A bug in the ointment: Topical antimicrobial usage and resistance in New Zealand

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.

Full text

103 NZMJ 4 December 2015, Vol 128 No 1426
ISSN 1175-8716 © NZMA
www.nzma.org.nz/journal
VIEWPOINT
A bug in the ointment:
topical antimicrobial usage
and resistance in
New Zealand
Deborah A Williamson, Stephen R Ritchie, Emma Best, Arlo Upton, Alison
Leversha, Alesha Smith, Mark G Thomas
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.
Background
Antimicrobial resistance has been
described as a “crisis for the health and
wealth of nations”.1 One of the key strat-
egies 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 antimi-
crobial resistance threats deemed as ‘critical’
or ‘urgent’ by the Centers for Disease Control
and Prevention.2 However, this may reect
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 mupi-
rocin.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 preva-
lence 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 alter-
native. Resistance to this topical
agent is reported, and unlike mupi-
rocin, 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 signicant 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

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present, topical fusidic acid is available by
prescription only, although it is fully subsi-
dised by the New Zealand Ministry of Health,
unlike mupirocin, which is only partially
subsidised.
The evidence for and against
topical antimicrobial use
Theoretically, the use of topical anti-
microbials 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 ecient 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 specic
indications, including nasal eradication of S.
aureus, treatment of acne, and treatment of
mild impetigo.8-10
Despite concerns about ecacy and
the promotion of even higher rates of
resistance, fusidic acid remains the recom-
mended agent in New Zealand for the
empiric treatment of impetigo.11,12 Impor-
tantly, 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 ecacy of topical
fusidic acid vs placebo in the treatment of
mild impetigo, conducted in the Nether-
lands between 1999 and 2000, found that
cure rates after one week of treatment
with topical fusidic acid were signicantly
higher than with placebo (55% vs 13%, odds
ratio [OR] 12.6, 95% condence 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 ndings are not directly applicable
to the New Zealand setting, where contem-
porary fusidic acid resistance rates are
high. In addition, another RCT conducted
in the UK, Germany and Sweden in 1994,
found no statistically signicant difference
in cure rates between topical fusidic acid
and hydrogen peroxide in the treatment
of localised impetigo (82% vs 72%, respec-
tively).18 Again, caution should be exercised
when extrapolating these results to the New
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.

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Figure 2: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand
community setting stratied by age group, January, 2006,–August, 2013.
Figure 3: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand
community setting stratied by ethnicity, January, 2006,–August, 2013.

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Zealand setting, as rates of fusidic acid resis-
tance in these countries are markedly lower
than New Zealand.14 However, despite the
limited application of overseas ndings 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 prophy-
lactically, 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 under-
standing 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).
When stratied by ethnicity, the highest
rates of dispensing were in Māori and
Pacic Peoples (Figure 3), and when strat-
ied by geographic region, the highest rates
of dispensing were in the Northern region
of New Zealand (Figure 4).
These dispensing patterns are consistent
with recent work showing the high rates
of skin infections in Pacic and Māori
Figure 4: Community dispensing rates per 1,000 population for topical fusidic acid in the New Zealand
community setting stratied 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, Whan-
ganui DHB, Capital and Coast DHB, Hutt DHB, Wairarapa DHB; Southern = Nelson Marlborough DHB,
West Coast DHB, Canterbury DHB, South Canterbury DHB, Southern DHB).

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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 reect
the higher incidence of skin disease in this
region, which has the highest population of
Māori and Pacic Peoples in New Zealand.
Furthermore, the relatively high rates of
topical fusidic acid usage in the over-75
year age group are concerning, partic-
ularly given the limited evidence-based
indications for prescribing topical anti-
microbials in older age groups.19 To date
however, there are no available data on
the clinical indications for topical antimi-
crobial 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 inap-
propriate 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 specic 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 multi-
resistant 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 anti-
microbial usage in New Zealand may be
considered ‘appropriate’, particularly given
the high burden of childhood skin infec-
tions 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 specically 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 rst step would be identication
and gathering of relevant stakeholders,
and formation of a clear ‘road-map’ to
address this signicant problem. These
stakeholders should include prescribers, the
Ministry of Health, PHARMAC and patient
representatives. New Zealand has already

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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.
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Competing interests: Nil
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.
Corresponding author:
Dr Deborah Williamson, Department of Pathology and Molecular Medicine, PO Box 7343,
Wellington South, 6242, New Zealand
Debbie.williamson@esr.cri.nz
URL:
www.nzma.org.nz/journal/read-the-journal/all-issues/2010-2019/2015/vol-128-no-1426-4-
december-2015/6753
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SUMMARIES
Drug misuse in sport: a New Zealand perspective
Andrew Curtis, David Gerrard, Peter Burt, Hamish Osborne
Drug misuse in sport is an international phenomenon that has not escaped the attention
of health professionals in New Zealand. Young athletes are vulnerable to the use of perfor-
mance-enhancing substances and the increasing use of sports supplements reects a
particularly worrying trend fostered by unscientic endorsements. Drug-Free Sport New
Zealand is the national anti-doping agency responsible for the oversight and education of our
athletes in an environment where sport is an integral part of our culture. Doctors respon-
sible for the care of athletes have an obligation to respect the Code of the World Anti-Doping
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To give informed consent to healthcare in New Zealand, competence is a requirement.
A person needs to understand the nature, purpose and consequences of treatment and
non-treatment in order to give a legally valid agreement to healthcare. However, New Zealand
law is unclear on this matter where children are concerned. Although not overtly stated, New
Zealand law infers that children under the age of 16 years may give or withhold consent to
healthcare, independent of their parents, so long as they are competent to do so. This article
raises the questions; what is ‘child competence’, why is it so important to acknowledge and
how do healthcare professionals assess for child competence? Unfortunately, there is meagre
research in this area and no clear answers. The assessment, recognition and respect for a
child’s level of competence not only supports ethical arguments regarding respect for their
rights and personhood; it has other more tangible benets to both the child and healthcare
services. These include improved treatment adherence, clinical effectiveness, health service
delivery and disease prevention. Therefore, this article addresses how these benets can be
realised through a better understanding and assessment of children’s abilities to participate
in and consent to healthcare.
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to 2013
Blake K Moore, Ryan B Smit, Angus N Colquhoun, W Murray Thomson
The rate of facial fractures presenting to Waikato Hospital has been increasing since 1989. In
addition the rate of violence-related facial fractures is now at almost double the rate seen in
1998-2000. It continues to be the dominant cause of injury, while road trac accident related
fractures are decreasing. This continual increase in fractures presenting to Waikato Hospital
places signicant demands on scarce clinical resources, such as operating theatre time and
stang numbers. Violence is an escalating cause of facial fractures that requires urgent and
interventional public health prevention strategies.
A bug in the ointment: topical antimicrobial usage and
resistance in New Zealand
Deborah A Williamson, Stephen R Ritchie, Emma Best, Arlo Upton, Alison Leversha,
Alesha Smith, Mark G Thomas
New Zealand has extremely high rates of bacterial resistance to topical antibiotics such as
Bactroban and Foban. This is because we use a lot of these antibiotics. In this article, we look
at who gets prescribed topical antibiotics in NZ, and suggest some ways in wihch we might
control and reduce rates of resistance.

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