Access to clean water may be as vital as cutting antibiotic use in the fight against superbugs



Trudi Schifter     10 June 2020 

Growing ​evidence ​suggests that ​environmental ​factors may ​even more ​important to ​the spread of ​antibiotic ​resistance than ​drug use ​

If a two-year-​old child ​living in ​poverty in ​India or ​Bangladesh gets ​sick with a ​common ​bacterial ​infection, ​there is ​more than a 50% chance ​an antibiotic ​treatment will ​fail. Somehow ​the child has ​acquired an ​antibiotic ​resistant ​infection ​– even to ​drugs to which ​they may never ​have been ​exposed. How? ​

Unfortunately,​ this child ​also lives in a ​place with ​limited clean ​water and less ​waste ​management, ​bringing them ​into frequent ​contact with ​faecal matter. ​This means they ​are regularly ​exposed to ​millions of ​resistant genes ​and bacteria, ​including ​potentially ​untreatable superbugs. This sad ​story is ​shockingly ​common, ​especially in ​places where ​pollution is ​rampant and ​clean water is ​limited. ​

For many ​years, people ​believed ​antibiotic ​resistance in ​bacteria was ​primarily ​driven by ​imprudent use ​of antibiotics ​in clinical and ​veterinary ​settings. ​But ​growing evidence suggests ​that environmental ​factors may be ​of equal or ​greater ​importance to ​the spread ​of ​antibiotic resistance, especially ​in the ​developing ​world. ​

Here we focus ​on antibiotic ​resistant ​bacteria, but ​drug resistance ​also occurs in ​types of other ​microorganisms ​– such as ​resistance in ​pathogenic ​viruses, fungi, ​and protozoa (​called ​antimicrobial ​resistance or ​AMR). This ​means that our ​ability to ​treat all sorts ​of infectious ​disease is ​increasingly ​hampered by ​resistance, ​potentially ​including ​coronaviruses ​like SARS-CoV-2,​ which causes ​COVID-19. ​

Overall, use ​of antibiotics, ​antivirals, and ​antifungals ​clearly must be ​reduced, but in ​most of the ​world, ​improving water,​ sanitation, ​and hygiene ​practice –​ a practice ​known as WASH ​– is also ​critically ​important. If ​we can ensure ​cleaner water ​and safer food ​everywhere, the ​spread of ​antibiotic ​resistant ​bacteria will ​be reduced ​across the ​environment, ​including ​within and ​between people ​and animals. ​

As recent recommendations on AMR from the ​Food and ​Agriculture ​Organization of ​the United ​Nations (FAO), ​the World ​Organisation ​for Animal ​Health (OIE), ​and World ​Health ​Organization (​WHO) suggest, ​to which David ​contributed, ​the “​superbug ​problem” ​will not be ​solved by more ​prudent ​antibiotic use ​alone. It also ​requires global ​improvements in ​water quality, ​sanitation, and ​hygiene. ​Otherwise, the ​next pandemic ​might be worse ​than COVID-19. ​

download - 2020-06-09T183536.946.jpegUntreated sewage. 

Bacteria under stress

To understand ​the problem of ​resistance, we ​must go back to ​basics. What is ​antibiotic ​resistance, and ​why does it ​develop? ​

Exposure to ​antibiotics ​puts stress on ​bacteria and, ​like other ​living ​organisms, they ​defend ​themselves. ​Bacteria do ​this by sharing ​and acquiring ​defence genes, ​often from ​other bacteria ​in their ​environment. ​This allows ​them to change ​quickly, ​readily ​obtaining the ​ability to make ​proteins and ​other molecules ​that block the ​antibiotic’​s effect. ​

This gene sharing process is ​natural and is ​a large part of ​what drives ​evolution. ​However, as we ​use ever ​stronger and ​more diverse ​antibiotics, ​new and more ​powerful ​bacterial ​defence options ​have evolved, ​rendering some ​bacteria ​resistant to ​almost ​everything ​– the ​ultimate ​outcome being ​untreatable ​superbugs. ​

