Comparing the Intravenous Treatment of Skin Infections in Children, Home Versus Hospital
Condition: Cellulitis
MeSH terms: Cellulitis
Study type: Interventional

Summary: 
      Many children every year present to the Emergency Department (ED) at The Royal Children's
      Hospital (RCH) with cellulitis (skin infection). If it is mild, the children can go home with
      oral antibiotic treatment. If it is complicated and severe, these children are admitted to
      hospital for intravenous (IV, through a drip) antibiotic treatment. There is a middle group
      with uncomplicated moderate/severe cellulitis who require IV antibiotics but who are not
      acutely unwell. In order to determine whether it is just as effective for children with
      uncomplicated moderate to severe cellulitis to receive antibiotic treatment at home (via
      Hospital-In-The-Home) as it is to receive antibiotic treatment in hospital, there is a need
      to conduct a larger study and randomly assign children to receive either HITH or hospital
      ward care.

      The primary research question to be addressed is:

      In children with moderate/severe uncomplicated cellulitis, is the failure rate at 2 days
      following the first dose of antibiotic non-inferior for children treated with IV antibiotics
      at home compared to the failure rate at 2 days following the first dose for children treated
      with IV antibiotics in hospital?
    

Detailed description: 
      INTRODUCTION AND BACKGROUND Adults with cellulitis commonly have IV antibiotics administered
      as outpatients, whereas most children are admitted to hospital. Based on a small amount of
      literature, it is known that some children with moderate/severe cellulitis can also be safely
      be treated at home.This study will include all children with uncomplicated moderate/severe
      cellulitis and will therefore demonstrate whether all children with uncomplicated
      moderate/severe cellulitis can be effectively treated at home.

      If the study demonstrates that it is just as effective to treat these children in the home,
      it has the potential to impact on the child and family's quality of life (QOL) as well as
      hospital resource management.

      PRIMARY OBJECTIVE To compare the failure rate of IV antibiotic treatment of children treated
      at home (iv ceftriaxone) with those treated in hospital (iv flucloxacillin) in the first 2
      days of treatment following the first dose given in the ED in children with moderate/severe
      cellulitis (Moderate/severe: defined in this study, as those assessed by ED doctor to need iv
      antibiotics)

      SECONDARY OBJECTIVES

      To compare:

      Time to no progression of cellulitis Time to discharge: number of days (including fractions
      of days) from the time of arrival in ED to the time the patient no longer needs
      hospital-based interventions/care, whether in hospital or at home Readmission rate
      Representation to ED Length of stay in ED Duration of IV antibiotics Rates of IV cannula
      needing at least one resiting Complications of cellulitis: development of abscess requiring
      drainage after starting IV antibiotics, bacteraemia Adverse events

      Microbiology:

        -  Rate of ceftriaxone susceptibility in bacteria isolated from a nasal or skin swab of the
           affected area

        -  Rate of S. aureus nasal carriage (methicillin-sensitive and methicillin-resistant)
           collected within 48 hours, after 7-14 days, 3 months and 1 year after starting
           antibiotics

        -  Rate of resistant bacteria present in stool samples collected within 48 hours, after
           7-14 days, 3 months and 1 year after starting antibiotics. Rates of clinical infection
           with resistant organisms up to 1 year after starting antibiotics

      Differential effect of narrow spectrum (flucloxacillin) and broad spectrum (ceftriaxone) on
      the nasal and gastrointestinal microbiome from nasal swabs and stool samples collected within
      48 hours, after 7-14 days, 3 months and 1 year after starting antibiotics.

      Costs of hospital versus HITH treatment: including costs of beds, consumables, nursing and
      medical time, and overheads including administrative time, information technology, use of
      hospital cars Quality of life (QOL) indicators Clinical assessments of cellulitis in terms of
      presence of systemic features, surface area affected (longest length axis multiply by the
      longest perpendicular axis measured in cm2), severity of swelling (judged by clinician as any
      one of the following: mild, moderate or severe), intensity of erythema (judged by clinician
      from a scale of 0 to 5, 0=no erythema and 5=severe and whether the function of the affected
      area is impaired

      STUDY METHODOLOGY ED clinicians (senior doctors, junior doctors or nurse practitioners) will
      identify patients with moderate/severe cellulitis presenting to RCH ED, at the point of
      triage or during clinical assessment. The consent will be for randomization, data collection
      and follow up which is not part of routine practice. Randomisation to the location of
      treatment is the essential difference from normal clinical practice. Where parents do not
      give consent, the ED clinician will make the decision on where the patient should be treated.

