Evaluation of mild periorbital cellulitis and home‐based therapy in children—EPOCH study: A prospective single centre cohort study

Paediatric periorbital cellulitis is a common eye condition and warrants prompt management for the prevention of complications. International consensus on the approach to optimal management of children with mild periorbital cellulitis including ambulatory management is lacking. We aimed to prospectively investigate the safety and effectiveness of ambulatory management of children with mild periorbital cellulitis.


| INTRODUCTION
Periorbital cellulitis (POC, also known as pre-septal cellulitis) is a relatively common condition in children. 1 Eyelid swelling and pain are the main reasons for presentation to the emergency department (ED). In POC, inflammation and/or infection is limited to structures anterior to the orbital septum. POC may result from localised infections following facial or eyelid injuries, facial and dental surgical procedures, insect bites, impetigo, conjunctivitis, chalazion and sinusitis. POC is usually a benign condition when treated in an appropriate and timely manner. However, either haematogenous or contiguous spread from associated sinus disease could cause orbital cellulitis. 2 Orbital cellulitis can lead to vision and life-threatening complications such as endophthalmitis, meningitis, cerebritis, intracranial abscess and cavernous sinus thrombosis. 3 Hence, the consensus is that POC is treated early with empirical antibiotics to limit the progression and prevent its complications. 4 Diagnosing POC in children is challenging as the distinction between POC and orbital cellulitis is often unclear. In addition, a detailed ocular examination is difficult in younger children, 5 leading to over reliance on radiological investigations. This often leads to variation in the clinical management of POC. This issue is compounded by the presence of many local institution specific guidelines, [5][6][7][8][9] and a lack of an international consensus on the management of POC in children. Also, there is paucity of evidence for the choice of empirical antibiotics, the route of administration and the duration of antibiotic therapy. 10 In the past, most children with POC were admitted for intravenous antibiotic therapy 11 and many underwent radiological investigations to identify orbital cellulitis. 12 More recently, new models of care from Canada and Australia have led to an emphasis on home-based care and outpatient parenteral antibiotic treatment for certain group of children with POC. [13][14][15] It is important to note the differences in the cohort characteristics between these studies and the current study in relation to the severity of POC and the anatomical sites of cellulitis. Home-based model of care for uncomplicated cellulitis management in children reduces financial burden on inpatient healthcare. 16 Retrospective studies report on the safety and the efficacy of ambulatory management of mild POC with antibiotics and regular follow up. 2,17 However, there is lack of prospective evaluation of this approach. The aims of our study were to prospectively ascertain the safety and the effectiveness of home-based strategy for the management of mild POC. We hypothesise that ambulatory management strategy for mild POC could be a safe and an effective alternative to inpatient management.

| METHODS
Prior to the commencement of this study, we undertook an extensive literature review on management practices for POC in children. An internal audit at our institution (unpublished work) identified variation in management practices with more than half of children with mild POC received inpatient antibiotic therapy. An evidence-based management protocol was then generated in collaboration with clinicians from the emergency, ophthalmology, ear, nose and throat and the ambulatory care teams.

| Study design
We conducted a prospective observational study and enrolled children with mild POC over a period of 23-months (1st November 2017 to 30th September 2019).

| Setting
This study was conducted at the emergency department at The Children's Hospital at Westmead, Sydney, Australia. The Children's Hospital at Westmead is a tertiary paediatric hospital providing emergency services to over 60 000 children annually.

