Effectiveness of dalbavancin compared to standard of care for the treatment of osteomyelitis: A real world analysis

Background Preliminary data suggest that the effectiveness of dalbavancin may be similar to current standard of care (SoC) treatment options for osteomyelitis with an advantageous dosing schedule. Methods This was a retrospective, observational cohort study of adult patients diagnosed with osteomyelitis. Patients were matched 1:2 to dalbavancin (administered as 2 doses separated by 1 week) or SoC treatment for osteomyelitis according to Charlson Comorbidity Index, site of infection, and causative pathogen. The primary objective was to determine the incidence of treatment failure after a one-year follow-up period. Secondary objectives included hospital length of stay (LOS), infection-related one-year readmission rates, and treatment-related adverse events. Results A total of 132 patients received dalbavancin (n = 42) or SoC (n = 90). Baseline characteristics, including the rates of surgical intervention, were similar between the two treatment groups. Treatment failure was similar between those who received dalbavancin and SoC (21.4% vs 23.3%, p = 0.81). Patients who received dalbavancin had a shorter hospital LOS (5.2 days vs 7.2 days, p = 0.01). There was no difference in the rates of infection-related readmission between the dalbavancin and the SoC group (31% vs 31.1%, p = 0.99). There were numerically fewer adverse events in the dalbavancin group compared to the SoC group (21.4% vs 36.7%, p = 0.08). Peripherally inserted central catheter line related complications were reported in 17.8% of patients in the SoC group. Conclusions Dalbavancin administered as a two-dose regimen is a safe and effective option for the treatment of osteomyelitis.

231. Retrospective Comparison of Intravenous Therapy, Oral Therapy, and Lipoglycopeptides for the Treatment of Osteomyelitis

Background The use of oral (PO) antibiotics and lipoglycopeptides are challenging the previous standard of osteomyelitis (OM) treatment, but there is currently a paucity of comparative data between these approaches. Methods This retrospective study included patients diagnosed with OM treated with intravenous (IV) antibiotics, PO antibiotics, or lipoglycopeptides between January 1, 2010 and June 1, 2020. Patients in the PO group could receive no more than 14 days of IV antibiotics prior to the PO course, and inclusion into the lipoglycopeptide group required at least 2 doses of drug to be administered. The primary outcome was occurrence of clinical failure within six months of completion of therapy, which was defined as new antibiotics or unplanned surgical intervention for an infection at the same site. Secondary outcomes included in-hospital length of stay (LOS), amputation within 6 months of therapy completion, and incidence of drug and line-related adverse effects. Previous osteomyelitis at index site, surgical intervention as a part of initial management, presence of Staphylococcus aureus on culture, utilization of outpatient parenteral antibiotic therapy (OPAT) services (IV group only), and concomitant PO therapy (lipoglycopeptide group only) were included in a bivariate analysis and variables with a p-value < 0.2 were included in a multivariate regression model. Results The IV group included 257 patients, while the PO and lipoglycopeptide groups included 20 and 15 patients respectively. In the IV group, 89 (35%) of the patients experienced clinical treatment failure compared to 5 (25%) in the PO group and 5 (33%) in the lipoglycopeptide group (p=0.71). Median LOS was significantly shorter in the PO group compared to the IV and LGP groups [1 day (IQR 0-2.5) vs. 7 days (IQR 4-10) and 4 days (IQR 4-9), p=0.003]. No difference between groups was observed for amputation within 6 months or incidence of adverse effects. The only variable included in the multivariate regression model was previous osteomyelitis at index site [OR 1.75, 95% CI (1.07 – 2.87)]. Conclusion PO and lipoglycopeptide therapy resulted in similar outcomes compared to IV antibiotics. Only previous OM at the same site was identified as an independent risk factor for failure. Disclosures Ryan P. Moenster, Pharm.D., FIDSA, AbbVie (Speaker’s Bureau)Melinta (Consultant, Speaker’s Bureau)

