For people infected with resistant bacteria there are many additional problems;

These factors result in

In food animals the consequences are similar (although the examples will be different).

Wherever antibiotics are used, resistant bacteria eventually develop and spread. This occurs both with people and animals. These resistant bacteria spread from person to person, animals to animals, people to animals and animals to people. They contaminate waterways when excretions or waste from either people or animals enters these waterways. They also are found frequently in food produced from animals that have received antibiotics. Slaughter processes and distribution networks result in cross contamination of many food products with resistant bacteria.

The extensive use of antimicrobials in all sectors (human and agriculture) means these drugs are often also found in the environment, especially in waterways and soils where bacteria are then again exposed to these drugs, often in low concentrations. Antibiotics are commonly used in aquaculture and in horticulture (e.g. gentamicin and streptomycin to spray apples). This results in much easier ingress of residual antibiotics used into waterways (Diwan et al. 2010; Mayerhofer et al. 2009; Zhou et al. 2011).

People and animals often come in contact with or ingest resistant bacteria because exposure to them is so widespread. If water and/or foods have antibiotic residues in them, then people and animals also ingest these residues. Acquired resistant bacteria are frequently carried by people and animals. These bacteria are then often reexposed to more antibiotics. A positive and very harmful feedback loop then results that leads to very high rates of resistant bacteria being found in many people and animals (or their products e.g. foods).

All sectors (people, animals and the environment) are directly and indirectly interconnected. A “One Health” approach to the problem of antimicrobial resistance means interventions will be better targeted against the complete and intertwined picture and not just, as occurs now, at subsections of this total picture.

Genes encoding for antibiotic resistant are present naturally in the environment for most, if not all, antibiotics. This is because most antibiotics are derived from precursors that are “natural products” produced by fungi or higher order bacteria to help them survive against other microbial competitors (Davies and Davies 2010; Webb and Davies 1993). The organisms’ that produce these antibiotics, however, usually need mechanisms to protect themselves against the effects of these toxic products they produce (after all antibiotics are designed to kill microorganisms). This means that often the microorganisms that produce antibiotics also have resistance genes and antibacterial products such as beta-lactamases etc. (Davies and Davies 2010; Webb and Davies 1993). This means whenever antibiotics are widely used, it is almost inevitable that resistance will develop as bacteria acquire resistance genes already present in the wider environment and these bacteria will then have a competitive advantage.

The greater the quantity of antibiotics used the more resistance will eventually develop. Resistant bacteria rapidly and easily move from site to site and from country to country. Because so much of this resistance is encoded by mobile genetic elements, the genes can move into other bacteria including quite different species. Thus the essential element to control antimicrobial resistance is to limit and decrease the amounts of antibiotics used in all sectors (i.e. human, agriculture, the environment). We need also to keep people and animals healthy so they do not need to receive antibiotics because they have less illness (good animal husbandry, immunisation etc.) and to stop the spread of resistant bacteria by better hygiene and infection control practices.

Resistant bacteria move readily from person to person, from hospital to hospital, from food animals to people and from country to country (Aarestrup et al. 2008b; Collignon et al. 2009; FAO 2003; Huijsdens et al. 2006; JETACAR 1999; Kennedy and Collignon 2010). Many spread through water and in foods. Foods (especially meats) also frequently contain bacteria that are multiresistant. Water is commonly contaminated with bacteria. When water is heavily contaminated with either human or animal faecal waste, then multiresistant bacteria can persist and even be distributed via chlorinated water supplies (e.g. in New Delhi with the MBL E. coli strains) (Walsh et al. 2011).

The bacterial genes that encode for antimicrobial resistance can also be readily transmitted between bacteria of the same species and also between bacteria of different species (Carlet et al. 2011; Kumarasamy et al. 2010; Walsh et al. 2011).

Infection control interventions help. In the UK a national program decreased the number of MRSA bacteraemia episodes per year from 2003 to 2007 by over 40 % (from 3,955 to 2,376 episodes) (Health Protection Agency 2009).

Immunisations such as Hib were very effective in decreasing the amount of resistant Hib that was seen and was causing increasing problems 20 years ago (Collignon et al. 2008a, b). This is an example where immunisation has had a profound effect on decreasing the number of resistant bacteria causing disease. Similar effects have also been seen with Pneumococcus with a successful conjugated vaccine with much less disease now in children and therefore less antibiotics having to be used to treat children because they have less serious disease from this organism (Collignon et al. 2008a, b). In animals and fish, vaccines have been very successful at preventing disease and through decreasing antimicrobial use (e.g. salmon and fluoroquinolone use in Norway) (Markestad and grave 1997).

Clean water is an essential component in controlling antimicrobial resistance. Water is likely to be the major vehicle, particularly in the developing world, where resistant bacteria spread from person to person. This means keeping contaminated animal waste and human waste out of water ways as much as is practicable and ensuring water is treated to such a standard that it minimises the risk that pathogens and commensal bacteria carrying resistant genes will be ingested by people or animals. Clean water considerably decreases the amount of GIT disease and transmission of Salmonella, Campylobacter and many other pathogens. This means less illness and thus less need for antibiotics.

We need to prevent multiresistant bacteria from being in our food supply. The best way to achieve this is to stop the use of “critically important” antibiotics in our food animals and better limit the use of all antibiotics in food animals. We can also decrease the number of organisms in food by better controls along the food chain such as the way animals are slaughtered so that there is less contamination of the carcass with bowel bacteria and find other ways to decrease the number of resistant bacteria in foods. At the other end of the food chain, after the food is produced, issues such as pasteurisation of milk and eggs or other heat treatment can considerably decrease the number of pathogens and therefore antibiotic resistant bacteria that are in the food that is subsequently distributed to consume. Obviously consumer education can also help stop cross contamination from uncooked foods and cooked foods but also to foods such as lettuce, tomatoes etc., which may not be cooked before they are ingested.

The use of animal and human manure to grow food is also an issue if it contains large numbers of pathogens including resistant bacteria that may not be inactivated or removed before the product reaches the market. This can have implication in the globalisation of food trade. A recent example was the Haemorrhagic E. coli outbreak in Germany. The bean sprouts involved came from bean seeds imported from Egypt. The seeds are presumed to have been contaminated by human or animal waste in Egypt. When germinated and grown in Germany, the E. coli already present, increased markedly in numbers. Then because these sprouts were not cooked before being ingested, large numbers of people became ill. This resulted in huge pressures on the hospitals and Intensive Care systems in Germany and was also associated with many deaths (CDC 2011).

Increasing resistance is occurring in almost all medically important bacteria, including to antimicrobials classified as “critically important” or “last line” for human health (Collignon et al. 2009). This means when resistance is present there will be very limited or no antimicrobial therapy that will still be effective to treat infections caused by these resistant bacteria. In hospitals we see increasing numbers of bacterial infections to which there are no effective antibiotics available. This includes infections caused by E. coli, Acinetobacter spp., Serratia spp. and Enterobacter spp. (Carlet et al. 2011; Fernando et al. 2010; Li et al. 2006; Walsh et al. 2011).

Resistance rates in almost all types of bacteria are much higher in developing countries. For most people living in developing countries this problem is compounded by poor access to appropriate diagnostic facilities, less resources being available to help institute and maintain appropriate hygiene and infections control practises as well as difficulties in accessing adequate and affordable medical care.

Many classes of critically important antibiotics are also used in food production animals. The most important of these from a human health consequence perspective have been identified by the World Health Organisation (WHO) as fluoroquinolones, third- and fourth-generation cephalosporins and macrolides (Collignon et al. 2009; WHO 2009).

Most antimicrobial classes were discovered decades ago. There have been very few new classes of antibiotics developed in the last 30 years (fluoroquinolones, lipopeptides, oxazolidinones). There have been some developments in classes of antibiotics that have already existed that have led to agents with much improved activity (ketolides and tigecycline). However, these latter two agents are just variations of macrolides and tetracycline’s respectively (Carlet et al. 2011; Collignon et al. 2009).

The problem we have is that antibiotic resistance is developing much faster than there are any new drugs or drug classes likely to be available in the near future. This is particularly a problem for Gram-negative bacteria where there does not even look that there are many promising drugs in any advanced research stage yet alone in the development pipeline. The financial rewards for pharmaceutical companies to research and then market completely new classes of antibiotics is relatively poor compared to the returns on drugs that need to be taken by a large percentage of the population continuously e.g. cholesterol-lowering drugs (Collignon et al. 2008a, b; Power 2006). Unfortunately this situation is not likely to change in the near future.

We need much better and timely surveillance of antimicrobial usage and of resistant bacteria—locally, nationally and internationally. The results need to be readily available so we can better see what is happening with resistance in different areas and needs to involve both the human and non-human sector. We need to know the volumes and types of antimicrobials being used. This will allow not only the better choice of empiric antibiotic therapy but also help us better target problem areas with preventive interventions, improved antibiotic stewardship and other programs. This will then help to stop or slow resistance from getting worse in those targeted areas and hopefully even reverse some of the resistance levels seen.