How can we reduce deaths from sepsis without contributing to the problem of antimicrobial resistance (AMR)?
Today on World Sepsis Day (13th September 2019), as both members of the public and health professionals alike, we can all learn more about how to spot signs of sepsis. Whilst there are many conditions where a watchful waiting approach to management can be taken, with sepsis speed really is of the essence. This means that it is important to be aware of and familiar with the classic signs of sepsis. However, actual diagnosis of sepsis is hard, so this heightened awareness inevitably leads to more and more patients receiving antibiotics ‘just in case’. So we are left with a balancing act between our desire to reduce the use of unnecessary antibiotics and the need to reduce deaths from this terrible condition.
BATCH and PRONTO
Current research is focussed on helping health professionals to use antibiotics judiciously – i.e. targeted to those who need them. This is the premise behind both the BATCH and the PRONTO trials run thorough the Centre for Trials Research. The BATCH trial is focused on children in hospital who have suspected infections who need intravenous antibiotics. It uses a protein biomarker (procalcitonin) found in the blood to see if this can shorten the time that they are on these intravenous antibiotics, by more accurately assessing recovery. The PRONTO trial is looking at adults in the emergency department with suspected sepsis to see if this blood marker can be used to decide whether to start antibiotic treatment. PRONTO also uses procalcitonin as the biomarker, but features a bench top machine which can provide an answer within 20 minutes. These studies are funded by the NIHR to provide vital evidence to guide future practice.
Both of these studies face a challenge in design. We want to reduce antibiotic use, but these are patients who are ill and there would be concerns that we might not give antibiotics to those who really need them. Therefore we have designed them to consider two outcomes simultaneously, which is unusual in clinical trials. Both studies are designed to look at reducing antibiotics, but without having a bad impact clinically on the patient. This second or ‘non-inferiority’ outcome to show that things do not get worse for patients when we use the blood marker to drive treatment is vital to the study, but also challenging. In order to design these studies we need to decide on a ‘non-inferiority margin’ which is what is considered a negligible difference.
For BATCH this is a safety measure made up of a number of different events including needing to restart the intravenous antibiotics, but also admission to intensive care, whilst for PRONTO this safety measure is death. We have two very active patient groups who have been involved in helping us design these studies and considering the acceptability of the outcomes. We have also planned the studies to allow us to stop them early if there is a concern regarding patient safety, or if there is a large benefit.
It is vitally important that as researchers we design and deliver studies which help health professionals and patients with diagnosing and managing sepsis. These studies may need us to think differently about how we design our studies, however working in partnership with patients makes this possible.