Antibiotic ​resistance has ​existed ​since life began, but has ​recently ​accelerated due ​to human use. ​When you take ​an antibiotic, ​it kills a ​large majority ​of the target ​bacteria at the ​site of ​infection ​– and so ​you get better. ​But antibiotics ​do not kill all ​the bacteria ​– some ​are naturally ​resistant; ​others acquire ​resistance ​genes from ​their microbial ​neighbours, ​especially in ​our digestive ​systems, throat,​ and on our ​skin. This ​means that some ​resistant ​bacteria always ​survive, and ​can pass to the ​environment via ​inadequately ​treated faecal ​matter, ​spreading ​resistant ​bacteria and ​genes wider. ​

The ​pharmaceutical ​industry ​initially ​responded to ​increasing ​resistance by ​developing new ​and stronger ​antibiotics, ​but bacteria ​evolve rapidly, ​making even new ​antibiotics ​lose their ​effectiveness ​quickly. As a ​result, new ​antibiotic ​development has ​almost stopped ​because it ​garners ​limited profit. Meanwhile, ​resistance to ​existing ​antibiotics ​continues to ​increase, which ​especially ​impacts places ​with ​poor water ​quality and ​sanitation.

Read more: Big Pharma has ​failed: the ​antibiotic ​pipeline needs ​to be taken ​under public ​ownership

This is ​because in the ​developed world ​you defecate ​and your poo ​goes down the ​toilet, ​eventually ​flowing down a ​sewer to a ​community ​wastewater ​treatment plant.​ Although ​treatment ​plants are not ​perfect, they ​typically ​reduce ​resistance ​levels by well ​over 99%, ​substantially ​reducing ​resistance ​released to the ​environment. ​

Modern sewage ​treatment ​plants remove ​most AMR ​microbes. But ​they are ​currently not ​affordable in ​much of the ​world. ​People Image ​Studio/​Shutterstock.​com

In contrast, over 70% of the world has no ​community ​wastewater ​treatment or ​even sewers; ​and most faecal ​matter, ​containing ​resistant genes ​and bacteria, ​goes directly ​into surface ​and groundwater,​ often via open ​drains. ​

This means ​that people who ​live in places ​without faecal ​waste ​management are ​regularly ​exposed to ​antibiotic ​resistance in ​many ways. ​Exposure is ​even possible ​of people who ​may not have ​taken ​antibiotics, ​like our child ​in South Asia. ​


Spreading through faeces

Antibiotic ​resistance is ​everywhere, but ​it is not ​surprising that ​resistance ​is greatest in ​places with ​poor sanitation ​because factors ​other than use ​are important. ​For example, a ​fragmented ​civil ​infrastructure, ​political ​corruption, and ​a lack of ​centralised ​healthcare also ​play key roles. ​

One might ​cynically argue ​that “​foreign” ​resistance is a ​local issue, ​but antibiotic ​resistance ​spread knows no ​boundaries ​– ​superbugs might ​develop in one ​place due to ​pollution, but ​then become ​global due to ​international ​travel. ​Researchers ​from Denmark ​compared ​antibiotic ​resistance ​genes in long-​haul airplane ​toilets and ​found ​major ​differences in ​resistance ​carriage among ​flight paths, ​suggesting ​resistance can ​jump-spread by ​travel. ​

The ​world’s ​current ​experience with ​the spread of ​SARS-CoV-2 ​shows just how ​fast infectious ​agents can move ​with human ​travel. The ​impact of ​increasing ​antibiotic ​resistance is ​no different. ​There are no ​reliable ​antiviral ​agents for SARS-​CoV-2 treatment,​ which is the ​way things may ​become for ​currently ​treatable ​diseases if we ​allow ​resistance to ​continue ​unchecked. ​

As an example ​of antibiotic ​resistance, the ​“​superbug” ​gene, blaNDM-1, ​was first ​detected ​in ​India in 2007 (​although it was ​probably ​present in ​other regional ​countries). But ​soon thereafter,​ it was found ​in a ​hospital patient in Sweden and then in Germany. It was ​ultimately ​detected in ​2013 in ​Svalbard ​in ​the High Arctic. In parallel, variants of this ​gene appeared ​locally, but ​have evolved as ​they move. ​Similar ​evolution has ​occurred ​as ​the COVID-19 virus has spread.

