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Background

Antimicrobial resistance has been described as a “crisis for the health and wealth of nations”.1 One of the key strategies to mitigate this public health crisis is to ensure that existing antimicrobials are used responsibly and judiciously. In general, New Zealand has relatively low rates of antimicrobial resistance threats deemed as ‘critical’ or ‘urgent’ by the Centers for Disease Control and Prevention.2 However, this may reflect relatively low levels of consumption of many antimicrobials in previous decades, rather than our relatively high levels of antimicrobial consumption in more recent years.3 In particular, high usage of topical antimicrobial agents over the past three decades in New Zealand has resulted in an ill-fated series of national population-level experiments, which clearly illustrate the relationships between antimicrobial consumption and resistance. Throughout the 1990s, the topical antimicrobial agent mupirocin (Bactroban©) was available to purchase ‘over-the-counter’ (OTC), which led to very high levels of use, and subsequent high rates of resistance, such that by 2000, approximately 14% of S. aureus isolates displayed high-level resistance to mupirocin.4 From April, 2000, regulatory changes meant that mupirocin could be obtained by ‘prescription only’, with a subsequent decrease in usage, and a fall in the prevalence of high-level mupirocin resistance in S. aureus from 14.2% in 2000, to 8.3% in 2014.5 Interestingly, the authors of a 2003 study describing mupirocin resistance in New Zealand concluded that:

“In cautioning against the use of mupirocin, we do not advocate using fusidic acid topically as an alternative. Resistance to this topical agent is reported, and unlike mupirocin, it is available in oral and intravenous formulations that are used for treatment of multiresistant S. aureus infections”.4

Similarly, an Australian commentary in 2006 on fusidic acid use stated:

“Ensuring that… the use of topical fusidic acid is either abolished or restricted will be vital if we are to prevent the loss of this potentially useful agent”, and “Common sense would suggest that antibiotics used topically should be ones that are not used systemically”.6

Despite these unambiguous warnings, regulatory changes and the promulgation of guidelines promoting the use of topical fusidic acid ointment and cream contributed to a significant increase in topical fusidic acid dispensing in New Zealand throughout the 2000s (Figure 1), with an associated increase in the prevalence of resistance in S. aureus from 17% in 1999, to 28% in 2013.7 At present, topical fusidic acid is available by prescription only, although it is fully subsidised by the New Zealand Ministry of Health, unlike mupirocin, which is only partially subsidised.

Figure 1: Community dispensing rates per 1,000 population for topical fusidic acid and mupirocin in the New Zealand community setting, January, 1993,–August, 2013. Reproduced from Reference 7.

b

The evidence for and against topical antimicrobial use

Theoretically, the use of topical antimicrobials is an attractive option to treat minor skin ailments. Topical application allows delivery of high concentrations of antimicrobial at the site of infection, while minimising systemic absorption. In practice however, topical antibiotic use has long been recognised as a very efficient method of rapidly promoting the emergence and proliferation of antibiotic resistant microbes.6 Furthermore, evidence-based prescribing supports the use of topical antimicrobial agents for only a few specific indications, including nasal eradication of S. aureus, treatment of acne, and treatment of mild impetigo.8-10

Despite concerns about efficacy and the promotion of even higher rates of resistance, fusidic acid remains the recommended agent in New Zealand for the empiric treatment of impetigo.11,12 Importantly, rates of resistance to fusidic acid in S. aureus remain comparatively lower in countries that have not adopted the widespread use of topical fusidic acid.13-15 In general, Streptococcus pyogenes, the other pathogen commonly associated with impetigo, is less susceptible to fusidic acid than S. aureus.16

One of the largest randomised control trials (RCTs) assessing the efficacy of topical fusidic acid vs placebo in the treatment of mild impetigo, conducted in the Netherlands between 1999 and 2000, found that cure rates after one week of treatment with topical fusidic acid were significantly higher than with placebo (55% vs 13%, odds ratio [OR] 12.6, 95% confidence interval [CI], 5.0–31.5).17 However, this difference reduced over time, with 92% of treated patients displaying cure at 28 days, vs 88% of patients in the placebo arm. It also must be noted that no fusidic acid resistance was detected in S. aureus isolates from this study population, meaning that these study findings are not directly applicable to the New Zealand setting, where contemporary fusidic acid resistance rates are high. In addition, another RCT conducted in the UK, Germany and Sweden in 1994, found no statistically significant difference in cure rates between topical fusidic acid and hydrogen peroxide in the treatment of localised impetigo (82% vs 72%, respectively).18 Again, caution should be exercised when extrapolating these results to the New Zealand setting, as rates of fusidic acid resistance in these countries are markedly lower than New Zealand.14 However, despite the limited application of overseas findings to the New Zealand setting, such studies have been used as the basis for guidelines that actively recommend topical fusidic acid in the empiric treatment of impetigo.11,12 Importantly, there are no published studies comparing the use of topical fusidic acid vs placebo, or vs antiseptic treatment for impetigo in high prevalence resistance settings, such as New Zealand. In particular, it is not yet known whether topical hydrogen peroxide is a feasible alternative for New Zealand children compared to topical fusidic acid.

Demographics of topical fusidic acid use in New Zealand

In addition to therapeutic usage, data suggest that, in some settings, topical antimicrobials may also be used prophylactically, particularly in elderly patients. For example, a study from the US assessing national usage of topical antimicrobials found that 40% of all topical antimicrobial usage was in the over-50 age group, with benign or malignant skin neoplasms being the most common diagnosis associated with topical antimicrobial usage.19 These authors hypothesised that in such instances, topical antimicrobials were being used as post-operative wound ‘prophylaxis’ following minor surgery, a practice that is not supported by available evidence.20,21

Information on the demographics and geographic variation of antimicrobial usage in a population is essential in understanding how and why antimicrobials are utilised, and identifying potential areas for reduction in usage. Information on all community prescriptions in New Zealand are maintained in a central data warehouse, the ‘Pharmaceutical Collection’. Data from this collection between January, 2006, and August, 2013, demonstrates that the highest rates of topical fusidic acid dispensing were in the under-5 year age group, followed by the 75 year and over age group (Figure 2).

Figure 2: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by age group, January, 2006,–August, 2013.

c

When stratified by ethnicity, the highest rates of dispensing were in Māori and Pacific Peoples (Figure 3), and when stratified by geographic region, the highest rates of dispensing were in the Northern region of New Zealand (Figure 4).

