Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections in Children, Known or Suspected to be Caused by Susceptible Gram-positive Organisms, Including MRSA

Inclusion Criteria:

- A clinical picture compatible with Acute Bacterial Skin and Skin Structure Infections
(ABSSSI) suspected or confirmed to be caused by Gram-positive bacteria, including
Methicillin-resistant Staphylococcus aureus (MRSA).

- In addition to local signs of ABSSSI, the patient has at least one of the following:

1. Fever, defined as body temperature ≥ 38.4°C (101.2°F) taken orally, ≥ 38.7°C
(101.6°F) tympanically, or ≥ 39°C (102.2°F) rectally (core temperature) OR

2. Leukocytosis (WBC > 10,000 mm3) or leukopenia (WBC < 2,000 mm3) or left shift of
>10% band neutrophils

- Infection either involving deeper soft tissue or requiring significant surgical
intervention:

1. Major cutaneous abscess characterized as a collection of pus within the dermis or
deeper that is accompanied by erythema, edema and/or induration which:

1. requires surgical incision and drainage, and

2. is associated with cellulitis such that the total affected area involves at
least 35 cm2 of erythema, or total affected area of erythema is at least BSA
(m2) x 43.0 (cm2/m2), OR

3. alternatively, involves the central face and is associated with an area of
erythema of at least 15 cm2

2. Surgical site or traumatic wound infection characterized by purulent drainage
with surrounding erythema, edema and/or induration which occurred within 30 days
after the trauma or surgery and is associated with cellulitis such that i. the
total affected area involves at least 35 cm2 of erythema, or total affected area
of erythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, involves
the central face and is associated with an affected area of at least 15 cm2

3. Cellulitis, defined as a diffuse skin infection characterized by spreading areas
of erythema, edema and/or induration and i. is associated with erythema that
involves at least 35 cm2 of surface area, or surface area of erythema is at least
BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, cellulitis of the central face
that is associated with an affected area of at least 15 cm2

- In addition to the requirement for erythema, all patients are required to have at
least two (2) of the following signs of ABSSSI:

1. Purulent drainage/discharge

2. Fluctuance

3. Heat/localized warmth

4. Tenderness to palpation

5. Swelling/induration

Exclusion Criteria:

- Clinically significant renal impairment, defined as calculated creatinine clearance of
less than 30 mL/min.

- Clinically significant hepatic impairment, defined as serum bilirubin or alkaline
phosphatase greater than 2 times the upper limits of normal (ULN) for age, and/or
serum aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3
times the upper limits of normal (ULN) for age.

- Treatment with an investigational drug within 30 days preceding the first dose of
study medication.

- Patients with sustained shock defined as systolic blood pressure < 90 mm Hg in
children ≥ 10 years old, < 70 mm Hg + [2 x age in years] in children 1 to <10 years,
or < 70 mmHg in infants 3 to <12 months old for more than 2 hours despite adequate
fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents
to maintain blood pressure.

- Receipt of a systemically or topically administered antibiotic with a Gram-positive
spectrum that achieves therapeutic concentrations in the serum or at the site of the
skin infection within 14 days prior to randomization. An exception is allowed for
patients receiving a single dose of a short-acting (half-life ≤ 12 hours)
antibacterial drug prior to randomization.

- Infection due to an organism known prior to study entry to be resistant to dalbavancin
(dalbavancin minimum inhibitory concentration (MIC) greater than 0.25 ug/mL) or
vancomycin (vancomycin minimum inhibitory concentration (MIC) greater than 2 ug/mL).

- Patients with necrotizing fasciitis, or deep-seated infections that would require > 2
weeks of antibiotics (e.g., endocarditis, osteomyelitis or septic arthritis).

- Infections caused exclusively by Gram-negative bacteria (without Gram-positive
bacteria present) and infections caused by fungi, whether alone or in combination with
a bacterial pathogen.

- Venous catheter entry site infection.

- Infections involving diabetic foot ulceration, perirectal abscess or a decubitus
ulcer.

- Patient with an infected device, even if the device is removed. Examples include
infection of: prosthetic cardiac valve, vascular graft, a pacemaker battery pack,
joint prosthesis, implantable pacemaker or defibrillator, intra-aortic balloon pump,
left ventricular assist device, or a neurosurgical device such as a ventricular
peritoneal shunt, intra-cranial pressure monitor, or epidural catheter.

- Gram-negative bacteremia, even in the presence of Gram-positive infection or
Gram-positive bacteremia. Note: If a Gram-negative bacteremia develops during the
study, or is subsequently found to have been present at Baseline, the patient should
be removed from study treatment and receive appropriate antibiotic(s) to treat the
Gram-negative bacteremia.

- Patients whose skin infection is the result of having sustained full or partial
thickness burns.

- Patients with uncomplicated skin infections such as superficial/simple
cellulitis/erysipelas, impetiginous lesion, furuncle, or simple abscess that only
requires surgical drainage for cure.

- Concomitant condition requiring any antibiotic therapy that would interfere with the
assessment of study drug for the condition under study.

- Sickle cell anemia

- Cystic fibrosis

- Anticipated need of antibiotic therapy for longer than 14 days.

- Patients who are placed in a hyperbaric chamber as adjunctive therapy for the ABSSSI.

- More than 2 surgical interventions (defined as procedures conducted under sterile
technique and typically unable to be performed at the bedside) for the skin infection,
or patients who are expected to require more than 2 such interventions.

- Medical conditions in which chronic inflammation may preclude assessment of clinical
response to therapy even after successful treatment (e.g., chronic stasis dermatitis
of the lower extremity).

- Immunosuppression/immune deficiency, including hematologic malignancy, recent bone
marrow transplant (in post-transplant hospital stay), absolute neutrophil count < 500
cells/mm3, receiving immunosuppressant drugs after organ transplantation, receiving
oral steroids ≥ 20 mg prednisolone per day (or equivalent) for > 14 days prior to
enrollment, and known or suspected human immunodeficiency virus (HIV) infected
patients with a CD4 cell count < 200 cells/mm3 or with a past or current acquired
immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.

- Known or suspected hypersensitivity to glycopeptide antibiotics, beta-lactam agents,
aztreonam, or cephalosporins.