AUTHOR INFORMATION

Section 1 of 11

Authored by Randy Park, MD, Chair, Associate Professor, Department of Emergency Medicine, Denton Regional Medical Center

Edited by Eric Kardon, MD, FACEP, Consulting Staff, Department of Emergency Medicine, Athens Regional Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eric L Weiss, MD, DTM&H, Director of Stanford Travel Medicine, Medical Director of Stanford Lifeflight, Assistant Professor, Departments of Emergency Medicine and Infectious Diseases, Stanford University School of Medicine; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Pamela Dyne, MD, Program Director, Associate Professor, Department of Medicine, Division of Emergency Medicine, University of California at Los Angeles School of Medicine

Author's Email:	Randy Park, MD
Editor's Email:	Eric Kardon, MD, FACEP

eMedicine Journal, February 27 2006, VOLUME 7, Number 2

INTRODUCTION

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Background: Impetigo is a term that is part of several different infectious skin diseases. Impetigo contagiosa is a superficial, intraepidermal, unilocular, vesiculopustular infection. Impetigo contagiosa is the most common skin infection in children. Bullous impetigo is a toxin-mediated erythroderma in which the epidermal layer of the skin sloughs resulting in large areas of skin loss. Common impetigo is the term applied when the infection occurs in preexisting wounds. Impetigo also can present as folliculitis, which is considered to be impetigo of the hair follicles caused by Staphylococcus aureus. Ecthyma is a deeper, ulcerated impetigo infection, often occurring with lymphadenitis.

Pathophysiology: Impetigo is an infection caused by group A beta-hemolytic streptococci (GABHS) or S aureus. The organisms are thought to enter through damaged skin and are transmitted through direct contact. After infection, new lesions may be seen on the patient with no apparent break in the skin. Frequently, however, upon close examination, these lesions will demonstrate some underlying physical damage.

The presentation of impetigo may take on more than one form. Some authors suggest that differences are due to the staphylococcal strain involved and the relative activity of the exotoxin.

In impetigo contagiosa, the lesions begin with a single 2- to 4-mm erythematous macule that rapidly evolves into a vesicle or a pustule. This vesicle is very fragile and ruptures early, leaving a crusted exudate of a honey or yellow color over the superficial erosion. The infection spreads to contiguous and distal areas through inoculation of other wounds from scratching.

Bullous impetigo presents with small or large, superficial, fragile bullae on the trunk and the extremities. Often, only the remnants of ruptured bullae are seen at the time of presentation. The separation of the epidermis is due to an exotoxin produced by staphylococci, which is the pathologic organism present in cases of bullous impetigo. In lesions of this type, isolation of methicillin-resistant S aureus has been as high as 20%. Some authors assert a continuum of disease including nonbullous impetigo, bullous impetigo, and abscess formation caused by S aureus with differing exotoxin characteristics.

On histologic examination, the lesions in all presentations reveal a subcorneal neutrophilic infiltrate.

Frequency:

• In the US: Approximately 9-10% of all children presenting to clinics with skin complaints have impetigo.

• Internationally: About 2.6 episodes per 100 person weeks has been reported.

Sex: Impetigo occurs equally in males and females.

Age:

• Impetigo occurs more commonly in children.

• The majority (90%) of bullous impetigo cases occur in children younger than 2 years.

CLINICAL

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History:

• Tender red rash

• Honey-colored crusts

• Pruritus

• Poorly healing wound

• The following symptoms usually are absent in impetigo contagiosa but may be present in bullous impetigo:

• Fever

• Diarrhea

• Generalized weakness

Physical:

• Type and location of lesions

• Most frequently on the face (around the mouth and the nose) or at a site of trauma

• Red macule or papule as early lesion

• Lesions with ruptured bullae and crusted edges

• Lesions with honey-colored crusts

• Thin-roofed vesicle or bullae (usually nontender)

• Pustules

• Weeping, shallow, erythematous ulcer

• Satellite lesions (often at multiple sites)

• Bullae on the buttocks, trunk, and face

• Regional lymphadenopathy

• Common in impetigo contagiosa

• Rare in bullous impetigo

Causes: The causative agents are coagulase-positive S aureus and GABHS. S aureus is cultured consistently from the lesions, but streptococci are found only occasionally. The infection may be caused by a mixture of the 2 organisms. GABHS rarely act as the sole causative agent, as was believed 10 years ago. The incidence of community-acquired methicillin-resistant S aureus (CA-MRSA) has increased in some locales to as high as 50% of the isolates.