Figure 3: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by ethnicity, January, 2006,–August, 2013.

c

Figure 4: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by geographic region, January, 2006–August, 2013. (Northern = Northland DHB, Waitemata DHB, Auckland DHB, Counties Manukau DHB; MidCentral = Waikato DHB, Lakes DHB, Bay of Plenty DHB, Tairawhiti DHB, Taranaki DHB; Central = Hawkes Bay DHB, MidCentral DHB, Whanganui DHB, Capital and Coast DHB, Hutt DHB, Wairarapa DHB; Southern = Nelson Marlborough DHB, West Coast DHB, Canterbury DHB, South Canterbury DHB, Southern DHB).

c

These dispensing patterns are consistent with recent work showing the high rates of skin infections in Pacific and Māori children,22 and further emphasise the considerable burden of skin disease in these groups. In addition, the high rates of dispensing in the Northern region reflect the higher incidence of skin disease in this region, which has the highest population of Māori and Pacific Peoples in New Zealand. Furthermore, the relatively high rates of topical fusidic acid usage in the over-75 year age group are concerning, particularly given the limited evidence-based indications for prescribing topical antimicrobials in older age groups.19 To date however, there are no available data on the clinical indications for topical antimicrobial prescribing in elderly patients in New Zealand. Such information is critical for determining whether current usage of topical antimicrobials is clinically indicated, and identifying strategies to reduce inappropriate prescribing.

Collateral damage caused by high levels of fusidic acid usage in New Zealand

Recent data suggest that, as might be expected, the high usage of topical fusidic acid in New Zealand is driving the increase in fusidic acid resistant S. aureus clones.5,7,23 Of specific concern is the emergence of a fusidic acid-resistant community-associated methicillin-resistant S. aureus (MRSA) clone, known in New Zealand as the ‘AK3’ clone.23 This clone has rapidly become the most common type of MRSA causing illness in New Zealand.5 Genomic data indicates that the gene conferring fusidic acid resistance (fusC) and the gene conferring methicillin resistance (mecA) are located together on the same mobile genetic element.7 In simple terms, this means that large-scale use of topical fusidic acid has favoured the proliferation of the AK3 MRSA clone, and has provided a ‘helping hand’ in allowing this clone to become established in New Zealand. In addition, a recent national study of antimicrobial resistance in New Zealand found that 36% of all fusidic acid-resistant methicillin-susceptible S. aureus (MSSA) strains were also resistant to mupirocin, highlighting the potential for treatment with one antimicrobial to select for multiresistant bacterial clones.5 In this context, it is important for practitioners to be aware of the wider ecological implications (or ‘collateral damage’) that can occur when prescribing what may be regarded as a benign treatment.

Collective action requires collective responsibility

It is clear from available data that the rate of fusidic acid resistance in New Zealand is one of the highest in the developed world, and that high levels of usage have contributed to proliferation of the AK3 MRSA clone. It is also important to note that a considerable proportion of topical antimicrobial usage in New Zealand may be considered ‘appropriate’, particularly given the high burden of childhood skin infections in our setting.22,24 However, in the face of high bacterial resistance, we question the value of continuing to recommend topical fusidic acid as empiric therapy in New Zealand, and suggest a multipronged approach aimed specifically at reducing rates of resistance:

  1. Consistent, evidence-based, national guidelines around the appropriate use of topical antimicrobials.
  2. Reduce the volume of agent dispensed to patients (eg, a 5g tube instead of a 15g tube).
  3. Regulatory measures around the use of topical fusidic acid, such as moving to ‘specialist-only’ prescribing in the elderly.
  4. Improved education to primary care practitioners about evidence-based prescribing of topical antimicrobials, particularly in elderly patients.
  5. Clear messaging to the public about the importance of not sharing topical antimicrobials amongst a household, and discarding any remaining topical agent once the treatment course has been completed.
  6. Robust clinical trials, conducted in a setting with a high prevalence of resistance to topical agents, assessing the clinical utility of antiseptic agents in the treatment of localised impetigo.

A key first step would be identification and gathering of relevant stakeholders, and formation of a clear ‘road-map’ to address this significant problem. These stakeholders should include prescribers, the Ministry of Health, PHARMAC and patient representatives. New Zealand has already had considerable success in reducing rates of topical antimicrobial resistance encountered in S. aureus isolates. This is highlighted by the reversal in mupirocin resistance in New Zealand over the past 15 years, which was, in part, due to both educational and regulatory measures. A similar concerted approach, involving prescribers, policy makers, and patients, is urgently required to tackle our unenviably high rates of fusidic acid resistance, and confront our over prescription of topical antimicrobial agents.

Summary

Abstract

New Zealand has unenviably high rates of bacterial resistance to topical antimicrobials. In this Viewpoint, we review the history and usage of topical antimicrobials in New Zealand, and suggest some strategies to mitigate further increases in antimicrobial resistance to topical agents.

Aim

Method

Results

Conclusion

Author Information

Deborah A Williamson, Institute of Environmental Science and Research, Wellington, New Zealand, and University of Otago, Wellington, New Zealand; Stephen R Ritchie, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Emma Best, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Arlo Upton, LabTests, Mount Wellington, Auckland, New Zealand; Alison Leversha, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Alesha Smith, School of Pharmacy, University of Otago, New Zealand and bpacnz, Dunedin, New Zealand; Mark G Thomas, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Acknowledgements

Correspondence

Dr Deborah Williamson, Department of Pathology and Molecular Medicine, PO Box 7343, Wellington South, 6242, New Zealand