| Participants
Children with POC were assessed in ED. The children between 2 and 16 years with mild POC were offered inclusion in the study.
Mild POC was defined by the following clinical characteristics: a. Systemically well, immunised children with mild eyelid swelling (not obstructing the view of the pupil) and erythema, b. Normal eye examination, c. Absence of fever (axillary temperature <38 C) d. No signs of orbital cellulitis (i.e., presence of visual compromise, ocular pain with eye movement, diplopia, ophthalmoplegia or proptosis), and e. Tolerating oral fluids and oral antibiotics (Table 1).
We excluded all children with moderate and severe POC, with orbital cellulitis, those requiring in-patient treatment, with recurrent or bilateral POC, or where parents refused consent.
Moderate or severe POC was diagnosed based on the following clinical characteristics: a. Fever (axillary temperature ≥38 C) or presence of signs of toxicity, b. Age less than 2 years, c. Unimmunised and/or immunocompromised, d. Suspected or confirmed orbital cellulitis with or without presence of intracranial complications, e. Reduced feeding (<50% normal intake) or intolerance to oral antibiotics, f. Reduced visual acuity and g. Unable to complete a full eye examination. Figure 1 illustrates the study process and management pathway followed by the staff The ambulatory care team is a multidisciplinary team comprising of paediatric nurses and doctors, allied health staff and administrative staff. They aim to provide care in the comfort of the patient's home or in the acute review clinic at the hospital. This service is accessible on all days of the week including weekends. In this study, children received a structured follow up with the ambulatory care nursing team at the acute review clinic in the hospital on days 1 and 2. At this review, vital signs including the heart rate, respiratory rate, blood pressure, body temperature and oxygen saturation were checked. The parents were asked details to explore the symptom progression or improvement. The ambulatory care nurses took a photograph of the affected eye on the dedicated hospital phone. Then a phone consult was made with the ophthalmology registrar on call who reviewed the photograph and provided guidance regarding further management. This telephonic consultation by the ophthalmology team in the early course of the illness was supplemented by a face-toface ophthalmology consult on day 7 at the eye clinic as required. A patient was formally discharged from our service after resolution of symptoms.
The outcome measures were: We collected demographic, clinical characteristics, investigations, complications, follow up, un-scheduled representation to the ED, hospitalisation and details of antibiotic treatment from the electronic medical records. Written informed consent was obtained from the parents. The families who were unable to comply with follow up or withdrew consent, were excluded from the final analysis.

| Statistical analysis
A pragmatic duration of 23 months was chosen for the study period. Descriptive statistics was used to report the cohort's characteristics. Symmetrically distributed variables are reported as mean (standard deviation). Categorical variables are reported as number (percentage). A representation rate of <30% was considered acceptable for pragmatic reasons to ascertain the safety and efficacy of ambulatory management approach.

| RESULTS
Over the study period, 76 children with mild POC were enrolled, 70 were included in the final analysis ( Figure 2).
The median age was 4 years (IQR 3-7) and 54% were males. Table 2 shows the baseline characteristics of the cohort.
F I G U R E 1 Study process and management pathway. D1: day 1, D2: day 2 One child had blood tests and intravenous (IV) antibiotics due to inappropriate severity classification on initial assessment. This child was reclassified into mild category after ophthalmology consultation and was treated accordingly. However, this case was classified as a protocol deviation and this child was excluded from the analysis. Our study cohort had younger children with 60% of children aged between 2 and 5 years. None of these children needed radiological investigations during initial assessment in the emergency department. Though none of the patients needed imaging at initial presentation, one patient had a CT orbit and sinuses performed due to clinical worsening. The CT revealed sinusitis and small nondrainable periosteal collection. Fifty-nine (84%) children had eye swabs performed and 49 (70%) had screening swabs for Methicillin resistant Staphylococcus aureus (MRSA). All children were treated as per protocol with appropriate oral antibiotics, amoxicillin-clavulanic acid or cefuroxime if allergic to penicillin.
Sixty-five (92%) children had a structured follow up review at 24 and 48 h of initial ED presentation. Five patients needed escalation of treatment and in-patient management, they either presented to ED within first 24 h (two children) or were identified at the first follow up on day 1 (three children) (Table 3).

| Treatment safety
No children had a major adverse event or minor side effects to oral antibiotics. No adverse events were reported with parenteral antibiotics (Cefotaxime and Clindamycin) in children who needed in-patient management.

| Progression of mild POC and failure of oral therapy
One child aged 6 years old developed orbital cellulitis and required inpatient management. Conservative management with 4 days of parenteral antibiotics followed by oral amoxicillin-clavulanate for 7 days upon discharge led to complete clinical recovery (Table 4). All children needing inpatient parenteral antibiotic therapy recovered completely without the need for surgical intervention for progression of their condition.

