High-dose dual-antibiotic loaded cement for hip hemiarthroplasty – Authors' reply
Authors: Matthew L Costa
Journal: The Lancet (2024)

We would like to thank Yi Liu and colleagues, Yang Liu and Hua Fa, and Po-Jui Chu and colleagues for their Correspondences about our WHiTE 8 trial.1Agni NR Costa ML Achten J et al.High-dose dual-antibiotic loaded cement for hip hemiarthroplasty in the UK (WHiTE 8): a randomised controlled trial.Lancet. 2023; 402: 196-202Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar Regarding long-term follow-up, Liu and colleagues raise an important point. Nearly all the literature pertaining to long-term outcomes following deep surgical site infection around a hip arthroplasty comes from planned surgery, most commonly hip replacement for arthritis.2Graves N Wloch C Wilson J et al.A cost-effectiveness modelling study of strategies to reduce risk of infection following primary hip replacement based on a systematic review.Health Technol Assess. 2016; 20: 1-144Crossref PubMed Scopus (31) Google Scholar These reports show that deep surgical site infection has implications for patients in the long term. However, it is important to note that hip fracture patients are a very different population, as they are older, frailer, and have greater comorbidity and much higher rates of cognitive impairment than individuals undergoing planned hip replacement.3Griffin XL Parsons N Achten J Fernandez M Costa ML Recovery of health-related quality of life in a United Kingdom hip fracture population. The Warwick Hip Trauma Evaluation—a prospective cohort study.Bone Joint J. 2015; 97-B: 372-382Crossref PubMed Scopus (150) Google Scholar There is a 50% mortality at 3 years in unselected patients with a hip fracture. Furthermore, patients with deep surgical site infection following a hip hemiarthroplasty have a 50% in-hospital mortality.4Masters J Metcalfe D Ha JS Judge A Costa ML Surgical site infection after hip fracture surgery: a systematic review and meta-analysis of studies published in the UK.Bone Joint Res. 2020; 9: 554-562Crossref PubMed Scopus (18) Google Scholar These differences are why we concentrated on the early effects of deep surgical site infection in the WHiTE 8 trial. Empirically, it would be interesting to follow up the patients who developed deep surgical site infection in the long term but, in reality, the number of patients available for such follow-up would be very small. With regard to surgical technique, the WHiTE 8 trial was designed to reflect current surgical practice in the UK. Hence, we involved a large number of surgeons, including supervised surgeons in training. In such a large trial, with so many surgeons, any effects due to surgical technique will certainly have been balanced between treatment groups. We accept that there might be some differences in surgical training in other countries, but how such differences might affect rates of deep surgical site infection is unclear. Regarding the pre-injury comorbidities raised by Liu and Fa, the inclusion criteria for the WHiTE 8 trial provided all patients older than 60 years who were having surgery for their hip hemiarthroplasty with the opportunity to participate (ie, to deliberately include a sample representative of the hip fracture population as a whole).5Metcalfe D Costa ML Parsons NR et al.Validation of a prospective cohort study of older adults with hip fractures.Bone Joint J. 2019; 101-B: 708-714Crossref PubMed Scopus (18) Google Scholar We agree that patients with, for example, diabetes are at higher risk of surgical site infection. However, any such pre-injury predisposition would have been balanced by the random allocation of participants to the two treatment groups. This balance is shown in the baseline characteristics table, which, for example, shows that 16·2% of participants in the single antibiotic group had diabetes and 16·7% of participants in the high-dose, dual-antibiotic group had diabetes. Regarding the subgroup analyses proposed by Chu and colleagues, given the much smaller numbers of participants in these subgroups, any such analyses would have been underpowered to detect differences in the rate of deep surgical site infection. Therefore, we did not include such analyses in our pre-specified statistical analysis plan for the WHiTE 8 trial. We would, however, agree with the authors that further investigation of the interaction between baseline patient characteristics and deep surgical site infection is warranted and we have plans to explore these data further in future work. MLC is a National Institute for Health and Care Research Senior Investigator. High-dose dual-antibiotic loaded cement for hip hemiarthroplastyNickil R Agni and colleagues' Article1 reports results for the use of high-dose dual-antibiotic loaded cement for hip hemiarthroplasty in a UK clinical trial, providing important insights into the management of surgical site infections. We would like to highlight a potential limitation in the criteria for participant enrolment in the trial, which did not mention participants' medical histories, medications, or lifestyles. Considering underlying conditions that are associated with infection risk (such as for diabetes, malignancies, lupus, etc) is essential,2 as these can weaken the immune system (making it more difficult for the body to fight off infections) and impair the body's ability to recover effectively. Full-Text PDF High-dose dual-antibiotic loaded cement for hip hemiarthroplastyIn contradiction to results from previous studies, Nickil R Agni and colleagues' Article1 on the WHiTE 8 randomised controlled trial showed that high-dose dual-antibiotic loaded bone cement resulted in a similar risk of deep surgical site infection at 90 days post-operation compared with standard care single-antibiotic loaded bone cement for patients aged 60 years or older with intracapsular hip fractures treated with hip hemiarthroplasties. Although the authors presented several baseline characteristics associated with increasing incidence of surgical site infection following hip hemiarthroplasties, such as cigarette use, alcohol consumption, diabetes, and renal failures, in table 1,1 they conducted subgroup analyses merely according to the included participants' age and sex (as noted in figure 2),1 which warrants further clarification. Full-Text PDF High-dose dual-antibiotic loaded cement for hip hemiarthroplastyWe read with interest Nickil R Agni and colleagues' Article on the WHiTE 8 trial.1 This study has substantial implications for doctors concerned about antibiotic resistance and its effect on patient care. Given the high expectations for the potential of high-dose dual-antibiotic loaded cement in reducing the rate of deep surgical site infections following hip hemiarthroplasty, the WHiTE 8 trial's findings were surprising. The statistically insignificant difference in the rate of deep surgical site infections at 90 days post-randomisation between the high-dose dual-antibiotic loaded cement group and the standard care single-antibiotic loaded cement group raises questions about the current approach to preventing infections in such surgical procedures. Full-Text PDF