Correspondence Email

Debbie.williamson@esr.cri.nz

Competing Interests

Nil

  1. ‘Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. 2014.’ Available at: www.amr-review.org, last accessed 25th April, 2015
  2. Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States. 2013. Available at: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf, last accessed 25th April, 2015
  3. Thomas MG, Smith AJ, Tilyard M. Rising antimicrobial resistance: a strong reason to reduce excessive antimicrobial consumption in New Zealand. N Z Med J. 2014;127(1394):72-84
  4. Upton A, Lang S, Heffernan H. Mupirocin and Staphylococcus aureus: A recent paradigm of emerging antibiotic resistance. J Antimicrob Chemother. 2003; 51: 613-7.
  5. Heffernan H, Bakker S, Woodhouse R, Dyet K, Williamson DA. Demographics, antimicrobial susceptibility and molecular epidemiology of Staphylococcus aureus in New Zealand, 2014 (https://surv.esr.cri.nz/PDF_surveillance/Antimicrobial/Staph /2104Saureussurveyreport.pdf, last accessed 20th April, 2015)
  6. Howden BP, Grayson ML. Dumb and dumber--the potential waste of a useful antistaphylococcal agent: Emerging fusidic acid resistance in Staphylococcus aureus. Clin Infect Dis. 2006; 42(3):394-400.
  7. Williamson DA, Monecke S, Heffernan H et al. A cautionary tale: High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus. Clin Infect Dis. 2014; 59(10):1451-4.
  8. Verhoeven PO, Gagnaire J, Botelho-Nevers E et al. Detection and clinical relevance of Staphylococcus aureus nasal carriage: An update. Expert Rev Anti Infect Ther. 2014; 12: 75-89.
  9. Koning S, van der Sande R, Verhagen AP et al. Interventions for impetigo. Cochrane Database Syst Rev. 2012; 1: CD003261.
  10. Thornton Spann C, Taylor SC, Weinberg JM. Topical antimicrobial agents in dermatology. Clin Dermatol. 2003; 21: 70-7.
  11. Vogel A, Lennon D, Gray S et al. Registered nurse assessment and treatment of skin sepsis in New Zealand schools: The development of protocols. N Z Med J. 2013; 126: 27-38.
  12. Best Practice Advisory Committee. Management of impetigo. Available at http://www.bpac.org.nz/BPJ/2009/february/docs/bpj19_impetigo_pages_8-11.pdf. 2009, last accessed 15th June, 2015
  13. Coombs GW1, Daly DA2, Pearson JC1, et al. Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012. Commun Dis Intell Q Rep. 2014; 38(1):E59-69.
  14. Castanheira M, Watters AA, Mendes RE et al. Occurrence and molecular characterization of fusidic acid resistance mechanisms among Staphylococcus spp. from European countries (2008). J Antimicrob Chemother. 2010; 65: 1353-
  15. Castanheira M, Watters AA, Bell JM, Turnidge JD, Jones RN. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008. Antimicrob Agents Chemother. 2010; 54(9):3614-7.
  16. Jones RN, Mendes RE, Sader HS et al. In vitro antimicrobial findings for fusidic acid tested against contemporary (2008-2009) gram-positive organisms collected in the United States. Clin Infect Dis. 2011; 52 Suppl 7: S477-86.
  17. Koning S, van Suijlekom-Smit LW, Nouwen JL, Verduin CM, Bernsen RM, Oranje AP, Thomas S, van der Wouden JC. Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial. BMJ. 2002; 324(7331):203-6
  18. Christensen OB, Anehus S. Hydrogen peroxide cream: an alternative to topical antibiotics in the treatment of impetigo contagiosa. Acta Derm Venereol. 1994; 74(6): 460-2
  19. Lapolla WJ, Levender MM, Davis SA et al. Topical antibiotic trends from 1993 to 2007: Use of topical antibiotics for non-evidence-based indications. Dermatol Surg. 2011; 37: 1427-33.
  20. McHugh SM, Collins CJ, Corrigan MA, Hill AD, Humphreys H. The role of topical antibiotics used as prophylaxis in surgical site infection prevention. J Antimicrob Chemother. 2011 Apr;66(4):693-701.
  21. White R, Cooper R, Kingsley A. Wound colonization and infection: the role of topical antimicrobials. Br J Nurs 2001; 10(9): 563-78
  22. Williamson DA, Zhang J, Ritchie SR et al. Staphylococcus aureus infections in New Zealand, 2000-2011. Emerg Infect Dis. 2014; 20: 1156-61.
  23. Williamson DA, Roberts SA, Ritchie SR et al. Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus in New Zealand: Rapid emergence of sequence type 5 (ST5)-SCCmec-IV as the dominant community-associated MRSA clone. PLoS One. 2013; 8: e62020.
  24. O’Sullivan CE, Baker MG, Zhang J. Increasing hospitalizations for serious skin infections in New Zealand children, 1990-2007. Epidemiol Infect. 2011; 139: 1794-804.

Contact diana@nzma.org.nz
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Background

Antimicrobial resistance has been described as a “crisis for the health and wealth of nations”.1 One of the key strategies to mitigate this public health crisis is to ensure that existing antimicrobials are used responsibly and judiciously. In general, New Zealand has relatively low rates of antimicrobial resistance threats deemed as ‘critical’ or ‘urgent’ by the Centers for Disease Control and Prevention.2 However, this may reflect relatively low levels of consumption of many antimicrobials in previous decades, rather than our relatively high levels of antimicrobial consumption in more recent years.3 In particular, high usage of topical antimicrobial agents over the past three decades in New Zealand has resulted in an ill-fated series of national population-level experiments, which clearly illustrate the relationships between antimicrobial consumption and resistance. Throughout the 1990s, the topical antimicrobial agent mupirocin (Bactroban©) was available to purchase ‘over-the-counter’ (OTC), which led to very high levels of use, and subsequent high rates of resistance, such that by 2000, approximately 14% of S. aureus isolates displayed high-level resistance to mupirocin.4 From April, 2000, regulatory changes meant that mupirocin could be obtained by ‘prescription only’, with a subsequent decrease in usage, and a fall in the prevalence of high-level mupirocin resistance in S. aureus from 14.2% in 2000, to 8.3% in 2014.5 Interestingly, the authors of a 2003 study describing mupirocin resistance in New Zealand concluded that:

“In cautioning against the use of mupirocin, we do not advocate using fusidic acid topically as an alternative. Resistance to this topical agent is reported, and unlike mupirocin, it is available in oral and intravenous formulations that are used for treatment of multiresistant S. aureus infections”.4

Similarly, an Australian commentary in 2006 on fusidic acid use stated:

“Ensuring that… the use of topical fusidic acid is either abolished or restricted will be vital if we are to prevent the loss of this potentially useful agent”, and “Common sense would suggest that antibiotics used topically should be ones that are not used systemically”.6

Despite these unambiguous warnings, regulatory changes and the promulgation of guidelines promoting the use of topical fusidic acid ointment and cream contributed to a significant increase in topical fusidic acid dispensing in New Zealand throughout the 2000s (Figure 1), with an associated increase in the prevalence of resistance in S. aureus from 17% in 1999, to 28% in 2013.7 At present, topical fusidic acid is available by prescription only, although it is fully subsidised by the New Zealand Ministry of Health, unlike mupirocin, which is only partially subsidised.

