A supplement to IMPETIGO: Addressing Treatment Adelaide A. Hebert, MD Challenges and Burden The UTHealth McGovern Medical School-Houston of Disease Houston, Texas Introduction Review of Impetigo Linda F. Impetigo, a very common bacterial Impetigo affects the epidermal skin Stein Gold, MD skin infection, is a moving target. Over layer with either nonbullous or bul- Henry Ford Health the past few decades there has been lous presentation. Approximately 70% System a shift in the associated bacteriology of all impetigo cases present as the Detroit, Michigan and resistance patterns, making the nonbullous form, which largely affects choice of best treatment more difficult preschool and school-aged children without the benefit of culture and sen- (ages 2-6 years), though all ages can sitivity guidance.1 Evidence that Staph- experience this contagious infection. ylococcus aureus (S. aureus) strains and Impetigo is predominantly caused by S. streptococcal species are developing aureus or Streptococcus pyogenes (S. Author Disclosures resistance to typical first-line topical pyogenes), sometimes referred to as Dr. Hebert: treatments is mounting.2-4 Emergence of group A beta-hemolytic streptococcus Research: Cassiopea, Cutanea, Mupirocin resistance has been reported (GABHS).9,10 Risk of infection increases Dermira, Galderma, GlaxoSmithKline, in several recent studies.5 Methicillin- in populations where hygiene is poor, Leo, Medimetrics, Novan, Pfizer, resistant S. aureus (MRSA) is also a or where there is inadequate access to Sienna, Valeant. All monies paid to growing concern in the community set- housing, health care, and other resourc- The UTHealth McGovern Medical School-Houston, Houston, Texas. ting. Oral penicillin and macrolides are es. Primary infection occurs in intact no longer viable treatment options and skin. Secondary infection occurs fol- Honoraria: Amgen, Cassiopea, resistance is emerging against clinda- lowing excoriation of scabies or insect Cutanea, Novan, Pfizer, Valeant mycin, cephalexin, and linezolid, lead- bites, and/or in the presence of comor- Data safety monitoring Boards (with ing to the potential for more expensive bid conditions such as atopic dermati- honoraria): Bausch, GlaxoSmithKline, and intensive therapies.2,6,7 tis (eczema) and diabetes. Nonbullous Sanofi Regeneron While often described as “self limit- impetigo is characterized by the pres- Dr. Stein Gold: ing,” treatment of impetigo is gener- ence of small pustules that form a Advisor: Cutanea ally advised as this disorder is highly yellow-gold crust located around the This supplement is sponsored by contagious, often requiring isolation nose and mouth as well as on extrem- from school, work, or social activities. ities; it is usually not associated with A multitude of blistering skin disorders systemic symptoms such as fever.6,7,9 S. complicate the differential diagnosis aureus has become more prominent as with no good immediate diagnostic the causative agent in the nonbullous This content was prepared by the tests.7 Additional concerns over disease form, though in more tropical locations specialized content division of progression to more serious problems and indigenous peoples S. pyogenes is Frontline Medical Communications, 7,11 publishers of Dermatology News. put primary caregivers on a precarious still of concern. The bullous form is tipping point, balancing the need for exclusively caused by S. aureus, which Copyright © 2019 Frontline Medical a quick and effective treatment with produces toxins that cause larger su- Communications Inc. All rights reserved. No part of this publication good antibiotic stewardship. Current perficial bullae filled with yellow fluid. may be reproduced or transmitted in treatments include a new topical anti- These occur on the trunk and inter- any form, by any means, without prior biotic, ozenoxacin (Xepi), retapamulin triginous skin of extremeties, mostly in written permission of the Publisher. (Altabax), and the old topical treat- diapered regions of children younger Frontline Medical Communications ments such as mupirocin and fusid- than 2 years of age.6,7,9 Inc. will not assume responsibility ic acid (not available in the United Globally, impetigo has been estimated for damages, loss, or claims of States), which are still widely used as to affect over 100 million people at any any kind arising from or related to first-line therapies. This, coupled with a one time and ranks within the top 50 the information contained in this recent study highlighting the need for burden-inducing disease states.3,12 In the publication, including any claims improved proficiency in impetigo rec- United States, approximately 3 million related to the products, drugs, or 13 services mentioned herein. The ognition, warrants a refresher to ensure cases occur annually. Heat, humid- opinions expressed in this supplement diagnosis and empiric treatment of the ity, and prior skin trauma are pre- do not necessarily reflect the views of infection is well understood by those disposing factors, and as such there the Publisher. on the front lines.7,8 can be