Geography of Tibet

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Yamdrok Lake

The geography of Tibet consists of the high mountains, lakes and rivers lying between Central, East and South Asia. Traditionally, Western (European and American) sources have regarded Tibet as being in Central Asia, though today's maps show a trend toward considering all of modern China, including Tibet, to be part of East Asia. Tibet is often called "the roof of the world," comprising tablelands averaging over 4,950 metres above the sea with peaks at 6,000 to 7,500 m, including Mount Everest, on the border with Nepal.

Description

It is bounded on the north and east by the Central China Plain, on the west by the Kashmir Region of India and on the south by Nepal, India and Bhutan. Most of Tibet sits atop a geological structure known as the Tibetan Plateau, which includes the Himalaya and many of the highest mountain peaks in the world.

High mountain peaks include Changtse, Lhotse, Makalu, Gauri Sankar, Gurla Mandhata, Cho Oyu, Jomolhari, Gyachung Kang, Gyala Peri, Mount Kailash, Kawagebo, Khumbutse, Melungtse, Mount Nyainqentanglha, Namcha Barwa, Shishapangma and Yangra. Mountain passes include Cherko la and North Col. Smaller mountains include Mount Gephel and Gurla Mandhata.

Regions

Physically, Tibet may be divided into two parts, the "lake region" in the west and north-west, and the "river region", which spreads out on three sides of the former on the east, south, and west. The region names are useful in contrasting their hydrological structures, and also in contrasting their different cultural uses which is nomadic in the "lake region" and agricultural in the "river region". Despite its large size and mountainous nature, variation of climate across the Tibetan Plateau is more steady than abrupt. The "river region" has a subtropical highland climate with moderate summer rainfall averaging around 500 millimetres (20 in) per year, and daytime temperatures ranging from around 7 °C (45 °F) in winter to 24 °C (75 °F) in summer – though nights are as much as 15 °C (27 °F) cooler. Rainfall decreases steadily to the west, reaching only 110 millimetres (4.3 in) at Leh on the edge of this region, whilst temperatures in winter become steadily colder. On the south the "river region" is bounded by the Himalayas, on the north by a broad mountain system. The system at no point narrows to a single range; generally there are three or four across its breadth. As a whole the system forms the watershed between rivers flowing to the Indian Ocean – the Indus, Brahmaputra and Salween and its tributaries – and the streams flowing into the undrained salt lakes to the north.

The "river region" is characterized by fertile mountain valleys and includes the Yarlung Tsangpo River (the upper courses of the Brahmaputra) and its major tributary, the Nyang River, the Salween, the Yangtze, the Mekong, and the Yellow River. The Yarlung Tsangpo Canyon, formed by a horseshoe bend in the river where it flows around Namcha Barwa, is the deepest, and possibly longest canyon in the world. Among the mountains there are many narrow valleys. The valleys of Lhasa, Shigatse, Gyantse and the Brahmaputra are free from permafrost, covered with good soil and groves of trees, well irrigated, and richly cultivated.

The South Tibet Valley is formed by the Yarlung Zangbo River during its middle reaches, where it travels from west to east. The valley is approximately 1200 kilometers long and 300 kilometers wide. The valley descends from 4500 meters above sea level to 2800 meters. The mountains on either side of the valley are usually around 5000 meters high. Lakes here include Lake Paiku and Lake Puma Yumco.

The "lake region" extends from the Pangong Tso Lake in Ladakh, Lake Rakshastal, Yamdrok Lake and Lake Manasarovar near the source of the Indus River, to the sources of the Salween, the Mekong and the Yangtze. Other lakes include Dagze Co, Nam Co, and Pagsum Co. The lake region is an arid and wind-swept desert. This region is called the Chang Tang (Byang thang) or 'Northern Plateau' by the people of Tibet. It is some 1100 km (700 mi) broad, and covers an area about equal to that of France. Due to the extremely high mountain barriers it has a very arid alpine climate with annual precipitation around 100 millimetres (4 in) and possesses no river outlet. The mountain ranges are spread out, rounded, disconnected, separated by flat valleys. The country is dotted over with large and small lakes, generally salt or alkaline, and intersected by streams. Due to the presence of discontinuous permafrost over the Chang Tang, the soil is boggy and covered with tussocks of grass, thus resembling the Siberian tundra. Salt and fresh-water lakes are intermingled. The lakes are generally without outlet, or have only a small effluent. The deposits consist of soda, potash, borax and common salt. The lake region is noted for a vast number of hot springs, which are widely distributed between the Himalaya and 34° N., but are most numerous to the west of Tengri Nor (north-west of Lhasa). So intense is the cold in this part of Tibet that these springs are sometimes represented by columns of ice, the nearly boiling water having frozen in the act of ejection.

The effects of climate change

The Tibetan Plateau contains the world's third-largest store of ice. Qin Dahe, the former head of the China Meteorological Administration, said that the recent fast pace of melting and warmer temperatures will be good for agriculture and tourism in the short term; but issued a strong warning:

"Temperatures are rising four times faster than elsewhere in China, and the Tibetan glaciers are retreating at a higher speed than in any other part of the world." "In the short term, this will cause lakes to expand and bring floods and mudflows." "In the long run, the glaciers are vital lifelines for Asian rivers, including the Indus and the Ganges. Once they vanish, water supplies in those regions will be in peril."

Tibet during the last glacial period

Today Tibet is the most essential heating surface of the atmosphere. During the Last glacial period a c. 2,400,000 square kilometres (930,000 sq mi) ice sheet covered the plateau. This glaciation took place in correspondence to a lowering of the snowline by 1,200 metres (3,900 ft). For the Last Glacial Maximum this means a depression of the average annual temperature by 7 to 8 °C (13 to 14 °F) at a minor precipitation compared with that one of today.

Owing to this drop in temperature a supposed drier climate has partly been compensated with regard to the glacier feeding by a minor evaporation and an increased relative humidity. Due to its great extension this glaciation in the subtropics was the most important climatically foreign element on earth. With an albedo about 80-90% this ice area of Tibet has reflected an at least 4 times greater global radiation energy per surface into space than the further inland ices at a higher geographical latitude. At that time the most essential heating surface of the atmosphere – which at present, i.e. interglacially, is the Tibetan plateau – was the most important cooling surface.

The annual low-pressure area induced by heat above Tibet as a motor of the summer monsoon was lacking. The glaciation thus caused a breaking-off of the summer monsoon with all the global-climatic consequences, e.g. the pluvials in the Sahara, the expansion of the Thar desert, the heavier dust influx into the Arabian Sea etc., and also the downward shifting of the timber line and all forest-belts from the alpine-boreal forests as far down as to the semi-humid mediterranean forest which has replaced the Holocene monsoon-tropical forests on the Indian subcontinent. But also the movements of animals including the Javan Rusa far into South Asia are a consequence of this glaciation.

Despite heavy ablation caused by heavy insolation, the discharge of the glaciers into the Inner-Asian basins was sufficient for the creation of meltwater lakes in the Qaidam Basin, the Tarim Basin and the Gobi Desert. The drop in temperature (see above) was in favour of their development. Thus, the clay fraction produced by the ground scouring of the important glaciation was ready to be blown-out. The blow-out of the limnites and the Aeolian long-distance transport were connected to the katabatic winds. Accordingly, the Tibetan glaciation was the actual cause of the enormous loess production and the transport of the material into the Chinese middle- and lowlands continuing to the east. During the Ice Age the katabatic air current – the name 'winter monsoon' is not quite correct – blew all year round.

The enormous uplift of Tibet by around 10 mm/year measured by triangulations since the 19th century and confirmed by glaciogemorphological findings as well as by seismological investigations equals the uplift of the Himalaya. However, these amounts of uplift are far too important as to a primarily tectonic uplift of the high plateau which only takes place epirogenetically. Actually they can be understood the better by a superimposed glacioisostatic compensation movement of Tibet about 650 m.

An alternative view held by some scientists is that the glaciers on the Tibetan Plateau have remained restricted over the entire data published since 1974 in the literature referred to in Kuhle (2004), which are relevant as to the maximum ice extent.

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  Himalayas near Lhasa

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  Tibet is located on the Tibetan Plateau, the world's highest region.

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  Tibetan Plateau and surrounding areas above 1600-m topography^[15][16]

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  The Tibetan plateau lies between the Himalayan range to the south and the Taklamakan plain to the north.