Figure 1: Community dispensing rates per 1,000 population for topical fusidic acid and mupirocin in the New Zealand community setting, January, 1993,–August, 2013. Reproduced from Reference 7.

b

The evidence for and against topical antimicrobial use

Theoretically, the use of topical antimicrobials is an attractive option to treat minor skin ailments. Topical application allows delivery of high concentrations of antimicrobial at the site of infection, while minimising systemic absorption. In practice however, topical antibiotic use has long been recognised as a very efficient method of rapidly promoting the emergence and proliferation of antibiotic resistant microbes.6 Furthermore, evidence-based prescribing supports the use of topical antimicrobial agents for only a few specific indications, including nasal eradication of S. aureus, treatment of acne, and treatment of mild impetigo.8-10

Despite concerns about efficacy and the promotion of even higher rates of resistance, fusidic acid remains the recommended agent in New Zealand for the empiric treatment of impetigo.11,12 Importantly, rates of resistance to fusidic acid in S. aureus remain comparatively lower in countries that have not adopted the widespread use of topical fusidic acid.13-15 In general, Streptococcus pyogenes, the other pathogen commonly associated with impetigo, is less susceptible to fusidic acid than S. aureus.16

One of the largest randomised control trials (RCTs) assessing the efficacy of topical fusidic acid vs placebo in the treatment of mild impetigo, conducted in the Netherlands between 1999 and 2000, found that cure rates after one week of treatment with topical fusidic acid were significantly higher than with placebo (55% vs 13%, odds ratio [OR] 12.6, 95% confidence interval [CI], 5.0–31.5).17 However, this difference reduced over time, with 92% of treated patients displaying cure at 28 days, vs 88% of patients in the placebo arm. It also must be noted that no fusidic acid resistance was detected in S. aureus isolates from this study population, meaning that these study findings are not directly applicable to the New Zealand setting, where contemporary fusidic acid resistance rates are high. In addition, another RCT conducted in the UK, Germany and Sweden in 1994, found no statistically significant difference in cure rates between topical fusidic acid and hydrogen peroxide in the treatment of localised impetigo (82% vs 72%, respectively).18 Again, caution should be exercised when extrapolating these results to the New Zealand setting, as rates of fusidic acid resistance in these countries are markedly lower than New Zealand.14 However, despite the limited application of overseas findings to the New Zealand setting, such studies have been used as the basis for guidelines that actively recommend topical fusidic acid in the empiric treatment of impetigo.11,12 Importantly, there are no published studies comparing the use of topical fusidic acid vs placebo, or vs antiseptic treatment for impetigo in high prevalence resistance settings, such as New Zealand. In particular, it is not yet known whether topical hydrogen peroxide is a feasible alternative for New Zealand children compared to topical fusidic acid.

Demographics of topical fusidic acid use in New Zealand

In addition to therapeutic usage, data suggest that, in some settings, topical antimicrobials may also be used prophylactically, particularly in elderly patients. For example, a study from the US assessing national usage of topical antimicrobials found that 40% of all topical antimicrobial usage was in the over-50 age group, with benign or malignant skin neoplasms being the most common diagnosis associated with topical antimicrobial usage.19 These authors hypothesised that in such instances, topical antimicrobials were being used as post-operative wound ‘prophylaxis’ following minor surgery, a practice that is not supported by available evidence.20,21

Information on the demographics and geographic variation of antimicrobial usage in a population is essential in understanding how and why antimicrobials are utilised, and identifying potential areas for reduction in usage. Information on all community prescriptions in New Zealand are maintained in a central data warehouse, the ‘Pharmaceutical Collection’. Data from this collection between January, 2006, and August, 2013, demonstrates that the highest rates of topical fusidic acid dispensing were in the under-5 year age group, followed by the 75 year and over age group (Figure 2).

Figure 2: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by age group, January, 2006,–August, 2013.

c

When stratified by ethnicity, the highest rates of dispensing were in Māori and Pacific Peoples (Figure 3), and when stratified by geographic region, the highest rates of dispensing were in the Northern region of New Zealand (Figure 4).

Figure 3: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by ethnicity, January, 2006,–August, 2013.

c

Figure 4: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by geographic region, January, 2006–August, 2013. (Northern = Northland DHB, Waitemata DHB, Auckland DHB, Counties Manukau DHB; MidCentral = Waikato DHB, Lakes DHB, Bay of Plenty DHB, Tairawhiti DHB, Taranaki DHB; Central = Hawkes Bay DHB, MidCentral DHB, Whanganui DHB, Capital and Coast DHB, Hutt DHB, Wairarapa DHB; Southern = Nelson Marlborough DHB, West Coast DHB, Canterbury DHB, South Canterbury DHB, Southern DHB).

c

These dispensing patterns are consistent with recent work showing the high rates of skin infections in Pacific and Māori children,22 and further emphasise the considerable burden of skin disease in these groups. In addition, the high rates of dispensing in the Northern region reflect the higher incidence of skin disease in this region, which has the highest population of Māori and Pacific Peoples in New Zealand. Furthermore, the relatively high rates of topical fusidic acid usage in the over-75 year age group are concerning, particularly given the limited evidence-based indications for prescribing topical antimicrobials in older age groups.19 To date however, there are no available data on the clinical indications for topical antimicrobial prescribing in elderly patients in New Zealand. Such information is critical for determining whether current usage of topical antimicrobials is clinically indicated, and identifying strategies to reduce inappropriate prescribing.

Collateral damage caused by high levels of fusidic acid usage in New Zealand

Recent data suggest that, as might be expected, the high usage of topical fusidic acid in New Zealand is driving the increase in fusidic acid resistant S. aureus clones.5,7,23 Of specific concern is the emergence of a fusidic acid-resistant community-associated methicillin-resistant S. aureus (MRSA) clone, known in New Zealand as the ‘AK3’ clone.23 This clone has rapidly become the most common type of MRSA causing illness in New Zealand.5 Genomic data indicates that the gene conferring fusidic acid resistance (fusC) and the gene conferring methicillin resistance (mecA) are located together on the same mobile genetic element.7 In simple terms, this means that large-scale use of topical fusidic acid has favoured the proliferation of the AK3 MRSA clone, and has provided a ‘helping hand’ in allowing this clone to become established in New Zealand. In addition, a recent national study of antimicrobial resistance in New Zealand found that 36% of all fusidic acid-resistant methicillin-susceptible S. aureus (MSSA) strains were also resistant to mupirocin, highlighting the potential for treatment with one antimicrobial to select for multiresistant bacterial clones.5 In this context, it is important for practitioners to be aware of the wider ecological implications (or ‘collateral damage’) that can occur when prescribing what may be regarded as a benign treatment.