      INTERVENTIONS Although in this proposed study the intervention is treating children at home,
      currently, based on the prospective observational study, 50% of children with uncomplicated
      moderate/severe cellulitis are already being sent home by ED clinicians to receive daily IV
      antibiotics at home. The only new intervention is the randomisation process which will
      provide a high level of evidence for this practice which has become a standard practice in
      ED. The researcher or ED clinician will have access to randomization software and perform the
      randomisation process. Patients who are randomised to HITH will be prescribed iv ceftriaxone
      (50mg/kg once daily) as per current practice and those randomised to the ward will be
      prescribed iv flucloxacillin (50mg/kg 6 hourly). On insertion of the IV cannula, the ED
      clinician will obtain a blood culture. If there is skin breakdown, a skin swab would be done
      as per routine clinical practice. Prior to commencing IV antibiotics. In addition, the
      researcher or ED clinician will ask parents to take 2 photos of the cellulitis area using
      their own camera/phone (if available) after the affected area is demarcated with indelible
      ink with a tape measure placed along side the area affected. This will be helpful for the
      reviewing doctor the following day to judge whether there is an improvement.

      The first dose of antibiotics will be commenced in ED. For children assigned to hospital ward
      treatment, the child will be transferred to the ward and the IV infusion continued. Children
      assigned to the HITH will complete their first dose in ED before going home. The management
      after this point will be as per usual practice. The responsible ward doctor will review and
      make all management decisions for patients admitted to the ward whereas the HITH registrar
      will review the patients on HITH. The research assistant (RA) (a paediatric registrar) will
      meet with the child and their parent(s) within 24 hours of consent being obtained to answer
      any further questions parents or participants may have about the study.

      Currently, there are no guidelines on when to start IV antibiotic in cellulitis. The
      investigators' recommendation is provided under section 'Inclusion criteria' and this
      reflects consensus among RCH ED clinicians. Some patients who did not require IV antibiotics
      may be recruited but they will exist in both groups.

      A nasal swab and stool sample will be requested at four different time points: 1) within 48
      hours of the first antibiotic dose; 2) 7-14 days after starting antibiotics; 3) 3 months
      after starting antibiotics; and 4) 1 year after starting antibiotics. At each time point,
      additional information will be collected: previous overseas travel, previous hospital
      admissions, household member who has been admitted to hospital overseas, other antibiotic
      use, other infections, medical visits or hospital admissions. These samples are optional and
      do not affect participation in the study.

      As per normal practice, patients will be switched to oral therapy after 2-4 days of IV
      antibiotics, when there is clinical improvement of the cellulitis. Based on the current
      prospective study, both HITH patients and ward patients are switched to oral antibiotics when
      there is a reduction in fever, swelling, erythema and improvement of function of affected
      area (eg. Previously limping, now walking). Once changed to oral antibiotics (as per RCH
      clinical practice guidelines; cephalexin 25mg/kg 6 hourly, total dose may be combined and
      divided to twice daily), patients are usually discharged from hospital care and normally not
      followed up any further in hospital. In this study, the investigators are offering all
      participants a follow up in clinic 7-14 days (by the RA who is a paediatric registrar) after
      discharge from hospital. Parents will be requested to bring a stool sample from the patient
      to the clinic review but this is not mandatory.
    

Intervention name(s): Home; Ward; ceftriaxone; flucloxacillin
Intervention type(s): Other; Other; Drug; Drug
Intervention description(s): The main intervention is for children with uncomplicated cellulitis to remain at home throughout the period of intravenous treatment but as it is not feasible to administer flucloxacillin four times a day by the Hospital-In-The-Home team, once daily ceftriaxone is the most ideal antibiotic to be given to this group; Admission to a hospital based ward; 50mg/kg once daily; 50mg/kg 6 hourly
Intervention MeSH terms: Ceftriaxone; Floxacillin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment