Article Text
PDF
Abstract
Objective Children with moderate/severe cellulitis requiring intravenous antibiotics are usually admitted to hospital. Admission avoidance is attractive but there are few data in children. We implemented a new pathway for children to be treated with intravenous antibiotics at home and aimed to describe the characteristics of patients treated on this pathway and in hospital and to evaluate the outcomes.
Methods This is a prospective, observational cohort study of children aged 6 months–18 years attending the ED with uncomplicated moderate/severe cellulitis in March 2014–January 2015. Patients received either intravenous ceftriaxone at home or intravenous flucloxacillin in hospital based on physician discretion. Primary outcome was treatment failure defined as antibiotic change within 48 hours due to inadequate clinical improvement or serious adverse events. Secondary outcomes include duration of intravenous antibiotics and complications.
Results 115 children were included: 47 (41%) in the home group and 68 (59%) in the hospital group (59 hospital-only, 9 transferred home during treatment). The groups had similar clinical features. 2/47 (4%) of the children in the home group compared with 8/59 (14%) in the hospital group had treatment failure (P=0.10). Duration of intravenous antibiotics (median 1.9 vs 1.8 days, P=0.31) and complications (6% vs 10%, P=0.49) were no different between groups. Home treatment costs less, averaging $A1166 (£705) per episode compared with $A2594 (£1570) in hospital.
Conclusions Children with uncomplicated cellulitis may be able to avoid hospital admission via a home intravenous pathway. This approach has the potential to provide cost and other benefits of home treatment.
- paediatric emergency medicine
- admission avoidance
- soft tissue infection
Statistics from Altmetric.com
Key messages
What is already known on this subject?
Children, their families and healthcare systems all benefit from home versus hospital treatment, where possible.
Children with moderate/severe cellulitis requiring intravenous antibiotics are usually treated in hospital.
What this study adds?
In a prospective, observational study of moderate/severe cellulitis, we compared outcomes of children treated at home with daily ceftriaxone with those treated in hospital.
Children selected by ED physicians to be treated at home had low rates of treatment failure and complications. In addition, treatment at home was associated with cost savings for the healthcare institution.
Home treatment of moderate/severe cellulitis with intravenous ceftriaxone may avoid hospital admission altogether.
Introduction
Skin and soft tissue infections are common in children and the majority are treated with oral antibiotics. A significant minority are treated with intravenous antibiotics for more acute clinical features, including rapid spreading of cellulitis, systemic features or if symptoms are progressing despite oral antibiotics. These infections usually require short-course intravenous antibiotics and in adults are commonly treated without hospital admission in an ambulatory setting (home, outpatient clinic or physician’s office).1–3 The well-documented benefits of avoiding hospital admission include psychological benefits, reduced risk of hospital-acquired infections and decreased use of healthcare resources.4–9 In contrast to adults, children with cellulitis are usually admitted to hospital due to a lack of evidence for outpatient intravenous treatment for skin and soft tissue infection even though they rarely have serious complications such as bacteraemia.10–12
To enable children to be treated in an outpatient setting, an antibiotic with a long half-life is ideal. First-line antibiotics for cellulitis (flucloxacillin, cephazolin) treat Staphylococcus aureus and group A streptococci (GAS) in settings of low prevalence of methicillin-resistant S. aureus (MRSA). However, they are dosed several times a day so are unsuitable for outpatient treatment, and bioavailable oral alternatives are often unsuitable in children due to taste and side effects.13–15 The third-generation cephalosporin ceftriaxone has antistaphylococcal activity and can be administered once a day.16 17 While in some studies ceftriaxone was used to treat cellulitis, none of these studies have compared outcomes with first-line antibiotics, and none have been administered at home.16–20
Our institution has a home outreach programme whereby nurses administer antibiotics to children in the home with medical staff oversight. This model uses once-daily ceftriaxone via a peripheral intravenous catheter, the venous access recommended by the Infectious Diseases Society of America practice guidelines for short-course outpatient intravenous therapy.3 Following a preliminary study, we formulated and implemented guidelines in the ED that allowed children with uncomplicated moderate/severe cellulitis requiring intravenous antibiotic therapy to be treated either at home or in hospital.21 While the benefits of being at home are not disputed, it is important to ensure that home intravenous treatment in children does not put them at risk, and therefore prospective evaluation of this new pathway is necessary to provide confidence that the guidelines are appropriate.