Collective action requires collective responsibility

It is clear from available data that the rate of fusidic acid resistance in New Zealand is one of the highest in the developed world, and that high levels of usage have contributed to proliferation of the AK3 MRSA clone. It is also important to note that a considerable proportion of topical antimicrobial usage in New Zealand may be considered ‘appropriate’, particularly given the high burden of childhood skin infections in our setting.22,24 However, in the face of high bacterial resistance, we question the value of continuing to recommend topical fusidic acid as empiric therapy in New Zealand, and suggest a multipronged approach aimed specifically at reducing rates of resistance:

  1. Consistent, evidence-based, national guidelines around the appropriate use of topical antimicrobials.
  2. Reduce the volume of agent dispensed to patients (eg, a 5g tube instead of a 15g tube).
  3. Regulatory measures around the use of topical fusidic acid, such as moving to ‘specialist-only’ prescribing in the elderly.
  4. Improved education to primary care practitioners about evidence-based prescribing of topical antimicrobials, particularly in elderly patients.
  5. Clear messaging to the public about the importance of not sharing topical antimicrobials amongst a household, and discarding any remaining topical agent once the treatment course has been completed.
  6. Robust clinical trials, conducted in a setting with a high prevalence of resistance to topical agents, assessing the clinical utility of antiseptic agents in the treatment of localised impetigo.

A key first step would be identification and gathering of relevant stakeholders, and formation of a clear ‘road-map’ to address this significant problem. These stakeholders should include prescribers, the Ministry of Health, PHARMAC and patient representatives. New Zealand has already had considerable success in reducing rates of topical antimicrobial resistance encountered in S. aureus isolates. This is highlighted by the reversal in mupirocin resistance in New Zealand over the past 15 years, which was, in part, due to both educational and regulatory measures. A similar concerted approach, involving prescribers, policy makers, and patients, is urgently required to tackle our unenviably high rates of fusidic acid resistance, and confront our over prescription of topical antimicrobial agents.

Summary

Abstract

New Zealand has unenviably high rates of bacterial resistance to topical antimicrobials. In this Viewpoint, we review the history and usage of topical antimicrobials in New Zealand, and suggest some strategies to mitigate further increases in antimicrobial resistance to topical agents.

Aim

Method

Results

Conclusion

Author Information

Deborah A Williamson, Institute of Environmental Science and Research, Wellington, New Zealand, and University of Otago, Wellington, New Zealand; Stephen R Ritchie, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Emma Best, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Arlo Upton, LabTests, Mount Wellington, Auckland, New Zealand; Alison Leversha, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Alesha Smith, School of Pharmacy, University of Otago, New Zealand and bpacnz, Dunedin, New Zealand; Mark G Thomas, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Acknowledgements

Correspondence

Dr Deborah Williamson, Department of Pathology and Molecular Medicine, PO Box 7343, Wellington South, 6242, New Zealand

Correspondence Email

Debbie.williamson@esr.cri.nz

Competing Interests

Nil

  1. ‘Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. 2014.’ Available at: www.amr-review.org, last accessed 25th April, 2015
  2. Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States. 2013. Available at: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf, last accessed 25th April, 2015
  3. Thomas MG, Smith AJ, Tilyard M. Rising antimicrobial resistance: a strong reason to reduce excessive antimicrobial consumption in New Zealand. N Z Med J. 2014;127(1394):72-84
  4. Upton A, Lang S, Heffernan H. Mupirocin and Staphylococcus aureus: A recent paradigm of emerging antibiotic resistance. J Antimicrob Chemother. 2003; 51: 613-7.
  5. Heffernan H, Bakker S, Woodhouse R, Dyet K, Williamson DA. Demographics, antimicrobial susceptibility and molecular epidemiology of Staphylococcus aureus in New Zealand, 2014 (https://surv.esr.cri.nz/PDF_surveillance/Antimicrobial/Staph /2104Saureussurveyreport.pdf, last accessed 20th April, 2015)
  6. Howden BP, Grayson ML. Dumb and dumber--the potential waste of a useful antistaphylococcal agent: Emerging fusidic acid resistance in Staphylococcus aureus. Clin Infect Dis. 2006; 42(3):394-400.
  7. Williamson DA, Monecke S, Heffernan H et al. A cautionary tale: High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus. Clin Infect Dis. 2014; 59(10):1451-4.
  8. Verhoeven PO, Gagnaire J, Botelho-Nevers E et al. Detection and clinical relevance of Staphylococcus aureus nasal carriage: An update. Expert Rev Anti Infect Ther. 2014; 12: 75-89.
  9. Koning S, van der Sande R, Verhagen AP et al. Interventions for impetigo. Cochrane Database Syst Rev. 2012; 1: CD003261.
  10. Thornton Spann C, Taylor SC, Weinberg JM. Topical antimicrobial agents in dermatology. Clin Dermatol. 2003; 21: 70-7.
  11. Vogel A, Lennon D, Gray S et al. Registered nurse assessment and treatment of skin sepsis in New Zealand schools: The development of protocols. N Z Med J. 2013; 126: 27-38.
  12. Best Practice Advisory Committee. Management of impetigo. Available at http://www.bpac.org.nz/BPJ/2009/february/docs/bpj19_impetigo_pages_8-11.pdf. 2009, last accessed 15th June, 2015
  13. Coombs GW1, Daly DA2, Pearson JC1, et al. Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012. Commun Dis Intell Q Rep. 2014; 38(1):E59-69.
  14. Castanheira M, Watters AA, Mendes RE et al. Occurrence and molecular characterization of fusidic acid resistance mechanisms among Staphylococcus spp. from European countries (2008). J Antimicrob Chemother. 2010; 65: 1353-
  15. Castanheira M, Watters AA, Bell JM, Turnidge JD, Jones RN. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008. Antimicrob Agents Chemother. 2010; 54(9):3614-7.
  16. Jones RN, Mendes RE, Sader HS et al. In vitro antimicrobial findings for fusidic acid tested against contemporary (2008-2009) gram-positive organisms collected in the United States. Clin Infect Dis. 2011; 52 Suppl 7: S477-86.
  17. Koning S, van Suijlekom-Smit LW, Nouwen JL, Verduin CM, Bernsen RM, Oranje AP, Thomas S, van der Wouden JC. Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial. BMJ. 2002; 324(7331):203-6
  18. Christensen OB, Anehus S. Hydrogen peroxide cream: an alternative to topical antibiotics in the treatment of impetigo contagiosa. Acta Derm Venereol. 1994; 74(6): 460-2
  19. Lapolla WJ, Levender MM, Davis SA et al. Topical antibiotic trends from 1993 to 2007: Use of topical antibiotics for non-evidence-based indications. Dermatol Surg. 2011; 37: 1427-33.
  20. McHugh SM, Collins CJ, Corrigan MA, Hill AD, Humphreys H. The role of topical antibiotics used as prophylaxis in surgical site infection prevention. J Antimicrob Chemother. 2011 Apr;66(4):693-701.
  21. White R, Cooper R, Kingsley A. Wound colonization and infection: the role of topical antimicrobials. Br J Nurs 2001; 10(9): 563-78
  22. Williamson DA, Zhang J, Ritchie SR et al. Staphylococcus aureus infections in New Zealand, 2000-2011. Emerg Infect Dis. 2014; 20: 1156-61.
  23. Williamson DA, Roberts SA, Ritchie SR et al. Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus in New Zealand: Rapid emergence of sequence type 5 (ST5)-SCCmec-IV as the dominant community-associated MRSA clone. PLoS One. 2013; 8: e62020.
  24. O’Sullivan CE, Baker MG, Zhang J. Increasing hospitalizations for serious skin infections in New Zealand children, 1990-2007. Epidemiol Infect. 2011; 139: 1794-804.

