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:

• Male or female patients birth to 17 years (inclusive)

• A clinical picture compatible with Acute Bacterial Skin and Skin StructureInfections (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:

• 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

• 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 surgicalintervention

• Major cutaneous abscess characterized as a collection of pus within the dermis ordeeper that is accompanied by erythema, edema and/or induration which i. requiressurgical incision and drainage, and ii. is associated with cellulitis such that thetotal affected area involves at least 35 cm2 of erythema, or total affected area oferythema is at least BSA (m2) x 43.0 (cm2/m2), OR iii. alternatively, involves thecentral face and is associated with an area of erythema of at least 15 cm2 b.Surgical site or traumatic wound infection characterized by purulent drainage withsurrounding erythema, edema and/or induration which occurred within 30 days afterthe trauma or surgery and is associated with cellulitis such that: i. the totalaffected area involves at least 35 cm2 of erythema, or total affected area oferythema is at least BSA (m2) x 43.0 (cm2/m2), OR ii. alternatively, involves thecentral face and is associated with an affected area of at least 15 cm2 c.Cellulitis, defined as a diffuse skin infection characterized by spreading areas oferythema, edema and/or induration and: i. is associated with erythema that involvesat 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 isassociated with an affected area of at least 15 cm2 5. In addition to therequirement for erythema, all patients are required to have at least two (2) of thefollowing signs of ABSSSI: a. Purulent drainage/discharge b. Fluctuance c.Heat/localized warmth d. Tenderness to palpation e. Swelling/induration

• In patients age birth to < 3 months, each patient must meet the followinginclusion criteria to be enrolled in this study.

1. Male or female patients from birth to < 3 months of age, includingpre-term neonates (gestational age ≥ 32 weeks)
2. A clinical picture compatible with an ABSSSI suspected or confirmed to becaused by Gram-positive bacteria, including MRSA. OR Suspected or confirmed sepsis including any of the following clinicalcriteria:
3. Hypothermia (<36°C) OR fever (>38.5°C)
4. Bradycardia OR tachycardia OR rhythm instability
5. Hypotension OR mottled skin OR impaired peripheral perfusion
6. Petechial rash
7. New onset or worsening of apnea episodes OR tachypnea episodes ORincreased oxygen requirements OR requirement for ventilation support
8. Feeding intolerance OR poor sucking OR abdominal distension
9. Irritability
10. Lethargy
11. Hypotonia
12. In addition, patients must meet at least one of the following laboratorycriteria: a. White blood cell count ≤4.0 × 10^9/L OR ≥20.0 × 10^9/L b, Immature tototal neutrophil ratio >0.2 c. Platelet count ≤100 × 10^9/L d. C-reactiveprotein (CRP) >15 mg/L OR procalcitonin ≥ 2 ng/mL e. Hyperglycemia ORHypoglycemia f. Metabolic acidosis
13. Infections must be of sufficient severity to merit hospitalization andparenteral antibiotic therapy. These infections may include:
14. Cutaneous or subcutaneous abscess
15. Surgical site or traumatic wound infection
16. Cellulitis, Erysipelas
17. Omphalitis
18. Impetigo and bullous impetigo
19. Pustular folliculitis
20. Scarlet fever
21. Staphylococcal scalded skin syndrome
22. Streptococcal toxic shock syndrome
23. Erythematous based-erosion
24. Other infections originating in the skin or subcutaneous tissue andassociated with signs and symptoms of sepsis as defined in InclusionCriterion 2.
25. Patients must be expected to survive with appropriate antibiotic therapyand appropriate supportive care throughout the study.

Exclusion Criteria:

1. Patients age 3 months to 17 years: Clinically significant renal impairment, definedas calculated creatinine clearance of less than 30 mL/min. (calculated by theSchwartz "bedside" formula). Patients birth to < 3 months of age: Moderate or severerenal impairment defined as serum creatinine ≥ 2 times the upper limit of normal (×ULN) for age OR urine output < 0.5 mL/kg/h (measured over at least 8 hours prior todosing) OR requirement for dialysis.

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

3. Treatment with an investigational drug within 30 days preceding the first dose ofstudy medication.

4. Patients with sustained shock defined as systolic blood pressure < 90 mm Hg inchildren ≥ 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 adequatefluid resuscitation, with evidence of hypoperfusion or need for sympathomimeticagents to maintain blood pressure.

5. More than 24 hours of any systemic antibacterial therapy within 96 hours beforerandomization. EXCEPTION: Microbiological or clinical treatment failure with asystemic antibiotic other than IV study drug that was administered for at least 48hours. Failure must be confirmed by either a microbiological laboratory report ordocumented worsening clinical signs or symptoms.

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

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

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

9. Venous catheter entry site infection.

10. Infections involving diabetic foot ulceration, perirectal abscess or a decubitusulcer.

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

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

13. Patients whose skin infection is the result of having sustained full or partialthickness burns.

14. Patients age 3 months to 17 years, with uncomplicated skin infections such assuperficial/simple cellulitis/erysipelas, impetiginous lesion, furuncle, or simpleabscess that only requires surgical drainage for cure. Patients birth to < 3 monthsof age may be enrolled if they have uncomplicated skin infections of sufficientseverity to require hospitalization and parenteral antibiotic therapy.

15. Patients age 3 months to 17 years: Concomitant condition requiring any antibiotictherapy that would interfere with the assessment of study drug for the conditionunder study.

16. Sickle cell anemia

17. Cystic fibrosis

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

19. Patients who are placed in a hyperbaric chamber as adjunctive therapy for theABSSSI.

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

21. Medical conditions in which chronic inflammation may preclude assessment of clinicalresponse to therapy even after successful treatment (e.g., chronic stasis dermatitisof the lower extremity).

22. Immunosuppression/immune deficiency, including hematologic malignancy, recent bonemarrow 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 daysprior 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 currentacquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count.

23. Known or suspected hypersensitivity to glycopeptide antibiotics, betalactam agents,aztreonam, or cephalosporins.

24. Patients with a rapidly fatal illness, who are not expected to survive for 3 months.

25. Positive urine (or serum) pregnancy test at screening (post-menarchal females only)or after admission (prior to dosing).

26. Pregnant or nursing females; sexually active females of childbearing potential whoare unwilling or unable to use adequate contraceptive precautions. Female patientsto have pregnancy testing are those who are at least 10 years old with menarcheand/or thelarche (beginning of breast development).