This study aimed to describe the characteristics of children treated via the direct-to-home from the ED pathway and to prospectively evaluate the outcomes of these children. We hypothesised that there would be a low treatment failure rate at home and the duration of treatment would be comparable to standard hospital care.
Methods
Study design and setting
This is a prospective, observational cohort study at the Royal Children’s Hospital (RCH) Melbourne, a tertiary paediatric hospital.
Selection of participants
Inclusion criteria
Children aged 6 months–18 years attending ED with uncomplicated moderate/severe cellulitis from March 2014 to January 2015 were eligible. As there is no validated objective score for distinguishing moderate/severe from mild cellulitis, this was defined in the study as including any of following clinical features: rapidly spreading erythema, significant swelling/redness/pain, systemic symptoms/signs (eg, fever, lethargy) or failed oral therapy leading to treatment with intravenous antibiotics.
Exclusion criteria
Patients with complicated cellulitis (orbital cellulitis, undrained abscess, large animal/human bite, penetrating injury, foreign body, suspected fasciitis, toxicity) and comorbidities (immunocompromise, varicella, any condition receiving different antibiotic treatment) were excluded. Patients with mild cellulitis (treated with oral antibiotics) were excluded.
Interventions
Study procedure
ED physicians were educated on the guidelines for the referral of children with cellulitis to the home intravenous antibiotic pathway (online supplementary figure). They were informed of the benefits and risks of the treatment locations for managing cellulitis prior to starting the study. If a patient was eligible, the ED physician followed an algorithm of inclusion and exclusion criteria, and after discussion with the family decided whether to treat the patient at home or in hospital. Physicians were asked for their reasons for treating with intravenous versus oral antibiotics and their reason for choosing home versus hospital. Patients meeting inclusion criteria were consented and recruited. Patients had cultures of blood, nose and the affected skin if indicated.
Supplementary file 1
Home group
To receive antibiotics at home, a referral was made to the home intravenous programme with handover to the home nursing team. After receiving the first dose of ceftriaxone 50 mg/kg in ED, the patient went home with the peripheral intravenous catheter in situ until intravenous antibiotics were ceased. On leaving the ED, families were provided with a contact telephone number for a (home intravenous programme) nurse available 24 hours a day, 7 days a week if they had any concerns about their child, while they were at home. A nurse visited the child daily at home and administered intravenous ceftriaxone until the child was deemed suitable for oral therapy. The medical staff overseeing patients at home aimed to review the child at least once during the course of treatment in person, and subsequently daily by teleconferencing or by reviewing digital photographs. The decision to cease intravenous antibiotics was made by the home programme medical staff.
Hospital group
The standard of care for moderate/severe cellulitis at RCH is admission to the short stay unit for intravenous flucloxacillin 50 mg/kg six hourly. There is at least daily review by medical staff and at least four hourly nursing observations.
In all patients, whether in hospital or at home intravenous antibiotics were ceased when clinically appropriate to switch to oral antibiotics. Any patient deemed to require a further observation period or ongoing interventions (eg, wound dressing) remained under medical care until these were no longer needed.
Sample size and data collection
Sample size calculation
Sample size was calculated based on a treatment failure rate of approximately 3% with standard treatment; a home treatment failure rate of 25% (ie, three of four children treated at home successfully) that was considered acceptable by a panel of senior ED physicians, based on the other advantages of home; and a power of 80%—47 children in each arm. We continued recruitment for all eligible patients until we had reached at least this sample size for each group.
