Long-acting Lipoglycopeptide Research Articles

One and Done? An Evaluation of the Clinical Outcomes of Single- and Multi-Dose Dalbavancin Use in the Pediatric Population

Staphylococcus aureus is a leading cause of invasive bacterial infections in the pediatric population. In general, data surrounding the use of newly approved antimicrobials within children are lacking. Dalbavancin is a long-acting lipoglycopeptide that shows promise for off-label use in adults given its unique pharmacokinetics and in vitro potency against common Gram-positive isolates; however, evidence to supports its use in children is limited. We report the use of dalbavancin in three pediatric cases in patients aged 17 months of age, 3 years of age, and 11 years of age. All infections were caused by S. aureus (66.7% methicillin-resistant S. aureus) representing varied disease, including an osteoarticular infection and catheter-related bloodstream infection. Furthermore, all patients had pediatric infectious diseases involvement. Following the utilization of DAL, high clinical success and low rates of adverse effects were observed with high patients’ and parents’ satisfaction. While larger, confirmatory real-world studies are needed, our findings support safe off-label DAL use in select pediatric patients.

Simulated Target Attainment of Multidose Regimens of Dalbavancin for Prolonged Durations of Therapy

Abstract Background Dalbavancin is a long-acting lipoglycopeptide antibiotic that is increasingly utilized for infections that require prolonged treatment durations despite the lack of Food and Drug Administration approval for these indications. There is no consensus regarding optimal dosing of dalbavancin for these infections and no available pharmacokinetic studies to identify optimal dosing for long-term use. Methods An in silico pharmacokinetic simulation was performed to assess the predicted dalbavancin concentration resulting from commonly utilized dosing regimens, in addition to modified regimens. The primary endpoint evaluated was days of median 24-hour free area under the curve over the minimum inhibitory concentration (AUC/MIC) >27.1, the established PK target. Results A dosing regimen of 1500 mg on day 0 and day 7 resulted in median AUC/breakpoint value above the target for 57 days (lower 95% confidence interval [CI], 37 days). A modified regimen of 1500 mg on day 0 and day 21 resulted in an additional 11 days of median AUC/breakpoint target attainment. The other standard dosing regimen modeled was 1000 mg on day 0, then 500 mg weekly for 5 doses. This regimen achieved the AUC/breakpoint target for 76 days (lower 95% CI, 59 days). This regimen was modified to 1000 mg on day 0, then 500 mg on days 14 and 28, which shortened the median effective treatment duration by 14 days but required 3 fewer doses. Conclusions These simulated results, when combined with the favorable observational data, support the use of commonly reported dalbavancin regimens for prolonged therapy durations. In addition, these pharmacokinetic/pharmacodynamic data support extending the dosing interval beyond the frequently reported weekly regimens, which should be investigated further with a clinical trial.

Head-to-head comparison of multi-dose oritavancin and dalbavancin for complicated infections: A propensity score-matched analysis

BackgroundOritavancin and dalbavancin are long-acting lipoglycopeptide antibiotics approved for the treatment of skin and skin structure infections. Recently, they have been used for outpatient antimicrobial therapy for complicated infections. No head-to-head studies exist for this purpose. ObjectiveTo compare outcomes of patients treated with multiple doses of oritavancin or dalbavancin for complicated infections. Patients and MethodsThis was a single-centre, retrospective cohort study evaluating adult patients who received two or more doses of lipoglycopeptides for complicated infections from February 2019 through December 2022. Patients receiving oritavancin were compared to dalbavancin after propensity score-matching. The primary endpoint was clinical success at 90 days. Other endpoints included: 30-day re-admission, 30-day mortality, adverse drug reactions (ADRs), and changes in white blood cell count and inflammatory markers after the first dose. ResultsAfter exclusions and propensity score-matching, 131 matched pairs (N = 262) were included in the analysis. Most patients were receiving lipoglycopeptide therapy for osteomyelitis. There was no significant difference in clinical success at 90 days in patients who received oritavancin compared to those who received dalbavancin (99 [76%] vs. 103 [79%], respectively; P = 0.556). There was no significant difference in secondary endpoints, however, there was a trend towards higher incidence of ADRs oritavancin compared to dalbavancin (9 [7%] vs. 2 [2%], respectively; P = 0.060) which led to more treatment discontinuation. ConclusionThere was no significant difference in efficacy between multi-dose oritavancin and dalbavancin for the treatment of complicated infections. Both agents were generally well tolerated; however, dalbavancin may be better tolerated when long-term treatment is warranted.

