Why Should Someone Learn about and Understand Resistance to Antimicrobials?
Before we begin, it is reasonable to ask ourselves the question embodied in the title of this contribution. One might respond by saying, the purpose of communicating information on resistance to antimicrobials is to enable the public to understand the phenomenon. But, why should they do so?
Everybody seems to think the answer to this question is so obvious; therefore, one may dismiss it as trivial. However, let us consider the commonest response to it, i.e., “everybody should learn about and understand it in order to address the problem.” Here, we run into several difficulties. One of the most important among them is who exactly is able to address it and precisely how. Let us deal with these two questions in turn.
We cannot determine which public group could do something practical about resistance to antimicrobials unless we know what to do about it. We have looked at many a learned suggestion, but none seem to have troubled to distinguish between these two logically linked categories before they were put forward. We cannot think of communication without making sure that each group is informed of what exactly it ought to do to resolve the current problem. Otherwise it would be a vain endeavour.
In order to place the discussion in the real world, let us first look at public behaviour associated with the use of antimicrobials. Most of them use today has been prescribed by authorised medical or veterinary professionals to lay people. In most countries, should the latter try to discuss the prudence of a prescription with the professional, one can nearly always expect a less than cordial response. This type of real life data is not within the domain of either ‘the big data’ or ‘research.’ So, even if the lay people should know about and understand resistence to antimicrobials, it does not seem to have a practical significance.
Even in affluent countries where the relationship between the professional and the seeker of help is cordial, wider implications of a prescribed treatment hardly enters the exchanges between them. Belief that one needs medical or veterinary help often precludes one from taking a wider view. It would be unrealistic to expect anything else. Worried people are very different from the theoretical ones, and hardly anybody remains coldly objective when one believes that one requires medical or veterinary help.
It is true that in some countries antimicrobials are available over the counter. Likewise the free trade in adulterated antimicrobials is a promoter of resistance to antimicrobials as well as serious ill health. Unfortunately, it is unrealistic to believe better information on the consequences of their dubious practise would have much influence on the public behaviour where these occur.
We may be charged being too pessimistic about the efficacy of better communications about the problem. This would be quite wrong; what we question here is the wisdom of directing one’s efforts at an enormous, vague target group hoping for the best. En passant, we should like to underline those efforts if appropriately targeted, would prove very useful, and they would be of universal applicability.
In his contribution, Prof. Moya has taken an important step in the right direction when he chooses health personnel as an appropriate target for the proposed communications strategy. However, this would entail a non-stop cycle of communication as new batches of health personnel are employed. We find this approach a partial solution at best.
We were personally involved in basic research on resistance to antimicrobials in early 1970’ies, albeit in a modest capacity. At that time, the problem was clearly understood by the medical microbiologists and they were investigating the extent of inter- and intra species plasmid transfer of such resistance. Quite a number of pharmacologists were collaborating with microbiologists, and the problem has been communicated to surgeons and clinicians via many a medical journal.
At this point, the perceptive reader would ask, “why wasn’t anything done then? Weren’t the health ministries informed of this?” The answer to both questions is the age-old one. First, word of a person investigating the basic principals is often ignored because it is not ‘glamorous’ as that of technologists who make use of basic research to make ‘novel’ inventions. Secondly, it is very rare for a health ministry to be headed by a medical professional or it to have officials with relevant medical competence in its higher echelons. This defect is universal, and now it seems to be worse.
We shall take Prof. Moya’s proposal a step further; the authorities should make teaching of appropriate use of antimicrobials a compulsory part of medical and veterinary syllabi. Once this is in place, effective communications may be directed at the established health personnel. It must be noted that the first part is the responsibility of the national authorities in consultation with competent medical microbiologists, pharmacologists, surgeons and clinicians.
One may now ask, “Shouldn’t the public be informed of this serious problem?” The answer to this depends on what one wishes to achieve by informing the general public. If it should cause undue alarm, then the answer is a firm “no!” On the other hand, if the purpose is to encourage the public to compel the authorities to take rapid, appropriate action, then the answer is a resounding “yes!”
Assuming our mythical reader has persisted in reading this far, he may now ask, “well, do you propose to communicate anything more to the authorities, and what would you like to say to the general public?” This indeed is the challenge, and its resolution is complex. We will look at what to say to the authorities first, and then direct our attention to the general public.
