Fusidic acid – first-choice option in the treatment of skin infection

Fusidic acid – first-choice option in the treatment of skin infection

The skin is the largest, and arguably, the most vulnerable organ in the human body. Scratches, scrapes, bites, and puncture wounds can all lead to pain, swelling, and infection. Patients with dermatological conditions such as atopic dermatitis are at great risk of infections due to an impaired skin barrier.1,2,3

The skin is the body’s first line of defence against microbial infection by secreting low pH, sebaceous fluid, and fatty acids to inhibit growth of pathogens and by possessing its own normal flora, thus deterring colonisation by other pathogenic organisms. Unfortunately, once an organism penetrates the skin barrier, it can cause tissue damage and incite an inflammatory response.2

Bacteria, initially in low numbers, colonise different layers of the skin architecture (eg epidermis, dermis, subcutaneous and adipose tissues, and muscle fascia). As bacteria increase in number where the skin barrier is disrupted, invasion by these colonising bacteria ensues and an infection develops.2

The main culprits in causing infections are Staphylococcus and beta-haemolytic streptococci. Organisms that colonise the skin above the waist are usually Gram-positive species such as Staphylococcus epidermidis, Corynebacterium species, Staphylococcus aureus and Streptococcus pyogenes. The latter two species are particularly significant because they contribute to a majority of skin infections.2,3

Organisms that colonise the skin below the waist are both Gram-positive and Gramnegative species. It is speculated that this difference is secondary to the proximity to the anorectal region. Enteric species, such as Enterobacteriaceae and Enterococcus species, gravitate to and colonise this area of the skin, the so-called ‘faecal veneer’.2

The minimum diagnostic criteria for a skin infection are erythema, oedema, warmth, and pain or tenderness. The affected area may also become dysfunctional (eg hands and legs) depending on the severity of the infection. A patient’s comorbidities (eg diabetes and HIV) can easily transform a normally mild infection into a rapidly advancing threat to life.2

Classification of skin infections

Skin infections can also be classified according to the anatomical tissue layers involved. Superficial infections such as erysipelas, impetigo, folliculitis, furuncles, and carbuncles are located at the epidermal and dermal layer, while cellulitis is located in the dermis and subcutaneous tissue.4

Deep infections extend below the dermis and may involve the subcutaneous tissue, fascial planes, or muscular compartments presenting as complex abscesses, fasciitis or myonecrosis.4

Treatment

Effective management of a skin infection starts with an assessment to determine whether the infection is mild, moderate, or severe. The majority of skin infections tend to be mild and generally resolve within seven to 10 days. Between 70% to 75% of all cases can be managed in the outpatient setting.1,2

Table 1: Mild-to-moderate skin infections1

Purulent: Incision and drainage

Non-purulent: Topical antibiotics; Oral antibiotics (cover GAS)

Topical therapies are a key component in the management of mild-to-moderate skin infections. In such cases, topical antibiotics may be preferable to systemic treatment since they maximise the effective doses at the site of infection while minimising the systemic side effects of the drugs.1,3

However, the prevalence of resistant strains is steadily increasing and cases of sensitisation are not uncommon. As a consequence, the ideal topical antibiotic should be selective (thus, minimising cross-resistance), have weak sensitisation potential, penetrate the skin efficiently, reach adequate local doses at the site of infection, and finally be available in different formulations matching patients’ preferences and needs.3

Fusidic acid (FA) is a selective antibiotic available in several topical formulations. Pharmacokinetic and pharmacodynamic studies have shown that, contrary to other topical antibiotics such as gentamicin or mupirocin, FA reaches high antimicrobial concentration at deep skin layers after topical application either on intact or damaged epidermis.3

Several randomised controlled trials demonstrated that FA, in its various topical formulations, is very effective in treating skin infections, given its high bactericidal activity against S. aureus (including strains resistant to penicillin, methicillin, ampicillin, cloxacillin), S. epidermidis, Streptococcus pyogenes, Propionibacterium acnes, Corinebatteria, Clostridia. Additionally, FA presents a low risk of resistance even in MRSA strains. Such features make FA particularly useful in the management of skin infections.3

Finally, possibly due to its large steric effect, FA has proved a very low risk of contact sensitisation. Overall, data on FA efficacy, safety, sensitisation potential, resistance profile and spectrum selectivity make it a first-choice option in the treatment of skin infection.3

References

1. Silverberg B. A Structured Approach to Skin and Soft Tissue Infections (SSTIs) in an Ambulatory Setting. Clin Pract, 2021.

2. Ki V and Rotstein C. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can J Infect Dis Med Microbiol, 2008.

3. Bonamonte D Belloni FA, Neri L and Patrizi A. Fusidic acid in skin infections and infected atopic eczema. Giornale Italiano di Dermatologia e Venereologia, 2014.

4. Sartelli M, Guirao X, Catena F, et al. 2018 WSES/ SIS-E consensus conference: recommendations for the management of skin and soft-tissue infections. World Journal of Emergency Surgery, 2018. SF