28th October 2016, Volume 129 Number 1444

Humphrey W Pullon, John Gommans, Mark G Thomas, Sarah Metcalf, Rebecca Grainger, Harriet Wild

Antimicrobials are effective in treating infections economically and achieve positive outcomes for patients.Antimicrobial resistance (AMR) results from infection-causing organisms surviving exposure to medicines that would normally eradicate or inhibit growth. Strains capable of surviving exposure to a particular drug and a lack of competition from other strains leads to increased resistance.1

AMR has been cited as the most significant health issue of the 21st century with potentially serious consequences for the health of global populations, including New Zealand, and its health system.1–3

The RACP has released a policy paper highlighting three common pathogens that pose a risk to the health of New Zealanders. Although AMR is a complex and urgent public health concern, RACP identifies specific causes where improved understanding and action would reduce potential threats.4

This paper outlines the international context of AMR and its impact on New Zealand. The RACP believes there should be an increased focus on pathogens active in hospital and community settings that show resistance to antibiotics and pose a risk to the health of New Zealanders. A strategy to minimise the impact of multi-drug resistant organisms through antimicrobial stewardship (AMS) is essential. A combination of prescribing guidelines and infection prevention and control (IPC) practices within an AMS framework will set the parameters for change. Coordinated interventions are designed to improve and measure the appropriate use of antimicrobials and promote effective prescribing practices such as selection of appropriate agents, dose, duration and route of admiinstration.5

Increasing use and misuse of antimicrobials needs tighter control. Inadequate IPC practices and the lack of programmes to develop new antimicrobials undermine the ability of prescribers to provide effective treatment for a growing number of infections. The projected effects on people and economies show spiralling costs. Without action, AMR could be attributed to 10 million deaths globally each year and cost 100 trillion USD to the global economy by 2050 (Figure 1).1

Figure 1: AMR-attributable deaths globally in 2050 compared to other major causes of mortality.

c 

International context

In 2001 the World Health Organization (WHO) announced a strategy for the containment of AMR, calling for an international response to position AMR at the forefront of health policy.2 The strategy encouraged member states to introduce national frameworks and surveillance with a focus on quality and safety, as follows:

  1. Adhere to a comprehensive, financed national plan with accountability and civil society engagement
  2. Strengthen surveillance and laboratory capacity
  3. Ensure uninterrupted access to essential medicines of assured quality
  4. Regulate and promote the rational use of medicines, and ensure proper patient care
  5. Enhance infection prevention and control
  6. Foster innovation, research and new tools.2

A 2015 evaluation examined national responses to AMR within the WHO regions and assessed member states’ ability to meet the strategy, and found that:

  • Only 25% of member states had a comprehensive plan
  • Public awareness of AMR remained limited, even among healthcare workers
  • Few member states had national IPC programmes and fewer had programmes in all tertiary hospitals.6

AMR containment and control in New Zealand

In the WHO 2015 Report on the response to AMR, healthcare-associated infections (HAIs) and vaccine-preventable infections are identified as the most common public health threats in high-income countries in the Western Pacific region, including New Zealand.6 Surveillance and monitoring data for New Zealand is gathered by the Antibiotic Reference Laboratory at the Institute of Environmental Science and Research (ESR) to show prevalence and contributing factors for AMR, and where to target interventions.7

The release of the New Zealand Ministry of Health AMR Action Plan scheduled for May 2017 is welcomed. This is an important step forward. The RACP supports inclusion of a national antimicrobial prescribing guideline, and systematic measuring, monitoring and surveillance of AMR to include human and animal populations, as well as surveillance of antimicrobial consumption in District Health Boards (DHBs) and community settings. The New Zealand Veterinary Association's (NZVA) commitment to eliminating the use of antimicrobials to maintain wellbeing in healthy animals by 2030 has called for a multidisciplinary ‘one world, one health’ approach. This aims to raise awareness of the links between animals, humans and the environment and reduce the threat of AMR to human and animal health.8

Three common pathogens of concern in New Zealand

In 2015, the WHO identified nine bacterial pathogens of international concern, and reported on member states’ monitoring and surveillance of resistant strains.6 Three of these nine bacterial pathogens are of particular concern in community and hospital settings in New Zealand. They cause a range of common diseases, may be community or hospital-onset, pose challenges for prescribers to effectively treat infections and result in additional costs to the health system.3,9 The three pathogens are:

  1. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
  2. Enterobacteriaceae
  3. Neisseria gonorrhoeae (N. gonorroheae).

