Galderma Media Center, November 2014

For medical journalists outside the U.S. only

Antibiotic resistance and acne treatment

Tackling the challenge

Key points

At the G8 Summit in June 2013, science ministers focused on antimicrobial drug resistance
(i.e. anti-viral, anti-bacterial, anti-fungal and anti-parasite) strategies to stem the misuse of
antibiotics by optimizing doctor prescribing patterns to preserve the efficacy of existing antibiotics
against infections1
Antibacterial resistance has been a major health issue for over 10 years. The over prescription of
antibiotics for the common cold in children has significantly contributed to bacterial resistance
to antibiotics2
If the global spread of resistance is not slowed, this could have serious health implications
many common infections would become difficult or impossible to treat and routine surgical
procedures could become life-threatening3,4
In acne therapy, the widespread use of antibiotics has led to the increased prevalence of
Propionibacterium acnes (P. acnes) resistant strains worldwide and is a contributing factor to the
global antimicrobial resistance issue5,6
The emergence of antibacterial resistance via several mechanisms7 has resulted in treatment
failures, decreased response in acne patients8,9
Oral antibiotics are an important treatment option for more severe acne patients and at this time,
other alternatives such as oral isotretinoin are associated with severe side effects. However,
there are highly effective alternatives to
topical antibiotics
Responding to the urgent need to tackle this growing threat, guidelines have been issued calling
for responsible and appropriate use of antibiotics, including those used in acne therapy1,4,9

Antibiotic resistance: a major security threat

High on the agenda of the Group of Eight (G8) Summit 2013 and headlining a landmark report from the
Center for Disease Control (CDC) in the U.S was antibiotic resistance, an issue that is escalating at an
alarming rate. Science ministers at the meeting identified it as a major health security challenge of the
21st century.1,9,10 More recently, the U.S. government released its National Strategy to Combat Antibiotic-
Resistant Bacteria (September 2014), promising to prevent, detect, and control illness and death related
to antibiotic-resistant bacteria, by implementing measures to mitigate its emergence and spread11,
signalling the seriousness of the situation worldwide.

In dermatology, the issue of antibiotic resistance is of rising importance due to the growing number of
bacterial strains exhibiting resistance in acne therapy. Guidelines published by the Global Alliance to
Improve Outcomes in Acne, and endorsed by the American Academy of Dermatology (AAD) in 2014,
outline recommended treatment and management steps dermatologists can take to limit the growing
threat of antibiotic resistance9. Specifically mentioned is that oral and topical antibiotics should not be
used as monotherapy, yet 35% of oral antibiotics and 46% of topical antibiotics are currently prescribed
alone.12

Drug resistance has resulted largely from the extensive use of antibiotics in human and animal health as
well as in food production.3,4 Antibiotic overuse for the treatment of the common cold in children is
thought to be a significant factor contributing to the rapid rise in antibiotic resistant bacteria2 and
traditionally this has been the focus of governments for tackling the misuse of antibiotics. In 2004, further
authority attention was aimed at hospital-acquired bacterial infections as the spread of Methicillin-
resistant Staphylococcus aureus (MRSA) and Clostridium difficile became headline news in the UK.
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Measures put in place successfully reduced the number of MRSA and C. difficile cases by 84.7% and
53% respectively.4

The prevalence of antibiotic resistance is rising rapidly around the world, with virtually every area of the
globe affected.12 The problem is also expanding in scope, with increasing numbers of microbial strains
exhibiting resistance against a growing list of antibiotics.6 Left unaddressed, antibiotic resistance could
escalate into a global outbreak of previously treatable diseases and could increase the risk of routine
surgical procedures.10

The impact of antibiotic resistant bacteria (ARB) is a global issue13

Antibiotic resistance poses a major public health risk as it is associated with prolonged illness and
hospital stays, more complicated treatments and higher mortality rates.3,13 In Europe, the estimated
annual impact of antibiotic resistance is signficant:14

25,000 excess deaths (due to resistant bacterial

hospital infections)
2.5 million avoidable days in hospital
1.5 billion in healthcare costs and
productivity losses

The emergence of antibiotic resistance

Antibiotic resistance occurs when strains of bacteria
no longer respond to the antibiotics used to treat
infections caused by these microbes. Resistance can
arise via several mechanisms:6,8

Random genetic mutations in bacterial DNA

Transfer of antibiotic-resistant genes
among bacteria
Intrinsic properties that neutralize the effect
of antibiotics

The use of antibiotics results in resistant bacteria surviving and reproducing, while susceptible strains get
eliminated.4,15 Over time, this has led to a gradually increasing spread of antibiotic-resistant bacterial
strains.4
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Rise in prevalence of P. acnes resistant strains

Until recently the focus of antibiotic misuse has been limited, but it is now shifting to include other
diseases where antibiotics have been the main treatment option, such as acne. Reflecting the global rise
in antibiotic resistance is the growing number of bacterial strains exhibiting resistance in acne therapy.
This emergence of resistant P. acnes, one of the factors involved in acne pathogenesis, has been
attributed to the widespread prescribing of both oral and topical antibiotics when treating acne.5,6 Reports
estimate that the global prevalence of P. acnes resistant strains has steadily increased over the last 30
years16,17 rising from 20% in 1978 to 62% in 1996.6

According to current guidelines, oral and topical antibiotics should not be used together to treat acne, yet
prescribing data indicates that 23% of oral antibiotic prescriptions continue to be combined with a topical
antibiotic.