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  Lake Pangong Tso

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  Glacier-capped mountains in Tibet

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  Animation of glacier-capped mountains in Tibet

Tibetan Plateau

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Tibetan_Plateau 

 

Tibetan Plateau
青藏高原 (Qīng–Zàng Gāoyuán, Qinghai–Tibet Plateau)
The Tibetan Plateau lies between the Himalayan range to the south and the Taklamakan Desert to the north. (Composite image)
Dimensions
Length	2,500 km (1,600 mi)
Width	1,000 km (620 mi)
Area	2,500,000 km2 (970,000 sq mi)
Geography
Tibetan Plateau and surrounding areas above 1600 m
Location	China (Tibet, Qinghai, Western Sichuan, Northern Yunnan, Southern Xinjiang, Western Gansu) India (Ladakh, Lahaul & Spiti), Pakistan (Gilgit Baltistan) Nepal (Northern Nepal) Bhutan Tajikistan (Eastern Tajikistan) Kyrgyzstan (Southern Kyrgyzstan)
Range coordinates	33°N 88°ECoordinates: 33°N 88°E

The Tibetan Plateau (Tibetan: བོད་ས་མཐོ།, Wylie: bod sa mtho), also known as the Qinghai–Tibet Plateau or the Qing–Zang Plateau (Chinese: 青藏高原; pinyin: Qīng–Zàng Gāoyuán) or as the Himalayan Plateau in India, is a vast elevated plateau in Central Asia and East Asia, covering most of the Tibet Autonomous Region, most of Qinghai, Northwestern Yunnan, Western half of Sichuan, Southern Gansu provinces in Western China, the Indian regions of Ladakh and Lahaul and Spiti (Himachal Pradesh) as well as Bhutan. It stretches approximately 1,000 kilometres (620 mi) north to south and 2,500 kilometres (1,600 mi) east to west. It is the world's highest and largest plateau above sea level, with an area of 2,500,000 square kilometres (970,000 sq mi) (about five times the size of Metropolitan France). With an average elevation exceeding 4,500 metres (14,800 ft) and being surrounded by imposing mountain ranges that harbor the world's two highest summits, Mount Everest and K2, the Tibetan Plateau is often referred to as "the Roof of the World".

The Tibetan Plateau contains the headwaters of the drainage basins of most of the streams in surrounding regions. Its tens of thousands of glaciers and other geographical and ecological features serve as a "water tower" storing water and maintaining flow. It is sometimes termed the Third Pole because its ice fields contain the largest reserve of fresh water outside the polar regions. The impact of global warming on the Tibetan Plateau is of intense scientific interest.

Description

The Tibetan Plateau is surrounded by the massive mountain ranges of high-mountain Asia. The plateau is bordered to the south by the inner Himalayan range, to the north by the Kunlun Mountains, which separate it from the Tarim Basin, and to the northeast by the Qilian Mountains, which separate the plateau from the Hexi Corridor and Gobi Desert. To the east and southeast the plateau gives way to the forested gorge and ridge geography of the mountainous headwaters of the Salween, Mekong, and Yangtze rivers in northwest Yunnan and western Sichuan (the Hengduan Mountains). In the west, the curve of the rugged Karakoram range of northern Kashmir embraces the plateau. The Indus River originates in the western Tibetan Plateau in the vicinity of Lake Manasarovar.

Tibetan Buddhist stupa and houses outside the town of Ngawa, on the Tibetan Plateau.

The Tibetan Plateau is bounded in the north by a broad escarpment where the altitude drops from around 5,000 metres (16,000 ft) to 1,500 metres (4,900 ft) over a horizontal distance of less than 150 kilometres (93 mi). Along the escarpment is a range of mountains. In the west, the Kunlun Mountains separate the plateau from the Tarim Basin. About halfway across the Tarim the bounding range becomes the Altyn-Tagh and the Kunluns, by convention, continue somewhat to the south. In the 'V' formed by this split is the western part of the Qaidam Basin. The Altyn-Tagh ends near the Dangjin pass on the Dunhuang–Golmud road. To the west are short ranges called the Danghe, Yema, Shule, and Tulai Nanshans. The easternmost range is the Qilian Mountains. The line of mountains continues east of the plateau as the Qinling, which separates the Ordos Plateau from Sichuan. North of the mountains runs the Gansu or Hexi Corridor which was the main silk-road route from China proper to the West.

The plateau is a high-altitude arid steppe interspersed with mountain ranges and large brackish lakes. Annual precipitation ranges from 100 to 300 millimetres (3.9 to 11.8 in) and falls mainly as hail. The southern and eastern edges of the steppe have grasslands that can sustainably support populations of nomadic herdsmen, although frost occurs for six months of the year. Permafrost occurs over extensive parts of the plateau. Proceeding to the north and northwest, the plateau becomes progressively higher, colder, and drier, until reaching the remote Changtang region in the northwestern part of the plateau. Here the average altitude exceeds 5,000 metres (16,000 ft) and winter temperatures can drop to −40 °C (−40 °F). As a result of this extremely inhospitable environment, the Changthang region (together with the adjoining Kekexili region) is the least populous region in Asia and the third least populous area in the world after Antarctica and northern Greenland.

NASA satellite image of the south-eastern area of Tibetan Plateau. Brahmaputra River is in the lower right.

Geology and geological history

Main article: Geology of the Himalaya

Yamdrok Lake is one of the three largest sacred lakes in Tibet.

The geological history of the Tibetan Plateau is closely related to that of the Himalayas. The Himalayas belong to the Alpine Orogeny and are therefore among the younger mountain ranges on the planet, consisting mostly of uplifted sedimentary and metamorphic rock. Their formation is a result of a continental collision or orogeny along the convergent boundary between the Indo-Australian Plate and the Eurasian Plate.

The collision began in the Upper Cretaceous period about 70 million years ago, when the north-moving Indo-Australian Plate, moving at about 15 cm (6 in) per year, collided with the Eurasian Plate. About 50 million years ago, this fast-moving Indo-Australian plate had completely closed the Tethys Ocean, the existence of which has been determined by sedimentary rocks settled on the ocean floor, and the volcanoes that fringed its edges. Since these sediments were light, they crumpled into mountain ranges rather than sinking to the floor. The Indo-Australian plate continues to be driven horizontally below the Tibetan Plateau, which forces the plateau to move upwards; the plateau is still rising at a rate of approximately 5 mm (0.2 in) per year.

Much of the Tibetan Plateau is of relatively low relief. The cause of this is debated among geologists. Some argue that the Tibetan Plateau is an uplifted peneplain formed at low altitude, while others argue that the low relief stems from erosion and infill of topographic depressions that occurred at already high elevations.

The current tectonics of the plateau is much debated. The two end-member models are the block model, in which the crust of the plateau is formed of several blocks with little internal deformation separated by major strike-slip faults. In the alternative continuum model, the plateau is affected by distributed deformation resulting from flow within the crust.

Environment

Typical landscape

The Tibetan Plateau supports a variety of ecosystems, most of them classified as montane grasslands. While parts of the plateau feature an alpine tundra-like environment, other areas feature monsoon-influenced shrublands and forests. Species diversity is generally reduced on the plateau due to the elevation and low precipitation. The Tibetan Plateau hosts the Tibetan wolf, and species of snow leopard, wild yak, wild donkey, cranes, vultures, hawks, geese, snakes, and water buffalo. One notable animal is the high-altitude jumping spider, that can live at elevations of over 6,500 metres (21,300 ft).

Ecoregions found on the Tibetan Plateau, as defined by the World Wide Fund for Nature, are as follows:

• The Pamir alpine desert and tundra covers the western end of the Tibetan Plateau where it transitions to the Pamir Mountains
• The North Tibetan Plateau-Kunlun Mountains alpine desert covers the northwestern limits of the Tibetan Plateau along the Kunlun Mountains
• The Karakoram-West Tibetan Plateau alpine steppe covers the westernmost parts of the Tibetan Plateau and Ladakh
• The Northwestern Himalayan alpine shrub and meadows on the edges mountains bordering the extreme west of the Tibetan Plateau
• The Central Tibetan Plateau alpine steppe covers most of the central portions of the Tibetan Plateau and the eastern Changtang
• The Western Himalayan alpine shrub and meadows covers the southwestern plateau in the Garuda Valley region
• The Qaidam Basin semi-desert located in the Qaidam Basin on the northern Tibetan Plateau
• The Qilian Mountains subalpine meadows covering the Qilian Mountains in the northernmost portions of the plateau
• The Qilian Mountains conifer forests covering parts of the mountain ranges in the northeastern Tibetan Plateau
• The Tibetan Plateau alpine shrub and meadows covering a swath of the central and northeastern Tibetan Plateau
• The Yarlung Tsangpo arid steppe in the Yarlung Tsangpo River Valley, where most of the permanent human population on the Tibetan Plateau lives
• The Eastern Himalayan alpine shrub and meadows cover the southern Tibetan Plateau on the north side of the Himalayas
• The Southeast Tibet shrub and meadows cover the southeastern and eastern parts of the plateau and are generally rainier than the other high-altitude Tibetan Plateau regions
• The Northeastern Himalayan subalpine conifer forests reach up mountain valleys in the southern plateau and contain some of the highest altitude forests in the world
• The Nujiang Langcang Gorge alpine conifer and mixed forests cover the mountain valleys that reach 500 km (310 mi) into the southeastern Tibetan Plateau
• The Hengduan Mountains subalpine conifer forests cover the southeasternmost mountain valleys on the plateau
• The Qionglai-Minshan conifer forests cover the eastern edges of the plateau and are the densest forests to be found anywhere on the Tibetan Plateau

Human history

Pastoral nomads camping near Namtso.

 

Main article: History of Tibet

 

Nomad camp near Tingri, Tibet. 1993

Nomads on the Tibetan Plateau and in the Himalayas are the remainders of nomadic practices historically once widespread in Asia and Africa. Pastoral nomads constitute about 40% of the ethnic Tibetan population. The presence of nomadic peoples on the plateau is predicated on their adaptation to survival on the world's grassland by raising livestock rather than crops, which are unsuitable to the terrain. Archaeological evidence suggests that the earliest human occupation of the plateau occurred between 30,000 and 40,000 years ago. Since colonization of the Tibetan Plateau, Tibetan culture has adapted and flourished in the western, southern, and eastern regions of the plateau. The northern portion, the Changtang, is generally too high and cold to support permanent population. One of the most notable civilizations to have developed on the Tibetan Plateau is the Tibetan Empire from the 7th century to the 9th century AD.

Impact on other regions

Role in monsoons

Main article: Monsoon

Natural-colour satellite image of the Tibetan Plateau

Monsoons are caused by the different amplitudes of surface temperature seasonal cycles between land and oceans. This differential warming occurs because heating rates differ between land and water. Ocean heating is distributed vertically through a "mixed layer" that may be 50 meters deep through the action of wind and buoyancy-generated turbulence, whereas the land surface conducts heat slowly, with the seasonal signal penetrating only a meter or so. Additionally, the specific heat capacity of liquid water is significantly greater than that of most materials that make up land. Together, these factors mean that the heat capacity of the layer participating in the seasonal cycle is much larger over the oceans than over land, with the consequence that the land warms and cools faster than the ocean. In turn, air over the land warms faster and reaches a higher temperature than does air over the ocean. The warmer air over land tends to rise, creating an area of low pressure. The pressure anomaly then causes a steady wind to blow toward the land, which brings the moist air over the ocean surface with it. Rainfall is then increased by the presence of the moist ocean air. The rainfall is stimulated by a variety of mechanisms, such as low-level air being lifted upwards by mountains, surface heating, convergence at the surface, divergence aloft, or from storm-produced outflows near the surface. When such lifting occurs, the air cools due to expansion in lower pressure, which in turn produces condensation and precipitation.

In winter, the land cools off quickly, but the ocean maintains the heat longer. The hot air over the ocean rises, creating a low-pressure area and a breeze from land to ocean while a large area of drying high pressure is formed over the land, increased by wintertime cooling. Monsoons are similar to sea and land breezes, a term usually referring to the localized, diurnal cycle of circulation near coastlines everywhere, but they are much larger in scale, stronger and seasonal. The seasonal monsoon wind shift and weather associated with the heating and cooling of the Tibetan plateau is the strongest such monsoon on Earth.

Glaciology: the Ice Age and at present

The Himalayas as seen from space looking south from over the Tibetan Plateau.

Today, Tibet is an important heating surface of the atmosphere. However, during the Last Glacial Maximum, an approximately 2,400,000 square kilometres (930,000 sq mi) ice sheet covered the plateau. Due to its great extent, this glaciation in the subtropics was an important element of radiative forcing. With a much lower latitude, the ice in Tibet reflected at least four times more radiation energy per unit area into space than ice at higher latitudes. Thus, while the modern plateau heats the overlying atmosphere, during the Last Ice Age it helped to cool it.

This cooling had multiple effects on regional climate. Without the thermal low pressure caused by the heating, there was no monsoon over the Indian subcontinent. This lack of monsoon caused extensive rainfall over the Sahara, expansion of the Thar Desert, more dust deposited into the Arabian Sea, and a lowering of the biotic life zones on the Indian subcontinent. Animals responded to this shift in climate, with the Javan rusa migrating into India.

In addition, the glaciers in Tibet created meltwater lakes in the Qaidam Basin, the Tarim Basin, and the Gobi Desert, despite the strong evaporation caused by the low latitude. Silt and clay from the glaciers accumulated in these lakes; when the lakes dried at the end of the ice age, the silt and clay were blown by the downslope wind off the Plateau. These airborne fine grains produced the enormous amount of loess in the Chinese lowlands.

Effects of climate change

Main article: Effects of global warming

The Tibetan Plateau contains the world's third-largest store of ice. Qin Dahe, the former head of the China Meteorological Administration, issued the following assessment in 2009:

Temperatures are rising four times faster than elsewhere in China, and the Tibetan glaciers are retreating at a higher speed than in any other part of the world. ... In the short term, this will cause lakes to expand and bring floods and mudflows. ... In the long run, the glaciers are vital lifelines for Asian rivers, including the Indus and the Ganges. Once they vanish, water supplies in those regions will be in peril.

Antimicrobial resistance

From Wikipedia, the free encyclopedia

 https://en.wikipedia.org/wiki/Antimicrobial_resistance

 

Antibiotic resistance tests: Bacteria are streaked on dishes with white disks, each impregnated with a different antibiotic. Clear rings, such as those on the left, show that bacteria have not grown—indicating that these bacteria are not resistant. The bacteria on the right are fully resistant to all but two of the seven antibiotics tested.

 

Media afspelen

 

Antibiotic resistance may claim as many as 10 million lives per year by the year 2050. That's more than all deaths caused by cancer combined. Chemist prof. dr. Nathaniel Martin (Leiden University) states that it's time for action. He explains how the problem can be fixed.

Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. Antibiotic resistance is a subset of AMR, that applies specifically to bacteria that become resistant to antibiotics. Infections caused by resistant microbes are more difficult to treat, requiring higher doses of antimicrobial drugs, or alternative medications which may prove more toxic. These approaches may also be more expensive. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR).

All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. Protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Those bacteria that are considered extensively drug resistant (XDR) or totally drug-resistant (TDR) are sometimes called "superbugs". Resistance in bacteria can arise naturally by genetic mutation, or by one species acquiring resistance from another. Resistance can appear spontaneously because of random mutations. However, extended use of antimicrobials appears to encourage selection for mutations which can render antimicrobials ineffective.

The prevention of antibiotic misuse, which can lead to antibiotic resistance, includes taking antibiotics only when prescribed. Narrow-spectrum antibiotics are preferred over broad-spectrum antibiotics when possible, as effectively and accurately targeting specific organisms is less likely to cause resistance, as well as side effects. For people who take these medications at home, education about proper use is essential. Health care providers can minimize spread of resistant infections by use of proper sanitation and hygiene, including handwashing and disinfecting between patients, and should encourage the same of the patient, visitors, and family members.

Rising drug resistance is caused mainly by use of antimicrobials in humans and other animals, and spread of resistant strains between the two. Growing resistance has also been linked to releasing inadequately treated effluents from the pharmaceutical industry, especially in countries where bulk drugs are manufactured. Antibiotics increase selective pressure in bacterial populations, causing vulnerable bacteria to die; this increases the percentage of resistant bacteria which continue growing. Even at very low levels of antibiotic, resistant bacteria can have a growth advantage and grow faster than vulnerable bacteria. As resistance to antibiotics becomes more common there is greater need for alternative treatments. Calls for new antibiotic therapies have been issued, but new drug development is becoming rarer.

