Prophylactic Antibiotics May Be Best Bet for Preventing Cellulitis Recurrence

A close-up image of cellulitis on a man's shins
A close-up image of cellulitis on a man’s shins
Antibiotic prophylaxis may be the best preventive treatment against recurrent cellulitis and erysipelas in patients who have had at least 2 episodes in 3 years.

Antibiotic prophylaxis may be the best preventive treatment against recurrent cellulitis and erysipelas in patients who have had at least 2 episodes in 3 years; however, protection does not last following discontinuation of antibiotic therapy, according to a Cochrane review conducted by a team of Israeli investigators.1

The team sought to assess the benefits and adverse effects of antibiotic prophylaxis and other prophylactic interventions in the prevention of recurrent cellulitis/erysipelas in adults age ≥16 via a systematic literature review of randomized controls trials (RCTs).

Of 5995 records reviewed, 16 articles were deemed potentially relevant and assessed for eligibility, with 7 articles reporting on 6 RCTs ultimately being included in the study. Of the 6 studies, 5 assessed antibiotic prophylaxis in patients with recurrent cellulitis of the legs, and the remaining study assessed selenium therapy in cellulitis of the arms. Antibiotics studies included erythromycin and penicillin.

The total study population was 573 patients with an average age between 50 and 70. Treatment duration varied from 6 to 18 months. Analysis of the results of the studies showed that antibiotic prophylaxis reduced the incidence rate of cellulitis/erysipelas recurrence by 69% vs placebo or no treatment (risk ratio [RR] 0.31; 95% CI 0.13-0.72; P =.007). The number of recurrences also was reduced by 56% (RR 0.44; 95% CI 0.22-0.89; P =.02)

Although the evidence was of low certainty due to the limited number of studies reviewed, the findings suggested that the protective effects of antibiotics were not sustained following prophylaxis discontinuation; no statistically significant differences in risk were seen between treated and untreated patients. No significant differences in adverse effects or hospitalization were identified either, although the investigators also noted that this evidence was of low certainty. The most common adverse events were gastrointestinal upset (eg, nausea, diarrhea), rash, and thrush. None of the studies reviewed assessed issues related to antibiotic resistance or quality of life.

The researchers concluded that antibiotic therapy is probably an effective preventive treatment for recurrent cellulitis of the lower limbs in patients receiving prophylactic treatment compared with patients receiving placebo or no treatment. These findings are significant because up to 50% of people with cellulitis experience repeat episodes.

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Risk factors include obesity, diabetes mellitus, immunosuppression, and alcoholism; skin maceration and inflammation such as that caused by athlete’s foot, lymphedema, or leg ulcers provide a setting for bacterial overgrowth, leading to infection of subcutaneous tissue (cellulitis) or lymphangitis (erysipelas). Numerous guidelines have advocated for the reduction of predisposing factors, including encouraging skin care to avoid dry, cracked skin and cutaneous fungal infections, wearing compression stockings, and using diuretics to prevent lower limb edema. Long-term antibiotic prophylaxis is also recommended, with evidence largely supported by observational studies and expert opinion.

Systemic analysis of high-quality research is lacking, according to the Cochrane Review investigators; optimal antibiotic selection, optimal time of initiation of therapy and length of therapy course, all require clarification, they said.


Moderate-certainty evidence based on 6 RCTs indicates that antibiotic prophylaxis is probably effective for preventing recurrent cellulitis and lengthening the time between recurrences. The protective effect is lost, however, once antibiotic prophylaxis is discontinued. High-quality studies are needed to confirm the study findings, clarify optimal use of antibiotic prophylaxis, and explore the impact of long-term antibiotic prophylaxis on antibiotic resistance.


Only a small number of studies were reviewed, and none of which were high-quality, and none which assessed the development of antimicrobial resistance or quality-of-life measures. Also, 3 studies were considered to be at high risk for bias, mainly due to lack of blinding.


  1. Dalal A, Eskin-Schwartz M, Mimouni D, et al. Interventions for the prevention of recurrent erysipelas and cellulitis. Cochrane Database Syst Rev. 2017; 6:CD009758.