Saq065 amrau report Internal V11

1. Surveillance and reporting of antimicrobial resistance and antibiotic usage in Australia

1.1 Antimicrobial resistance and antibiotic usage – a global threat to human health

Antimicrobial resistance (AMR) is not a recent phenomenon, but it is a critical health issue today. Over several decades, to varying degrees, bacteria causing common infections have developed resistance to each new antibiotic, and AMR has evolved to become a worldwide health threat. With a dearth of new antibiotics coming to market, the need for action to avert a developing global crisis in health care is increasingly urgent … The World Health Organization (WHO) has long recognized AMR as a growing global health threat, and the World Health Assembly, through several resolutions over two decades, has called upon Member States and the international community to take measures to curtail the emergence and spread of AMR … On World Heath Day 2011, WHO again highlighted AMR and urged countries to commit to a comprehensive financed national plan to combat AMR, engaging all principal stakeholders including civil society.

Dr Marie-Paule Kieny¹

Assistant Director General, Innovation,
Information, Evidence and Research
World Health Organization

Antimicrobial resistance (AMR) is an important global public health priority, with the World Health Organization calling for urgent action.^{1, 2} Globally, the threat of AMR features more and more in the new and popular press. For example, in the United States (US), a ‘Dead Brooklyn boy had drug-resistant infection’ (26 October 2007, New York Times³). In the United Kingdom (UK), there are warnings that ‘Antibiotic-resistant diseases pose “apocalyptic” threat’ (23 January 2013, The Guardian⁴). In Australia, AMR is reported to be the ‘Greatest threat to human health’ (16 February 2011, Sydney Morning Herald⁵) because of the ‘Rise of the superbugs’ (29 October 2012, Four Corners, ABC television⁶). Some resistant bacterial pathogens that were once primarily the concern of hospitals are now seen more often in the community, and patients are arriving in hospitals carrying resistant bacteria acquired in the community setting. These bacteria cause opportunistic infections that are difficult to treat, and impact clinical care. AMR contributes to increased patient morbidity and mortality, complexity and duration of treatments, and hospital stay, resulting in substantial increases to healthcare system costs and financial burden to the community.^{7, 8}

The evolving threat that AMR presents to human health is demonstrated by international evidence and data, which are validating an increase in AMR pathogens responsible for infections in healthcare facilities and in the community.⁹ The number of antimicrobial-resistant pathogens is increasing at an alarming rate. Moreover, the prevalence of resistance of human pathogens to all clinically important antibiotics is rising at varying levels in different parts of the world; the highest levels outside of Europe are observed in Asia, Africa and South America.⁷ The situation is exacerbated by the ability of many bacteria to share genetic material and pass on resistance genes, as well as by international travel and medical tourism. To understand the challenges AMR presents to human health and society more broadly, it is useful to explore its scientific foundations.

1.2 Microbes, antimicrobials and antibiotics

Microbe is a term used to describe organisms that are too small to be seen with the naked eye. The term can be used to encompass bacteria, fungi, parasites and viruses. Although many microorganisms exist in a symbiotic, commensal or innocuous relationship with humans – some are essential to life – others cause significant morbidity and mortality. Some exist as part of the ‘normal flora’ of the human body under normal circumstances, but can create opportunistic infections in altered surroundings, such as after a dental extraction or penetrating injury, or when a person is immunocompromised due to illness or chemotherapy. Under these circumstances, it is desirable to either stop the replication or impede the growth of the microorganism that is contributing to a diseased state.

Some of the earliest antimicrobials were compounds derived from a species of fungus, Penicillium rubens.¹⁰ The discovery that, if grown on an appropriate substrate, this species would inhibit the growth of bacteria is credited to Scottish scientist and Nobel Laureate Alexander Fleming in 1928. An Australian Nobel Laureate, Howard Florey, later worked with colleagues to transform this discovery into a medicine, penicillin. Introduction of sulfonamides or ‘sulfa drugs’ in the early 1930s heralded the beginning of the modern era of antibiotic discovery and use, which are fundamental to contemporary health and medical practice today.

Antibiotics used against bacteria are the most commonly recognised form of antimicrobials. Other types of antimicrobials are used against viruses (e.g. human immunodeficiency virus [HIV] or influenza virus) or against parasites (e.g. Plasmodium spp. that cause malaria), and as disinfectants. For the purposes of AMR in this document, the focus is on the antibiotics that are used to treat bacterial infections. The importance and role of antibiotics in medicine for the treatment and control of infectious diseases in humans and domestic animals are irrefutable. Antibiotics used for treatment and prophylaxis are also critical to the success of complex surgery, intensive care, organ transplants, and survival of immunosuppressed and older people.²

Antibiotics suppress the growth of bacteria and the infections they cause by stopping bacterial cell division (bacteriostatic), thus preventing bacterial growth, or by killing the bacteria themselves (bactericidal).There are a large number of antibiotics available for the treatment of bacteria that cause infections or infectious diseases (within differing classes of structurally related agents and/or with similar mechanisms of action – refer to Table 1). The largest group are beta-lactam antibiotics, and include penicillins, cephalosporins, carbapenems and monobactams. Other antibiotic groups include aminoglycosides, tetracyclines, macrolides, fluoroquinolones and glycopeptides. Some antibiotics are effective against a limited range of infectious agents (narrow spectrum); others are effective against many different pathogens (broad spectrum). Antibiotics in the same families are generally used in both human medicine and animal husbandry.

It has long been assumed that the challenges of AMR would be overcome by the ongoing development of new compounds. Since the innovation of antibiotics, new classes of antibiotics have been discovered, existing antibiotics and synthetic components to combat emerging resistant bacteria have been modified and adjusted, and the clinical qualities of existing antibiotics have been improved.² However, for many bacterial pathogens, resistance to last-line antibiotics, such as carbapenems, fluoroquinolones, glycopeptides and third-generation cephalosporins, is now commonly found in Australian hospitals and, to an increasing extent, in the community.¹¹

In addition, there has been an alarming decline in antibiotic development over time.¹¹

Table 1: Mechanism of action of different groups of antibiotics

Mechanism of action	Antibiotic group
Inhibits cell wall synthesis	Beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), bacitracin, glycopeptides
Inhibits protein synthesis	Aminoglycosides, aminocycitols, amphenicols, macrolides, lincosamides, streptogramins, tetracyclines
Interferes with cell membrane function	Polypeptides
Interferes with DNA or RNA synthesis	Quinolones, rifamcyins
Inhibits metabolism	Sulfonamides, sulfones, trimethoprim, nitrofurans, nitroimidazoles
Unknown	Polyethers