Authors: Mackenzie G. Pearsall, John Williamson, Mary Banoub, Charles Hartis, Elizabeth Palavecino, Vera Luther, Erin Barnes, Erika Swintosky, Michael DeWitt, Jennifer J. Wenner, Olivia Randazza
Background/Purpose: Staphylococcus aureus is a common organism associated with bone and joint infections (BJI). Historically, the standard of care (SOC) treatment for BJIs is prolonged intravenous (IV) antibiotic therapy. Studies have compared alternative BJI treatments, including oral antibiotics and long acting lipoglycopeptides like dalbavancin, to SOC with no significant differences in clinical outcomes. This study aims to compare the clinical success of dalbavancin with or without an oral antibiotic versus oral antibiotics alone for the treatment of S. aureus BJI after IV lead-in.
Methods: This is a multisite, retrospective, cohort study including adult patients with a documented S. aureus BJI. Patients were randomly identified using microbiologic culture data until there were 52 matched pairs on initial or recurrent infection. Eligible patients were those treated with dalbavancin with or without an oral antibiotic or an oral antibiotic alone who received 50% or less of the planned total treatment duration as IV lead-in. Patients were excluded if they had a polymicrobial BJI, concomitant endocarditis, valvular abscess, or infectious central nervous system involvement, if the S. aureus isolate was resistant to the antibiotic received, or if they had persistent bacteremia. The primary outcome was clinical success at 90 days from the end of therapy. Secondary outcomes included identification of factors associated with clinical failure, incidence of adverse events, therapy discontinuation, incomplete therapy, and hospital readmission at 30 and 90 days. The results were analyzed using descriptive statistics. Categorical data was analyzed using Pearson’s chi-squared or Fisher’s exact test, and continuous data was analyzed using the Wilcoxon rank sum test. A univariate logistic regression was completed to identify factors associated with clinical failure.
Results: In total, 1287 patients were screened, and 104 patients were included in the study with 52 patients in each cohort. The sample size was limited by the number of patients who received dalbavancin within the study period.
The median age of the overall cohort was 50 years. There was a significant difference in the incidence of current or history of illicit intravenous drug use (IVDU) between the two cohorts, representing 19.2% of the oral cohort compared to 55.8% of the dalbavancin cohort (p<0.001). Types of BJI were similar between the groups (dalbavancin vs. orals), including native osteomyelitis (37% vs. 50%, p=0.2), native joint septic arthritis (21% vs.17%, p=0.6), and prosthetic joint or hardware-associated infection (35% vs. 25%, p=0.3). However, the dalbavancin cohort contained significantly more cases of vertebral osteomyelitis (15% vs.1.9%, p=0.031) and MRSA isolates (77% vs. 52%, p=0.008). There was no difference in presence of source control (81% vs. 92%, p=0.085), however the dalbavancin group had significantly longer duration of IV lead-in (median 160 vs. 96 hours, p<0.001).
The incidence of clinical success was 71% in the dalbavancin cohort compared to 69% in the oral cohort (p=0.8). There was a non-significant trend towards a higher rate of incomplete therapy in the dalbavancin cohort compared to the oral cohort (21% vs 9.6%, p=0.10). There were no significant differences in the rates of other secondary outcomes. The estimated cost savings were not significantly different between cohorts, with a median savings of $79006 in the dalbavancin cohort compared to $65580 in the oral cohort (p=0.5).
None of the factors assessed in the univariate logistic regression (bacteremia, retained prosthetic material, IVDU, source control, incomplete therapy, isolate resistance to methicillin, and vertebral osteomyelitis) were significantly associated with clinical failure. Patients who obtained source control had a numerically lower rate of clinical failure (OR 0.36, p=0.084).
Conclusions: In this cohort, there was no difference in clinical success between the oral antibiotic and dalbavancin treatment strategies after IV lead-in in S. aureus bone and joint infections.