Oral antibiotics continue to be an important treatment option for patients with moderate to severe acne.
Oral isotretinoin can be used in patients with severe acne but it may induce numerous serious side
effects such as teratogenicity (fetal malformation). However, there are alternatives to topical antibiotics
including topical retinoids and benzoyl peroxide (BPO). An important tactic to preserve the efficacy of
antibiotics is to ensure that oral antibiotics are only used for a limited time and not used in combination
with a topical antibiotic.16

Antibiotic resistance can have serious implications for patients and the wider community. For acne
patients, resistant P. acnes can result in failed treatments, with acne patients displaying decreased, poor
or no response to therapy, or possibly suffering relapses that may otherwise have been prevented.8,9 P.
acnes has also been rarely associated with more severe infections in conditions such as arthritis,18,19
endocarditis 20 and generally associated with surgeries, implants and immunocompromized patients.21 In
addition, bacteria present in other areas of the body, such as normal, protective flora present in the gut or
those carried as human commensals, may be submitted to changes due to antibiotic selection pressure.9

Contributing factors
The rapid rise of antibiotic resistance in acne therapy has been attributed to a number of factors:

Prescribing practices16 Antibiotic use3,16 Limited monitoring3

Inappropriate and/or Poor adherence Lack of surveillance
indiscriminate use Failing to complete the full systems tracking
of antibiotics course of antibiotics antibiotic use and
Long-term antibiotic treatment Multiple antibiotic courses emergence and spread
(>12 weeks) Easy access to antibiotics of resistant strains
Dosing below Insufficient cross-
recommended levels infection control
Antibiotics in monotherapy
Concurrent use of oral and
topical antibiotics Community transmission6
Close contact between individuals results in the spread of
Simultaneous use of
resistant strains
chemically different antibiotics
International travel and commerce facilitates easy and quick
dissemination of bacteria across the world
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Addressing the overall antibiotic resistance problem

There is an urgent need for governments, the medical profession, the pharmaceutical industry and
individuals to work together and combat the threat of antibiotic resistance.

Recommendations to address the challenge include:1,3,4

Preserving the efficacy of existing antibiotic agents

Fostering the appropriate use of antibiotic drugs
Developing rapid diagnostics to inform use
Supporting international cooperation and sharing of surveillance data
Encouraging the development of new antibiotics

What can we do in dermatology to help combat antibiotic resistance?

Oral antibiotics are an important treatment option for acne and have helped many patients, but clinicians
now have a responsibility to ensure that they optimize their prescribing patterns to reduce the spread of
antibiotic-resistant acne; responsibly prescribing oral antibiotics and avoiding the use of any topical
antibiotics. Oral antibiotics should be prescribed for moderate to moderately severe acne for only short
treatment durations and be combined with BPO and topical retinoids to target as many
physiopathological factors as possible and reduce the risk of new acne lesions forming.9

Combination therapy should be started as early as possible, preferably at the initiation of treatment, to
simultaneously attack as many different pathogenic factors as possible.22

The key recommendations by the Global Alliance to Improve Outcomes in Acne, endorsed by the AAD in
2014, provides clear guidance on appropriate acne treatments which takes into account both the
physiopathology of acne, and the issue of antibiotic resistance.9

Guidelines from the Global Alliance to Improve Outcomes in Acne recommend:9

Oral antibiotics are recommended for moderate to moderately severe acne

Using a combination of topical retinoid and antimicrobial as first-line therapy as it achieves
significantly faster and greater clearing versus monotherapy
Avoiding oral and topical antibiotics as monotherapy or using them concurrently
Limiting to use of antibiotics to short periods
Discontinuing antibiotic use when there is no further improvement or only a slight improvement
is seen
Using topical retinoids rather than antibiotics for maintenance therapy, adding benzoyl peroxide
 Galderma Media Center, November 2014
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References
1. Group of Eight (2013). G8 science ministers statement London UK, 12 June 2013. Available at:
https://www.gov.uk/government/publications/g8-science-ministers-statement-london-12-june-2013 (date accessed: November
2014).
2. Nyquist A-C, Gonzales R, Steiner JF. Antibiotic prescribing for children with colds, upper respiratory tract infections, and
bronchitis. JAMA 1998;279(11):875877.
3. World Health Organization (2012). The evolving threat of Antibiotic resistance: options for action. Available at:
http://www.who.int/patientsafety/implementation/amr/publication/en/ (date accessed: November 2014).
4. Department of Health (2013). Annual report of the Chief Medical Officer, volume two, 2011:infections and the rise of
antimicrobial resistance. Available at:
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/138331/CMO_Annual_Report_Volume_2_2011.p
df (date accessed: November 2014).
5. Dreno B. Topical antibacterial therapy for acne vulgaris. Drugs 2004;64(21):23892397.
6. Rosen T. Antibiotic resistance: an editorial review with recommendations. J Drugs Dermatol 2011;10(7):724733.
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10. BBC news (2013). Antibiotics resistance as big a risk as terrorism medical chief. Available at:
http://www.bbc.co.uk/news/health-21737844 (date accessed: November 2014).
11. United States government. National Strategy For Combating Antibiotic-Resistant Bacteria, September 2014. Available at:
http://www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf (date accessed November 2014)
12. Market Insights IMS D+J Market - MAT Q4 2012 - WW (39 Countries)
13. World Economic Forum (2013). The dangers of hubris on human health. Available at: http://reports.weforum.org/global-risks-
2013/view/risk-case-1/the-dangers-of-hubris-on-human-health/ (date accessed: November 2014).
14. European Centre for Disease Prevention and Control and European Medicines Agency (2009). ECDC/EMEA Joint Technical
Report - The bacterial challenge: time to react. Available at:
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2014).
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in nondebilitated patients. Infect Control Hosp Epidemiol 2006;27:987990.
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