Antimicrobial resistance is increasing globally due to increased prescription and dispensing of antibiotic drugs in developing countries. Estimates are that 700,000 to several million deaths result per year and continues to pose a major public health threat worldwide. Each year in the United States, at least 2.8 million people become infected with bacteria that are resistant to antibiotics and at least 35,000 people die and US$55 billion in increased health care costs and lost productivity. According to World Health Organization (WHO) estimates, three hundred and fifty million deaths could be caused by AMR by 2050. By then, the yearly death toll will be ten million, according to a United Nations report.

There are public calls for global collective action to address the threat that include proposals for international treaties on antimicrobial resistance. Worldwide antibiotic resistance is not completely identified, but poorer countries with weaker healthcare systems are more affected. During the COVID-19 pandemic, action against antimicrobial resistance slowed due to scientists focusing more on SARS-CoV-2 research.

Definition

Diagram showing the difference between non-resistant bacteria and drug resistant bacteria. Non-resistant bacteria multiply, and upon drug treatment, the bacteria die. Drug resistant bacteria multiply as well, but upon drug treatment, the bacteria continue to spread.

The WHO defines antimicrobial resistance as a microorganism's resistance to an antimicrobial drug that was once able to treat an infection by that microorganism. A person cannot become resistant to antibiotics. Resistance is a property of the microbe, not a person or other organism infected by a microbe.

Antibiotic resistance is a subset of antimicrobial resistance. This more specified resistance is linked to pathogenic bacteria and thus broken down into two further subsets, microbiological and clinical. Resistance linked microbiologically is the most common and occurs from genes, mutated or inherited, that allow the bacteria to resist the mechanism associated with certain antibiotics. Clinical resistance is shown through the failure of many therapeutic techniques where the bacteria that are normally susceptible to a treatment become resistant after surviving the outcome of the treatment. In both cases of acquired resistance, the bacteria can pass the genetic catalyst for resistance through conjugation, transduction, or transformation. This allows the resistance to spread across the same pathogen or even similar bacterial pathogens.

Overview

WHO report released April 2014 stated, "this serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country. Antibiotic resistance—when bacteria change so antibiotics no longer work in people who need them to treat infections—is now a major threat to public health." In 2018, WHO considered antibiotic resistance to be one of the biggest threats to global health, food security and development. The European Centre for Disease Prevention and Control calculated that in 2015 there were 671,689 infections in the EU and European Economic Area caused by antibiotic-resistant bacteria, resulting in 33,110 deaths. Most were acquired in healthcare settings.

Causes

Antimicrobial resistance is mainly caused by the overuse of antimicrobials. This leads to microbes either evolving a defense against drugs used to treat them, or certain strains of microbes that have a natural resistance to antimicrobials becoming much more prevalent than the ones that are easily defeated with medication.  While antimicrobial resistance does occur naturally over time, the use of antimicrobial agents in a variety of settings both within the healthcare industry and outside of has led to antimicrobial resistance becoming increasingly more prevalent.

Natural occurrence

A CDC infographic on how antibiotic resistance (a major type of antimicrobial resistance) happens and spreads.

Antimicrobial resistance can evolve naturally due to continued exposure to antimicrobials. Natural selection means that organisms that are able to adapt to their environment, survive, and continue to produce offspring. As a result, the types of microorganisms that are able to survive over time with continued attack by certain antimicrobial agents will naturally become more prevalent in the environment, and those without this resistance will become obsolete. Over time most of the strains of bacteria and infections present will be the type resistant to the antimicrobial agent being used to treat them, making this agent now ineffective to defeat most microbes. With the increased use of antimicrobial agents, there is a speeding up of this natural process.

Self-medication

Self-medication by consumers is defined as "the taking of medicines on one's own initiative or on another person's suggestion, who is not a certified medical professional", and it has been identified as one of the primary reasons for the evolution of antimicrobial resistance. In an effort to manage their own illness, patients take the advice of false media sources, friends, and family causing them to take antimicrobials unnecessarily or in excess. Many people resort to this out of necessity, when they have a limited amount of money to see a doctor, or in many developing countries a poorly developed economy and lack of doctors are the cause of self-medication. In these developing countries, governments resort to allowing the sale of antimicrobials as over the counter medications so people could have access to them without having to find or pay to see a medical professional. This increased access makes it extremely easy to obtain antimicrobials without the advice of a physician, and as a result many antimicrobials are taken incorrectly leading to resistant microbial strains. One major example of a place that faces these challenges is India, where in the state of Punjab 73% of the population resorted to treating their minor health issues and chronic illnesses through self-medication.

The major issue with self-medication is the lack of knowledge of the public on the dangerous effects of antimicrobial resistance, and how they can contribute to it through mistreating or misdiagnosing themselves.  In order to determine the public's knowledge and preconceived notions on antibiotic resistance, a major type of antimicrobial resistance, a screening of 3537 articles published in Europe, Asia, and North America was done.  Of the 55,225 total people surveyed, 70% had heard of antibiotic resistance previously, but 88% of those people thought it referred to some type of physical change in the body.  With so many people around the world with the ability to self-medicate using antibiotics, and a vast majority unaware of what antimicrobial resistance is, it makes the increase of antimicrobial resistance much more likely.

Clinical misuse

Clinical misuse by healthcare professionals is another cause leading to increased antimicrobial resistance. Studies done by the CDC show that the indication for treatment of antibiotics, choice of the agent used, and the duration of therapy was incorrect in up to 50% of the cases studied.  In another study done in an intensive care unit in a major hospital in France, it was shown that 30% to 60% of prescribed antibiotics were unnecessary. These inappropriate uses of antimicrobial agents promote the evolution of antimicrobial resistance by supporting the bacteria in developing genetic alterations that lead to resistance. In a study done by the American Journal of Infection Control aimed to evaluate physicians’ attitudes and knowledge on antimicrobial resistance in ambulatory settings, only 63% of those surveyed reported antibiotic resistance as a problem in their local practices, while 23% reported the aggressive prescription of antibiotics as necessary to avoid failing to provide adequate care.  This demonstrates how a majority of doctors underestimate the impact that their own prescribing habits have on antimicrobial resistance as a whole. It also confirms that some physicians may be overly cautious when it comes to prescribing antibiotics for both medical or legal reasons, even when indication for use for these medications is not always confirmed. This can lead to unnecessary antimicrobial use.

Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse.

Environmental pollution

Untreated effluents from pharmaceutical manufacturing industries, hospitals and clinics, and inappropriate disposal of unused or expired medication can expose microbes in the environment to antibiotics and trigger the evolution of resistance.

Food production

Livestock

A CDC infographic on how antibiotic resistance spreads through farm animals.

The antimicrobial resistance crisis also extends to the food industry, specifically with food producing animals.  Antibiotics are fed to livestock to act as growth supplements, and a preventative measure to decrease the likelihood of infections.  This results in the transfer of resistant bacterial strains into the food that humans eat, causing potentially fatal transfer of disease.  While this practice does result in better yields and meat products, it is a major issue in terms of preventing antimicrobial resistance. Though the evidence linking antimicrobial usage in livestock to antimicrobial resistance is limited, the World Health Organization Advisory Group on Integrated Surveillance of Antimicrobial Resistance strongly recommended the reduction of use of medically important antimicrobials in livestock. Additionally, the Advisory Group stated that such antimicrobials should be expressly prohibited for both growth promotion and disease prevention.

In a study published by the National Academy of Sciences mapping antimicrobial consumption in livestock globally, it was predicted that in the 228 countries studied, there would be a total 67% increase in consumption of antibiotics by livestock by 2030. In some countries such as Brazil, Russia, India, China, and South Africa it is predicted that a 99% increase will occur. Several countries have restricted the use of antibiotics in livestock, including Canada, China, Japan, and the US. These restrictions are sometimes associated with a reduction of the prevalence of antimicrobial resistance in humans.

