal synthesis of the evidence has been published.

The solution: We plan to undertake systematic reviews of the literature to summarise the evidence about the benefits and harms of antibiotics for these conditions. We have already undertaken a scoping exercise to preliminary examine the literature and know that there are sufficient studies that formal systematic reviews should be conducted. We have already conducted a harms systematic reviews of RCTs for amoxicillin28 and are currently preparing the same for cephalosporins and macrolides, which we anticipate being published in 2018. Without quantification of the benefits and harms of antibiotics for UTIs and SSTIs, attempts at providing the evidence in order to decrease the use of antibiotics (for example, through shared decision making which involves communicating the benefits and harms to assist with informed decision-making) are severely hampered.

Systematic reviews planned Purpose
Harms of commonly used antibiotic groups
     Amoxicillin +– clavulanate (completed)
     Cephalosporins (started)
     Macrolides (started)
To better inform decision making, we need to:
a)  quantify the harms of antibiotics in general;
Benefits of antibiotics for uncomplicated UTI
Benefits of antibiotics for SSTI
b) quantify the benefits specifically for these infections

We expect to find a paucity of placebo-controlled trials for uncomplicated UTIs and SSTIs. If so, we plan to initiate a series of key RCTs to start this off. These will be the subject of a separate project grant for the Australian arm of international multicentre trials. These studies will examine antibiotic reduction interventions (combining delayed antibiotics and shared decision-making). This will enable better estimates of the benefits of antibiotics in patients choosing to delay antibiotics initially, expected to be small.

The trial will have two purposes: (i) enable an analysis of (a+b vs c+ d) to test the effect of antibiotic interventions on the outcomes of antibiotic use for these infections; and (ii) additionally, (a vs b) to identify patient and clinical factors associated with good outcomes with no antibiotic use, accepting the limitations that the latter does not use a randomised design, Figure 3 (below).