DIFFERENTIALS

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Burns, Thermal
Candidiasis
Cellulitis
Dermatitis, Atopic
Dermatitis, Contact
Erythema Multiforme
Herpes Simplex
Herpes Zoster
Pediculosis
Scabies
Staphylococcal Scalded Skin Syndrome
Stevens-Johnson Syndrome
Tinea

Other Problems to be Considered:

Folliculitis
Erysipelas
Insect bites
Severe eczematous dermatitis
Tinea corporis
Pemphigus vulgaris
Bullous pemphigoid

WORKUP

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Lab Studies:

• In special situations, such as a questionable diagnosis, the existence of epidemic conditions, or poor response to treatment, studies may be required as follows:

• The Gram stain will reveal neutrophils with gram-positive cocci in chains or clusters.

• Cultures of the fluid will reveal S aureus, most commonly in combination with Streptococcus pyogenes or other GABHS, but either may occur alone.

• Antibiotic sensitivity testing may be required to isolate MRSA and identify appropriate antibiotics.

• A biopsy may be indicated.

Other Tests:

• Antistreptolysin-O (ASO) titer may be weakly positive for streptococci, but it rarely is performed.

• Streptozyme is positive for streptococci, but it rarely is performed.

TREATMENT

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Emergency Department Care: The emerging resistance of S aureus to beta-lactams, macrolides, and even mupirocin requires consideration of the prevalence of CA-MRSA in the locale of the patient. Treatment of bullous impetigo should now always consider this possibility. Trimethoprim-sulfamethoxazole, clindamycin, and rifampin all retain sensitivity in the vast majority of CA-MRSA strains.

• Wound cleaning with gentle abrasion is indicated. Deep abrasive scrubbing is not required.

• Topical mupirocin is adequate treatment for single lesions of nonbullous impetigo or small areas of involvement.

• Systemic antibiotics are indicated for extensive involvement or for bullous impetigo.

• If there are large areas of involvement resulting in denuded skin from ruptured bullae, then adequate fluid resuscitation is indicated with intravenous rehydration fluid at a volume and rate similar to standard volume replacement for burns.

• Early and appropriate treatment usually prevents scarring and localized spread.

Consultations: The need for consultation is determined by the extent of involvement and the age of the patient. Neonates with bullous impetigo require a consultation with neonatology.

MEDICATION

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Antibiotics are the mainstay of therapy. The drug chosen must provide coverage against coagulase-positive S aureus and GABHS. In areas with high percentage of CA-MRSA, the empiric antibiotic choice should provide coverage for this possibility.

Drug Category: Topical antibiotics -- These agents pose fewer potential problems than systemic antibiotics, but their use is reserved only for cases involving lesions that are small or few in number.

In addition to mupirocin, fusidic acid (not available in the United States) is a commonly used topical antibiotic for impetigo.

Drug Name	Mupirocin ointment (Bactroban) -- DOC for few small lesions in absence of lymphadenopathy.
Adult Dose	Apply to lesions tid for 5 d; clean lesions prior to application
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Prolonged use may result in growth of nonsusceptible organisms

Drug Category: Systemic antibiotics -- Therapy must cover all likely pathogens in the context of the clinical setting.