Pesticides

Most pesticides protect crops against insects and plants, but in some cases antimicrobial pesticides are used to protect against various microorganisms such as bacteria, viruses, fungi, algae, and protozoa. The overuse of many pesticides in an effort to have a higher yield of crops has resulted in many of these microbes evolving a tolerance against these antimicrobial agents. Currently there are over 4000 antimicrobial pesticides registered with the EPA and sold to market, showing the widespread use of these agents. It is estimated that for every single meal a person consumes, 0.3  g of pesticides is used, as 90% of all pesticide use is used on agriculture. A majority of these products are used to help defend against the spread of infectious diseases, and hopefully protect public health. But out of the large amount of pesticides used, it is also estimated that less than 0.1% of those antimicrobial agents, actually reach their targets. That leaves over 99% of all pesticides used available to contaminate other resources. In soil, air, and water these antimicrobial agents are able to spread, coming in contact with more microorganisms and leading to these microbes evolving mechanisms to tolerate and further resist pesticides.

Prevention

Mission Critical: Preventing Antibiotic Resistance (CDC report, 2014)

There have been increasing public calls for global collective action to address the threat, including a proposal for international treaty on antimicrobial resistance. Further detail and attention is still needed in order to recognize and measure trends in resistance on the international level; the idea of a global tracking system has been suggested but implementation has yet to occur. A system of this nature would provide insight to areas of high resistance as well as information necessary for evaluating programs and other changes made to fight or reverse antibiotic resistance.

Duration of antibiotics

Antibiotic treatment duration should be based on the infection and other health problems a person may have. For many infections once a person has improved there is little evidence that stopping treatment causes more resistance. Some therefore feel that stopping early may be reasonable in some cases. Other infections, however, do require long courses regardless of whether a person feels better.

Monitoring and mapping

There are multiple national and international monitoring programs for drug-resistant threats, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), extended spectrum beta-lactamase (ESBL), vancomycin-resistant Enterococcus (VRE), and multidrug-resistant Acinetobacter baumannii (MRAB).

ResistanceOpen is an online global map of antimicrobial resistance developed by HealthMap which displays aggregated data on antimicrobial resistance from publicly available and user submitted data. The website can display data for a 25-mile radius from a location. Users may submit data from antibiograms for individual hospitals or laboratories. European data is from the EARS-Net (European Antimicrobial Resistance Surveillance Network), part of the ECDC.

ResistanceMap is a website by the Center for Disease Dynamics, Economics & Policy and provides data on antimicrobial resistance on a global level.

Limiting antibiotic use

Further information: Antibiotic misuse

Further information: Antimicrobial spectrum

Antibiotic stewardship programmes appear useful in reducing rates of antibiotic resistance. The antibiotic stewardship program will also provide pharmacists with the knowledge to educate patients that antibiotics will not work for a virus.

Excessive antibiotic use has become one of the top contributors to the evolution of antibiotic resistance. Since the beginning of the antibiotic era, antibiotics have been used to treat a wide range of disease. Overuse of antibiotics has become the primary cause of rising levels of antibiotic resistance. The main problem is that doctors are willing to prescribe antibiotics to ill-informed individuals who believe that antibiotics can cure nearly all illnesses, including viral infections like the common cold. In an analysis of drug prescriptions, 36% of individuals with a cold or an upper respiratory infection (both viral in origin) were given prescriptions for antibiotics. These prescriptions accomplished nothing other than increasing the risk of further evolution of antibiotic resistant bacteria. Using antibiotics without prescription is another driving force leading to the overuse of antibiotics to self-treat diseases like the common cold, cough, fever, and dysentery resulting in a pandemic of antibiotic resistance in countries like Bangladesh, risking its spread around the globe. Introducing strict antibiotic stewardship in the outpatient setting may reduce the emerging bacterial resistance.

At the hospital level

Antimicrobial stewardship teams in hospitals are encouraging optimal use of antimicrobials. The goals of antimicrobial stewardship are to help practitioners pick the right drug at the right dose and duration of therapy while preventing misuse and minimizing the development of resistance. Stewardship may reduce the length of stay by an average of slightly over 1 day while not increasing the risk of death.

At the farming level

It is established that the use of antibiotics in animal husbandry can give rise to AMR resistances in bacteria found in food animals to the antibiotics being administered (through injections or medicated feeds). For this reason only antimicrobials that are deemed "not-clinically relevant" are used in these practices.

Recent studies have shown that the prophylactic use of "non-priority" or "non-clinically relevant" antimicrobials in feeds can potentially, under certain conditions, lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics. The possibility for co-selection of AMR resistances in the food chain pipeline may have far-reaching implications for human health.

At the level of GP

Given the volume of care provided in primary care (General Practice), recent strategies have focused on reducing unnecessary antibiotic prescribing in this setting. Simple interventions, such as written information explaining the futility of antibiotics for common infections such as upper respiratory tract infections, have been shown to reduce antibiotic prescribing.

The prescriber should closely adhere to the five rights of drug administration: the right patient, the right drug, the right dose, the right route, and the right time.

Cultures should be taken before treatment when indicated and treatment potentially changed based on the susceptibility report.

About a third of antibiotic prescriptions written in outpatient settings in the United States were not appropriate in 2010 and 2011. Doctors in the U.S. wrote 506 annual antibiotic scripts for every 1,000 people, with 353 being medically necessary.

Health workers and pharmacists can help tackle resistance by: enhancing infection prevention and control; only prescribing and dispensing antibiotics when they are truly needed; prescribing and dispensing the right antibiotic(s) to treat the illness.

At the individual level

People can help tackle resistance by using antibiotics only when prescribed by a doctor; completing the full prescription, even if they feel better; never sharing antibiotics with others or using leftover prescriptions.

Country examples

• The Netherlands has the lowest rate of antibiotic prescribing in the OECD, at a rate of 11.4 defined daily doses (DDD) per 1,000 people per day in 2011.
• Germany and Sweden also have lower prescribing rates, with Sweden's rate having been declining since 2007.
• Greece, France and Belgium have high prescribing rates of more than 28 DDD.

Water, sanitation, hygiene

Infectious disease control through improved water, sanitation and hygiene (WASH) infrastructure needs to be included in the antimicrobial resistance (AMR) agenda. The "Interagency Coordination Group on Antimicrobial Resistance" stated in 2018 that "the spread of pathogens through unsafe water results in a high burden of gastrointestinal disease, increasing even further the need for antibiotic treatment." This is particularly a problem in developing countries where the spread of infectious diseases caused by inadequate WASH standards is a major driver of antibiotic demand. Growing usage of antibiotics together with persistent infectious disease levels have led to a dangerous cycle in which reliance on antimicrobials increases while the efficacy of drugs diminishes. The proper use of infrastructure for water, sanitation and hygiene (WASH) can result in a 47–72 percent decrease of diarrhea cases treated with antibiotics depending on the type of intervention and its effectiveness. A reduction of the diarrhea disease burden through improved infrastructure would result in large decreases in the number of diarrhea cases treated with antibiotics. This was estimated as ranging from 5 million in Brazil to up to 590 million in India by the year 2030. The strong link between increased consumption and resistance indicates that this will directly mitigate the accelerating spread of AMR. Sanitation and water for all by 2030 is Goal Number 6 of the Sustainable Development Goals.

An increase in hand washing compliance by hospital staff results in decreased rates of resistant organisms.

Water supply and sanitation infrastructure in health facilities offer significant co-benefits for combatting AMR, and investment should be increased. There is much room for improvement: WHO and UNICEF estimated in 2015 that globally 38% of health facilities did not have a source of water, nearly 19% had no toilets and 35% had no water and soap or alcohol-based hand rub for handwashing.

Industrial wastewater treatment

Manufacturers of antimicrobials need to improve the treatment of their wastewater (by using industrial wastewater treatment processes) to reduce the release of residues into the environment.

Management in animal use

Main article: Antibiotic use in livestock § Antibiotic resistance

Europe

In 1997, European Union health ministers voted to ban avoparcin and four additional antibiotics used to promote animal growth in 1999. In 2006 a ban on the use of antibiotics in European feed, with the exception of two antibiotics in poultry feeds, became effective. In Scandinavia, there is evidence that the ban has led to a lower prevalence of antibiotic resistance in (nonhazardous) animal bacterial populations. As of 2004, several European countries established a decline of antimicrobial resistance in humans through limiting the use of antimicrobials in agriculture and food industries without jeopardizing animal health or economic cost.