Data collection
Data collected included age, sex, clinical features, systemic symptoms at presentation (fever >38°C reported or documented at home or in the ED, vomiting, tachycardia or hypotension) and prior oral antibiotics. Physicians were asked their reason for intravenous versus oral antibiotics and hospital versus home treatment.
Outcomes
The primary outcome was measured as treatment failure defined as any change of initial empiric antibiotics within 48 hours due to inadequate clinical improvement or serious adverse events (anaphylaxis, suspected allergic reaction, sepsis). Secondary outcomes were readmission after discharge, rates of repeat intravenous catheterisation, complications, length of stay in ED, duration of intravenous antibiotics and length of stay under medical care (from the time of arrival in ED to the time of official discharge from medical care from the home or ward team). A cost comparison between home and hospital, provided by our institution’s business department, included the cost of nursing and medical resources, consumable items, and indirect overhead costs including administrative time, information technology and use of hospital vehicles for visiting patients.
Analysis
For univariate analysis, Mann-Whitney U test was used to compare continuous data with non-normal distribution and Χ2 test for categorical data. Fisher’s exact test was used where variable count was less than 5. All demographics and clinical features at presentation included in univariate analyses were considered for a multivariate model. Likelihood ratio tests were conducted to assess the best fit for the multivariable model through risk factor inclusion, with the most parsimonious model to be presented. Multivariable logistic regression analysis was conducted using SPSS V.22.0.
Results
Over 10 months, 400 children presented to ED with cellulitis, of whom 189 (47%) were discharged on oral antibiotics and 96 (24%) other patients were excluded from the study (figure 1). There were 115 (29%) children who were eligible for the study. Of these children, 47 were treated entirely at home and 68 were admitted to hospital. Nine of the children admitted to hospital were subsequently transferred home during treatment.
Disposition of patients presenting to the ED with cellulitis.
Demographics and clinical features
Patients were similar in terms of sex and age in both groups (table 1).
Comparison of demographics and clinical features between home and hospital groups
There was no difference in systemic features between groups. Lower limb cellulitis was more commonly treated at home (P<0.01, OR 3.24 (95% CI 1.49 to 7.06)), and although a lower proportion of children with periorbital cellulitis were treated at home, this was not significant (P=0.11, OR 0.50 (95% CI 0.20 to 1.20)). A multivariable analysis was performed for factors potentially affecting the decision to treat at home or in hospital: age and sex, systemic symptoms, antibiotics (having taken at least one dose of oral antibiotics for the same cellulitis prior to ED presentation), proportion of body surface area affected, presence of periorbital cellulitis and lower limb cellulitis. Having lower limb cellulitis was the only factor independently associated with home versus hospital admission (P=0.02, OR 3.91, (95% CI 1.24 to 12.30)).
Reasons for choosing hospital versus home treatment
The most common reasons cited by clinicians for hospitalising patients were rapidly spreading erythema/significant swelling, unsuitable for home treatment (over 40 km from hospital or non-English-speaking family) and presence of systemic features (table 2).
Reasons cited by ED physicians for hospital admission and patient outcome
Microbiology
None of the blood cultures grew pathogens (table 3). Fifty-two (45%) skin swabs were taken, with methicillin-sensitive S. aureus being the most commonly cultured. The rate of MRSA infection overall was 6% (7/115), with similar numbers in the two treatment groups.