Drug Name	Cephalexin (Keflex) -- First-generation cephalosporin that inhibits bacterial growth by inhibiting bacterial cell wall synthesis; bactericidal and effective against rapidly growing organisms forming cell walls. Primarily active against skin flora; typically used for skin-structure coverage and as prophylaxis in minor procedures. Does not cover MRSA. DOC for cases involving large number of lesions, large areas of involvement, or regional lymphadenopathy.
Adult Dose	250-500 mg PO qid for 7 d
Pediatric Dose	25-50 mg/kg/d PO divided qid
Contraindications	Documented hypersensitivity
Interactions	Aminoglycosides increase nephrotoxic potential
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment

Drug Name	Erythromycin (EES, Erythrocin, Ery-Tab) -- DOC in penicillin- or cephalosporin-allergic patient. Inhibits RNA-dependent protein synthesis, possibly by stimulating dissociation of peptidyl tRNA from ribosomes, which inhibits bacterial growth. Does not cover MRSA.
Adult Dose	250-500 mg PO qid for 7 d
Pediatric Dose	30-50 mg/kg/d PO divided qid for 7 d
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	May increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; lovastatin or simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Resistance may exist in some areas (as many as 30% of cases); caution in liver disease; estolate preparations may cause cholestatic jaundice; GI adverse effects, including nausea and vomiting, are common (administer doses after meals); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Dicloxacillin (Dycill, Dynapen) -- Bactericidal antibiotic that inhibits cell wall synthesis. Used in treatment of infections caused by penicillinase-producing staphylococci; may be used to initiate therapy when staphylococcal infection suspected. Very effective, but less well tolerated than cephalexin. Does not cover MRSA.
Adult Dose	250 mg PO qid for 7 d
Pediatric Dose	20-50 mg/kg/d PO divided qid for 7 d
Contraindications	Documented hypersensitivity
Interactions	Decreases efficacy of oral contraceptives; increases effects of anticoagulants; probenecid and disulfiram may increase levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Monitor PT in patients taking anticoagulant medications; toxicity may increase in renal impairment

Drug Name	Clindamycin (Cleocin) -- Semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of parent compound lincomycin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Widely distributes in the body without penetration of CNS. Protein bound and excreted by the liver and kidneys. Alternative therapy for S aureus resistant to erythromycin and MRSA. Used for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci).
Adult Dose	300 PO q8h for 10 d
Pediatric Dose	10-30 mg/kg/d PO divided q6-8h for 10 days
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile

FOLLOW-UP

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Further Inpatient Care:

• Inpatient care is required for patients with widespread disease or for infants at risk of sepsis and/or dehydration due to skin loss.

Further Outpatient Care:

• A follow-up examination is required if lesions have not cleared in 7 days.

Transfer:

• Transfer care to a neonatologist for neonates with bullous impetigo.

Deterrence/Prevention:

• Avoid contact with infected persons.

• Keep wounds clean.

• Wash hands after contacting lesions or infected patients.

Complications:

• Poststreptococcal glomerulonephritis (all age groups)

• Meningitis or sepsis (infants)

• Ecthyma

• Erysipelas

• Deep cellulitis

• Bacteremia

• Osteomyelitis

• Septic arthritis

• Pneumonia

• Lymphadenitis

Prognosis:

• Beyond the neonatal period, patients who receive early and appropriate therapy have an excellent chance of recovery without scarring or complications.

• Neonates have a much higher incidence of developing a more generalized infection and meningitis.

• Lesions usually resolve completely in 7-10 days with treatment.

• Antibiotic treatment will not prevent or halt glomerulonephritis.

• Culture lesions to find resistant organisms if the lesions have not resolved within 7-10 days.

Patient Education:

• Children must not return to daycare or school before the lesions clear.

• Caretakers must know how to avoid infection.

• This infection is transmitted by direct contact and by fomites, including hygiene items, clothing, and toys.

• For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center and Skin, Hair, and Nails Center. Also, see eMedicine's patient education articles Impetigo, Skin Rashes in Children, and Antibiotics.

MISCELLANEOUS

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Medical/Legal Pitfalls:

• Failure to use antibiotics with coverage against staphylococci may result in failure of treatment.

• Failure to recognize signs of dehydration and treat appropriately may result in hypovolemic and/or septic shock.

