FDA gives manufacturers 1 year to remove certain antibacterials from hand soaps

I have written previously about the undesirability of including antibacterial chemicals in hand washing soaps https://foodsafetywithjaybee.blogspot.co.nz/2016/01/do-antibacterial-soaps-and-wipes-have.html

In late 2013, FDA gave soap manufacturers a year to demonstrate that adding the antibacterial chemicals triclosand and triclocarban to "antibacterial soaps" had any benefit, compared with regular soaps, in terms of preventing illness and the spread of certain infections.

It appears that insufficient information was provided to FDA to convince the regulator, and so manufacturers now have a year to remove these ingredients from their products.

The new regulation does not currently affect chemicals including benzalkonium chloride, benzethonium chloride and chloroxylenol.  It also applies only to hand soaps and body washes.  It does not apply to toothpaste, for example.  It also doesn't apply to hand sanitizers, such as alcohol preparations, and products intended for use in hospitals, etc.

So, what are we to do?  The simple answer is to continue hand washing with regular soap - it's just as effective as "antibacterial soap".

Do antibacterial soaps and wipes have any effect on antibiotic resistance? Should we use them in the home?

Over the Christmas holiday, our kitchen has fed more people than normal and cleaning has therefore increased.  I have been giving a lot of thought to the possible benefits and risks of using antimicrobial cleaners and soaps.  When you get into this subject, you find it is actually quite complex.

I have written about something similar before, but there is now a lot of published work that suggests that in most cases, there is no benefit to using antibacterial soaps in the home - there is no statistically significant reduction in infectious disease if antibacterial preparations are used in preference to soap and water*.  Nevertheless, in the US alone, nearly $1 billion per year is spent on antibacterial soaps**.

Of course, many infectious diseases are caused by viruses; they are probably not affected by antibacterial compounds, which have a definite target in the bacterial cell.  Thus, an antibacterial soap or wipe will be no better at preventing transmission of cold viruses than a thorough cleaning with soap or detergent and water.

I have recently been asked to review a couple of scientific papers in which evidence is presented that suggests cleaning agents commonly used in the food industry may induce antibiotic resistance in bacteria.  Antibiotic resistance results when bacteria develop enzymes capable of breaking down the active component of the antibiotic.  One of the first instances of antibiotic resistance occurred very soon after the introduction of penicillin.  Bacteria developed the ability to break the beta-lactam ring of penicillin with an enzyme called beta-lactamase.  (Antibiotic resistance genes can often be transferred from one bacterium to another, so in time, many bacterial strains become resistant.)

We already know that many of our antibiotics are no longer effective because of resistance.  Overuse of antibiotics is blamed.  It is ironic that our cleaning agents may also be causing resistance.

But there is another potential driver for antibiotic resistance: sub-lethal exposure of bacteria to certain herbicides have been shown to change antibiotic susceptibility of Escherichia coli and Salmonella enterica serovar Typhimurium***.  This is not a straightforward relationship, but it is clear that there is the potential to select for antibiotic resistance in these bacteria, which, if transferred to humans by contact with animals and food, can potentially reduce the effectiveness of antibiotic therapy.

Well, that's fairly heavy for the first post of 2016, but it should cause us to think when purchasing home cleaning agents and soaps, or chemicals for use in agriculture and domestic gardens.




* Effect of Antibacterial Home Cleaning and Handwashing Products on Infectious Disease Symptoms.  Larson, Elaine L;Lin, Susan X;Gomez-Pichardo, Cabilia;Della-Latta, Phyllis.  Annals of Internal Medicine; Mar 2, 2004; 140, 5

** https://www.nrdc.org/health/files/antimicrobials.pdf

*** Kurenbach B, Marjoshi D, Amábile-Cuevas CF, Ferguson GC, Godsoe W, Gibson P, Heinemann JA. 2015. Sublethal exposure to commercial formulations of the herbicides dicamba, 2,4-dichlorophenoxyacetic acid, and glyphosate cause changes in antibiotic susceptibility in Escherichia coli and Salmonella enterica serovar Typhimurium.  
mBio 6(2):e00009-15. doi:10.1128/mBio.00009-15.

Is vinegar just for fish and chips?

My sister in Australia recently sent me a link to the ABC website "Fact Buster".  The page was entitled "Does vinegar really kill household germs?"

See:  http://www.abc.net.au/health/talkinghealth/factbuster/stories/2012/02/02/3407024.htm

The article concluded that vinegar is an inexpensive, non-toxic, biodegradable antimicrobial, but that it is not as good as commercial cleaners.

