ARTICLE

Where to from here? The
treatment of impetigo in
children as resistance to
fusidic acid emerges
Alison Vogel, Diana Lennon, Emma Best, Alison Leversha

ABSTRACT
Admissions for skin and soft-tissue infections have been increasing steadily in children and in the general
population. Concerns have been raised recently about the increasing widespread use of topical fusidic
acid and concurrent increase of fusidic acid-resistant Staphylococcus aureus. Fusidic acid resistance and
methicillin resistant Staphylococcus aureus (MRSA) are both more prevalent in youngest age group (<5
year-olds) and particularly in the North island. In New Zealand, fusidic acid is recommended for treatment
of minor impetigo and is the only fully-funded topical antibiotic. The evidence base for alternative
treatment strategies for mild impetigo is limited. Most children with impetigo in the current skin and sore
throat schools programmes received care with wound management with only a few requiring escalation.
An upcoming randomised controlled trial comparing topical hydrogen peroxide cream, topical fusidic
acid and wound management only (clean and cover) will help provide evidence about the effectiveness of
alternative treatments in the New Zealand setting.

Background antibiotic treatment has been
commenced.10,11 With recurrent and
Hospitalisations due to Staphylococcus household re-infections, such measures
aureus (S. aureus) infections have been can potentially result in significant time off
steadily increasing in New Zealand; a trend school with consequent educational impact
also recognised internationally.1–4 In New for children and impact on work for parents.
Zealand, admissions are predominantly due
Current treatment advice for minor
to community-onset, methicillin suscep-
skin infections outlines a small number
tible S. aureus (MSSA) skin and soft tissue
of indications for topical antibiotics12–15
infections (SSTI) with admission rates
including children with localised impetigo
for staphylococcal SSTIs in New Zealand
(no more than three areas of the body
increasing approximately 5% per year from
affected or <5cm;2,12 <5% of body surface
2000 to 2011.5 SSTI admission rates are
area14) with topical fusidic acid being the
highest for preschool children, the elderly,
first choice. In addition it is the Phar-
Māori and Pacific populations, among those
mac-subsidised topical antimicrobial. The
living in the most deprived deciles and in
second-line topical antibiotic, mupirocin,
Northern and Central regions.5 It is esti-
which has additional methicillin resistant
mated that for each hospital admission,
S. aureus (MRSA) activity, is reserved for
up to 14 children may visit their general
small localised areas of infection resistant
practice with an SSTI.6
to fusidic acid12 with funding restricted
Impetigo has often been regarded as a to proven MRSA infection. For other
minor skin complaint. However, the high infective skin conditions such as boils
burden and the possibility of more serious and carbuncles, treatment is incision and
sequelae (serious skin sepsis leading drainage without antibiotics and oral antibi-
to hospitalisation or post-streptococcal otics are reserved for more extensive areas
glomerulonephritis) is acknowledged.5,7–9 In of infection, cellulitis or skin infection with
addition, current guidance includes recom- systemic symptoms.12 However, increased
mendations that children should not attend resistance amongst S. aureus to fusidic
school or day-care until 24 hours after acid is a concerning development and has

77
NZMJ 14 October 2016, Vol 129 No 1443
ISSN 1175-8716 © NZMA
www.nzma.org.nz/journal

4 13.org. pyogenes may be more common Fusidic acid resistance is important for in warmer.3 3.0 13.0 0.3 Ciprofloxacin 0. aureus MRSA: methicillin-resistant S. MSSA MRSA All S.0 0.0 0. The gene conferring fusidic acid resistance patterns and molecular epide- resistance (FusC) and the gene conferring miology from community laboratory methicillin resistance (MecA) are located isolates for children with skin and soft on the same mobile genetic element.0 0.7 93.0 0. especially of bone the youngest age group (<5 year olds) and and joints (including those caused by particularly in the North Island.0 0. and 20% of those from acid is also available in oral and intra- school age children.0 Co-trimoxazole 0.nzma.0 0.17.1 46.0 0. and the role of co-infection with S.0 0. Most studies do not include rocin dispensing have fallen significantly. aureus skin and soft tissue infections in children by age: New Zealand 2014.0 MSSA: methicillin-sensitive S. humid regions.0 0.21 S. A tissue infections is available from a national specific fusidic acid-resistant community survey of laboratory isolates performed associated methicillin-resistant clone (AK3) in 2014 by ESR.0 0. fusidic fusidic acid resistant.5 6.17 Dispensing due to Streptococcus pyogenes although rates are highest for Pacific and Māori.2 10.0 0. Almost the current dominant MRSA clone causing half the isolates from pre-schoolers were illness in New Zealand.7 2. It may lead to ineffective published New Zealand data describing the treatment in SSTI.17 Thirdly. MRSA) and efficacy in these situations might be impacted.7 Mupirocin 10. aureus may in the Northern regions. (Table 1: reproduced with has recently emerged to rapidly become permission Helen Heffernan ESR).18.3 13.7 70. aureus antimicrobial of MRSA. pyogenes in may be associated with other antimicrobial impetigo in the community.0 0. phage typing which if done suggests S.4 8.0 0.8 0.16 Concern about the increasing not require specific treatment. resistance and an increasing prevalence National data for S. coincident with removal of the Pharmac aureus may only be a secondary invader and subsidy. Vol 129 No 1443 ISSN 1175-8716 © NZMA www. Fusidic acid resistance venous formulations with a limited role as and methicillin resistant Staphylococcus part of combination adjunctive treatment aureus (MRSA) are both more prevalent in for invasive infections.18 while S.17 Rates of mupi- be important. aureus is resistance to fusidic acid has led to calls to thought to be the more common causative consider limiting access via prescriber and impetigo pathogen in temperate climates funding restrictions.0 Vancomycin 0. aureus Source: Heffernan et al 2015.16.19 The call to reduce fusidic acid use requires urgent reconsideration of the best strategies Table 1: Antimicrobial resistance for community acquired S.0 0. ESR 78 NZMJ 14 October 2016. aureus 0–4 y 5–14y 0–4 y 5–14y 0–4 y 5–14y N=82 N=92 N=16 N=7 N=98 N=99 (16%) (7%) Antimicrobial % resistant % resistant % resistant Fusidic acid 36.17 Rates of prescribing are patterns highest for preschool children followed by Impetigo has traditionally been considered those age 75+ and 5–14 years.8 16.5 11.0 Erythromycin 14.22 There are no three reasons. aureus and S.13. ARTICLE coincided with rising prescription rates Microbiology and resistance for fusidic acid.nz/journal . Fusidic acid resistance prevalence of S.0 20.

year Site Age Comparison Number Outcomes Results Comments Type measured Hydrogen peroxide RCT Christensen UK. Vol 129 No 1443 ISSN 1175-8716 © NZMA www. 2–74 Hydrogen 256 Healing. reviewed abstracts to determine relevance. The effective compared with placebo cream Cochrane review demonstrated studies with in RCTs.28 topical antibiotic available overseas. Cover’ advice. Resistance to retapamulin has Treatment strategies for impetigo also been reported (seen in almost 10% of S. Although inappropriate use of subsidy and restricted prescribing indi- topical fusidic acid may also occur in other cations. aureus25 which New Zealand pathogenesis and resistance has dropped following removal of Pharmac patterns. ARTICLE for impetigo treatment relevant to current mupirocin resistance in S. and rheumatic fever and serious skin infection.nz/journal . 14.26 again indicating for childhood impetigo treatment in New that use of topical antibiotics is likely to lead Zealand is a Cochrane review of treatment to resistance in skin pathogen flora.23 from 8–42% at 7–10 days. use in routine treatment of impetigo in the community.22 There is no difference in cure rates between fusidic acid and mupirocin22 or between Antiseptic creams retapamulin and fusidic acid.22 Evidence is high and associated with higher rates of summarised in the table below (Table 2). along use of fusidic acid and very high rates of with prior resistance in the face of high resistance in young children means the community use. with local guidelines influenced by considerations of availability and funding. mupirocin was used to treat impetigo include hydrogen available as a pharmacy dispensed agent peroxide. Community dispensing research gap in the evidence about the effec- rates of mupirocin in the late 1990s were tiveness of antiseptic agents. Cut.27 Analysis of a sample shows that only In New Zealand. Cover’ advice trials identified to July 2010. Table 2: Evidence for use of antiseptic creams. means it is inappropriate to problem needs to be addressed at this level. The Cochrane review is a meta-analysis The simplest treatment strategy is using of evidence from randomised controlled ‘Clean. high decontamination for MRSA and this. Cover”.24 Antiseptic topical agents that have been Prior to the year 2000. HP 72% Composite 199430 Sweden. fusidic acid or retapamulin are more with the ‘Clean. Cut. mostly biotics.org.nzma. In 2013 6. Povidine iodine cream No trials Chlorhexidine cream No trials HP: hydrogen peroxide 79 NZMJ 14 October 2016. fusidic trials. yrs peroxide vs composite healed report Germany fusidic acid. although some of this evidence placebo cream found cure rates ranging includes studies aged up to 30 years old. Mupi- Therefore the vast majority were treated rocin. Hygiene intervention: “Clean.29 There is an identified on prescription. Poor sites maximum assessed acid quality-in- 21 days 3. the large burden of SSTI. The basis of current recommendations aureus in a Texan study). Cut (finger nails).000 in the first nine months of 2014. fusidic acid and 4% of those assessed with skin infections mupirocin are the two available topical anti- were prescribed antimicrobials. povidine iodine and chlorhex- with no restrictions and was also subsidised idine solution. Retapamulin is a newer alternative topical fusidic acid or oral cephalexin.12 Nurse-led article we applied the search strategy from school clinics have been implemented since the Cochrane review to search for further 2012 in 61 Counties Manukau schools as relevant literature indexed in Medline part of initiatives to address high rates of or Embase from 2010 to March 2016.11. severity vs 82% of three total 47 2–3x daily to score.774 skin infections were treated Topical antibiotics and over 10.22. 21 NS adequate days blinding. Treatment Evidence Author. 7.17 Mupirocin remains useful for age groups. for impetigo.22 For this without topical or oral agents.