United States

The United States Department of Agriculture (USDA) and the Food and Drug Administration (FDA) collect data on antibiotic use in humans and in a more limited fashion in animals. The FDA first determined in 1977 that there is evidence of emergence of antibiotic-resistant bacterial strains in livestock. The long-established practice of permitting OTC sales of antibiotics (including penicillin and other drugs) to lay animal owners for administration to their own animals nonetheless continued in all states. In 2000, the FDA announced their intention to revoke approval of fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone-resistant Campylobacter infections in humans. Legal challenges from the food animal and pharmaceutical industries delayed the final decision to do so until 2006. Fluroquinolones have been banned from extra-label use in food animals in the USA since 2007. However, they remain widely used in companion and exotic animals.

Global action plans and awareness

The increasing interconnectedness of the world and the fact that new classes of antibiotics have not been developed and approved for more than 25 years highlight the extent to which antimicrobial resistance is a global health challenge. A global action plan to tackle the growing problem of resistance to antibiotics and other antimicrobial medicines was endorsed at the Sixty-eighth World Health Assembly in May 2015. One of the key objectives of the plan is to improve awareness and understanding of antimicrobial resistance through effective communication, education and training. This global action plan developed by the World Health Organization was created to combat the issue of antimicrobial resistance and was guided by the advice of countries and key stakeholders. The WHO's global action plan is composed of five key objectives that can be targeted through different means, and represents countries coming together to solve a major problem that can have future health consequences. These objectives are as follows:

• improve awareness and understanding of antimicrobial resistance through effective communication, education and training.
• strengthen the knowledge and evidence base through surveillance and research.
• reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures.
• optimize the use of antimicrobial medicines in human and animal health.
• develop the economic case for sustainable investment that takes account of the needs of all countries and to increase investment in new medicines, diagnostic tools, vaccines and other interventions.

Steps towards progress

• React based in Sweden has produced informative material on AMR for the general public.
• Videos are being produced for the general public to generate interest and awareness.
• The Irish Department of Health published a National Action Plan on Antimicrobial Resistance in October 2017. The Strategy for the Control of Antimicrobial Resistance in Ireland (SARI), Iaunched in 2001 developed Guidelines for Antimicrobial Stewardship in Hospitals in Ireland in conjunction with the Health Protection Surveillance Centre, these were published in 2009. Following their publication a public information campaign 'Action on Antibiotics' was launched to highlight the need for a change in antibiotic prescribing. Despite this, antibiotic prescribing remains high with variance in adherence to guidelines.

Antibiotic Awareness Week

The World Health Organization has promoted the first World Antibiotic Awareness Week running from 16 to 22 November 2015. The aim of the week is to increase global awareness of antibiotic resistance. It also wants to promote the correct usage of antibiotics across all fields in order to prevent further instances of antibiotic resistance.

World Antibiotic Awareness Week has been held every November since 2015. For 2017, the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO) and the World Organisation for Animal Health (OIE) are together calling for responsible use of antibiotics in humans and animals to reduce the emergence of antibiotic resistance.

United Nations

In 2016 the Secretary-General of the United Nations convened the Interagency Coordination Group (IACG) on Antimicrobial Resistance. The IACG worked with international organizations and experts in human, animal, and plant health to create a plan to fight antimicrobial resistance. Their report released in April 2019 highlights the seriousness of antimicrobial resistance and the threat it poses to world health. It suggests five recommendations for member states to follow in order to tackle this increasing threat. The IACG recommendations are as follows:

• Accelerate progress in countries
• Innovate to secure the future
• Collaborate for more effective action
• Invest for a sustainable response
• Strengthen accountability and global governance

Mechanisms and organisms

Bacteria

Further information: List of antibiotic resistant bacteria

 

Diagram depicting antibiotic resistance through alteration of the antibiotic's target site, modeled after MRSA's resistance to penicillin. Beta-lactam antibiotics permanently inactivate PBP enzymes, which are essential for bacterial life, by permanently binding to their active sites. MRSA, however, expresses a PBP that does not allow the antibiotic into its active site.

The five main mechanisms by which bacteria exhibit resistance to antibiotics are:

1. Drug inactivation or modification: for example, enzymatic deactivation of penicillin G in some penicillin-resistant bacteria through the production of β-lactamases. Drugs may also be chemically modified through the addition of functional groups by transferase enzymes; for example, acetylation, phosphorylation, or adenylation are common resistance mechanisms to aminoglycosides. Acetylation is the most widely used mechanism and can affect a number of drug classes.
2. Alteration of target- or binding site: for example, alteration of PBP—the binding target site of penicillins—in MRSA and other penicillin-resistant bacteria. Another protective mechanism found among bacterial species is ribosomal protection proteins. These proteins protect the bacterial cell from antibiotics that target the cell's ribosomes to inhibit protein synthesis. The mechanism involves the binding of the ribosomal protection proteins to the ribosomes of the bacterial cell, which in turn changes its conformational shape. This allows the ribosomes to continue synthesizing proteins essential to the cell while preventing antibiotics from binding to the ribosome to inhibit protein synthesis.
3. Alteration of metabolic pathway: for example, some sulfonamide-resistant bacteria do not require para-aminobenzoic acid (PABA), an important precursor for the synthesis of folic acid and nucleic acids in bacteria inhibited by sulfonamides, instead, like mammalian cells, they turn to using preformed folic acid.
4. Reduced drug accumulation: by decreasing drug permeability or increasing active efflux (pumping out) of the drugs across the cell surface These pumps within the cellular membrane of certain bacterial species are used to pump antibiotics out of the cell before they are able to do any damage. They are often activated by a specific substrate associated with an antibiotic, as in fluoroquinolone resistance.
5. Ribosome splitting and recycling: for example, drug-mediated stalling of the ribosome by lincomycin and erythromycin unstalled by a heat shock protein found in Listeria monocytogenes, which is a homologue of HflX from other bacteria. Liberation of the ribosome from the drug allows further translation and consequent resistance to the drug.

A number of mechanisms used by common antibiotics to deal with bacteria and ways by which bacteria become resistant to them.

There are several different types of germs that have developed a resistance over time. For example, Penicillinase-producing Neisseria gonorrhoeae developed a resistance to penicillin in 1976. Another example is Azithromycin-resistant Neisseria gonorrhoeae, which developed a resistance to azithromycin in 2011.

In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug's effectiveness.

Some bacteria are naturally resistant to certain antibiotics; for example, gram-negative bacteria are resistant to most β-lactam antibiotics due to the presence of β-lactamase. Antibiotic resistance can also be acquired as a result of either genetic mutation or horizontal gene transfer. Although mutations are rare, with spontaneous mutations in the pathogen genome occurring at a rate of about 1 in 10⁵ to 1 in 10⁸ per chromosomal replication, the fact that bacteria reproduce at a high rate allows for the effect to be significant. Given that lifespans and production of new generations can be on a timescale of mere hours, a new (de novo) mutation in a parent cell can quickly become an inherited mutation of widespread prevalence, resulting in the microevolution of a fully resistant colony. However, chromosomal mutations also confer a cost of fitness. For example, a ribosomal mutation may protect a bacterial cell by changing the binding site of an antibiotic but may result in slower growth rate. Moreover, some adaptive mutations can propagate not only through inheritance but also through horizontal gene transfer. The most common mechanism of horizontal gene transfer is the transferring of plasmids carrying antibiotic resistance genes between bacteria of the same or different species via conjugation. However, bacteria can also acquire resistance through transformation, as in Streptococcus pneumoniae uptaking of naked fragments of extracellular DNA that contain antibiotic resistance genes to streptomycin, through transduction, as in the bacteriophage-mediated transfer of tetracycline resistance genes between strains of S. pyogenes, or through gene transfer agents, which are particles produced by the host cell that resemble bacteriophage structures and are capable of transferring DNA.

Antibiotic resistance can be introduced artificially into a microorganism through laboratory protocols, sometimes used as a selectable marker to examine the mechanisms of gene transfer or to identify individuals that absorbed a piece of DNA that included the resistance gene and another gene of interest.

