Study overview
We conducted a multi-center, prospective, observational cohort study to investigate the incidence of infections within one year for open and closed tibia fracture patients who were treated with internal fixation. The method of internal fixation was left to the discretion of the attending surgeon. After obtaining informed consent, baseline and surgical data were recorded. Approval was obtained from the Institutional Review Board (Aurora, Ontario) and each hospital’s local Ethics Committee prior to commencing study activities.
Participant identification and eligibility criteria
Patients who presented to one of the participating hospitals with a tibia fracture treated with internal fixation were screened for study eligibility. The inclusion criteria were: 1) Men and women who are 18 years of age or older. 2) Open or closed tibia fracture (AO 41, 42, and 43) treated by internal fixation (plate or nail) or by external fixation with planned conversion to plate or nail. 3) Ability to understand the content of the subject information/informed consent form and to be willing to participate in the clinical investigation. 4) Provided written informed consent.
The exclusion criteria were: 1) Previous wound infection or osteomyelitis at the same limb (according to subject history). 2) Patients who plan to undergo conversion surgery at a different hospital. 3) Previous fracture with retained hardware in injured extremity that will interfere with implant fixation. 4) Immunological deficiency disease. 5) Tumor related fractures. 6) Any severe systemic disease: class V-VI of the American Society of Anesthesiologists (ASA) physical status classification [8]. 6) Recent history of substance abuse that would preclude reliable assessment. 7) Patient is a prisoner. 8) Participation in any other medical device or medicinal product study within the previous month that could influence the results of the present study. Reasons for ineligibility were documented.
Data collection
After providing informed consent, baseline information was documented and participants underwent a haematology analysis (Leucocyte count, CRP level, and ESR level) and radiographs (AP, lateral) before surgery. Details regarding the surgical procedure, including antibiotic prophylaxis, were documented. Post-operatively participants underwent a haematology analysis and x-rays.
Participants with any symptoms of surgical site infections underwent further investigations including radiological assessment, hematological analysis and bacteriological culture and antibiogram whenever possible to determine whether infection was present. If infection was diagnosed, infection management including administered antibiotics, wound care, surgical intervention performed, and infection treatment outcome were recorded.
Participants attended clinic visits at 3 months, 6 months, and 12 months post-surgery, or were contacted by telephone to collect as much information as possible if unable to attend a follow-up visit. At each visit, patients were assessed for infections and fracture healing. Haematology and radiographs were taken as standard of care. Antibiotic use was documented. Participants also completed the EuroQol-5 Dimensions (EQ-5D). The EQ-5D is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion. At the 12 month visit, any planned revision surgeries were also documented.
Confirmation of eligibility and review of infections
An independent Adjudication Committee comprised of three orthopaedic trauma surgeons confirmed the eligibility for cases in which patient eligibility was in doubt. They also reviewed reported infections to confirm the presence of infection and classify the infection as a superficial incisional surgical site infection (SSI) or a deep incisional SSI using CDC criteria [9]. They also confirmed the timing of infection as early (onset of symptoms within 2 weeks of injury), delayed (onset of symptoms 2–10 weeks after injury) or, late (onset of symptoms more than 10 weeks after injury).
Data analysis
We summarize participant characteristics using descriptive statistics expressed as means and standard deviations for continuous variables) or counts and percentages for categorical variables. For analysis of primary outcomes, the incidence of infection within one year of the internal fixation surgery was reported as a proportion. A Fisher’s exact test was used to determine if the incidence of infection and infection type (superficial versus deep) differed across fracture types (open versus closed fractures). Infections were classified by timing of onset and a Chi-square test was used to compare the incidence of early versus delayed versus late onset infections across fracture types.
For analysis of secondary outcomes, infection symptoms and management in open and closed fracture patients were summarized using descriptive statistics. Infection outcomes and fracture healing at 12 months for open and closed fracture patients are reported as proportions. A Chi-square test was used to compare if the incidence of infections differed by hospital type (public versus private versus combination), as well as by fixation technique used and Gustilo classification for open fractures. Fisher’s exact tests were used to determine if the incidence of infection differed across timing of surgery (within 6 h of injury versus greater than 6 h from injury), and by fixation device material (stainless steel versus titanium). Fracture healing status at 12 months in patients with an infection versus those without was also compared using a Fischer’s exact test. The EQ-5D scores are reported as means and standard deviations for participants with and without infections. Time to healing in patients with and without infections was explored using a t-test, and EQ-5D scores in patients with and without infections were compared using two-way repeated measures ANOVA. Level of significance was determined as p < 0.05. Data analysis was done using Statistical Analysis Software (SAS, v9.2, Cary, North Carolina, United States).