Cost evaluation of continuation of therapy with dalbavancin compared to standard-of-care antibiotics alone in hospitalized persons who inject drugs with severe gram-positive infections.

Persons who inject drugs (PWID) are at risk for severe gram-positive infections and may require prolonged hospitalization and intravenous (IV) antibiotic therapy. Dalbavancin (DBV) is a long-acting lipoglycopeptide that may reduce costs and provide effective treatment in this population. This was a retrospective review of PWID with severe gram-positive infections. Patients admitted from January 1, 2017, to November 1, 2019 (standard-of-care [SOC] group) and from November 15, 2019, to March 31, 2022 (DBV group) were included. The primary outcome was the total cost to the healthcare system. Secondary outcomes included hospital days saved and treatment failure. A total of 87 patients were included (37 in the DBV group and 50 in the SOC group). Patients were a median of 34 years old and were predominantly Caucasian (82%). Staphylococcus aureus (82%) was the most common organism, and bacteremia (71%) was the most common type of infection. Compared to the SOC group, the DBV group would have had a median of 14 additional days of hospitalization if they had stayed to complete their therapy (P = 0.014). The median total cost to the healthcare system was significantly lower in the DBV group than in the SOC group ($31,698.00 vs $45,093.50; P = 0.035). The rate of treatment failure was similar between the groups (32.4% in the DBV group vs 36% in the SOC group; P = 0.729). DBV is a cost-saving alternative to SOC IV antibiotics for severe gram-positive infections in PWID, with similar treatment outcomes. Larger prospective studies, including other patient populations, may demonstrate additional benefit.

Oritavancin as sequential therapy for Gram-positive bloodstream infections

BackgroundOritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE).MethodsWe conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance.ResultsOverall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5–17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient).ConclusionsThe use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.

Therapeutic Drug Monitoring of Dalbavancin in Real Life: A Two-Year Experience.

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42-48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment.

Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection in Patients With Obesity or Diabetes: A Subgroup Analysis of Pooled Phase 3 Clinical Trials.

We assessed the efficacy and safety of dalbavancin, a long-acting lipoglycopeptide with activity against Gram-positive pathogens, for treatment of acute bacterial skin and skin structure infections (ABSSSI) in patients with high body mass index (BMI) and/or diabetes. Data from two phase 3 trials of dalbavancin (1000 mg intravenous [IV], day 1; 500 mg IV, day 8) versus comparator and one phase 3b trial of single-dose (1500 mg IV, day 1) versus 2-dose (1000 mg IV, day 1; 500 mg IV, day 8) dalbavancin in adults with ABSSSI were pooled and summarized separately by baseline BMI and diabetes status. Clinical success at 48 to 72 hours (≥20% reduction in lesion size), end of treatment ([EOT] day 14), and day 28 was evaluated in the intent-to-treat (ITT) and microbiological ITT (microITT) populations. Safety data were reported in patients who received ≥1 dose of study drug. In the dalbavancin ITT population (BMI, n = 2001; diabetes, n = 2010), at 48 to 72 hours (and EOT) clinical success was achieved in 89.3% (EOT, 90.9%) of patients with normal BMI and 78.9% to 87.6% (EOT, 91.0% to 95.2%) of patients with elevated BMI. Clinical success after dalbavancin treatment was achieved in 82.4% (EOT, 90.8%) of patients with diabetes and 86.0% (EOT, 91.6%) of patients without diabetes. Similar trends were observed for infections due to methicillin-resistant Staphylococcus aureus or methicillin-susceptible S aureus (microITT population). Dalbavancin is effective, with sustained clinical success rates in patients with obesity or diabetes, with a similar safety profile across patient groups.