108. Efficacy of Dalbavancin Compared to Standard of Care for the Treatment of Osteomyelitis: A Retrospective Study

Background Preliminary data suggest that the efficacy of dalbavancin, a long-acting lipoglycopeptide, may be similar to current standard of care (SoC) treatment options for osteomyelitis, and may be associated with fewer treatment related adverse events. This study assessed the incidence of treatment failure in patients receiving either dalbavancin or SoC for the treatment of osteomyelitis. Methods This was a multi-center, retrospective, observational cohort study of adult patients diagnosed with osteomyelitis. Patients were matched 1:2 to either dalbavancin (1500 mg infused intravenously on days 1 and 8) or SoC for osteomyelitis (oral or intravenous antibiotics) by Charlson Comorbidity Index, site of infection, and causative pathogen. The primary objective was to determine the incidence of treatment failure after a one-year follow-up period. Secondary objectives included hospital length of stay (LOS), infection related one-year readmission rates, and treatment related adverse events. Results A total of 132 patients were matched to receive dalbavancin (n = 42) or SoC (n = 90). Baseline characteristics were similar between the two treatment groups. The majority of patients had lower extremity osteomyelitis (76.2% vs 73.3%) with an etiology of diabetic foot infection (45.2% vs 46.7%) in the dalbavancin and SoC groups, respectively. Treatment failure was similar between those who received dalbavancin and SoC (21.4% vs 23.3%, p = 0.808). Patients who received dalbavancin had a significantly shorter hospital LOS compared to patients who received SoC regimens (5.2 days vs 7.2 days, p = 0.013). There was no difference in the rates of infection related readmissions between the dalbavancin and the SoC group (31% vs 31.1%, p = 0.985). Peripherally inserted central catheter line related complications were reported in 17.8% of patients in the SoC group, however the lower incidence of overall adverse events in the dalbavancin group was not significantly different than the SoC group (21.4% vs 36.7%, p = 0.08). Conclusion Dalbavancin administered as a two-dose regimen is a safe and effective option for the treatment of osteomyelitis Disclosures Dustin R. Carr, PharmD, BCPS, BCIDP, AAHIVP, Merck (Speaker's Bureau) Thomas L. Walsh, MD, Accelerate Diagnostics (Other Financial or Material Support, speaking fees)

TRLS-07. Intracavitary carrier-embedded Cs131 brachytherapy for recurrent brain metastases: A randomized phase II study

Background The salvage treatment of recurrent brain metastases after failed irradiation is a clinical challenge. Adjuvant SRS is standard of care for resected brain metastases in the upfront post-resection setting given a significant local control advantage over surgery alone. However, the role of reirradiation following salvage resection of recurrent post-irradiation metastases is unclear owing to both reduced efficacy of subsequent courses of external beam radiation, and likely increased risk of radiation injury. Intracavitary cesium 131 (Cs131) brachytherapy offers a highly conformal adjunct radiation option that we hypothesize may allow for improved local control while also theoretically conveying a low risk of radiation necrosis. In this randomized controlled study, we aim to define the potential benefits and risks of resection plus permanently implanted, carrier-embedded intracavitary Cs131 brachytherapy versus conventional care (surgery alone). Methods This is a single-center randomized controlled study of patients undergoing resection of recurrent, previously-irradiated brain metastases. Exclusion criteria include prior in-field infection, prior radiation >100Gy (in 2Gy fraction equivalents), >5 additional active or untreated CNS lesions, or leptomeningeal carcinomatosis. Subjects are randomized 1:1 to undergo either surgery with placement of Cs131 brachytherapy or surgery alone. The primary endpoint is freedom from treated-site progression at 9 months. Secondary endpoints include wound complications at 3 months and time to local retreatment at the index site, and exploratory objectives include neurocognitive function prior to surgery and at 3 and 12 months postoperatively, with correlative analyses of the previously irradiated brain metastasis tissue. Accrual began on December 24, 2020 and 5 of a planned 76 patients have enrolled. This is the first randomized controlled trial of surgery plus permanently implanted intracavitary Cs131 brachytherapy versus surgery alone for recurrent brain metastases. ClinicalTrials.gov Identifier: NCT04690348

Are surrogate markers for diabetic foot osteomyelitis remission reliable?

Background: The aim of this study was to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections. Methods: Thirty-five patients with diabetic foot infections were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histology initially and for recurrence. Chi square and Fischer's exact test were used for dichotomous variables and the student's t-test and Mann-Whitney U test for continuous variables with an alpha of 0.05. Results: Twenty-four patients were diagnosed with osteomyelitis and eleven patients with soft-tissue infections. 16.7% (n=) of patients with osteomyelitis had a re-infection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), re-ulceration (20.8%), re-admission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed with osteomyelitis and soft tissue infections. There were no differences in osteomyelitis re-infection (16.7% vs 45.5%, p=0.07), wounds that failed to heal (8.3% vs 9.1%, p=0.94), re-ulceration (20.8% vs 27.3%, p=0.67), re-admission for diabetic foot infections at the same site (16.7% vs 36.4%, p=0.20), amputation at the same site after discharge (12.5% vs 36.4%, p=0.10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate ranging from 8.3-20.8%. Conclusions: Most osteomyelitis markers were similar to markers in soft tissue infection subjects. Commonly reported surrogate markers were not shown to be specific to identify patients that failed osteomyelitis treatment when compared with patients that had soft tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

Breast cancer events in women with atypical ductal hyperplasia who do not undergo surgical excision.