seasonal variation favoring warmer weather and exposure to insect outside of the United States, vary great- clothing in hot water (60°C/140°F), and bites.3,7 Incidence rates have been not- ly among studies and demonstrate the keeping fingernails short can help miti- ed to vary over the course of several importance of knowing local resistance gate the spread of bacteria.7,9,19 Natural years, and children with atopic derma- patterns.3 Overall resistance rates to the remedies, such as tea tree oil and Manu- titis are at greater risk for infection.3 commonly prescribed topical antibiot- ka honey have been used with anecdot- Placing a dollar value on the overall ics are reportedly as high as 81%.15 As al success, but are not well studied and burden is difficult as costs of treatment resistance is known to increase health may not satisfy daycare requirements.6,7 constitute only a portion of the total costs due to hospitalization and the Access to readily available disinfec- encumbrance. Lesions in either form need for more expensive and intensive tants and over-the-counter (OTC) top- are highly contagious and require that treatment, this is considered a major ical antibiotics may entice individuals the affected individual be kept from threat to public health.6 or families to self treat. Topical antisep- school or work. Families are impacted Proper diagnosis adds to the diffi- tics are not well studied as comparator when parents must care for infected culty of treatment choice, with both agents, and there is little evidence to children, or when cross-contamination family/caregivers and medical person- support routine use for primary ther- results in the need to treat more than 1 nel potentially attributing skin blisters apy over topical antibiotics.6,7,10 While individual.3,6 Though less severe cases to other causes. Nonbullous impetigo certain alcohol-based hand cleansers,* will self resolve after 4 weeks, treat- may be mistaken as atopic dermatitis, hydrogen peroxide, povidone-iodine, ment is recommended to hasten re- contact dermatitis, scabies, herpes sim- and chlorhexidine solutions are not covery time or prevent progression plex, or varicella zoster virus, and not shown to cause resistance and may to more severe disease and spread to be prescribed the appropriate treat- therefore be used concomitantly, there others. Poststreptococcal glomerulo- ment. The bullous form may be misin- is still the need to consider their overall nephritis and rheumatic heart disease terpreted as insect bites, tinea corporis, environmental impact, and the Dutch have become less common with the eczema, contact dermatitis, or a drug College of General Practitioner’s guide- shift toward S. aureus as the causative eruption.7,8,16 A 2015 survey of pedia- lines recommend they be avoided.3,4,10 pathogen, though glomerulonephritis tricians at Johns Hopkins University Bacitracin is available in combination can occur in up to 5% of nonbullous found that only 31.9% were able to cor- with polymixin B and/or neomycin OTC cases in areas where impetigo is highly rectly diagnose bullous impetigo, and in the United States, and while this OTC prevalent.6,7,10 Antibiotic treatment has though most chose mupirocin as first- product appears to have good labora- not been proven to reduce the inci- line therapy for localized infections, tory data to support its effectiveness dence of glomerulonephritis.7,9 31.3% chose bacitracin, which is not against Gram-positive bacteria, it has Despite the pressure to treat impeti- recommended in either form of impeti- not stood the test of clinical applica- go, clinicians may also feel sanctioned go as a first- or second-line treatment.8 bility and is feared to not effectively to limit antibiotic use in the face of While skin swabs may not be help- eradicate bacteria.1,10 Additionally, it is growing microbial resistance.3,6,7 Anton- ful in determining empiric treatment, implicated in severe contact allergic ov et al reported that 31.3% of all S. cultures should be obtained if MRSA reactions in people both with and with- aureus isolates collected from children is suspected, and serologic tests can out preexisting conditions.4 seen in a predominantly outpatient set- help determine poststreptococcal glo- Most recent reviews indicate that ting in New York City were resistant merulonephritis or herpes simplex vi- there is no significant data to rec- to mupirocin, and that prior mupirocin rus (HSV).7,9,10,17 Differentiation between ommend one topical antibiotic over use was strongly correlated.14 McNeil impetigo and herpes gladiatorum is of another, or to recommend oral ther- et al documented that up to 10% of in particular importance with athletes of apy over topical, and there remains vitro S. aureus isolates from healthy, close-contact sports to ensure early variations across countries on thera- community-based children in the Hous- effective treatment and to avoid trans- py standards.3,7 The topical antibiotics ton area displayed resistance to topical mission.17,18 Of note, many of the di- mupirocin, fusidic acid, or retapamu- antibiotics, including MRSA.