ARTICLE Table 3: Alternative antiseptic topical treatments in New Zealand. The primary outcome was treatment lower for topical antiseptics and mecha. Treatment with intramus. Some reports33 Contact dermatitis. development of resistance is less pyogenes from 90% and both from 74% concerning. Treatment Resistance Adverse events Funding in New Cost Zealand31. The only independent predictor of treatment success was clearance of S. The (4mg/kg plus 20mg/kg) for three days or once current large scale (population served 5–12 daily co-trimoxazole (8mg/kg plus 40mg/ year-olds~ n=30.27 dine cream Interference with thyroid function tests 25g Avoid if breastfeeding General sale Chlorhexi.nzma. success at day seven as measured by blinded nisms of resistance more complex for the assessment of photographs of the most organism.36 Important For moderate to severe impetigo. this problem there is insufficient evidence cular benzathine penicillin was compared to guide informed treatment of childhood with the use of twice daily co-trimoxazole impetigo in the New Zealand context. Ninety-percent of adverse effects and current funding/availability are events occurred in the benzathine peni- shown in Table 3.22 Cotrimoxazole was used advance knowledge. differences about health access mean that recommendations are for the use of oral in remote communities where close super- antibiotics. Treatment was successful to antibiotics used for systemic treatment at 85% in each arm at seven days. occur. aureus was not treatment for impetigo an independent predictor.27 These include studies due to high community prevalence of MRSA to determine the relative frequency of S. Vol 129 No 1443 ISSN 1175-8716 © NZMA www. Antiseptics are also not related severe lesion(s). The use of shorter A recent rigorously performed courses of oral antibiotic treatment however randomised controlled trial in the Northern is effective in severe lesions.35 Erythromycin is indicated in peni- groups is usually possible via school-based cillin allergy and co-trimoxazole for MRSA.32 Hydrogen Not reported Short term burning Funded $8.36 This non-inferiority trial Conclusion enrolled 508 indigenous children aged The dual concerns of increasing rates three months to 13 years. cillin group.56 peroxide Mild SE 11% HP vs 7% fusidic acid30 per General sale 15g Povidine io. being reported and isolated from impetigo aureus and S. S. adverse pre-treatment. rare severe hyper.12 The preferred options are vision is difficult the use of long acting IM flucloxacillin or cephalexin in children agents was justified. reported resistance is much lesions. or five or more deliberation. Despite the prevalence of sores in total).org. Oral or intramuscular antibiotic pyogenes.000) community interven- kg) for five days. General sale Cost?? dine cream sensitivity (Medsafe warning)34 Importantly. Benzathine penicillin has tions to manage skin infections in school been widely used in tropical settings to treat age children such as those occurring in extensive impetigo although oral penicillin Auckland offer an excellent opportunity to is not effective. pyogenes and of mixed 80 NZMJ 14 October 2016.12 clinics or primary care. aureus of infection therefore even if it does was identified from 81% of children. 72% of whom had of skin infection and increasing antibiotic severe impetigo (as defined as two or more resistance to fusidic acid require careful purulent or crusted sores. Clearance of S. Reported resistance. S. in contrast to New where palatability of flucloxacillin elixir is Zealand where close follow-up of high risk an issue.nz/journal . Territory of Australia raises pertinent ques- tions for the management of impetigo in New Zealand. Some Sensitivity (rare) Funded $3.

