Q&A: Richard Brindle, MD, on the Efficacy of Antibiotics for Cellulitis

According to the findings of a recent systematic review, there is no one antibiotic that is superior to others for the treatment of cellulitis.¹

“This systematic review is designed to provide the evidence for the antibiotic treatment of cellulitis and erysipelas. It should therefore form the basis of therapeutic guidance,” said corresponding author Richard Brindle, MD, who holds an honorary appointment at the University of Bristol in Bristol, UK.

In the review, Dr Brindle and his colleagues analyzed data from 43 randomized, clinical trials that compared different antibiotics, routes of administration, and treatment duration for the treatment of cellulitis and erysipelas, which included a total of 5999 participants. Primary outcomes included the proportion of participants cured, improved, recovered, symptom free or symptom reduced at the end of treatment. Adverse events were evaluated as secondary outcomes.¹

Only 15 studies (35%) had cellulitis as a primary diagnosis. In other studies of skin and soft tissues infections, the median proportion of patients with cellulitis was 29.7%.¹

Brindle et al found no evidence that supported the superiority of one antibiotic over another, and no advantage for antibiotics with activity against methicillin-resistant Staphylococcus aureus. Additionally, they found no support for the use of intravenous antibiotics over oral antibiotics, as well as no support for treatment duration longer than 5 days.¹

“The evidence tells us that we do not need long courses of broad-spectrum antibiotics, that patients will get better on oral antibiotics and that intravenous antibiotics add nothing but expense and adverse events,” said Dr Brindle. “We also know that combinations of antibiotics do not improve outcome but add cost and side effects.”

He further discussed the implications of these findings for dermatologists in an interview with The Dermatologist.

The Dermatologist: How can dermatologists and other providers utilize your findings and what are your recommendations at this point?

Dr Brindle: Dermatologists are positioned to provide expert advice on the management of cellulitis which has historically been a condition managed by a wide range of clinical teams. Most cases of cellulitis are managed by family physicians and emergency departments, with dermatologists only being involved in complicated, recurrent, or slowly resolving cases. There is a need for leadership in managing a common condition, which is internationally often treated sub-optimally.

The Dermatologist: What are some of the challenges for determining optimum dose, antibiotic, and duration for patients with cellulitis? What were some of the challenges of conducting this study?

Dr Brindle: The review could not provide evidence on the optimum dose of any antibiotic but with the relatively low dose of oral antibiotics used in many of the earlier trials, we can be confident that large doses are not needed in most cases. However, given the epidemic of obesity, we need to know how we should calculate dosing so that we avoid treatment failures. The trial of penicillin prophylaxis in recurrent cellulitis noted an increased risk of prophylaxis failure in those patients with a body mass index of 33 or higher²; this supports the view that dosing trials are necessary.

Additionally, the review did not find evidence to support one antibiotic over any other, with narrow spectrum penicillins as effective as other broader agents. Given the concerns with the over usage of broad-spectrum antibiotics on the development of antimicrobial resistance, an oral penicillin should be the preferred agent. The causative agents, hemolytic streptococci, are susceptible to penicillins.

We also could not find evidence to support durations of therapy longer than five days and, where short durations were compared with longer durations, the outcomes were similar. It is likely that most patients with cellulitis or erysipelas could be treated with very short courses but there are no trials that test this hypothesis. The most significant problem in reducing treatment durations is that the skin damage may take several days or even weeks to repair. This encourages physicians to prolong the treatment duration, mistakenly thinking that continued antibiotic therapy is necessary for recovery.

Furthermore, this review has been challenging as a large number of studies had to be examined and decisions made concerning inclusion. We originally set out to update the 2010 Cochrane review, which looked at all interventions, but there were very few trials that studied anything other than antibiotics.³ We had hoped to include a significant number of large trials looking at interventions directed at symptom relief, as pain and swelling are of concern to patients. In the absence of these we limited our review to antibiotics.

The Dermatologist: What are some of the limitations and what are the next steps for future research?

Dr Brindle: The limitations of this review are in the clinical trials analyzed; most were trials of skin and soft tissues infections designed to collect drug licensing data for new antibiotics rather than to answer appropriate questions concerning the management of cellulitis. Future trials about cellulitis should include only participants with cellulitis and are needed to clarify the duration of antibiotic therapy, antibiotic dosing and whether longer durations are necessary with more severe disease. We think that there should also be trials focusing on reducing symptoms such as analgesics and corticosteroids as there is some limited evidence of benefit.

Clinical trials are needed to clarify the role of intravenous antibiotics, specifically within a community setting. Future trials need to have standardized criteria for severity scoring and outcomes; these should include systemic features, local, blood and patient-focused parameters, with exclusions and times of follow up standardized wherever possible.

References

1. Brindle R, Williams OM, Barton E, Featherstone P. Assessment of antibiotic treatment of cellulitis and erysipelas: A systematic review and meta-analysis [Published online June 12, 2019]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.0884
2. Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis. N Engl J Med. 2013;368(18):1695-703. doi:10.1056/NEJMoa1206300
3. Kilburn SA, Featherstone P, Higgins B, Brindle R. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev. 2010;6. doi:10.1002/14651858.CD004299.pub2.