Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 22/04/2025
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Robert M. Burd and Michael Sladden
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Impetigo is a superficial bacterial infection of the skin. The most common pathogen is Staphylococcus aureus, although β-hemolytic streptococci may also be implicated. The infection is highly contagious and can easily spread to other body sites or close contacts.
Impetigo may be primary, with direct bacterial invasion of previously normal skin, or secondary, where infection develops due to an underlying skin disease, such as scabies or eczema, disrupting the skin barrier.
Impetigo is classified as bullous or non-bullous. In the more common non-bullous form, thin-walled vesicles rupture to form superficial erosions with yellowish-brown crusts, which eventually heal without scarring. Bullous impetigo is characterized by larger bullae or blisters, which may continue to develop for several days.
The main aim of treatment is to eradicate the infecting bacteria to allow rapid healing of skin lesions and control the spread of infection. This requires the use of an appropriate antimicrobial delivered in an effective manner. Antibiotics may be administered either orally or topically. The choice between topical or oral therapy depends on:
The experience of the practitioner
The preference of the patient
The extent and severity of the disease
The local bacterial resistance patterns
The cost and availability of local resources.
In Europe, S. aureus has been recognized as the major pathogen in both bullous and non-bullous impetigo. Traditionally, in the US, non-bullous impetigo was considered to be caused primarily by streptococci, but recent evidence indicates that S. aureus is now the most common pathogen in both forms of impetigo in the US as well.
Oral or topical antibiotics with proven efficacy against S. aureus are the first choice of therapy. It is reasonable to use short courses of topical antibiotics for mild, limited impetigo, while reserving oral antibiotics for recalcitrant, extensive, systemic disease.
Globally, the majority of isolates of S. aureus are resistant to penicillin. Erythromycin resistance is also becoming more prevalent.
In developing countries, where impetigo causes a significant burden of disease, streptococcus is often the predominant pathogen. In these countries, topical agents are expensive and may be unavailable. Treatment strategies have to be sufficiently flexible to meet local needs.
Historically, topical treatment of impetigo was ineffective due to the emergence of bacterial resistance to tetracyclines and gentamicin, and problematic because of contact sensitivity to topical antimicrobials. More recently introduced topical antibiotics are as effective as traditional oral antibiotics. When used in courses of less than 2 weeks, bacterial resistance does not appear to be a major problem. However, bacterial resistance patterns vary with geographical location, and treatment should be influenced by local data and expertise.
Recent studies of retapamulin, a pleuromutilin antibacterial developed for topical use, indicate that it is effective and safe in the treatment of primary impetigo.
Strains of bacteria causing impetigo are often extremely virulent. Patients therefore need to be educated on personal hygiene methods to avoid the spread of infection. The use of topical antiseptics and soaks to remove dried exudate and crusts has not been shown to be of benefit. Evidence regarding the value of disinfecting measures is limited. However, common sense would indicate that cleaning lesional skin with soap and water or a mild, non-irritant antiseptic will aid the application of topical antibiotics and reduce the spread of infection.
Nasal carriage of S. aureus occurs in a high proportion of both patients and asymptomatic family members. Therefore, in recurrent cases or multiple familial cases, treatment of nasal and pharyngeal carriage may be necessary.
Increasingly, methicillin-resistant S. aureus (MRSA) has become an important cause of impetigo. MRSA poses a challenge because of its enhanced virulence and resistance to standard antibiotic therapy. Antibiotic treatment should be guided by the likely causative agent and knowledge of local resistance patterns, as well as bacterial susceptibility testing.
Skin swabs for Gram stain, culture and sensitivity
Nasal swabs from patients and immediate relatives in recalcitrant cases
A Gram stain of a swab from the lesion or exudate will reveal Gram positive cocci, confirming the clinical diagnosis. Bacterial culture and sensitivity from a pretreatment swab is useful to assess suitable alternative antibiotics in cases that do not respond to conventional treatment.
Koning S, van der Sande R, Verhagen AP, van Suijlekom-Smit LW, Morris AD, Butler CC, et al. Cochrane Database Syst Rev 2012; 1: CD003261.
Bullous impetigo is always caused by S. aureus. S. aureus is considered to be the main bacterium that causes non-bullous impetigo. However, S. pyogenes, or both S. pyogenes and S. aureus, are sometimes isolated. In moderate climates, staphylococcal impetigo is more common, whereas in warmer and more humid climates the streptococcal form predominates. Worldwide, bacteria causing impetigo show increasing rates of resistance for commonly used antibiotics. No resistance has yet been reported for retapamulin.
Rortveit S, Rortveit G. Br J Dermatol 2007; 157: 100–5.