| Representations
All five children who represented received inpatient intravenous Cefotaxime and Clindamycin under the ophthalmology team ( Table 4). The mean length of inpatient stay was 66 h (2-4 days). Of these, three children received oral amoxicillin-clavulanate at discharge, one child received oral clindamycin (for suspected MRSA infection) and one child received oral cephalexin. The choice of oral antibiotics at discharge was at the discretion of the treating team based on the local departmental guideline. The duration of total antibiotic therapy was between 7 and 10 days.

| Structured follow up
Out of the 76 children enrolled in the study and successfully discharged from the emergency department, families of 5 children withdrew consent and 1 child was excluded from analysis due to protocol deviation ( Figure 2). This child was followed up by the ambulatory care team on days 1 and 2 along with ophthalmology team review on day 7 with complete resolution of the symptoms. Sixty-eight children (97%) had follow up review after initial ED presentation with two children representing to ED prior to the day 1 acute clinic review. Out of the 68 children presenting for day 1 clinic review three children were admitted to the hospital for parenteral antibiotics therapy. All of the remaining 65 children completed days 1 and 2 review with the ambulatory care team (Figure 3). The use of telephonic follow up was encouraged in 6 children. Parents were provided information on seeking advice from the family physician if they were unable to or elected not to attend the follow up review if there was resolution of symptoms. None of the