Comparison of microbiology results between home and hospital groups
Outcomes
Overall, the rate of treatment failure was low with no difference between groups (table 4). Of the two patients who failed treatment at home, one developed an abscess resulting in admission to hospital and change of antibiotic to flucloxacillin despite his skin swab being positive for GAS (sensitive to ceftriaxone). The other was not improving and subsequently cultured MRSA, necessitating a change in antibiotics. Of the eight patients in hospital, three changed antibiotics within 24 hours, one due to allergy and two due to spreading erythema and fever. The remaining five changed antibiotics at 36–48 hours due to worsening or lack of improvement in the extent of the erythema or increasing swelling. Three of these eight children subsequently cultured MRSA from their skin swab. There was one child from the hospital group who was readmitted with recurrence of cellulitis following discharge. Complications during treatment were few. Two children (one in each group) developed abscesses requiring drainage after 48 hours of antibiotics, but the other complications (including rash) were considered non-significant and did not require change in antibiotics. The duration of intravenous antibiotics and length under medical care were comparable to hospital care.
Outcomes of home and hospital groups
Cost analysis
The cost of treating a patient with moderate/severe cellulitis at home at our institution is A$530 (£320) per patient per day, compared with the cost of an inpatient bed on the short stay unit, which is A$1297 (£785) per patient per day. The patients treated at home were in the home intravenous programme for a combined total of 176 days. The home patients therefore cost A$93 280 (£56 429) in total compared with A$228 720 (£138 378) if they had been treated in hospital, a real cost saving of A$134 992 (£81 949). If all of the hospitalised patients (combined total of 295 days) had been treated at home, the estimated cost saving would have been A$226 265 (£136 877) presuming that none of these patients had treatment failures and were subsequently hospitalised.
Discussion
This is the first, prospective, observational cohort study of children treated with intravenous antibiotics for uncomplicated moderate/severe cellulitis evaluating an admission-avoidance strategy of home management. The results of this study support the use of intravenous antibiotics under a home intravenous programme for a portion of patients, in terms of efficacy, safety and cost. They support the findings of other studies that have either been retrospective or did not collect data from the hospitalised group.18 20 21
In our previous study we concluded that older children with lower limb cellulitis can be treated at home based on the patient cohort that had predominantly been treated via this model to date.21 We hypothesised that this model could be applicable to all patients with uncomplicated moderate/severe cellulitis. We formulated and implemented a guideline that included a wider age range with different sites of cellulitis and prospectively evaluated this. The success of the guideline implementation is reflected in the increase in the proportion of all eligible patients referred via the home intravenous pathway, from 28% in the previous period studied to 41% in this study. In addition, in the previous study only 24% of children treated at home were aged under 4 years old compared with 53% in this study. Although the guideline was cautious with periorbital cellulitis, requiring discussion with senior clinicians, the proportion of these cases referred for home intravenous antibiotics increased from 11% in the previous study to 29%.
In the current study the success rate was high for patients treated at home with intravenous ceftriaxone (96%). However, despite the introduction of guidelines, 59% of patients were still hospitalised. Reasons for hospitalisation were clinical in 56% of admitted patients. Almost all of the remaining hospitalised patients could potentially have been treated at home. We had excluded patients with complicated cellulitis/comorbidities. Reasons for physician hesitation may relate to lack of confidence with this relatively novel home treatment approach or a generally conservative approach.
Regarding efficacy, ceftriaxone is not the usual first-line treatment for cellulitis, but it is suitable for home-based treatment because it can be administered once daily via a peripheral catheter. The short intravenous duration for cellulitis would not have warranted central venous catheter insertion, and peripheral catheter use at home was safe and acceptable to parents. However, uncertainties have remained around the efficacy of ceftriaxone against S. aureus. Although one study suggested high rates of resistance to ceftriaxone in methicillin-sensitive S. aureus (MSSA),22 it was subsequently retracted due to methodological flaws.23 24 A more recent study found 99% of MSSA isolates were ceftriaxone-susceptible.25 The in vitro findings are borne out by our study, which had a high clinical success rate. This corroborates clinical studies where ceftriaxone has been effective for skin and soft tissue infection.17 26
Regarding the broader effects of ceftriaxone, although emergence of resistance is a concern for broad-spectrum antibiotics, this has never been shown for short-course antibiotics in children or for patients receiving outpatient/home intravenous antibiotics.21 While antibiotic resistance is a global problem, it is important not to extrapolate effects of longer duration broad-spectrum antibiotics administered in hospital into every situation, particularly where there are other benefits of home treatment such as avoidance of hospital-acquired infections. Further studies in this area are urgently needed and should encompass the impact of short-term antibiotic use on the microbiome.