Special Concerns:

• The incidence of poststreptococcal glomerulonephritis is not affected by the treatment of the infection in the index patient, but antibiotic treatment will limit the endemic nature by limiting its spread to other hosts.

TEST QUESTIONS

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CME Question 1: Which of the following complications of impetigo is not influenced by early and appropriate treatment?

A: Scarring
B: Localized spread
C: Poststreptococcal glomerulonephritis
D: Meningitis
E: Sepsis

The correct answer is C: The incidence of glomerulonephritis in the index patient is not decreased by treatment.

CME Question 2: Which bacteria are most likely responsible for impetigo?

A: Streptococcus pyogenes and group A beta-hemolytic streptococci (GABHS)
B: Coagulase-positive Staphylococcus aureus and occasionally group A beta-hemolytic streptococci (GABHS)
C: Group A beta-hemolytic streptococci (GABHS) and Staphylococcus haemolyticus
D: Corynebacteria and coagulase-positive Staphylococcus aureus
E: Toxigenic Escherichia coli and coagulase-positive Staphylococcus aureus

The correct answer is B: S aureus is cultured consistently from the lesions, but streptococci are found only occasionally.

Pearl Question 1 (T/F): Mupirocin ointment is the antibiotic of choice for a patient with 3 small lesions of impetigo.

The correct answer is True: Mupirocin ointment is the most cost-effective and the least toxic treatment.

Pearl Question 2 (T/F): The organism responsible for a bullous impetigo outbreak in a newborn nursery is Escherichia coli.

The correct answer is False: Staphylococcus aureus is the common organism in this setting.

Pearl Question 3 (T/F): Bullous impetigo is universally caused by Staphylococcus aureus and is sensitive to cephalexin.

The correct answer is False: In some localities, as many as 50% of the S aureus cases are community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which is universally resistant to beta-lactam antibiotics such as cephalexin.

Pearl Question 4 (T/F): The patient has been noncompliant if a case of impetigo worsens after treatment with erythromycin.

The correct answer is False: Noncompliance is always possible; however, in some areas, up to 30% of Staphylococcus aureus are resistant to erythromycin.

BIBLIOGRAPHY

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• Allen CH, Patel B, Endom EE: Primary bacterial infections of the skin and soft tissues, changes in epidemiology and management. Clin Ped Emerg Med 2004; 5: 246-255.
• Cherry JD: Contemporary infectious exanthems. Clin Infect Dis 1993 Feb; 16(2): 199-205[Medline].
• Dagan R: Impetigo in childhood: changing epidemiology and new treatments. Pediatr Ann 1993 Apr; 22(4): 235-40[Medline].
• Darmstadt GL, Lane AT: Impetigo: an overview. Pediatr Dermatol 1994 Dec; 11(4): 293-303[Medline].
• Elsayed S, Laupland KB: Emerging gram-positive bacterial infections. Clin Lab Med 2004 Sep; 24(3): 587-603[Medline].
• Epps RE: Impetigo in pediatrics. Cutis 2004 May; 73(5 Suppl): 25-6[Medline].
• Leyden JJ: Review of mupirocin ointment in the treatment of impetigo. Clin Pediatr (Phila) 1992 Sep; 31(9): 549-53[Medline].
• Luby S, Agboatwalla M, Schnell BM, et al: The effect of antibacterial soap on impetigo incidence, Karachi, Pakistan. Am J Trop Med Hyg 2002 Oct; 67(4): 430-5[Medline].
• Nishijim S, Ohshima S, Higashida T, et al: Antimicrobial resistance of Staphylococcus aureus isolated from impetigo patients between 1994 and 2000. Int J Dermatol 2003 Jan; 42(1): 23-5[Medline].
• Shriner DL, Schwartz RA, Janniger CK: Impetigo. Cutis 1995 Jul; 56(1): 30-2[Medline].
• Zetola N, Francis JS, Nuermberger EL, Bishai WR: Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis 2005 May; 5(5): 275-86[Medline].

eMedicine Journals > Emergency Medicine > Infectious Diseases > Impetigo

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