University of Auckland. 10. Epidemiol Infect. Baker MG. trends and and abscesses in UK Child and Youth Epide- demographics of Staphy. Williamson DA. 2015. 2000–2012. infections in New Zealand impetigo-more-detail. The Health Status of http://www. Shallcross LJ.org. Ministry of Health 2013. Auckland. Ministry of Health New 4. 5. Lim increasing severity of children and young people A. KidsHealth. Paediatrician.health. Petersen I. 143:2426–9. KidzFirst Children’s Hospital. Williamson DA. New Zealand.net/10523/6129. The University of Auckland. Wong W. Diana Lennon. 20:1156–61. go—more details. Craig E.ac. Fraser JD. 10. hospitalised children in Zealand: a national Skin infections in chil. d. Johnson AM. 2001–2011. Camargo Med J. An upcoming funded randomised schools across the Auckland region provide controlled trial (ACTRN 1261600356460p)37 an ideal opportunity for this to be examined. topical fusidic acid and antibiotics may be effective and could be local therapies only (clean and cover) should subject to study.nzma. [Epub ahead of print]. 2012.nz URL: http://www. 2014. there is a provide evidence about the effectiveness need for well conducted trials of alternative of alternative treatments. Community Paediatrician. ARTICLE infections and ongoing surveillance of of mild to moderate impetigo in school resistance patterns among isolates from children comparing topical hydrogen skin infections. Zealand. AC. Professor of Population Child and Youth Health. 8. Professor of Population Child and Youth Health. Incidence. Baker MG. Dis. Emma Best. clinical features Lancet. 3. Author information: Alison Vogel. Adams J. Vol 129 No 1443 ISSN 1175-8716 © NZMA www. 13:569. Trends 7. Mansbach JM. Hayward 139: 1794–804. on the burden of disease ing incidence of serious 2000–2011. Hasegawa K.nz/ Children. Senior Lecturer. Emerg Infect from post-streptococcal infectious diseases and Dis. Staphylococcus aureus population-based study Kvalsvig A et al. Tsugawa Y. 9. Increasing hospi. Dunedin. in Infectious Disease Zhang J. 11. Evidence for et al. Ritchie SR. Corresponding author: Professor Diana Lennon.govt. Oben G. exploring beneath the Paediatr Child Health. General Practice. Auckland. Shorter courses of oral peroxide cream. Department of Paediatrics. University of Auckland. 49:850–5.org. Available from http:// Hospitalizations in US talizations for serious skin www. J Epub 2012 Feb 20. Baker MG. Department of Paediatrics. Thomas MG. Lennon DR. primary care setting: and complications. Starship Children’s Health. 1990–2007. 379: 1112–9. Increas. Epidemi. The school-based treatments particularly the use of antiseptic health services operating in low decile creams. 2013.nz/ 81 NZMJ 14 October 2016. tip of the iceberg. glomerulonephritis of inequalities in New 6. Alison Leversha. O’Sullivan C. et al. Department of Paediatrics.nz/journal . in Auckland.lennon@auckland. dren in a New Zealand ology. Barnard LT. 2012. O’Sullivan CE. New Zealand: epidemi- epidemiological study. University of Auckland. Auckland. Auckland. N Z 2013.kidshealth. Goto T.nz/journal/read-the-journal/all-issues/2010-2019/2016/vol-129-no-1443- 14-october-2016/7036 REFERENCES: 1. Starship Children’s Health. Crone S. lococcus aureus infections ol Infect 2015. BMC Infect J. Zhang handle. Baker MG. Competing interests: Nil. community-onset boils in New Zealand.nzma. Impeti- CA Jr. Starship Children’s Health. Pedi. Available from http://hdl. More pressingly. Prospective 2. 2011. 2016 Mar children. Accessed August 2015. miology Service. Paediatrician. 2013. et al. atr Infect Dis J. Roberts S. 125:70–9. Impetigo. Auckland.org. infections in New Zealand.

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