Recent findings show no necessity of large populations of bacteria for the appearance of antibiotic resistance. Small populations of Escherichia coli in an antibiotic gradient can become resistant. Any heterogeneous environment with respect to nutrient and antibiotic gradients may facilitate antibiotic resistance in small bacterial populations. Researchers hypothesize that the mechanism of resistance evolution is based on four SNP mutations in the genome of E. coli produced by the gradient of antibiotic.

In one study, which has implications for space microbiology, a non-pathogenic strain E. coli MG1655 was exposed to trace levels of the broad spectrum antibiotic chloramphenicol, under simulated microgravity (LSMMG, or, Low Shear Modeled Microgravity) over 1000 generations. The adapted strain acquired resistance to not only chloramphenicol, but also cross-resistance to other antibiotics; this was in contrast to the observation on the same strain, which was adapted to over 1000 generations under LSMMG, but without any antibiotic exposure; the strain in this case did not acquire any such resistance. Thus, irrespective of where they are used, the use of an antibiotic would likely result in persistent resistance to that antibiotic, as well as cross-resistance to other antimicrobials.

In recent years, the emergence and spread of β-lactamases called carbapenemases has become a major health crisis. One such carbapenemase is New Delhi metallo-beta-lactamase 1 (NDM-1), an enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. The most common bacteria that make this enzyme are gram-negative such as E. coli and Klebsiella pneumoniae, but the gene for NDM-1 can spread from one strain of bacteria to another by horizontal gene transfer.

See also: AAC/AAD leader

Viruses

Specific antiviral drugs are used to treat some viral infections. These drugs prevent viruses from reproducing by inhibiting essential stages of the virus's replication cycle in infected cells. Antivirals are used to treat HIV, hepatitis B, hepatitis C, influenza, herpes viruses including varicella zoster virus, cytomegalovirus and Epstein-Barr virus. With each virus, some strains have become resistant to the administered drugs.

Antiviral drugs typically target key components of viral reproduction; for example, oseltamivir targets influenza neuraminidase, while guanosine analogs inhibit viral DNA polymerase. Resistance to antivirals is thus acquired through mutations in the genes that encode the protein targets of the drugs.

Resistance to HIV antivirals is problematic, and even multi-drug resistant strains have evolved. One source of resistance is that many current HIV drugs, including NRTIs and NNRTIs, target reverse transcriptase; however, HIV-1 reverse transcriptase is highly error prone and thus mutations conferring resistance arise rapidly. Resistant strains of the HIV virus emerge rapidly if only one antiviral drug is used. Using three or more drugs together, termed combination therapy, has helped to control this problem, but new drugs are needed because of the continuing emergence of drug-resistant HIV strains.

Fungi

Infections by fungi are a cause of high morbidity and mortality in immunocompromised persons, such as those with HIV/AIDS, tuberculosis or receiving chemotherapy. The fungi candida, Cryptococcus neoformans and Aspergillus fumigatus cause most of these infections and antifungal resistance occurs in all of them. Multidrug resistance in fungi is increasing because of the widespread use of antifungal drugs to treat infections in immunocompromised individuals.

Of particular note, Fluconazole-resistant Candida species have been highlighted as a growing problem by the CDC. More than 20 species of Candida can cause Candidiasis infection, the most common of which is Candida albicans. Candida yeasts normally inhabit the skin and mucous membranes without causing infection. However, overgrowth of Candida can lead to Candidiasis. Some Candida strains are becoming resistant to first-line and second-line antifungal agents such as azoles and echinocandins.

Parasites

The protozoan parasites that cause the diseases malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis are important human pathogens.

Malarial parasites that are resistant to the drugs that are currently available to infections are common and this has led to increased efforts to develop new drugs. Resistance to recently developed drugs such as artemisinin has also been reported. The problem of drug resistance in malaria has driven efforts to develop vaccines.

Trypanosomes are parasitic protozoa that cause African trypanosomiasis and Chagas disease (American trypanosomiasis).  There are no vaccines to prevent these infections so drugs such as pentamidine and suramin, benznidazole and nifurtimox are used to treat infections. These drugs are effective but infections caused by resistant parasites have been reported.

Leishmaniasis is caused by protozoa and is an important public health problem worldwide, especially in sub-tropical and tropical countries. Drug resistance has "become a major concern".

History

The 1950s to 1970s represented the golden age of antibiotic discovery, where countless new classes of antibiotics were discovered to treat previously incurable diseases such as tuberculosis and syphilis. However, since that time the discovery of new classes of antibiotics has been almost nonexistent, and represents a situation that is especially problematic considering the resiliency of bacteria shown over time and the continued misuse and overuse of antibiotics in treatment.

The phenomenon of antimicrobial resistance caused by overuse of antibiotics was predicted as early as 1945 by Alexander Fleming who said "The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant." Without the creation of new and stronger antibiotics an era where common infections and minor injuries can kill, and where complex procedures such as surgery and chemotherapy become too risky, is a very real possibility. Antimicrobial resistance threatens the world as we know it, and can lead to epidemics of enormous proportions if preventive actions are not taken. In this day and age current antimicrobial resistance leads to longer hospital stays, higher medical costs, and increased mortality.

Society and culture

Since the mid-1980s pharmaceutical companies have invested in medications for cancer or chronic disease that have greater potential to make money and have "de-emphasized or dropped development of antibiotics". On 20 January 2016 at the World Economic Forum in Davos, Switzerland, more than "80 pharmaceutical and diagnostic companies" from around the world called for "transformational commercial models" at a global level to spur research and development on antibiotics and on the "enhanced use of diagnostic tests that can rapidly identify the infecting organism".

Legal frameworks

Some global health scholars have argued that a global, legal framework is needed to prevent and control antimicrobial resistance. For instance, binding global policies could be used to create antimicrobial use standards, regulate antibiotic marketing, and strengthen global surveillance systems. Ensuring compliance of involved parties is a challenge. Global antimicrobial resistance policies could take lessons from the environmental sector by adopting strategies that have made international environmental agreements successful in the past such as: sanctions for non-compliance, assistance for implementation, majority vote decision-making rules, an independent scientific panel, and specific commitments.

United States

For the United States 2016 budget, U.S. president Barack Obama proposed to nearly double the amount of federal funding to "combat and prevent" antibiotic resistance to more than $1.2 billion. Many international funding agencies like USAID, DFID, SIDA and Bill & Melinda Gates Foundation have pledged money for developing strategies to counter antimicrobial resistance.

On 27 March 2015, the White House released a comprehensive plan to address the increasing need for agencies to combat the rise of antibiotic-resistant bacteria. The Task Force for Combating Antibiotic-Resistant Bacteria developed The National Action Plan for Combating Antibiotic-Resistant Bacteria with the intent of providing a roadmap to guide the US in the antibiotic resistance challenge and with hopes of saving many lives. This plan outlines steps taken by the Federal government over the next five years needed in order to prevent and contain outbreaks of antibiotic-resistant infections; maintain the efficacy of antibiotics already on the market; and to help to develop future diagnostics, antibiotics, and vaccines.

The Action Plan was developed around five goals with focuses on strengthening health care, public health veterinary medicine, agriculture, food safety and research, and manufacturing. These goals, as listed by the White House, are as follows:

• Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections
• Strengthen National One-Health Surveillance Efforts to Combat Resistance
• Advance Development and use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria
• Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines
• Improve International Collaboration and Capacities for Antibiotic Resistance Prevention, Surveillance, Control and Antibiotic Research and Development

The following are goals set to meet by 2020:

• Establishment of antimicrobial programs within acute care hospital settings
• Reduction of inappropriate antibiotic prescription and use by at least 50% in outpatient settings and 20% inpatient settings
• Establishment of State Antibiotic Resistance (AR) Prevention Programs in all 50 states
• Elimination of the use of medically important antibiotics for growth promotion in food-producing animals.

United Kingdom

Public Health England reported that the total number of antibiotic resistant infections in England rose by 9% from 55,812 in 2017 to 60,788 in 2018, but antibiotic consumption had fallen by 9% from 20.0 to 18.2 defined daily doses per 1,000 inhabitants per day between 2014 and 2018.

Policies

According to World Health Organization, policymakers can help tackle resistance by strengthening resistance-tracking and laboratory capacity and by regulating and promoting the appropriate use of medicines. Policymakers and industry can help tackle resistance by: fostering innovation and research and development of new tools; and promoting cooperation and information sharing among all stakeholders.