Staphylococcus aureus (S. aureus), Enterobacteriaceae and N. gonorrhoea are medically important bacteria and increased resistance in these and other pathogens present a major threat to human health.3 We have chosen to focus on resistance in these pathogens as these bacteria are common in community and hospital settings, present as a range of infections (for example, skin and soft tissue infections, urinary tract infections) and are increasingly resistant to major classes of antibiotics including penicillins, fluoroquinolones and third-generation cephalosporins.3 We are concerned that the impact of resistance is driven by practices such as antimicrobial prescribing and consumption, the profile of infectious diseases in the community, population movement and IPC programmes.3,9

1. Community-associated methicillin-resistant S. aureus

New Zealand has a higher prevalence of S. aureus infections than comparable countries, including the UK and Australia. Although the majority of infections are attributed to community-associated methicillin-susceptible S. aureus (CA-MSSA), presentations of CA-MRSA have increased significantly since the early 1990s.9,10

This increase has been linked to high use of topical antibiotic treatments containing either mupirocin or fusidic acid to treat skin and soft tissue infections.10,11 Between 1991 and 2000 topical antibiotics could be purchased without a prescription, contributing to further use of these medicines and to marked increases in resistance to mupirocin, the active ingredient in the topical antibiotic Bactroban©. By 2000 resistance to mupirocin was present in over 20% of S. aureus isolates, up from less than 5% of isolates in 1992.10,11

While topical antibiotics are commonly prescribed to treat several dermatological conditions, evidence-based guidelines support its use only for localised impetigo and eczema. Antibiotics for treatment of S. aureus should be as narrow-spectrum as possible; for example, flucloxacillin should be favoured over cephalexin or amoxicillin/clavulanate.3,12

2. Enterobacteriaceae

Rates of infection due to extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) have risen steadily in New Zealand, as they have in many regions globally.6 In 2012, 4,000 cases of ESBL-producing E. coli and Klebsiella pneumoniae (K. pneumoniae) infections were observed in hospital and community settings.3 In 2006–8 approximately 2.6% of bloodstream isolates were ESBL-producers; by 2011, this figure had nearly doubled to 4.7%.2,3 Reported prevalence of ESBL-producing isolates in K. pneumoniae are higher, at 10–15%.9

ESBL-producing E. coli and K. pneumoniae are typically resistant to all penicillins and most currently available cephalosporins.2 People with serious ESBL-producing Enterobacteriaceae infections were commonly found to require hospital-based intravenous antibiotic therapy as the most effective treatment, because carbapenem antibiotics are not absorbed orally.3

Treatment in hospital for resistant infections has led to additional healthcare costs.3,9 Increasing rates of resistance will put hospitals under greater pressure, and could undermine the viability of other interventions, including surgery, organ transplantation and chemotherapy.1

Infections due to carbapenem-resistant Enterobacteriaceae (CRE) have been detected in New Zealand. While the majority of these cases were contracted overseas, in 2015 a limited outbreak in two hospitals was reported in New Zealand.13 We note there is a greater risk of pathogens spreading geographically as populations are increasingly mobile in a globalised society, through migration, trade and tourism.14 The number of CREs has increased dramatically since 2009. In 2015 alone 41 isolates were identified, compared to 35 isolates in total between 2009 and 2014.13

There is a risk that CRE isolates may be resistant to all known antibiotics. Hospital IPC practices such as isolation and surveillance are known to be effective in preventing and minimising the risk of patient-to-patient spread, particularly for patients susceptible to CRE infection in areas such as intensive care or neonatal units.1,5,9

3. Neisseria gonorrhoeae

N. gonorrhoeae is the causal bacteria of gonorrhoea, the second most-prevalent STI, with approximately 62 million new cases globally each year.15 Gonorrhoea is asymptomatic in up to 50% of infected women; as such it proves harder to treat in a timely and effective manner. Untreated it can lead to an increased risk of pelvic inflammatory disease and infertility.16

Increasing resistance in N. gonorrhoea has limited the efficacy of first-line antimicrobials, including penicillins, narrow-spectrum cephalosporins, tetracyclines and fluoroquinolones. Globally and in New Zealand, most people with gonorrhoea now receive combined treatment of an intramuscular injection of ceftriaxone, plus azithromycin orally.9,17

While there have been no isolates of ceftriaxone-resistant N. gonorrhoeae identified in New Zealand, isolates of decreased susceptibility have been reported as emerging in some geographical areas and this is raising concerns.9,16 The emergence of infection resistant to ceftriaxone would raise the spectre of untreatable disease and there would be significant public health implications, particularly for disease control and an increased prevalence of disseminated gonococcal and neonatal infections.2

Antimicrobial governance and stewardship

Implementation of evidence-based treatment guidelines to reduce selective pressure on bacterial pathogens that drive the spread of resistance would be an important first step to preventing increases in AMR. This would guide change in the selection, dose and delivery of antimicrobials and minimise unnecessary use.1,3,9

The Ministry of Health's role in fostering a nationwide programme is essential to lead a whole of sector response for AMR. DHBs have a key coordinating role in responding to and engaging with their local health services, practitioners, local communities and populations and are well placed to develop and support AMS through their existing IPC programmes, which involve Primary Health Organisations and services within their communities.

