Impact of Narrow Empiric Antibiotic Spectrum and Patient Characteristics on Clinical Outcomes in Bone and Joint Infections: A Retrospective Cohort Study

Background: Bone and joint infections (BJIs) are a significant clinical challenge due to their tendency to recur, increased healthcare expenses, reduced quality of life, and mortality. Patients with BJIs are a heterogeneous group due to their different clinical presentations as well as patient-related risk factors. Empiric antibiotic regimens are commonly based on deductions from in vitro microbiologic findings, despite the fact that their relative efficacy and optimal antibiotic choices are underexplored. Methods: This retrospective cohort study included 521 patients surgically treated for BJIs at a specialized orthopedic infection unit between 2016 and 2023. Treatment strategies were guided by the Oral Versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial. All patients received a narrow-spectrum Gram-positive–targeted empiric systemic antibiotic regimen determined according to regional recommendations in collaboration with infectious disease specialists. The primary outcome was clinical failure within one year, with a minimum follow-up of 12 months. For the analyses, the patients were divided into three groups based on microbiological susceptibility: susceptible (SusEmp), non-susceptible (NonSus) and culture-negative (CulNeg) patients. Results: The three groups were found to differ significantly in seven patient-related factors: sex, age at primary operation (OP age), BMI, ASA group, diabetes status, peripheral arterial disease status (PAD), and endocrinopathy status (other than diabetes). In performing multivariate analyses, OP age was found to be independently associated with the overall failure rate (p = 0.04) and ASA group (p = 0.047), and PAD (p = 0.043) was independently associated with the secondary outcome of proximal amputation. Patients with non-susceptible pathogens (NonSus) had more than twice the odds of clinical failure (OR: 2.10; 95% CI: 1.12–3.95) and nearly fivefold higher odds of secondary proximal amputation (OR: 4.95; 95% CI: 1.41–23.2) compared with patients with susceptible pathogens (SusEmp). Conclusions: The current study demonstrates that a large group of patients can presumably be treated safely with a more restrictive narrow approach. More studies are needed to identify subgroups suited for the safe use of a narrow-spectrum empiric regimen, hereby reserving the broad-spectrum antibiotics for patients with the right indications and for whom it would have a positive effect on the clinical outcome. Such an approach would justify a more restrictive stewardship of broad-spectrum antibiotic use without negatively impacting patient outcomes.