Vinegar contains about 5% acetic acid.  The article said that this acid kills bacteria and viruses, and suggested that the effect was probably brought about by denaturing the proteins and fats.  If proteins are denatured (their shape and hence functionality changed) the bacteria may no longer be capable of growth.  I'm not sure that the rate of fat trans-esterification would be very high, but it might contribute to damage of the microorganisms.

The action of vinegar on bacteria is quite interesting.  Strong acids completely dissociate into ions.  For example, hydrochloric acid dissociates into hydrogen and chloride ions.  These particles carry a charge and cannot enter the bacterial cell through the cell membrane.
                                         

                            HCl  ⇒  H⁺  +  Cl^-

Weak acids, such as acetic, citric and ascorbic acids, don't fully dissociate; in solution, a significant proportion of the acid remains undissociated and therefore uncharged.  So for acetic acid:

                        CH₃COOH  ⇔  H⁺  + CH₃COO^-

This is where it gets interesting; the weak acid solution outside the cell has a moderately low pH, which keeps a proportion of the weak acid in the undissociated form (the equilibrium is driven to the left).  The uncharged molecule can pass through the cell membrane into the cell.  Here it encounters a higher pH (the interior of the cell is closer to neutral pH) and so the equilibrium is driven to the right and more hydrogen ions are produced.  These ions interfere with the cell proteins and hence cell metabolism, since many cell proteins are actually enzymes.  The cells are either slowed or prevented from growing.  A multipurpose cleaner favoured by my wife claims to "kill 99.9% of germs" ***.  The active ingredient is 3.2% citric acid.

However,  the Fact Buster authors also consulted an infectious diseases specialist, Professor Peter Collignon, at the Australian National University.  He made the point that concentration on disinfection is the wrong emphasis.  Thorough cleaning would practically remove the need for disinfection in many cases - remove the dirt and you remove practically all the bacteria.  Disinfectants may not penetrate a layer of dirt or the slime produced by a bacterial biofilm.  The film may actually neutralise the disinfectant by reacting with it.

The priority should therefore be to remove dirt and bacteria and only then apply a disinfectant if it is required.

***  This claim is ambiguous.  Does it mean that 99.9% of all known germs are killed by the product, or does it kill 99.9% of the organisms on the surface?  These are very different statements.  And never forget: 0.1% of a very large number may still be a large number!

More on antibiotic use in animal rearing

I wrote last month, suggesting that it is high time we banned the sub-therapeutic use of antibiotics currently used in human therapy for animal rearing. 

When I wrote the article, I was not aware that the Food and Drug Administration had, around 9th November 2011, rejected two petitions to ban antibiotics from being used in food animal production. The petitions were filed by a coalition that included  the American Public Health Association and the Union of Concerned Scientists.

It is troubling that in its denial letter, the FDA acknowledged that its “experience with contested, formal withdrawal proceedings is that the process can consume extensive periods of time and agency resources.”  I interpret that to mean that FDA may well think that antibiotic use should be banned, but it can't afford to force the issue.

Meanwhile, researchers at McGill University have shown that bacteria resistant to tetracycline and tylosin can be isolated from pigs raised in a swine complex 2.5 years after administration of these antibiotics ceased.  See Microbial Ecology  DOI 10.1007/s00248-011-9954-0  published on-line 14th October 2011.  Antibiotic resistance genes were found in the bacteria, though the workers were not able to explain their persistence long after antibiotic use ceased.  The results are of significance for both animal and public health because these antibiotic resistant bacteria can be transferred between animals, humans and the environment.

Time to ban antibiotic use in animal husbandry?

As a microbiologist, I sometimes worry that we are killing the golden goose in terms of our ability to combat human disease.  As I wrote earlier, the cost of developing and bringing to market new drugs is astronomical and many companies are shunning new drug development in favour of more lucrative endeavours, such as development of molecular-based test kits for human disease diagnosis.

In this light, it is disturbing to read of the amount of antibiotics used in animal production.  In 2001, Kristin Leutwyler wrote in Scientific American that a study by the Union for Concerned
Scientists had shown meat producers in the USA feed around 25 million pounds of antibiotics to chickens, pigs and cows for non-therapeutic purposes each year (the antibiotics suppress microbial populations and lead to increased growth rates of the animals).  Compared with this, only 3 million pounds per year are used for treating human disease.

In 2009, the House Committee on Rules held a hearing: H.R. 1549 - Preservation of Antibiotics for Medical Treatment Act of 2009, which would have amended the Federal Food, Drug, and Cosmetic Act to require the Secretary of Health and Human Services to deny an application for a new animal drug that is a "critical antimicrobial animal drug" (CAAD) unless the applicant demonstrated a reasonable certainty of no harm to human health due to the development of antimicrobial resistance attributable to the non-therapeutic use of the drug.