AMS is a whole of sector responsibility and collaborative approaches to engage clinicians, services, and communities in the design of AMR solutions and interventions will improve sector participation; and uptake will increase the likelihood of clinical practice improvements.

We note that New Zealand DHBs that have implemented a centrally-driven plan and provided funding for AMS programmes have achieved lower rates of antimicrobial use than hospitals in the UK and Australia.18 Successful and sustained AMR initiatives were those that engaged clinical leaders in their AMS committees and IPC programmes.19,20 These AMS teams worked collaboratively to create links between clinical teams, infectious disease physicians, clinical microbiologists and hospital pharmacists.1,18,19

We consider that New Zealand’s best practice guidelines to prevent antimicrobial resistance would sit within a quality improvement programme to support organised implementation of measures by clinical and operational teams and integrate collaborative processes. The programme would include maintenance and implementation of a restricted antimicrobial formulary policy, IPC programmes and auditing against outcome measures to evaluate and inform change and improvement.2,18

Safe prescribing of antimicrobials

Community-based prescribing and consumption of antibiotics increased dramatically between 2005 and 2012 in New Zealand, when annual per capita consumption of antimicrobials rose an average of 6% per year. By 2012 the level of community antimicrobial consumption was higher than that of Spain and most other European countries.9

Despite the lack of evidence of significant benefit from antibiotic treatment, prescribers report that they are under pressure from patients to prescribe antibiotics, when symptom management may be more effective.21,22

Excessive use of antimicrobials in outpatient settings, over-the-counter purchasing and risky prescribing practices have also contributed to a rise in the incidence of AMR.1,2,21 In high-income countries the majority of prescriptions for antibiotics for human health are prescribed in ambulatory care settings. Approximately half of these prescriptions are for self-limiting respiratory tract infections, which infrequently require antibiotic treatment.22

Given rates of community prescribing and increasing rates of AMR in pathogens of concern, we consider public health approaches would increase understanding of AMR in New Zealand.1–3 Key messages focused on consumption, prescribing and the links between human, animal and environmental health would mitigate local and regional variation. Potential factors that may influence prescribing practices and attitudes include prescriber and patient education; access to healthcare; actions to reduce the incidence of infectious diseases within the community (for example, acute rheumatic fever and skin infections); and socioeconomic conditions and cultural beliefs.23

We note that increasing best practice prescribing through good clinical governance and clinical guidelines is known to be effective.2,3,20 We support the uptake of New Zealand-specific guidance, such as the Antibiotics: Choices for Common Infections Guideline developed by the Best Practice Advocacy Centre, which provides guidance for antimicrobial prescribing in community settings and primary care; PHARMAC’s Hospital Medicine List; and the New Zealand Formulary, which are available for prescribers practicing in all settings.24–26

Infection prevention and control practices in healthcare settings

Preventing the spread of harmful bacteria to reduce reliance on antimicrobials is proven to reduce subsequent infections. Health systems that invested in hygiene programmes have shown a reduction in the risk of infection both in community and in hospital settings.20,28 Education and professional development programmes are vital to maintain IPC practices.19,20

Hand hygiene is the single most effective practice proven to prevent transmission of infection.1 Compliance with hand hygiene guidelines in New Zealand is improving, with the rate at or above 80% across all observed interactions between patients and their health practitioner, in the audits conducted by the New Zealand Health Quality and Safety Commission between November 2015 and March 2016.29 Improvements in hand hygiene have resulted in lower rates of HAIs, which reduces the use of antimicrobials needed to treat these infections.19,20

IPC programmes provide guidance on interventions to reduce the incidence and prevalence of HAIs, which cause significant mortality in hospital settings.1,9 In New Zealand, health workforce buy-in, education and compliance with best practice hand hygiene has minimised transmission of pathogens between health practitioners, patients, staff, visitors and surfaces. The widespread availability of alcohol-based hand rub in hospitals and clinics has also contributed to the broad adoption and acceptance of hand hygiene practices by health practitioners, patients and their families/whānau.28,29

Effective hand hygiene practices reduce harm to patients, and subsequent costs to the healthcare system.28 To be effective, comprehensive hand hygiene requires full health workforce understanding of hand hygiene practices to effect a safer environment for health practitioners, patients and their families/whānau.

Recommendations for action

Action by the Ministry of Health in collaboration with the Ministry of Primary Industries and other stakeholders to develop a national plan must be consistent with global approaches. We recommend that action is based on the WHO Strategy to ensure changes can be measured and compared to understand the effectiveness of global efforts.