1562 Background: Atypical ductal hyperplasia (ADH) found on core needle biopsy is associated with an upgrade to carcinoma in 10-30% of women, thus surgical excision remains the standard of care. We sought to review the incidence of breast cancer in women with ADH managed by either observation or surgical excision over a 15 year period. Methods: Our prospectively maintained registry was reviewed to identify patients with ADH diagnosed by core needle biopsy between 1/2004 and 10/2018. Observed patients were deemed low risk for upgrade after multidisciplinary review confirmed adequate sampling, limited atypia and concordance between imaging and histology. Surgical patients were excluded if upstaged to carcinoma following excision. Patients with < 1 year follow-up were excluded. Subsequent breast cancer was classified as ipsilateral or contralateral to the previous ADH and was further classified as index site if the new cancer was identified in the same quadrant as prior ADH. Multivariate logistic regression models were used to assess potential predictors of subsequent breast cancer events. Results: Four hundred and seventy-eight women with 483 ADH lesions met criteria; 305 were observed and 173 underwent excision. Median follow-up was 5.2 years, range 1.1-15.3. At the time of ADH diagnosis, 91 women had a personal history of breast cancer. Age < 50 was the only statistically significant difference between the groups (24.6% vs. 33.3%, p = 0.04). Race, receipt of chemoprevention, prior breast cancer history and median follow-up were not significant between the groups. Prior history of breast cancer was associated with subsequent breast cancer risk in multivariate analysis (OR 2.25, 95% CI 1.04-4.87, p = 0.04). After excluding patients with a history of breast cancer, multivariate analysis demonstrated no association of age, race, use of chemoprevention or surgical excision with future cancer risk. Among the 387 patients without a prior breast cancer history, 21 patients developed a subsequent cancer; 10 in the surgical group and 11 in the observed group (7.3% vs. 4.4% respectively, p = 0.2). Two cancers were identified at the index site in the surgery group (2/137, 1.5%) and three in those observed (3/250, 1.2%). Conclusions: Observation, rather than surgical excision, is safe in selected women that have a core biopsy diagnosis of ADH. Index site failures are rare and are superseded by cancer risk elsewhere in the breast. National screening and diagnosis recommendations should consider recommending observation for this select group of patients with ADH.

Myocardial infarction and peripheral arterial disease: Treatment patterns and long-term outcome in men and women results from a Swedish nationwide study

Background Differences in comorbidity, pharmacotherapy, cardiovascular (CV) outcome, and mortality between myocardial infarction (MI) patients and peripheral arterial disease (PAD) patients are not well documented. Aim The aim of this study was to compare comorbidity, treatment patterns, CV outcome, and mortality in MI and PAD patients, focusing on sex differences. Methods This observational, population-based study used data retrieved from mandatory Swedish national registries. The risks of MI and death were assessed by Kaplan–Meier analysis. Secondary preventive drug use was characterized. Cox proportional risk hazard modelling was used to determine the risk of specific events. Results Overall, 91,808 incident MI patients and 52,408 PAD patients were included. CV mortality for MI patients at 12, 24, and 36 months after index was 12.3%, 19.3%, and 25.4%, and for PAD patients it was 15.5%, 23.4%, and 31.0%. At index, 89% of MI patients and 65% of PAD patients used aspirin and 74% and 53%, respectively, used statins. Unlike MI women, women with PAD had a lower rate of other CV-related comorbidities and a lower risk of CV events (age-adjusted hazard ratio 0.81, 95% confidence interval 0.79‒0.84), CV death (0.78, 0.75‒0.82), and all-cause death (0.78, 0.76‒0.80) than their PAD male counterparts. Conclusion PAD patients were less intensively treated and had a higher CV mortality than MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI. This result indicates that the lower-limb vasculature may more often be the index site for atherosclerosis in women.

KEYNOTE-629: Phase 2 study of pembrolizumab for recurrent/metastatic or locally advanced unresectable cutaneous squamous cell carcinoma (cSCC).

TPS9598 Background: Findings from phase 1 and 2 studies suggest that targeting programmed death 1 (PD-1)/PD-L1 pathway can provide durable antitumor activity in patients with local/regionally advanced or metastatic cSCC and may be a promising treatment option. The open-label, single-arm, phase 2 KEYNOTE-629 trial (NCT03284424) will be conducted to test the clinical activity of the PD-1 inhibitor pembrolizumab in locally advanced, unresectable, and recurrent or metastatic cSCC. Methods: Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for up to 35 infusions (≤24 months) or until protocol-specified treatment discontinuation. Treatment will not be stratified in this study. Eligibility criteria include age ≥18 years; locally advanced cSCC for which the patient is ineligible for resection or radiotherapy (RT) or for which the patient previously underwent RT to the index site or systemic therapy for curative intent; presence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; and Eastern Cooperative Oncology Group performance status 0 or 1. Treatment will be discontinued for progressive disease, unacceptable toxicity, intercurrent illness preventing administration, investigator’s decision, patient withdrawal of consent, pregnancy, or cessation for administrative reasons. Response will be assessed by imaging 6 weeks after treatment initiation, every 6 weeks through year 1, and every 9 weeks thereafter or more frequently if clinically indicated. After disease progression or the start of new anticancer therapy, the patient will be followed up every 12 weeks until death, consent withdrawal, or study end, whichever occurs first. Safety will be monitored throughout the study and for 30 days after treatment end or 90 days if the patient experiences serious adverse events. The primary end point is objective response rate (RECIST v1.1). Secondary end points include response duration, disease control rate, progression-free survival, overall survival, and safety. Recruitment is ongoing in 10 countries and will continue until approximately 50 additional patients with locally advanced, unresectable cSCC are enrolled. Clinical trial information: NCT03284424.