Contact diana@nzma.org.nz
for the PDF of this article

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Background

Antimicrobial resistance has been described as a “crisis for the health and wealth of nations”.1 One of the key strategies to mitigate this public health crisis is to ensure that existing antimicrobials are used responsibly and judiciously. In general, New Zealand has relatively low rates of antimicrobial resistance threats deemed as ‘critical’ or ‘urgent’ by the Centers for Disease Control and Prevention.2 However, this may reflect relatively low levels of consumption of many antimicrobials in previous decades, rather than our relatively high levels of antimicrobial consumption in more recent years.3 In particular, high usage of topical antimicrobial agents over the past three decades in New Zealand has resulted in an ill-fated series of national population-level experiments, which clearly illustrate the relationships between antimicrobial consumption and resistance. Throughout the 1990s, the topical antimicrobial agent mupirocin (Bactroban©) was available to purchase ‘over-the-counter’ (OTC), which led to very high levels of use, and subsequent high rates of resistance, such that by 2000, approximately 14% of S. aureus isolates displayed high-level resistance to mupirocin.4 From April, 2000, regulatory changes meant that mupirocin could be obtained by ‘prescription only’, with a subsequent decrease in usage, and a fall in the prevalence of high-level mupirocin resistance in S. aureus from 14.2% in 2000, to 8.3% in 2014.5 Interestingly, the authors of a 2003 study describing mupirocin resistance in New Zealand concluded that:

“In cautioning against the use of mupirocin, we do not advocate using fusidic acid topically as an alternative. Resistance to this topical agent is reported, and unlike mupirocin, it is available in oral and intravenous formulations that are used for treatment of multiresistant S. aureus infections”.4

Similarly, an Australian commentary in 2006 on fusidic acid use stated:

“Ensuring that… the use of topical fusidic acid is either abolished or restricted will be vital if we are to prevent the loss of this potentially useful agent”, and “Common sense would suggest that antibiotics used topically should be ones that are not used systemically”.6

Despite these unambiguous warnings, regulatory changes and the promulgation of guidelines promoting the use of topical fusidic acid ointment and cream contributed to a significant increase in topical fusidic acid dispensing in New Zealand throughout the 2000s (Figure 1), with an associated increase in the prevalence of resistance in S. aureus from 17% in 1999, to 28% in 2013.7 At present, topical fusidic acid is available by prescription only, although it is fully subsidised by the New Zealand Ministry of Health, unlike mupirocin, which is only partially subsidised.

Figure 1: Community dispensing rates per 1,000 population for topical fusidic acid and mupirocin in the New Zealand community setting, January, 1993,–August, 2013. Reproduced from Reference 7.

b

The evidence for and against topical antimicrobial use

Theoretically, the use of topical antimicrobials is an attractive option to treat minor skin ailments. Topical application allows delivery of high concentrations of antimicrobial at the site of infection, while minimising systemic absorption. In practice however, topical antibiotic use has long been recognised as a very efficient method of rapidly promoting the emergence and proliferation of antibiotic resistant microbes.6 Furthermore, evidence-based prescribing supports the use of topical antimicrobial agents for only a few specific indications, including nasal eradication of S. aureus, treatment of acne, and treatment of mild impetigo.8-10

Despite concerns about efficacy and the promotion of even higher rates of resistance, fusidic acid remains the recommended agent in New Zealand for the empiric treatment of impetigo.11,12 Importantly, rates of resistance to fusidic acid in S. aureus remain comparatively lower in countries that have not adopted the widespread use of topical fusidic acid.13-15 In general, Streptococcus pyogenes, the other pathogen commonly associated with impetigo, is less susceptible to fusidic acid than S. aureus.16

One of the largest randomised control trials (RCTs) assessing the efficacy of topical fusidic acid vs placebo in the treatment of mild impetigo, conducted in the Netherlands between 1999 and 2000, found that cure rates after one week of treatment with topical fusidic acid were significantly higher than with placebo (55% vs 13%, odds ratio [OR] 12.6, 95% confidence interval [CI], 5.0–31.5).17 However, this difference reduced over time, with 92% of treated patients displaying cure at 28 days, vs 88% of patients in the placebo arm. It also must be noted that no fusidic acid resistance was detected in S. aureus isolates from this study population, meaning that these study findings are not directly applicable to the New Zealand setting, where contemporary fusidic acid resistance rates are high. In addition, another RCT conducted in the UK, Germany and Sweden in 1994, found no statistically significant difference in cure rates between topical fusidic acid and hydrogen peroxide in the treatment of localised impetigo (82% vs 72%, respectively).18 Again, caution should be exercised when extrapolating these results to the New Zealand setting, as rates of fusidic acid resistance in these countries are markedly lower than New Zealand.14 However, despite the limited application of overseas findings to the New Zealand setting, such studies have been used as the basis for guidelines that actively recommend topical fusidic acid in the empiric treatment of impetigo.11,12 Importantly, there are no published studies comparing the use of topical fusidic acid vs placebo, or vs antiseptic treatment for impetigo in high prevalence resistance settings, such as New Zealand. In particular, it is not yet known whether topical hydrogen peroxide is a feasible alternative for New Zealand children compared to topical fusidic acid.

