The implications of AMR for New Zealanders and the imminent threat it represents have been made plain by the Royal Society Te Apārangi in 201715 and the Office of the Prime Minister’s Chief Science Advisor in 2021.1 Estimates suggest, without urgent action, infections due to resistant microorganisms could kill 10 million people globally each year by 2050.16 A systematic analysis published in The Lancet in 2022 has already estimated global mortality in 2019 attributable to bacterial AMR to be approximately 1.3 million, with almost 5 million deaths associated with bacterial AMR, according to the predictive model used.17
The consequences of increases in AMR for New Zealand will be enormous given the reliance we have on effective antimicrobial therapy throughout medicine. What is certain is that AMR will disproportionately impact the most socioeconomically disadvantaged New Zealanders.1 Rates of some infections, including sepsis, in Māori and Pacific peoples are about twice those in people of European descent and other ethnic groups, and rates are significantly above average in the youngest, oldest and most deprived population groups.18
One of the biggest drivers for AMR is antimicrobial use. Antimicrobial use in New Zealand human populations is high compared with many developed countries7,19 as indicated by having:
- the fourth highest level of antibiotic prescribing (measured in defined daily dose per 1000 people) in 2017, surpassed only by Greece, Italy, and Korea1,3
- a community antibacterial consumption rate that increased 49 per cent between 2006 and 201419
- near-universal (97 per cent) antibiotic exposure by school age20
- 95 per cent of human antibiotic use being in the community.7
Small positive trends can be found. Over three years (2015 to 2018) community antibiotic use reduced by 14 per cent, mainly due to reductions in children under five years old.5 And during lockdown (2020), antimicrobial use decreased considerably, by 36 per cent, without evidence of harm.4 Thus, much of the previous “usual” antibiotic use may have been for viral respiratory tract infections, and unnecessary.
The consequence of antimicrobial use is that it produces selection pressure on the microbial environment and promotes a proliferation of resistant strains with the potential for harm.2 Multi-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and ciprofloxacin-resistant Neisseria gonorrhoeae already challenge clinical care in this country. However, the steadily increasing incidence of infections caused by multi-resistant Enterobacterales, such as Escherichia coli and Klebsiella pneumoniae, in hospitalised and community patients, are of greatest concern.20–22
- Extended spectrum β-lactamase-producing Enterobacterales (ESBL-E) are resistant to most penicillins and cephalosporins, and often also to other unrelated agents like trimethoprim and ciprofloxacin.
- Carbapenemase-producing Enterobacterales (CPE) are resistant to almost all antimicrobial agents, including “ultra-broad-spectrum” carbapenems (a sub family of β-lactams mainly used in hospital settings), and have 30 to 50 per cent mortality when they cause invasive infections.23 The Institute of Environmental Science and Research (ESR) recorded a greater than 10-fold increase in identified CPE isolates during 2010–2019.22
At the patient–clinician level, the impact of an infection due to a multi-resistant pathogen means:
- reduced, and in some cases no, effective funded oral antimicrobials (this is increasingly seen with cystitis due to ESBL-E in the community)
- reduced efficacy when using second-line antimicrobials
- higher toxicity and rates of adverse effects from the use of second-line agents
- patient cost/inconvenience with hospital visits for antimicrobial therapy (affecting rural/low socioeconomic groups disproportionately)
- longer hospital stays
- poorer outcomes from surgery (eg, joint replacement), cancer care and other interventions
- increased mortality
- elevated healthcare costs.6
In addition to the selection pressure for AMR caused by antimicrobial use, adverse drug events (ADE) are also common when antimicrobials are used. A 2017 study found 20 per cent of hospitalised patients in the US receiving at least 24 hours of antibiotic therapy developed an antibiotic-associated ADE. Moreover, 20 per cent of ADEs were attributable to antibiotics prescribed for conditions for which antibiotics were not indicated.24
The overarching goal of AMS is wider than counteracting AMR alone – it is to improve patient outcomes as well. Prescribing a first-line antibiotic choice, where one is indicated and appropriate, helps to achieve improved patient outcomes, partly by reducing the risk of ADEs. Non-β-lactam antibiotics are commonly used as second-choice agents, but they carry a raised ADE risk, eg, hyperkalaemia with trimethoprim + sulfamethoxazole. Adverse effects with quinolone antibiotic use are numerous and they have led to US Food and Drug Administration25 and European Medicines Agency26 warnings regarding their use. First-line antibiotic prescribing helps to avoid this risk.
Patient outcome is also impacted by the effect of antibiotic use on the microbiome, which can result in greater risk for infection associated with Clostridioides difficile (formerly named Clostridium difficile) or candida.
Antimicrobials are the only class of medicine where the treatment decisions made for an individual have broader ramifications for their whānau and the wider community. This means that decisions around treating infections affects the outcomes for patients in general, not just the one sitting in front of you.