| DISCUSSION
This is the first prospective study evaluating the safety and efficacy of a home-based management model of care for children with mild POC. Overall, only 7% of children with mild POC needed inpatient management due to worsening of local symptoms. No children from the cohort required surgical intervention for complications of POC and they all made a complete recovery. Our findings demonstrate the safety and efficacy of home-based care with a structured follow up approach for the management of children with mild POC. Most children (93%) with mild POC can be successfully managed in an ambulatory fashion at a tertiary care centre. Retrospective studies have reported on the use and the safety of oral antibiotics for all grades of severity of POC. James et al reported 46.8% admission rate for 614 patients with POC who represented after being managed with oral antibiotics on an outpatient basis but this study lacked clarity in risk stratification of POC and the definition of mild POC. 17 Compared to this study, the current study had low admission rate (7%). This is presumably related to the strict definition of mild POC used in the current study. Ibrahim et al have alluded to the inconsistency in the definition of mild POC. 18 Although the risk stratification of POC is challenging, we incorporated a safe and a conservative approach in defining mild POC. We excluded children younger than 2 years as they could have a higher risk of complications due to an underdeveloped orbital septum as compared to older children. There is lack of evidence on the safe age ranges for the outpatient management of POC in younger children using oral antibiotics. 3,19 Although most experts recommend inpatient parenteral antibiotic therapy for children with POC with evidence of systemic illness, 3 there is no consensus on the age limit for safe discharge with oral antibiotic. A guideline from Queensland state, Australia has suggested that children over 3 months of age with mild POC could be treated with oral antibiotics using home-based care. 20 Lee et al provides his opinion and supports the practice of use of oral antibiotics therapy in children over 1 year of age with mild POC provided there is reliable follow up and no signs of systemic toxicity. 19 Further evidence is needed regarding ambulatory care management strategies for younger children (<2 years of age) with mild POC before changing clinical practice in this age group.
The risk stratification process at our institute did not use an objective scoring system to guide the severity of the disease. Goldman et al reported that the presence of local eye symptoms and fever predicted admission to the ED, hence they recommended creating a scoring system to guide criteria-based admission. 21 Vu et al developed an objective severity index focusing on systemic and local features to guide the modality of treatment. 22 This scoring system was validated by James et al in his study suggesting that a higher severity index score was associated with the need for parenteral therapy and development of complications or progression of disease. However, this scoring system has not been widely accepted globally including by the paediatric hospitals in Australia. The ASSET clinical risk scoring system used by the Melbourne group to determine the need for intravenous therapy for children with cellulitis, has not been validated externally. 23 The need to select the right group of patients for safe ambulatory management is highlighted in the study by James et al where the rate of children representing to ED after home discharge on oral antibiotics and receiving parenteral antibiotics was high (46.8%). 17 We used a pragmatic representation rate of <30% to ascertain safety of the ambulatory management strategy based on collaborative consensus opinion in our group due to variation in representation rates.
Sinusitis can cause periorbital cellulitis, and it often associated with orbital cellulitis. 24 Yalçınkaya et al retrospectively evaluated clinical and laboratory characteristics of children with POC and orbital cellulitis. They reported a significant difference in the incidence of sinusitis between the two groups [POC; 26/340 (7.6%) compared to OC; 20/35 (57.1%)]. This study also observed a strong association between presence of fever and the occurrence of orbital cellulitis. 25 In our study, we observed a low incidence (1%) of sinusitis. There were several possible reasons for this observation. Our study focused on milder cases of POC with strict definitions and risk stratification as per our guideline. There was no clinical need for imaging in this group. The cohort in our study included younger aged patients with physiologically underdeveloped sinuses who posed challenges in eliciting signs of sinusitis in younger children. Febrile F I G U R E 3 Details of the patients at follow-up children with mild POC were excluded from our study and all children had short duration of symptoms before presenting.
It has been suggested that routinely performing eye swab cultures may not be helpful due to risk of contamination from local commensals, 6 it may assist guiding management in certain cases. We screened our population for local peri-orbital MRSA colonisation to review the need for change in antibiotic therapy. The incidence of MRSA colonisation varies from 1.3% to 19%, 26 our study cohort had a low MRSA colonisation rate (4%). All patients in our study responded well to first line antibiotic treatment irrespective of MRSA colonisation status. This suggests that MRSA swab culture may not be indicated and children may not need MRSA coverage unless there is clinical indication or lack of improvement.
There is variation in practice on the speciality teams who are involvement in managing children with POC and this often depends on the availability of local resources and clinical expertise. Where possible, a multidisciplinary approach involving ear, nose and throat surgeons, ophthalmologists, paediatricians and family physicians is suggested for management of children with POC and orbital cellulitis. 27 There is variation in practice on a structured follow up plan regarding which speciality team leads the follow up and the timing of follow up following discharge home from ED. As complications of POC are often related to involvement of vision, a review by the ophthalmologist should be sought. 6 Based on the review of 18 out of 24 guidelines (two paediatric guidelines), the authors found that in 51 acute admitting otolaryngology units, that was lack of clarity on the inclusion of ophthalmology review in the guidelines. 7 Some have included daily temperature checks and daily ophthalmology assessment in their protocol. 17 We opted for daily ambulatory team review for the first 2 days after discharge and telephonic ophthalmology consultation (including sending a photograph of the affected eye to the ophthalmologist on call by the ambulatory care team) followed by face-to-face ophthalmology review on day 7. In our study, the progression of symptoms for all five patients was recognised within 24 h, which highlights the importance of the review in first 24 h. We speculate that a follow up at 48 h may not be indicated after the first follow up at 24 h if there is clinical improvement. The type of review (face-to-face/telemedicine) and the team conducting the review can be determined based on available resources. A structured follow up (like that in the current study) may assist in reducing representation to the ED thus easing the pressure on health care services. Our study suggests that an alternative model of care with the hospital in the home (HITH) team follow up and virtual consult strategy at 24 h with the primary care physician could assist in managing children with mild POC. This strategy allows patients to be managed in the comfort of their own home with the nursing staff initiating virtual consultation if required. This model of care involving virtual consultation is even more applicable and relevant in current setting with the pandemic. Our suggestion on the virtual models of care is speculative due to the relatively small sample size and perhaps this can be addressed by future studies. We used clinical photography in conjunction with telephonic consultation for speciality consults on initial presentation and on subsequent reviews over the following 48 h for managing mild POC cases in our study. Our study shows that telemedicine can be used effectively to review patients safely and to reduce the number of face-to-face speciality consults thus reducing burden on the subspeciality teams.
The major strengths of this study include a focus on management of patients in an outpatient setting by ambulatory care team and a combination of initial virtual and later face-to-face review by the ophthalmologist as needed. This is the first prospective study involving risk stratification and a structured follow up of children with mild POC. We acknowledge certain limitations as well. We excluded children less than 2 years; future studies should consider including this age group. We missed enrolling eligible patients due to lack of research personnel availability round the clock.
In summary, children with mild POC can be safely and effectively managed by discharging them on oral antibiotics, following a structured ambulatory management strategy and a combination of virtual and face-toface consultation with specialist as needed. This finding has important implications for changing practice for children with mild POC and easing pressure on busy healthcare services.