Further research

Rapid viral testing

Clinical investigation to rule out bacterial infections are often done for patients with pediatric acute respiratory infections. Currently it is unclear if rapid viral testing affects antibiotic use in children.

Vaccines

Microorganisms usually do not develop resistance to vaccines because vaccines reduce the spread of the infection and target the pathogen in multiple ways in the same host and possibly in different ways between different hosts. Furthermore, if the use of vaccines increases, there is evidence that antibiotic resistant strains of pathogens will decrease; the need for antibiotics will naturally decrease as vaccines prevent infection before it occurs. However, there are well documented cases of vaccine resistance, although these are usually much less of a problem than antimicrobial resistance.

While theoretically promising, antistaphylococcal vaccines have shown limited efficacy, because of immunological variation between Staphylococcus species, and the limited duration of effectiveness of the antibodies produced. Development and testing of more effective vaccines is underway.

Two registrational trials have evaluated vaccine candidates in active immunization strategies against S. aureus infection. In a phase II trial, a bivalent vaccine of capsulat protein 5 & 8 was tested in 1804 hemodialysis patients with a primary fistula or synthetic graft vascular access. After 40 weeks following vaccination a protective effect was seen against S. aureus bacteremia, but not at 54 weeks following vaccination. Based on these results, a second trial was conducted which failed to show efficacy.

Merck tested V710, a vaccine targeting IsdB, in a blinded randomized trial in patients undergoing median sternotomy. The trial was terminated after a higher rate of multiorgan system failure–related deaths was found in the V710 recipients. Vaccine recipients who developed S. aureus infection were 5 times more likely to die than control recipients who developed S. aureus infection.

Numerous investigators have suggested that a multiple-antigen vaccine would be more effective, but a lack of biomarkers defining human protective immunity keep these proposals in the logical, but strictly hypothetical arena.

Alternating therapy

Alternating therapy is a proposed method in which two or three antibiotics are taken in a rotation versus taking just one antibiotic such that bacteria resistant to one antibiotic are killed when the next antibiotic is taken. Studies have found that this method reduces the rate at which antibiotic resistant bacteria emerge in vitro relative to a single drug for the entire duration.

Studies have found that bacteria that evolve antibiotic resistance towards one group of antibiotic may become more sensitive to others. This phenomenon can be used to select against resistant bacteria using an approach termed collateral sensitivity cycling, which has recently been found to be relevant in developing treatment strategies for chronic infections caused by Pseudomonas aeruginosa.

Development of new drugs

Since the discovery of antibiotics, research and development (R&D) efforts have provided new drugs in time to treat bacteria that became resistant to older antibiotics, but in the 2000s there has been concern that development has slowed enough that seriously ill people may run out of treatment options. Another concern is that doctors may become reluctant to perform routine surgeries because of the increased risk of harmful infection. Backup treatments can have serious side-effects; for example, treatment of multi-drug-resistant tuberculosis can cause deafness or psychological disability. The potential crisis at hand is the result of a marked decrease in industry R&D. Poor financial investment in antibiotic research has exacerbated the situation. The pharmaceutical industry has little incentive to invest in antibiotics because of the high risk and because the potential financial returns are less likely to cover the cost of development than for other pharmaceuticals. In 2011, Pfizer, one of the last major pharmaceutical companies developing new antibiotics, shut down its primary research effort, citing poor shareholder returns relative to drugs for chronic illnesses. However, small and medium-sized pharmaceutical companies are still active in antibiotic drug research. In particular, apart from classical synthetic chemistry methodologies, researchers have developed a combinatorial synthetic biology platform on single cell level in a high-throughput screening manner to diversify novel lanthipeptides.

In the United States, drug companies and the administration of President Barack Obama had been proposing changing the standards by which the FDA approves antibiotics targeted at resistant organisms.

On 18 September 2014 Obama signed an executive order to implement the recommendations proposed in a report by the President's Council of Advisors on Science and Technology (PCAST) which outlines strategies to stream-line clinical trials and speed up the R&D of new antibiotics. Among the proposals:

• Create a 'robust, standing national clinical trials network for antibiotic testing' which will promptly enroll patients once identified to be suffering from dangerous bacterial infections. The network will allow testing multiple new agents from different companies simultaneously for their safety and efficacy.
• Establish a 'Special Medical Use (SMU)' pathway for FDA to approve new antimicrobial agents for use in limited patient populations, shorten the approval timeline for new drug so patients with severe infections could benefit as quickly as possible.
• Provide economic incentives, especially for development of new classes of antibiotics, to offset the steep R&D costs which drive away the industry to develop antibiotics.

Biomaterials

Using antibiotic-free alternatives in bone infection treatment may help decrease the use of antibiotics and thus antimicrobial resistance. The bone regeneration material bioactive glass S53P4 has shown to effectively inhibit the bacterial growth of up to 50 clinically relevant bacteria including MRSA and MRSE.

Nanomaterials

During the last decades, copper and silver nanomaterials have demonstrated appealing features for the development of a new family of antimicrobial agents.

Rediscovery of ancient treatments

Similar to the situation in malaria therapy, where successful treatments based on ancient recipes have been found, there has already been some success in finding and testing ancient drugs and other treatments that are effective against AMR bacteria.

Rapid diagnostics

Antimicrobial susceptibility testing: Thin paper discs containing an antibiotic have been placed on an agar plate growing bacteria. Bacteria are not able to grow around antibiotics to which they are sensitive.

Distinguishing infections requiring antibiotics from self-limiting ones is clinically challenging. In order to guide appropriate use of antibiotics and prevent the evolution and spread of antimicrobial resistance, diagnostic tests that provide clinicians with timely, actionable results are needed.

Acute febrile illness is a common reason for seeking medical care worldwide and a major cause of morbidity and mortality. In areas with decreasing malaria incidence, many febrile patients are inappropriately treated for malaria, and in the absence of a simple diagnostic test to identify alternative causes of fever, clinicians presume that a non-malarial febrile illness is most likely a bacterial infection, leading to inappropriate use of antibiotics. Multiple studies have shown that the use of malaria rapid diagnostic tests without reliable tools to distinguish other fever causes has resulted in increased antibiotic use.

Antimicrobial susceptibility testing (AST) can help practitioners avoid prescribing unnecessary antibiotics in the style of precision medicine, and help them prescribe effective antibiotics, but with the traditional approach it could take 12 to 48 hours. Rapid testing, possible from molecular diagnostics innovations, is defined as "being feasible within an 8-h working shift". Progress has been slow due to a range of reasons including cost and regulation.

Optical techniques such as phase contrast microscopy in combination with single-cell analysis are another powerful method to monitor bacterial growth. In 2017, scientists from Sweden published a method that applies principles of microfluidics and cell tracking, to monitor bacterial response to antibiotics in less than 30 minutes overall manipulation time. Recently, this platform has been advanced by coupling microfluidic chip with optical tweezing in order to isolate bacteria with altered phenotype directly from the analytical matrix.

Phage therapy

Main article: Phage therapy

Phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections.  Phage therapy has many potential applications in human medicine as well as dentistry, veterinary science, and agriculture.

Phage therapy relies on the use of naturally-occurring bacteriophages to infect and lyse bacteria at the site of infection in a host. Due to current advances in genetics and biotechnology these bacteriophages can possibly be manufactured to treat specific infections. Phages can be bioengineered to target multidrug-resistant bacterial infections, and their use involves the added benefit of preventing the elimination of beneficial bacteria in the human body. Phages destroy bacterial cell walls and membrane through the use of lytic proteins which kill bacteria by making many holes from the inside out. Bacteriophages can even possess the ability to digest the biofilm that many bacteria develop that protect them from antibiotics in order to effectively infect and kill bacteria. Bioengineering can play a role in creating successful bacteriophages.

Understanding the mutual interactions and evolutions of bacterial and phage populations in the environment of a human or animal body is essential for rational phage therapy.

Bacteriophagics are used against antibiotic resistant bacteria in Georgia (George Eliava Institute) and in one institute in Wrocław, Poland. Bacteriophage cocktails are common drugs sold over the counter in pharmacies in eastern countries. In Belgium, four patients with severe musculoskeletal infections received bacteriophage therapy with concomitant antibiotics. After a single course of phage therapy, no recurrence of infection occurred and no severe side-effects related to the therapy were detected.