Relative to ​antibiotic ​resistance, ​humans are not ​the only “​travellers”​ that can carry ​resistance. ​Wildlife, such ​as migratory ​birds, can also ​acquire ​resistant ​bacteria and ​genes from ​contaminated ​water or soils ​and then fly ​great distances ​carrying ​resistance in ​their gut from ​places with ​poor water ​quality to ​places with ​good water ​quality. During ​travel, they ​defecate along ​their path, ​potentially ​planting ​resistance ​almost anywhere.​ The global ​trade of foods ​also facilitates ​spread of ​resistance from ​country to ​country and ​across the ​globe. ​

Resistant ​microbes ​don’t ​need planes to ​travel.  ​

What is ​tricky is that ​the spread by ​resistance by ​travel is often ​invisible. In ​fact, the ​dominant ​pathways of ​international ​resistance ​spread ​are largely unknown because ​many pathways ​overlap, and ​the types and ​drivers of ​resistance are ​diverse. ​

Resistant ​bacteria are ​not the only ​infectious ​agents that ​might be spread ​by environmental ​contamination. ​SARS-CoV-2 has ​been found in ​faeces and ​inactive virus ​debris found in ​sewage, but all ​evidence ​suggests water ​is ​not a major route of COVID-​19 spread ​– ​although there ​are limited ​data from ​places with ​poor sanitation.​

So, each case ​differs. But ​there are ​common roots to ​disease spread ​– ​pollution, poor ​water quality, ​and inadequate ​hygiene. Using ​fewer ​antibiotics is ​critical to ​reducing ​resistance. ​However, ​without also ​providing safer ​sanitation and ​improved water ​quality at ​global scales, ​resistance will ​continue to ​increase, ​potentially ​creating the ​next pandemic. ​Such a combined ​approach is ​central to the ​new WHO/FAO/OIE ​recommendations ​on AMR. ​

Other types ​of pollution ​and hospital ​waste ​

Industrial ​wastes, ​hospitals, ​farms, and ​agriculture are ​also possible ​sources or ​drivers of ​antibiotic ​resistance. ​

For example, ​about ten years ​ago, one of us (​David) studied ​metal pollution ​in a Cuban ​river and ​found the ​highest levels ​of resistant ​genes were near ​a leaky solid ​waste landfill ​and below where ​pharmaceutical ​factory wastes ​entered the ​river. The ​factory ​releases ​clearly ​impacted ​resistance ​levels ​downstream, but ​it was metals ​from the ​landfill that ​most strongly ​correlated with ​resistance gene ​levels in the ​river. ​

There is a ​logic to this ​because toxic ​metals can ​stress bacteria,​ which makes ​the bacteria ​stronger, ​incidentally ​making them ​more resistant ​to anything, ​including ​antibiotics. We ​saw the same ​thing with ​metals in ​Chinese landfills where ​resistance gene ​levels in the ​landfill drains ​strongly ​correlated with ​metals, not ​antibiotics. ​

In fact, ​pollution of ​almost any sort ​can promote ​antibiotic ​resistance, ​including ​metals, ​biocides, ​pesticides, and ​other chemicals ​entering the ​environment. ​Many pollutants ​can promote ​resistance in ​bacteria, so ​reducing ​pollution in ​general will ​help reduce ​antibiotic ​resistance ​– an ​example of ​which is ​reducing metal ​pollution. ​


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