Demographics of topical fusidic acid use in New Zealand

In addition to therapeutic usage, data suggest that, in some settings, topical antimicrobials may also be used prophylactically, particularly in elderly patients. For example, a study from the US assessing national usage of topical antimicrobials found that 40% of all topical antimicrobial usage was in the over-50 age group, with benign or malignant skin neoplasms being the most common diagnosis associated with topical antimicrobial usage.19 These authors hypothesised that in such instances, topical antimicrobials were being used as post-operative wound ‘prophylaxis’ following minor surgery, a practice that is not supported by available evidence.20,21

Information on the demographics and geographic variation of antimicrobial usage in a population is essential in understanding how and why antimicrobials are utilised, and identifying potential areas for reduction in usage. Information on all community prescriptions in New Zealand are maintained in a central data warehouse, the ‘Pharmaceutical Collection’. Data from this collection between January, 2006, and August, 2013, demonstrates that the highest rates of topical fusidic acid dispensing were in the under-5 year age group, followed by the 75 year and over age group (Figure 2).

Figure 2: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by age group, January, 2006,–August, 2013.

c

When stratified by ethnicity, the highest rates of dispensing were in Māori and Pacific Peoples (Figure 3), and when stratified by geographic region, the highest rates of dispensing were in the Northern region of New Zealand (Figure 4).

Figure 3: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by ethnicity, January, 2006,–August, 2013.

c

Figure 4: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand community setting stratified by geographic region, January, 2006–August, 2013. (Northern = Northland DHB, Waitemata DHB, Auckland DHB, Counties Manukau DHB; MidCentral = Waikato DHB, Lakes DHB, Bay of Plenty DHB, Tairawhiti DHB, Taranaki DHB; Central = Hawkes Bay DHB, MidCentral DHB, Whanganui DHB, Capital and Coast DHB, Hutt DHB, Wairarapa DHB; Southern = Nelson Marlborough DHB, West Coast DHB, Canterbury DHB, South Canterbury DHB, Southern DHB).

c

These dispensing patterns are consistent with recent work showing the high rates of skin infections in Pacific and Māori children,22 and further emphasise the considerable burden of skin disease in these groups. In addition, the high rates of dispensing in the Northern region reflect the higher incidence of skin disease in this region, which has the highest population of Māori and Pacific Peoples in New Zealand. Furthermore, the relatively high rates of topical fusidic acid usage in the over-75 year age group are concerning, particularly given the limited evidence-based indications for prescribing topical antimicrobials in older age groups.19 To date however, there are no available data on the clinical indications for topical antimicrobial prescribing in elderly patients in New Zealand. Such information is critical for determining whether current usage of topical antimicrobials is clinically indicated, and identifying strategies to reduce inappropriate prescribing.

Collateral damage caused by high levels of fusidic acid usage in New Zealand

Recent data suggest that, as might be expected, the high usage of topical fusidic acid in New Zealand is driving the increase in fusidic acid resistant S. aureus clones.5,7,23 Of specific concern is the emergence of a fusidic acid-resistant community-associated methicillin-resistant S. aureus (MRSA) clone, known in New Zealand as the ‘AK3’ clone.23 This clone has rapidly become the most common type of MRSA causing illness in New Zealand.5 Genomic data indicates that the gene conferring fusidic acid resistance (fusC) and the gene conferring methicillin resistance (mecA) are located together on the same mobile genetic element.7 In simple terms, this means that large-scale use of topical fusidic acid has favoured the proliferation of the AK3 MRSA clone, and has provided a ‘helping hand’ in allowing this clone to become established in New Zealand. In addition, a recent national study of antimicrobial resistance in New Zealand found that 36% of all fusidic acid-resistant methicillin-susceptible S. aureus (MSSA) strains were also resistant to mupirocin, highlighting the potential for treatment with one antimicrobial to select for multiresistant bacterial clones.5 In this context, it is important for practitioners to be aware of the wider ecological implications (or ‘collateral damage’) that can occur when prescribing what may be regarded as a benign treatment.

Collective action requires collective responsibility

It is clear from available data that the rate of fusidic acid resistance in New Zealand is one of the highest in the developed world, and that high levels of usage have contributed to proliferation of the AK3 MRSA clone. It is also important to note that a considerable proportion of topical antimicrobial usage in New Zealand may be considered ‘appropriate’, particularly given the high burden of childhood skin infections in our setting.22,24 However, in the face of high bacterial resistance, we question the value of continuing to recommend topical fusidic acid as empiric therapy in New Zealand, and suggest a multipronged approach aimed specifically at reducing rates of resistance:

  1. Consistent, evidence-based, national guidelines around the appropriate use of topical antimicrobials.
  2. Reduce the volume of agent dispensed to patients (eg, a 5g tube instead of a 15g tube).
  3. Regulatory measures around the use of topical fusidic acid, such as moving to ‘specialist-only’ prescribing in the elderly.
  4. Improved education to primary care practitioners about evidence-based prescribing of topical antimicrobials, particularly in elderly patients.
  5. Clear messaging to the public about the importance of not sharing topical antimicrobials amongst a household, and discarding any remaining topical agent once the treatment course has been completed.
  6. Robust clinical trials, conducted in a setting with a high prevalence of resistance to topical agents, assessing the clinical utility of antiseptic agents in the treatment of localised impetigo.

A key first step would be identification and gathering of relevant stakeholders, and formation of a clear ‘road-map’ to address this significant problem. These stakeholders should include prescribers, the Ministry of Health, PHARMAC and patient representatives. New Zealand has already had considerable success in reducing rates of topical antimicrobial resistance encountered in S. aureus isolates. This is highlighted by the reversal in mupirocin resistance in New Zealand over the past 15 years, which was, in part, due to both educational and regulatory measures. A similar concerted approach, involving prescribers, policy makers, and patients, is urgently required to tackle our unenviably high rates of fusidic acid resistance, and confront our over prescription of topical antimicrobial agents.

