Feasibility of shortening intravenous antibiotic therapy based on bacterial load- a proof of concept randomised controlled trial

Introduction There is lack of evidence to guide duration of intravenous antibiotics for bronchiectasis exacerbations. Aims To assess whether it is feasible based on bacterial load to shorten intravenous antibiotics during exacerbations and whether 14days treatment is superior. Method We recruited participants requiring intravenous antibiotics for exacerbations. Participants were randomised into two groups to receive antibiotics for 14days or bacterial load guided group(BLGG). Bacterial load was checked on day 0/7/10/14/21. If bacterial load was <106cfu/ml on day7 or 10 in BLGG, antibiotics were stopped the following day. Results 47 received 14days antibiotics and 43 were in BLGG. 88% of participants in the BLGG were able to stop antibiotics by day8 and potentially 81% could have stopped antibiotics at day8 in the 14day arm. There was a non-significant trend for increased clinical improvement by day21 with 14days compared to BLGG. However, overall group data showed the median (interquartile range) time to next exacerbation was 27.5(12.5-60)days in the group receiving antibiotics for 14days and 60(18-110)days in the in BLGG; p=0.0034. In Cox proportional hazard model, 14days was more likely to experience exacerbations (Hazard Ratio(95% CI)1.80 (1.16-2.80), p=0.009 compared to BLGG and those with mild bronchiectasis less likely to experience exacerbations than patients with more severe bronchiectasis (HR 0.359 (0.13-0.99), p=0.048). Conclusion Bacterial load guided therapy is feasible in most exacerbations requiring intravenous antibiotics. There was a non-significant trend for increased clinical improvement by day21 with 14day antibiotics compared with BLGG but paradoxically there was a prolonged time to next exacerbation in BLGG.