Dalbavancin and moleculight in the COVID-19 pandemic

The COVID-19 Pandemic, which began in March 2020, and its associated surges, had an immense impact on our medical staff and their ability to perform their daily duties. The COVID-19 Pandemic necessitated hospital modifications, including the expansion of the Emergency Department, ICU, and Isolation units. The overwhelmed staff and overburdened ER and ICU required adjustments to deal with the Inpatient impasse. For example, temporary patient care rooms needed to be set up for the overflow of patients. The tsunami of the Pandemic almost overwhelmed our hospital. With the challenges presented to our hospital during the Pandemic, we needed a fresh perspective to our multi-disciplinary approach. Thus, we fathomed that the use and cost-effectiveness of both Dalbavancin, a long-acting lipoglycopeptide antibiotic combined with the diagnostic Moleculight Imaging Device would be a sound decision. We hypothesized that with the use of this cost-effective antibiotic in conjunction with the use of the Moleculight Imaging Device, with its fluorescent imaging, we could detect the presence of bacteria and assist our wound treatment and decision-making. A shift in patients from the Emergency Room/Inpatient Department to the Outpatient Department/Wound Care Center was made possible with the use of these two novel products.

Role of Oritavancin in the Treatment of Infective Endocarditis, Catheter- or Device-Related Infections, Bloodstream Infections, and Bone and Prosthetic Joint Infections in Humans: Narrative Review and Possible Developments.

Oritavancin is a long-acting lipoglycopeptide with in vitro activity against Gram-positive pathogens, as well as good bactericidal activity and sterilisation ability in biofilm. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, such as for vancomycin resistant enterococci (VRE), deep-seated infections including those involving prosthetic material and invasive infections. The aim of this work is to review the uses of oritavancin outside of ABSSSI, focusing on its real-life applications on infective endocarditis, catheter- or device-related infections, bloodstream infections, and bone and prosthetic joint infections in humans, as well as possible future applications. We performed a narrative review, collecting the literature published between 1 December 2002 and 1 November 2022 on PubMed and the Cochrane Library using the term 'oritavancin'. Available studies have shown how effective it is in different settings, suggesting an opportunity for step-down strategies or outpatient management of infections requiring a long duration of antibiotic treatment. So far, evidence is still scarce, and limited to a few studies and case reports, mostly focusing on Staphylococcus aureus as the major isolate. Concerns about fluid intake for dilution and interaction with coagulation markers also need to be taken into account. Further studies are required in order to assess the safety and effectiveness of Oritavancin in vascular, prosthetic, or device-related infections, as well as in resistant Gram-positive bacteria or enterococcal infections.

A HPLC-DAD method to facilitate large-scale therapeutic drug monitoring of dalbavancin

Dalbavancin, a long-acting lipoglycopeptide antibiotic targeting susceptible Gram-positive bacteria, is WHO critically important antibiotic, increasingly used in critical situations such as osteoarticular infections. To ensure its effectiveness and its safety, the therapeutic drug monitoring (TDM) of dalbavancin is strongly recommended. In the absence of an available minimum inhibitory concentration (MIC), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommends a breakpoint of 0.125 mg/L for Staphylococcus aureus, corresponding to a trough target concentration of 25 mg/L. Nowadays, the TDM is usually performed using a high-performance liquid chromatography (HPLC) method coupled with a tandem mass spectrometry. However, this expensive and specialized equipment and reagents may be difficult to acquire for non-specialized laboratories. The use of HPLC coupled with diode array detector (DAD) facilitates TDM with a lower cost, while preserving the reliability of the results. Our aim was to provide a sensitive and specific method, relying on HPLC-DAD for extending the TDM of dalbavancin beyond non-specialized labs, therefore maximizing its efficiency and Benefit/risk ratio. Our method complied with the European Medicines Agency guidelines of bioanalytical validation. Irrespective of the concentrations of dalbavancin, the coefficient of variation < 10% confirmed the reliability of this analytical method, with a calibration curve ranging from 5 to 100 mg/L. No interferences nor carryover was observed. Our HPLC-DAD method, combined with a simple extraction, provides a widely usable, inexpensive and easy-to-implement new asset for the TDM of Dalbavancin.