In this population-based study of impetigo, S. aureus was the causal bacterium in 89% (117/132) and 68% (84/123) of cases during epidemic and non-epidemic periods, respectively (p<0.01). S. aureus was resistant to fusidic acid in 84% (98/117) and 64% (54/84) of cases in epidemic and non-epidemic periods, respectively (p<0.01).
Rørtveit S, Skutlaberg DH, Langeland N, Rortveit G. J Antimicrob Chemother 2011; 66: 1360–4.
S. aureus resistance to fusidic acid in relation to impetigo is now less frequent in this population than at the start of the 21st century. Most S. aureus bacteria resistant to fusidic acid in impetigo belong to the European fusidic acid-resistant impetigo clone (EEFIC).
Capoluongo E, Giglio A, Leonetti F, Belardi M, Giannetti A, Caprilli F, et al. Res Microbiol 2000; 151: 53–61.
Samples from lesional skin, nose, and pharynx were taken from 26 patients and their families and the strain of S. aureus was typed; 54% of the patients had the same strain in both the nose and the lesion. In over half the families at least one other family member was found to be carrying the same strain as the patient’s lesion.
Iovino SM, Krantz KD, Blanco DM, Fernández JA, Ocampo N, Najafi A, et al. J Clin Exp Pathol 2011; 4: 587–95.
In 129 patients with clinically diagnosed impetigo, the majority of the infections were caused by S. aureus alone (106/125, 85%), of which approximately 10% were MRSA.
A systematic review of 68 trials including 5578 participants, reporting on 50 different treatments, including placebo. There is good evidence that topical mupirocin and topical fusidic acid are equal to, or possibly more effective than, oral antibiotics for people with limited impetigo. Fusidic acid, mupirocin, and retapamulin are probably equally effective; other topical antibiotics seem less effective. Due to lack of studies in patients with extensive impetigo, it is unclear whether oral antibiotics are superior to topical antibiotics in this group.
Based on the available evidence on efficacy for treating impetigo, no clear preference can be given for β-lactamase resistant narrow-spectrum penicillins such as flucloxacillin, cloxacillin or dicloxacillin, or for broad-spectrum penicillins such as amoxicillin with clavulanic acid, cephalosporins or macrolides. Penicillin was not as effective as most other antibiotics.
Bolaji RS, Dabade TS, Gustafson CJ, Davis SA, Krowchuk DP, Feldman SR. J Drugs Dermatol 2012; 11: 489–94.
Oral antibiotics are the most common class of medications used to treat impetigo. There is an opportunity for physicians to take advantage of the equally efficacious topical antibiotics for treating impetigo. A shift towards topical antibiotics would likely decrease morbidity (resulting from adverse effects) associated with use of oral agents.
Sladden MJ, Johnston GA. Br Med J 2004; 329: 95–9.
In this evidence-based review, the authors suggest using topical mupirocin or fusidic acid for 7 days in mild impetigo. They advise that oral antibiotics be reserved for recalcitrant, extensive, systemic disease.
Oranje AP, Chosidow O, Sacchidanand S, Todd G, Singh K, Scangarella N. et al. TOC100224 Study Team. Dermatology 2007; 215: 331–40.
Retapamulin and sodium fusidate had comparable clinical efficacies (intention-to-treat population 94.8% and 90.1%, respectively; p=0.062). Success rates in the small numbers of sodium fusidate-, methicillin-, and mupirocin-resistant S. aureus were good for retapamulin (9/9, 8/8, and 6/6, respectively). Both drugs were well tolerated. The authors concluded that retapamulin is a highly effective and convenient new treatment option for impetigo, with efficacy against isolates resistant to existing therapies.
Parish LC, Jorizzo JL, Breton JJ, Hirman JW, Scangarella NE, Shawar RM et al. SB275833/032 Study Team. J Am Acad Dermatol 2006; 55: 1003–13.
Retapamulin was as effective as cephalexin (clinical success rates 85.9% and 89.7%, respectively) in the treatment of patients with secondarily infected dermatitis. Microbiologic success rates were 87.2% for retapamulin and 91.8% for cephalexin. Retapamulin was well tolerated and the topical formulation was preferred over the oral drug.
Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, Montalvo J. Arch Dermatol 1989; 125: 1069–73.
Seventy-five patients were treated in an investigator-blinded study comparing topical mupirocin applied three times daily with oral erythromycin 30–50 mg/kg daily. The mupirocin treated patients experienced similar clinical results to those treated with oral erythromycin, although mupirocin was superior in the microbiological eradication of S. aureus.