Although this study was not designed to assess the use of oral antibiotics, it is possible that some of these patients could have been treated with oral antibiotics with high oral bioavailability (eg, clindamycin, high-dose flucloxacillin). However, even disregarding taste and adherence issues, data collected on reasons for the decision to treat with intravenous antibiotics are hard to refute: failed oral antibiotics (31%), severe clinical features of rapid spreading, significant swelling, thrombophlebitis or systemic features (44%) and large or hard to treat areas (15%), leaving 10% (only 4% of all patients with uncomplicated cellulitis) where patients could potentially have been treated with oral antibiotics. As there are no comparative safety data for treating moderate/severe cellulitis at home via any route, this study provides valuable evidence that hospital admission may not always be required for this condition.
The strength of this study is its systematic evaluation after formulating and implementing a novel pathway to treating moderate/severe cellulitis in children. Implementation of this new pathway was considered successful with the increase in the proportion of admissions avoided. Our data suggest that increasing ED physician education and awareness of this new pathway may improve the proportion of referrals.
The main potential limitation of this study is that this pathway is specific to institutions that have a home intravenous team. For institutions without a home outreach programme, the antibiotics could be delivered via an outpatient clinic or in the ED, but returning to the hospital daily may be less acceptable to patients. Second, as this study was not a randomised trial, other unknown factors which may have influenced the treatment location could not be fully addressed. In addition, this study took place in a locale with low MRSA prevalence, so the results may not be externally valid to MRSA-prevalent regions. Lastly, although our study used the actual costs from our institution’s operational budget to compare the cost of home versus hospital treatment, a thorough assessment of cost-effectiveness to include patient returns was not performed.
In summary, children with uncomplicated moderate/severe cellulitis may be successfully treated at home with intravenous ceftriaxone directly from the ED, avoiding hospital admission altogether. Applying the results across other ambulatory/outpatient settings should include physician oversight until there is evidence to the contrary. Even though we found no significant differences in patient characteristics between the groups, because this study was not randomised, at this stage physicians prescribing intravenous antibiotics for children with cellulitis can select patients for home/outpatient treatment with daily review based on the home cohort in this study. Evaluation of this novel pathway has provided sufficient feasibility, efficacy and safety cohort data to recommend a randomised controlled trial to answer this question for all children presenting to ED with uncomplicated moderate/severe cellulitis.
Acknowledgments
We would like to acknowledge the participation of patients and families.
References
Footnotes
PAB and FEB contributed equally.
Contributors LFI conceptualised, designed and coordinated the study, carried out the initial data analysis, drafted the initial manuscript, and approved the final manuscript as submitted. PAB, FEB and SMH were involved in the design of the study, data analysis, reviewed and revised the manuscript, and approved the final draft. TGC and AJD were involved in the design of the study, reviewed and revised the manuscript, and approved the final draft. PAB had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This study is funded in part by grants from the RCH Foundation, the Murdoch Childrens Research Institute (MCRI) and the Victorian Department of Health, Melbourne, Australia. LFI was supported in part by a scholarship from Avant Mutual Group. PAB was in part supported by a Clinician Scientist Fellowship from the MCRI. FEB was supported in part by a grant from the RCH Foundation. The emergency research group, MCRI, is in part supported by a Centre for Research Excellence Grant for Paediatric Emergency Medicine from the National Health and Medical Research Council, Canberra, Australia, and the Victorian government infrastructure support programme.
Competing interests None declared.
Ethics approval The Royal Children’s Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.