1774. Impact of Dalbavancin as Step-Down or Salvage Therapy on Duration of Hospitalization Among People Who Inject Drugs

Abstract Background A well-known clinical dilemma complicating the management of infections in people who inject drugs (PWID) is the restriction of outpatient parenteral antimicrobial therapy. As a result, PWID experience prolonged hospitalizations to complete parenteral antimicrobial courses inpatient. This strategy is also associated with increased rates of patient-directed discharge (PDD). Dalbavancin, a long-acting lipoglycopeptide, serves two unique roles in this population: step-down therapy to decrease inpatient length of stay once clinically stable and salvage therapy in the setting of imminent PDD. Methods This retrospective review of PWID from November 2019 through October 2021 identified patients in which on- or off-label dalbavancin could be considered. Day of hypothetical dalbavancin administration was determined when both ≥7 days of therapy and ≥48 hours of clinical stability (non-critical unit, afebrile, resolved leukocytosis, and source control or negative blood cultures) were completed. Included patients had ≥7 days of therapy remaining at time of hypothetical dalbavancin administration. A one-time dalbavancin dose was considered to provide up to 14 days of antimicrobial coverage. Patients were included in either the step-down cohort (completed entire parenteral antimicrobial course inpatient) or salvage therapy cohort (PDD prior to completing course). The number of potentially preventable inpatient days with dalbavancin and readmissions due to infection progression were assessed in each cohort, respectively. Results Nineteen patients were identified as potential dalbavancin candidates. In the step-down cohort (n=11) a one-time dalbavancin dose prevented a maximum of 146 inpatient days. In the salvage cohort (n=8), hypothetical dalbavancin administration at time of PDD could have prevented six readmissions due to infection progression, associated with 36 additional inpatient days. Conclusion Inpatient administration of dalbavancin may bridge treatment disparities experienced by PWID by reducing unnecessary inpatient days for parenteral antibiotic administration and by preventing hospital readmissions attributable to inadequate antimicrobial course. Disclosures All Authors: No reported disclosures.

1660. Dalbavancin Utilization Registry Investigating Value and Effectiveness (DRIVE): Outcomes Report on Real-World Use

Abstract Background Dalbavancin (dalba), a long-acting lipoglycopeptide approved by the US FDA and EMA for acute bacterial skin and skin structure infections (ABSSSI) has potent activity against Gram-positive pathogens including MRSA. We describe the real-world use of dalba in patients with ABSSSI, bloodstream infections (BSI), bone and joint infection (BJI), or other infections (OI) from a retrospective registry study of dalba. Methods Dalbavancin Utilization Registry Investigating Value and Effectiveness (DRIVE) was a phase 4 observational, multicenter, retrospective cohort study of the real-world use of dalba in adults geographically spread across the US. Patients were treated entirely at the physicians’ discretion. Data were collected from 25 Mar 2017–27 Nov 2018 and included patient demographics, diagnosis, microbiology, antibiotic use, clinical outcome, and safety until 60 days after last dalba dose. A post hoc analysis applied definitions for clinical success and failure similar to the dalba phase 3 clinical trials. Results The Safety Population comprised 1168 patients treated at 31 healthcare sites. Of 957 evaluable patients, 815 (85.2%) had ABSSSI, 48 (5.0%) had BSI, 87 (9.0%) had BJI, and 7 (0.7%) had OI. Clinical success was achieved in 91.7%, 89.6%, 86.2%, and 100% of patients with ABSSSI, BSI, BJI, and OI, respectively (Figure 1). Median cumulative dose of dalba for the index infection was 1500 mg for all categories, most commonly as 1 infusion (86.7% ABSSSI, 63.1% BSI, 41.4% BJI, 37.5% OI; Figure 2). 36.9% of patients with BSI and 58.6% with BJI received ≥ 2 infusions. Most patients were treated as outpatients (87.8%, 76.9%, 89.2%, 100%, with ABSSSI, BSI, BJI, and OI, respectively). Mean (SD) total cost of care associated with dalba use (medications, hospital stay, surgeries/procedures) was 5261.2 (1604.55), 7710.5 (7144.1), 8393.5 (5296.8), and 6305.8 (3338.1) USD for patients with ABSSSI, BSI, BJI, and OI, respectively. Adverse events evaluated as possibly related to dalba were reported in 33/1168 (2.8%) patients: 29 (2.9%) with ABSSSI, and 4 (3.6%) with BJI. Conclusion Dalba demonstrated high rates of clinical success and safety in the real-world setting when used to treat patients for suspected or confirmed Gram-positive infections. Disclosures Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|La Jolla: Honoraria|Melinta: Advisor/Consultant|Paratek: Honoraria|Regeneron: Honoraria Kerry O. Cleveland, MD, AbbVie: Honoraria|Cumberland: Honoraria|Merck: Honoraria|Pfizer: Honoraria Pedro L. Gonzalez, MD, MT, AbbVie: Employee of AbbVie at the time of study conduct and analysis.|AbbVie: Stocks/Bonds|Becton Dickinson: Employee Urania Rappo, MD, AbbVie: Employee of Allergan, before its acquisition by AbbVie, at the time of study conduct and analysis|BiomX: Employee Todd Riccobene, PhD, AbbVie: Employee|AbbVie: Stocks/Bonds Rosie D. Lyles, MD, MHA, MSc, AbbVie: AbbVie Employee|AbbVie: Stocks/Bonds.

