Management of CRE Infections: High Time for an RCT?

We read with interest the study by Vijayakumar et al. 1 on the comparative efficacy of Ceftazidime-Avibactam (CAZ-AVI) with or without aztreonam (AZT) vs polymyxins for the treatment of carbapenem-resistant enterobacteriaceae (CRE) infections.We would like to congratulate the authors for this much-needed study, and it definitely adds to the ever-increasing evidence favoring the CAZ-AVI aztreonam combination over polymyxins in treating NDM and OXA-48 strains, which seems to be the predominant subtype in our country. 2 However, we felt certain aspects of the study need further review.One of the primary outcomes of the study included clinical success on day 14.This was defined as patient survival, hemodynamic stability, or an improvement of their SOFA scores on day 14.Improvement of the SOFA scores was defined as a fall in SOFA score by 1 point when baseline SOFA was <3, and a drop in SOFA scores >30% when SOFA was more than 3.The demographic data outlined in Table 1 shows that patients in the Polymyxin group have higher baseline SOFA scores compared to the CAZ-AVI ± AZT group [(6 vs 9); p = 0.09].We wonder if this could have led to a better outcome in terms of the clinical success in the CAZ-AVI ± AZT group, given that they would need a lower absolute SOFA score change to be labeled as a clinical success due to their lower baseline SOFA scores, to begin with.Interestingly, there was no difference in other secondary outcomes including 14-and 28-day mortality, days free from mechanical ventilation, ICU and hospital length of stay, and incidence of renal failure.While chasing mortality as an endpoint in ICU trials has its own pitfalls, it's disappointing that the better clinical cure did not translate into better mortality outcomes for this cohort.Finally given the small sample size of the study, the possibility of inflated effect size remains. 3 We would nonetheless laud the authors for the valuable insights of this study.A well-designed RCT perhaps is much needed to put all speculations to rest regarding the efficacy of CAZ-AVI ± AZT when compared to polymyxins in the treatment of CRE strains prevalent in this part of the world.