We recommend that a national stewardship programme incorporates quality improvement processes and supports clinicians to maintain knowledge and currency on the patterns and management of resistance in key pathogens in New Zealand.

To provide consistency and reduce duplication, we recommend that the New Zealand antimicrobial strategy incorporates a single national prescribing guideline and plan informed by infectious diseases physicians and paediatricians, microbiologists, general practitioners and pharmacologists to ensure relevance in hospital and community settings. Implementation through clinical networks and a public awareness campaign will increase understanding of the use of antimicrobials and the risks of resistance.

AMS and multidisciplinary teams are an essential component of an effective system. We recommend approaches that are evidence-based and support systematic improvements in practice, and recognise the skills and experience of clinical leaders as a key resource for contributing to improvements in AMS.

As an example of successful professionally-led practice, the RACP is collaborating with specialty societies in New Zealand and Australia through its EVOLVE initiative. The process encourages each medical specialty to think about the clinical circumstances in which some of the practices, whether medical tests, procedures or interventions—should have their indication or value questioned and discussed by physicians. These may be overused, inappropriate or of limited clinical effectiveness in a given clinical context. The RACP is facilitating the development of top-five lists of low value practices, including that of the Australasian Society for Infectious Diseases (ASID). Three of the five ASID recommendations discourage antibiotics, stating that use of therapies are not indicated, increase the risk of resistance and may pose additional costs.30 Consideration should be given to developing a similar approach involving health practitioners, services, patients, families/whānau to reduce AMR.

We encourage all health practitioners to remain informed and up to date on the patterns of resistance for pathogens in New Zealand and engage in stewardship activities in their workplaces and communities. Health practitioners have a responsibility to inform patients and their family/whānau when symptom management will have greater efficacy for viruses. Effective communication through public health campaigns will also reinforce appropriate use of antimicrobial therapies.

Finally, we support increased collaboration within and across the human health, scientific and agricultural sectors led by central government agencies, will enable New Zealand to respond effectively to AMR.

Summary

Microorganisms (eg bacteria) are developing resistance to a range of antimicrobial drugs, including antibiotics: this is known as antimicrobial resistance (AMR). Standard treatments are now becoming ineffective, which increases the risk of adverse outcomes (including death) and the spread of the infection. AMR is increasing globally where poor sanitation, close contact between humans and animals and unregulated prescribing are common. In New Zealand, there is increasing resistance in infections caused by Staphylococcus aureus, Enterobacteriaceae (eg E. Coli) and Neisseria gonorrhoeae. These bacteria are common causes of infection, and may occur in hospital and community settings. New Zealand must prioritise a plan to prevent increasing AMR, which includes prescribing guidelines, antimicrobial stewardship programmes to promote optimal use of antibiotics and public health campaigns.

Abstract

AMR has been cited as the most significant health issue of the 21st century with potentially serious consequences for the health of global populations, including New Zealand, and its health system. Proactive approaches to combating AMR through better understanding of the causes will inform measures required to reduce potential threats. The Royal Australasian College of Physicians (RACP) identifies three pathogens where increased resistance is of concern and recommends collaborative responses to prevent emerging threats to New Zealand populations. An international best practice AMR programme would include antimicrobial stewardship (AMS) building on evidence, policy, organisational support, multidisciplinary teams and patient experience. The planned Ministry of Health-led collaborative approach to developing a national strategy and programme will provide sector direction. Implementation will require extensive engagement with the health sector and communities to develop joint solutions that prevent further increases in AMR.

Author Information

Humphrey W Pullon, Haematologist, Department of Haematology, Waikato Hospital, Hamilton; John Gommans, General Physician and Chief Medical Officer, Hawkes Bay Hospital, Hastings; Mark G Thomas, Infectious Diseases Physician, Faculty of Medical and Health Sciences, University of Auckland, Auckland; Sarah Metcalf, Infectious Diseases Physician, Department of Infectious Diseases, Christchurch Hospital, Christchurch; Rebecca Grainger, Rheumatologist, Hutt Hospital, Lower Hutt and Department of Medicine, University of Otago, Wellington; Harriet Wild, Policy and Advocacy Officer, The Royal Australasian College of Physicians, Wellington.

Acknowledgements

This article has been developed by the New Zealand Adult Medicine Division Committee of the Royal Australasian College of Physicians (RACP). The Committee works across education and training, continuing professional development, policy and advocacy in relation to Adult Medicine in New Zealand. 

Correspondence

Dr Humphrey Pullon, New Zealand Adult Medicine Division Committee, The Royal Australasian College of Physicians, Wellington.

Correspondence Email

policy@racp.org.nz

Competing Interests

Nil.

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