Dalbavancin During the COVID-19 Pandemic.

The COVID-19 pandemic, which started in March of 2020, and its associated surges have had an immense impact on the ability of medical staff to perform their daily activities. Thus, we sought to direct patients who had gram-positive Acute Bacterial Skin and Skin Structure Infections (ABSSSI) to our Outpatient Department/Wound Care Center for treatment. We met the challenge of the pandemic by shifting care in the treatment of ABSSSI using a new antibiotic delivery system. We examined the use and cost-effectiveness of Dalbavancin, a unique long-acting lipoglycopeptide antibiotic that is used in the treatment of acute bacterial skin and skin structure infections, during the COVID-19 pandemic. A total of 631 patients were treated in the Outpatient Department/Wound Care Center, with re-evaluation at the Wound Care Center on Day 3 post-infusion. The primary test of cure or major improvement was based on a 4- to 6-week re-assessment by the Wound Care Center Faculty (i.e., Podiatric, Vascular, Plastics, and Infectious Diseases). Treatment effectiveness was determined by examining documentation at follow-up. We also looked at the number of Outpatient Department treatments at the Wound Care Center for the periods 2018-2019 and 2020-2021. The shift of patients from the Emergency Department/Inpatient Department to the Outpatient Department/Wound Care Center was made possible by the use of the novel, streamlined, safe, Food and Drug Administration (FDA)-approved, well-tolerated antibiotic Dalbavancin. Dalbavancin is not prescribed for gram-negative infections, or for random prescribing, contamination, colonization, or prophylaxis. Dalbavancin has a low infusion reaction, low toxicity, long half-life, and low incidence of adverse reactions. Use of this medication was helpful for decreasing the inpatient burden in our facility.

Emergency department care of ABSSSI with dalbavancin infusion, direct discharge, and outpatient telemedicine follow up: a study protocol

Novel therapeutic strategies such as the long-acting lipoglycopeptide antibiotics allow for the treatment and discharge of selected emergency department (ED) patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI), who require intravenous antibiotics and would otherwise be hospitalized. The COVID-19 pandemic highlighted the need to develop strategies that may reduce hospitalization. The telehealth approach has shown success in remote management of cellulitis patients and could aid in the remote follow up of overall ABSSSI patients. This article describes a study protocol for the telemedicine follow up of patients diagnosed with ABSSSI in the ED, requiring intravenous treatment, receiving a single dalbavancin dose, and directly discharged. A telehealth system for remote follow up is evaluated as well as the possible inclusion of point-of-care ultrasound for the appropriate diagnosis of ABSSSI. The study will be conducted in compliance with regulatory requirements; and all collected data will be kept strictly confidential and in accordance with all relevant legislation on the control and protection of personal information. Dissemination of the study protocol may help increasing knowledge and awareness on this topic, with the aim of optimizing patient management, reducing hospitalization and lower the impact on healthcare associated costs.

Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections.

BackgroundDalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs).MethodsWe conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW).ResultsOverall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333–2.32).ConclusionsThis study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Evaluating the Use of Dalbavancin for Off-Label Indications.

(1) Background: Dalbavancin is a long-acting lipoglycopeptide antibiotic approved for skin and soft-tissue infections. Post-marketing experience suggests dalbavancin is being used for off-label indications that normally require long-term intravenous (IV) antibiotics; however, data assessing this off-label usage are limited. The purpose of this study was to evaluate the real-world efficacy, safety, and financial impact of off-label dalbavancin use. (2) Methods: This is a retrospective, observational study conducted within a 4-hospital health system. Adult patients who received dalbavancin from January 2018 to January 2021 for an off-label indication were included. The primary outcome was clinical success at 90 days. Secondary outcomes included safety (nephrotoxicity and hepatotoxicity). A pharmacoeconomic analysis was performed by comparing the cost of dalbavancin to the anticipated cost of patient stay if standard IV therapy was given. (3) Results: Forty-eight patients met study criteria. Indications included osteomyelitis (54%), endocarditis (23%), bacteremia (15%), and prosthetic joint infection (8%). The predominant organism was S. aureus (60%), with 42% caused by methicillin-resistant S. aureus. Overall, 41 (85%) patients achieved clinical success at 90 days, including 85% with osteomyelitis, 82% with endocarditis, and 86% with bacteremia. There were no instances of nephrotoxicity or hepatotoxicity. Estimated cost avoidance per patient was USD 5313 and USD 1683 if traditional IV therapy would have been completed in the hospital and skilled nursing facility, respectively. (4) Conclusion: Dalbavancin was associated with a relatively high success rate for the treatment of off-label indications and may be a cost-effective alternative to traditional IV antibiotic therapy.

Oritavancin (KIMYRSA™) in acute bacterial skin and skin structure infections: a profile of its use in the USA

Oritavancin, a long-acting lipoglycopeptide, is the first single-dose intravenous (IV) antibacterial therapy approved in the USA for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible isolates of designated gram-positive microorganisms. With its well-established antibacterial activity, efficacy and safety profiles, a new IV formulation of oritavancin (KIMYRSA™) has been developed to offer a more convenient treatment option for patients with ABSSSIs. Relative to the originally approved IV formulation of oritavancin (ORBACTIV®), the new IV formulation has better diluent compatibility, simpler preparation steps, a shorter infusion time of 1 h in a lower infusion volume of 250 mL. Approval was based on results of a phase 1 study in which pharmacokinetic similarity between the two IV formulations of oritavancin was demonstrated in patients with ABSSSIs. The tolerability profile of the new IV formulation of oritavancin revealed no new safety signals.

108. Evaluation of the Impact of Dalbavancin Usage on Clinical Outcomes, Cost-Savings, and Adherence at a Large Safety Net Hospital