The CAAD is a drug intended for use in food-producing animals that contains specified antibiotics, or other drugs used in humans to treat or prevent disease or infection caused by microorganisms. The Rule would also require the Secretary to withdraw approval of a non-therapeutic use of such drugs in food-producing animals two years after the date of enactment of the Act unless certain safety requirements are met.

That rule died in Committee.  It has been reintroduced in the 2011-2012 Congress, and went to Committee on 9th March, 2011. 

It has been argued that there are no good studies linking antibiotic use in animal rearing to the development of antibiotic-resistant diseases.

While this may be so, and I'm not sure that it is, it is hard to imagine how else multiple antibiotic resistant strains of bacteria could be found in animals and ultimately in humans.  A classic experiment shown to most undergraduate students of microbiology over the last 50 years is the selection of antibiotic-resistant bacteria.  All that is required is the production of a concentration gradient of antibiotic across a Petri dish.  The agar is seeded with the target bacteria and those that grow at the most concentrated side are picked off and recultured on another gradient.  Very quickly, a resistant strain can be isolated.

This laboratory procedure is effectively repeated in animals fed sub-therapeutic levels of antibiotics in their diet or drinking water - the survivors of the first dose are constantly exposed and eventually dominate the population.  As microorganisms transfer genetic information among themselves, the number of different strains resistant to the antibiotics also increases.

I would be less concerned if the antibiotics used for treating animals were no longer in use for human therapy.  Then the benefits could perhaps be justified, though even then, the class of antibiotic is important, as bacteria becoming resistant to one member of the class might also develop resistance to others.  If humans become infected by strains resistant to antibiotics used in human therapy, there may be no cure available for the infection.  These infections could easily be transferred by handling raw meats from treated animals, though there is again a lack of sound scientific evidence.

The view is clouded by the indiscriminate use of antibiotics by humans.  It's not just a case of doctors prescribing antibiotics when they are not justified, though I have seen antibiotics prescribed for viral diseases, which generally can't be treated with these chemicals.  Look up "availability of antibiotics over the counter" and you will get pages telling you that there is none.  However, it is well known that antibiotics can be bought freely over the counter in some countries.  Even the antibiotics of last resort - the only ones that can treat certain diseases - can be bought in pharmacies in some Asian countries and there are papers in the scientific literature showing the levels of resistance in bacterial populations.

I truly hope that President Obama eventually signs this legislation and that leaders of other countries do likewise.  I would hate for us to descend to the state before the introduction of penicillin, when even a scratch from a rose thorn could result in painful death.

Tha’s gorra eat a peck o’ muck afore tha dies.

For those readers not lucky enough to have been born in Yorkshire, northern England, an approximate translation of this old expression is “You will eat a barrel-full of dirt during your lifetime”.

What brought that on? According to Abby Alford, writing in the Western Mail (1), there may have been some scientific basis to the saying. Bangor University lecturer, Dr Prysor Williams, believes that an obsession with cleanliness reduces contact with dirt and thus with harmful bacteria. Our immune systems become weakened, leaving us susceptible to infection. Unfortunately, the evidence for this view is somewhat lacking, though Dr. Williams is not the only one to have argued this.

Stuart Levy, Director of the Center of Adaptation Genetics and Drug Resistance at Tufts University, provided substantial evidence that the substitution of anti-bacterial agents for good old soap and water increases the ability of bacteria to develop resistance. A few bacterial cells containing genes that confer resistance to the antibiotics can protect neighbouring sensitive cells, rendering the antibacterial agent ineffective. Levy’s group tested the ability of Escherichia coli to mutate to become resistant to triclosan, which inhibits an enzyme involved in fatty acid biosynthesis and thus interferes with membrane biosynthesis. The work was published in the prestigious journal Nature.

In a carefully constructed randomized, double-blind trial, Elaine Larson and her co-workers have also shown that using antibacterial home cleaning and hand-washing products has no significant effect on the incidence of infectious disease symptoms (2).

The take-home message is that while cleanliness may be next to godliness, we do not live in a sterile environment. If we try too hard to protect ourselves and our children from microorganisms, we don’t give our immune systems the chance to develop resistance to bacterial pathogens.

(1) http://www.walesonline.co.uk/news/wales-news/2009/02/16/
how-obsession-with-cleanliness-could-be-making-us-ill-91466-22935582/

(2) Annals of Internal Medicine, 2 March 2004, Volume 140 • Number 5 321