Demidovich CW, Wittler RR, Ruff ME, Bass JW, Browning WC. Am J Dis Child 1990; 144: 1313–15.
A randomized trial of 73 children with impetigo treated with either penicillin V, erythromycin, or cefalexin. S. aureus was the most common pathogen and cefalexin the most effective treatment, although erythromycin may be preferred on grounds of cost-effectiveness.
Misko ML, Terracina JR, Diven DG. Pediatr Dermatol 1995; 12: 12–5.
Despite significant in vitro erythromycin resistance in a series of 98 outpatients, there was still a low frequency of treatment failure in this group. This suggested that erythromycin may still be a reasonable agent in the treatment of uncomplicated superficial skin infections in that community at that time.
The emergence of resistance to penicillin and erythromycin is so common in isolates of S. aureus that alternative antibiotics should be considered.
Carr WD, Wall AR, Georgala-Zervogiani S, Stratigos J, Gouriotou K. Eur J Clin Res 1994; 5: 87–95.
Fusidic acid tablets, 250 mg twice daily, 500 mg twice daily, and the standard regimen of 500 mg three times daily, were compared in a randomized, double-blind study in 617 patients with skin and soft tissue infections. Each treatment was given for five to 10 days. Cure rates after 5 days of treatment were 34.7%, 37.8%, and 37.2%, respectively. End of treatment cure rates were 75.5%, 81.1%, and 74.0%, respectively.
Feder Jr HM, Pond KE. Clin Pediatr 1996; 35: 205–8.
Two children with staphylococcal infections failing to respond to standard antibiotics responded when rifampin was added.
Christensen OB, Anehus S. Acta Derm Venereol 1994; 74: 460–2.
A prospective comparison of hydrogen peroxide cream with fusidic acid cream in 256 patients with impetigo. Over a 3-week treatment period, 92 of 128 (72%) patients in the hydrogen peroxide group were classified as healed, compared with 105 of 128 (82%) in the fusidic acid group. This difference was not statistically significant.
Zafar AB, Butler RC, Reese DJ, Gaydos LA, Mennonna PA. Am J Infect Control 1995; 23: 200–8.
A nosocomial outbreak of infection with MRSA in a neonatal nursery proved difficult to control even with aggressive conventional measures. The additional use of a handwashing and bathing soap containing 0.3% triclosan immediately ended the outbreak.
Aihara M, Sakai M, Iwasaki M, Shimakawa K, Kozaki S, Kubo M, et al. Postgrad Med J 1993; 69: S117–21.
An outbreak of MRSA causing impetigo was halted by wiping the body surface of the infants with a diluted povidone-iodine solution (10% povidone-iodine; 1 : 100 dilution) to prevent colonization.
Johnston GA. Expert Rev Anti Infect Ther 2004; 2: 439–46.
It is important to swab the skin for bacteriological confirmation and antibiotic sensitivities. Nasal swabs from the patient and immediate relatives should be performed to identify asymptomatic nasal carriers of S. aureus. In the case of outbreaks on wards and in nurseries, healthcare professionals should also be swabbed.
Failure of first-line therapy may indicate the presence of a resistant organism or poor patient compliance. The choice of antibiotic should be based on the sensitivities of organisms cultured from the pretreatment swab. In recurrent cases, consider the possibility of nasal or pharyngeal colonization with pathogenic S. aureus in either the patient or a close family member. This may require eradication by the use of a systemic antibiotic in conjunction with the nasal application of a topical antibiotic and an antiseptic skin cleanser. Topical antiseptics have also proved useful in nosocomial outbreaks.
An example of a 10-day Staphylococcus eradication program used by one of the authors (M.S.) consists of nasal mupirocin (thrice daily), antiseptic shampoo (e.g., cetrimide on days 1, 3, 7, 10), daily chlorhexidine body wash and oral antibiotics (rifampicin 300 mg twice a day and fusidic acid 500 mg twice a day).
Luby SP, Agboatwalla M, Feikin DR, Painter J, Billhimer W, Altaf A, et al. Lancet 2005; 366: 225–33.
In squatter settlements in Karachi, children younger than 15 years in households that received plain soap and handwashing promotion had a 34% lower incidence of impetigo than controls (95% CI, −52% to −16%).
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Topical mupirocin, fusidic acid, or retapamulin
Oral flucloxacillin, cloxacillin, dicloxacillin, cephalexin, erythromycin
Intravenous antibiotics
Other oral antibiotic depending on sensitivity, including rifampicin and fusidic acid
Topical antiseptics
Systemic antibiotic, topical antibiotic plus a formal anti-staphylococcal regimen to reduce nasal and pharyngeal carriage to prevent cross infection