BackgroundDalbavancin is a long-acting second-generation lipoglycopeptide antibiotic with potent activity against Gram-positive organisms. Dalbavancin is currently FDA approved for acute bacterial skin and soft tissue infections (ABSSTIs). Growing evidence suggests that patients can be successfully treated with dalbavancin for indications outside of skin and soft tissue infections which include bacteremia and osteomyelitis (OM) with significant cost savings and reduced length of stay. We developed a protocol for the use of dalbavancin in patients who required intravenous antibiotics for serious bacterial infections but did not qualify for outpatient parenteral antibiotic therapy (OPAT). During the COVID-19 pandemic, we expanded the protocol to reduce the amount of clinical contact required for all patients.MethodsIn this retrospective observational study, we reviewed all patients that received at least one dose of dalbavancin in either inpatient or outpatient setting at Parkland Hospital from July 2019 through February 2021. Patient demographics, type of infection, and rationale for dalbavancin were collected at baseline. Clinical response was measured by avoidance of Emergency Department (ED) visits or hospital readmission at 30, 60, and 90 days. In addition, a separate analysis was conducted to estimate hospital, rehabilitation, or nursing home days saved based on their diagnosis and projected length of treatment. ResultsTwenty-eight patients (24 inpatient, 4 outpatient) were included in the study. The majority were uninsured (89%), homeless (64%), or had active intravenous drug use (IDU) (60%). Indications for use included SSTI (42.9%), bacteremia (64.3%), and OM (42.6%). Clinical failure was observed in 4 (14%), 1 (3.5%), and 2 (7.1%) patients at 30, 60, or 90 days (respectively). Nonadherence to medical recommendations, lack of source control, and ongoing IDU increased risk of returning to the hospital. Dalbavancin use saved a total of 381 days of inpatient/rehab/facility stay. Baseline Characteristics of Patients Types of Infections and Microbiology ED Visit or Readmissions at 30, 60, or 90 DaysConclusionDalbavancin showed similar rates of success with improved length of stay and cost savings. The use of long acting lipoglycopeptides are desirable alternatives to traditional OPAT for patients that otherwise would not qualify for OPAT or desire less hospital contact.Disclosures All Authors: No reported disclosures

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

BackgroundPreliminary 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.MethodsThis 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.ResultsA 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).ConclusionDalbavancin administered as a two-dose regimen is a safe and effective option for the treatment of osteomyelitisDisclosures Dustin R. Carr, PharmD, BCPS, BCIDP, AAHIVP, Merck (Speaker's Bureau) Thomas L. Walsh, MD, Accelerate Diagnostics (Other Financial or Material Support, speaking fees)

234. Dalbavancin versus Outpatient Parenteral Antimicrobial Therapy with Vancomycin for Treatment of Bone and Joint Infections in a Veteran Population

BackgroundDalbavancin is a long-acting lipoglycopeptide with broad gram-positive activity. A long half-life makes it an attractive treatment option for bone and joint infections (BJI). Previous studies have demonstrated efficacy of dalbavancin in the treatment of BJI. Based on these studies, our institution established a protocol for using dalbavancin as an alternative to IV antibiotics via PICC line. MethodsChart review was performed to compare outcomes of patients who were treated with dalbavancin versus vancomycin for BJI from 8/2017 –7/2020. Patients that received two doses of dalbavancin for BJI were compared with patients who received OPAT with vancomycin during the same time period. Patients were excluded if they were bacteremic or received dalbavancin for another indication. Data was collected from the Veterans Health Administration’s Corporate Data Warehouse and retrospective chart review. No statistical analyses were performed due to the descriptive nature of this study.ResultsA total of 59 patients were included; 25 received dalbavancin and 34 received vancomycin. Relevant differences in baseline characteristics included a higher proportion of patients with osteomyelitis (88% vs 74%) and refractory infection (64% vs 44%) in the dalbavancin group. More patients in the dalbavancin group (38% vs 24%) were readmitted for the same infection within one year, required (29% vs 21%) additional surgical intervention, and had increased CRPH on follow-up labs (32% vs 3%). Dalbavancin use likely expedited discharge in at least 5 cases where vancomycin levels were not therapeutic. No significant adverse effects due to dalbavancin were noted, aside from one patient with an increase in serum creatinine. In the vancomycin group, 8 patients changed antibiotics due to adverse effects or difficulty managing levels and 3 patients had ED visits for PICC line care.ConclusionDalbavancin may be a safe PICC-sparing treatment for BJI, particularly in cases where compliance is of concern, or there are logistical or tolerability issues with vancomycin. Our findings do raise concern for worse outcomes with dalbavancin, but the small sample size, difference in baseline characteristics between groups and descriptive nature of the study preclude any conclusions from being drawn. Disclosures All Authors: No reported disclosures