Hospital Avoidance Strategies for ABSSSI

This study seeks to establish the feasibility and acceptability of an alternative treatment
strategy for uncomplicated acute bacterial skin and skin structure infection (ABSSSI) in the
Barnes Jewish Hospital (BJH) Emergency Department (ED) focusing on hospital admission
avoidance using single-dose, long-acting antimicrobial therapy complemented by close
follow-up in the ambulatory setting. The extended half-life of these new antimicrobials
(dalbavancin, oritavancin) allows for an effective treatment course of >7 days with a single
dose, which is the accepted duration for which ABSSSI is usually treated with daily doses of
other intravenous or oral antimicrobials. The investigators believe that such an approach
will conserve hospital resources by reducing admissions for uncomplicated ABSSSI while
delivering comparable if not superior care for this disease, allowing optimal utilization of
BJH inpatient beds for other serious medical conditions requiring inpatient care. The
investigators believe this novel alternative approach will allow hospitals such as BJH to
more cost-effectively and efficiently manage ABSSSI patients. This study will reduce the
number of >2 midnight observation admissions to BJH for ABSSSI, thereby improving inpatient
capacity to care for patients requiring >2 midnight hospital inpatient admission.

The investigators will conduct a randomized controlled trial comparing patients treated with
a single-dose of intravenous dalbavancin (an antibiotic that has been FDA-approved for the
treatment of ABSSSI and is currently being used in clinical practice in the U.S.) and
discharged home from the ED with close ambulatory care follow-up in clinic vs. patients
treated with "usual care" (hospital admission for multiple doses of intravenous vancomycin or
other antibiotic directed towards Gram-positive bacteria). Clinical outcomes, healthcare
utilization, hospital costs, and patient satisfaction will be evaluated.

Inclusion Criteria:

- Adult (age ≥18 years)

- Diagnosis of uncomplicated ABSSSI suspected to be due to Gram-positive bacteria by
treating ED clinician, with presence of the following:

1. Skin lesion size ≥75 cm2 (measured by area of erythema, edema, and/or induration)
AND

2. Signs of systemic inflammation (at least 1 of the following: WBC >12,000 or
<4,000 cells/mm3; ≥10% immature neutrophils on peripheral smear; temperature
>38.3˚C or <36˚C; heart rate >90 bpm, respiratory rate >20 bpm). Signs of
systemic inflammation not required if the patient is age >70 years, has diabetes
mellitus, or has been treated with immunosuppressive or chemotherapy in the past
90 days.

- Clinical determination by treating ED clinician that patient will need hospital
admission for the sole purpose of receiving intravenous antibiotics directed only
towards Gram-positive bacteria (e.g., vancomycin, cefazolin) to treat uncomplicated
ABSSSI

Exclusion Criteria:

- Risk for ABSSSI due to Gram-negative bacteria (neutropenia with absolute neutrophil
count <500 cells/µL, HIV or severely immunocompromised, burns, infection after trauma
or as a result of an aquatic environment, infection after skin graft)

- Any abscess requiring bedside or operative drainage

- Infection due to a vascular catheter or prosthetic device

- Infection of a diabetic foot ulcer or decubitus ulcer

- Necrotizing soft tissue infection

- Sepsis (quick SOFA score ≥2) or septic shock (requiring vasopressors to maintain mean
arterial pressure ≥65 mmHg despite resuscitation with at least 30mL/kg of IV
crystalloid within first 3 hours)

- Recent antibiotics in prior 14 days

- Hypersensitivity to glycopeptides (vancomycin, televancin, dalbavancin, oritavancin)

- Severe renal insufficiency (CrCl <30 mL/min)

- Severe hepatic insufficiency (Child-Pugh Class C)

- Pregnant or nursing