Are we certain that chlorhexidine gluconate bathing is not beneficial in reducing central line associated blood stream infections among children with cancer or undergoing hematopoietic stem cell transplantation?

Abstract

As pediatric oncologists who both are members of the Children's Oncology Group (COG) and have devoted significant effort to reducing central line–associated bloodstream infections (CLABSIs) in children with cancer, we were excited in 2013 when the COG decided to study the impact of daily chlorhexidine gluconate (CHG) bathing on the incidence of CLABSIs in the pediatric oncology population. Before the opening of COG study ACCL1034, which was conducted under Zerr et al's direction,1 the efficacy of CHG bathing in reducing CLABSIs had been demonstrated only in adults and critically ill children, and there were little data evaluating the impact of CHG bathing on CLABSIs specifically in pediatric oncology patients.2-4 Results from the aforementioned study were published in the October 20, 2020, issue of Cancer,1 and on the basis of those results, the principal investigators concluded that the data “do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT [hematopoietic stem cell transplantation].” After careful review of the publication, we have several concerns about the study and the conclusions that were drawn. First, in our clinical experience, most children with cancer in the United States complete their therapy with only an implanted tunneled catheter or port. This population was excluded from this study, so the conclusions cannot be applied to all pediatric oncology patients. Among the most striking observations about this study is that the adherence to the CHG and control bathing regimen was very poor, and the rate of refusal to continue assigned therapy was very high. Only 111 of 165 assessed patients (67%) had an adherence rate of ≥80%. It is also unclear why such large proportions of patients in both the CHG group (48 of 88) and the control group (35 of 89) discontinued the intervention before the end of the planned observation period. The authors give “refusal of further therapy” as the explanation for most patients' discontinuation. The majority of subjects reported satisfaction with the bathing cloths and reported that they were easy to use; this raises the question of whether there were other logistical difficulties in conducting the study. The intent-to-treat analysis included an intervention group in which less than half of the enrollees (40 of 88) received the intervention for the full anticipated observation period. Notably, there were 10 more patients with acute myeloid leukemia in the CHG intervention group than the control group (32 vs 22). It is known that pediatric patients with acute myeloid leukemia are among the patients at highest risk for CLABSIs, especially those with external tunneled catheters.5-7 This imbalance between groups is one potential factor in the higher CLABSI rate observed in the CHG group and may have influenced the overall results. Other concerns are the result of poor accrual and early termination of the study. Less than 50% of the accrual goal was achieved during the 4-year study period. The original sample size calculation indicated that 400 total evaluable patients would be required, each with a 90-day observation period, to determine a difference of 2 infections per 1000 line-days with 85% power. This would lead to 18,000 line-days of observation per group, but when the study was stopped early with only 174 evaluable patients and an average of 74 days of observation, there were approximately 6500 line-days observed per group. With the lower than planned accrual, the power to detect a 2 CLABSI/1000 line-day difference dropped to 44%. In our work to better understand and reduce CLABSIs through a national quality collaborative called Solutions for Patient Safety, we have come to believe that multiple interventions performed reliably over a long period of time are necessary to significantly reduce the incidence of CLABSIs in the pediatric oncology population. We feel strongly that it would be a mistake to hastily discard any intervention that might reduce this serious harm without reliable data that refute other published studies' findings. We recommend that readers consider this article's conclusions with caution and keep the previously delineated concerns in mind. No specific funding was disclosed. Jeffrey D. Hord and Christopher E. Dandoy are volunteer leaders for a national quality improvement initiative to reduce central line–associated bloodstream infections that is directed and managed by Solutions for Patient Safety. Christopher E. Dandoy reports a consulting fee from Omeros outside the submitted work.