Summary

Abstract

New Zealand has unenviably high rates of bacterial resistance to topical antimicrobials. In this Viewpoint, we review the history and usage of topical antimicrobials in New Zealand, and suggest some strategies to mitigate further increases in antimicrobial resistance to topical agents.

Aim

Method

Results

Conclusion

Author Information

Deborah A Williamson, Institute of Environmental Science and Research, Wellington, New Zealand, and University of Otago, Wellington, New Zealand; Stephen R Ritchie, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Emma Best, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Arlo Upton, LabTests, Mount Wellington, Auckland, New Zealand; Alison Leversha, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Alesha Smith, School of Pharmacy, University of Otago, New Zealand and bpacnz, Dunedin, New Zealand; Mark G Thomas, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Acknowledgements

Correspondence

Dr Deborah Williamson, Department of Pathology and Molecular Medicine, PO Box 7343, Wellington South, 6242, New Zealand

Correspondence Email

Debbie.williamson@esr.cri.nz

Competing Interests

Nil

  1. ‘Review on Antimicrobial Resistance. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. 2014.’ Available at: www.amr-review.org, last accessed 25th April, 2015
  2. Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States. 2013. Available at: http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf, last accessed 25th April, 2015
  3. Thomas MG, Smith AJ, Tilyard M. Rising antimicrobial resistance: a strong reason to reduce excessive antimicrobial consumption in New Zealand. N Z Med J. 2014;127(1394):72-84
  4. Upton A, Lang S, Heffernan H. Mupirocin and Staphylococcus aureus: A recent paradigm of emerging antibiotic resistance. J Antimicrob Chemother. 2003; 51: 613-7.
  5. Heffernan H, Bakker S, Woodhouse R, Dyet K, Williamson DA. Demographics, antimicrobial susceptibility and molecular epidemiology of Staphylococcus aureus in New Zealand, 2014 (https://surv.esr.cri.nz/PDF_surveillance/Antimicrobial/Staph /2104Saureussurveyreport.pdf, last accessed 20th April, 2015)
  6. Howden BP, Grayson ML. Dumb and dumber--the potential waste of a useful antistaphylococcal agent: Emerging fusidic acid resistance in Staphylococcus aureus. Clin Infect Dis. 2006; 42(3):394-400.
  7. Williamson DA, Monecke S, Heffernan H et al. A cautionary tale: High usage of topical fusidic acid and rapid clonal expansion of fusidic acid-resistant Staphylococcus aureus. Clin Infect Dis. 2014; 59(10):1451-4.
  8. Verhoeven PO, Gagnaire J, Botelho-Nevers E et al. Detection and clinical relevance of Staphylococcus aureus nasal carriage: An update. Expert Rev Anti Infect Ther. 2014; 12: 75-89.
  9. Koning S, van der Sande R, Verhagen AP et al. Interventions for impetigo. Cochrane Database Syst Rev. 2012; 1: CD003261.
  10. Thornton Spann C, Taylor SC, Weinberg JM. Topical antimicrobial agents in dermatology. Clin Dermatol. 2003; 21: 70-7.
  11. Vogel A, Lennon D, Gray S et al. Registered nurse assessment and treatment of skin sepsis in New Zealand schools: The development of protocols. N Z Med J. 2013; 126: 27-38.
  12. Best Practice Advisory Committee. Management of impetigo. Available at http://www.bpac.org.nz/BPJ/2009/february/docs/bpj19_impetigo_pages_8-11.pdf. 2009, last accessed 15th June, 2015
  13. Coombs GW1, Daly DA2, Pearson JC1, et al. Community-onset Staphylococcus aureus Surveillance Programme annual report, 2012. Commun Dis Intell Q Rep. 2014; 38(1):E59-69.
  14. Castanheira M, Watters AA, Mendes RE et al. Occurrence and molecular characterization of fusidic acid resistance mechanisms among Staphylococcus spp. from European countries (2008). J Antimicrob Chemother. 2010; 65: 1353-
  15. Castanheira M, Watters AA, Bell JM, Turnidge JD, Jones RN. Fusidic acid resistance rates and prevalence of resistance mechanisms among Staphylococcus spp. isolated in North America and Australia, 2007-2008. Antimicrob Agents Chemother. 2010; 54(9):3614-7.
  16. Jones RN, Mendes RE, Sader HS et al. In vitro antimicrobial findings for fusidic acid tested against contemporary (2008-2009) gram-positive organisms collected in the United States. Clin Infect Dis. 2011; 52 Suppl 7: S477-86.
  17. Koning S, van Suijlekom-Smit LW, Nouwen JL, Verduin CM, Bernsen RM, Oranje AP, Thomas S, van der Wouden JC. Fusidic acid cream in the treatment of impetigo in general practice: double blind randomised placebo controlled trial. BMJ. 2002; 324(7331):203-6
  18. Christensen OB, Anehus S. Hydrogen peroxide cream: an alternative to topical antibiotics in the treatment of impetigo contagiosa. Acta Derm Venereol. 1994; 74(6): 460-2
  19. Lapolla WJ, Levender MM, Davis SA et al. Topical antibiotic trends from 1993 to 2007: Use of topical antibiotics for non-evidence-based indications. Dermatol Surg. 2011; 37: 1427-33.
  20. McHugh SM, Collins CJ, Corrigan MA, Hill AD, Humphreys H. The role of topical antibiotics used as prophylaxis in surgical site infection prevention. J Antimicrob Chemother. 2011 Apr;66(4):693-701.
  21. White R, Cooper R, Kingsley A. Wound colonization and infection: the role of topical antimicrobials. Br J Nurs 2001; 10(9): 563-78
  22. Williamson DA, Zhang J, Ritchie SR et al. Staphylococcus aureus infections in New Zealand, 2000-2011. Emerg Infect Dis. 2014; 20: 1156-61.
  23. Williamson DA, Roberts SA, Ritchie SR et al. Clinical and molecular epidemiology of methicillin-resistant Staphylococcus aureus in New Zealand: Rapid emergence of sequence type 5 (ST5)-SCCmec-IV as the dominant community-associated MRSA clone. PLoS One. 2013; 8: e62020.
  24. O’Sullivan CE, Baker MG, Zhang J. Increasing hospitalizations for serious skin infections in New Zealand children, 1990-2007. Epidemiol Infect. 2011; 139: 1794-804.

Contact diana@nzma.org.nz
for the PDF of this article

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