The authorities should require the relevant syllabi to embody the appropriate use of antimicrobials. What is appropriate use of antimicrobials? This seems to be easy as it is concerned with medical appropriateness. Hence, it would be appropriate to use antimicrobials when it is clinically indicated. This applies with equal force to human and animal patients as well as to the crops.
We are sceptical about blanket recommendations based on case numbers, for we hold that each living entity of a given species has a certain degree of singularity which can also vary with circumstances. This somatic variability makes statistical recommendations on antimicrobial use nothing short of being mischievous. Hence it should be left to the surgeon or the clinician to determine the appropriate treatment on a case by case basis.
But this recommendation is too general, for it does not indicate how one may determine medical appropriateness. Once again, this would have to be determined by the competent professionals in medical microbiology, pharmacology, clinical practice, etc., which would have to be supplemented by the experience to be acquired by every newly qualified practitioner. This then is what the authorities should be made to understand and take steps to implement.
Up to this point, the task may seem feasible given the seriousness of the current situation with respect to the antimicrobials. Unfortunately however, there are already in our environment a vast number of pathogenic organisms that are resistant to a variety of antimicrobials. Even scrupulous personal hygiene is no guarantee against them. For instance, all it takes is an unforeseen minor accident out of doors leading to an injury that might be infected by an organism resistant to some common antimicrobials. This also applies to domestic animals and crops
Thus, nothing short of creating some fictional gnotobiotic environment where people, can live raising domestic animals and crops, there is no way to totally safeguard ourselves and our food sources from microbes resistant to antimicrobials. It must be noted that higher the population density around one’s residence, greater the one’s chances of being threatened by such microbial pathogens. Birth control is necessary to diminish this problem, but efforts to achieve this objective have shown meagre results.
Another great stumbling block is our unwillingness to take sufficient responsibility for our own good health. An impartial pharmacologist would recommend intake of smaller doses of antimicrobials at shorter intervals. Indeed, this has been the case previously. But, patients’ reluctance to wake up at night and take one’s medicine made them skip a dose, which results in the development of resistance to antimicrobials. Sadly, nobody dares to talk of prudence among the patients.
In order to deal with this patient lethargy, a dubious change in treatment regimen was undertaken. It simply involved oral administration of higher doses of antimicrobials at longer intervals. So, previous 6 hourly smaller doses were ‘revised’ to 8 hourly high doses, and even to 12 hourly massive doses. We know of some northern holiday makers who visited the ‘sunny south’ armed with such prescriptions for potential tourist diarrhoea and use them. They found that the resultant extermination of gut flora gave them greater discomfort and required treatment.
Therefore, we think it is important to communicate to the professionals and the public that the optimal dose should be taken at proper intervals and this should override their reluctance to be responsible for their own health. Their ease must not prevail over medical appropriateness. This should be impressed on the general public. In affluent countries with adequate primary and specialist care this is difficult enough, but how about the situation elsewhere.
It is precisely in countries where even primary health care is either absent in most areas or when available, a service of indifferent quality, one encounters hawking of adulterated antimicrobials and their over the counter sales respectively. It is unlikely that public communications would deter those unscrupulous sellers or their helpless victims from continuing these practices. When one has what one believes to be a health problem and when there are no really competent people to help them, they will resort to any means supposed to offer relief.
A survey of the distribution of indifferent primary health care and its absence will show a remarkable one to one correspondence between those two and the two problems just discussed. Do consider now how many ‘patent medicines’ and useless ‘health supplements’ are sold even in the most affluent countries where the authorities proudly claim high levels of public education and health care. The plain fact is that one knowing something does not necessarily mean one is going to act in accordance with what one knows.
Therefore, we think that rapid improvements in the quality and the availability of primary health care combined with stricter control of the antimicrobial sales are necessary. So, communications should encourage the public to demand the authorities to do so while simultaneously requesting powers that be to undertake those actions. Judging by the evident laxity in personal hygiene noticeable everywhere, we think a vigorous global advocacy to counter this challenge is long overdue.
We have identified two target groups for a communications strategy viz., authorities and the public as well as two types of content, each specific for a target group. Further, we have recommended a global action to promote better personal hygiene everywhere as an adjunct to reduce the risk of infection and infestations. At this point, every competent biologist would raise an objection which has been blissfully ignored by various fraternities of experts on resistance to antimicrobials.
It is an elementary fact of biology viz., viruses and all other things identified as living tend to adapt to adverse variations in their environment. Those who fail to do so become extinct like the dinosaurs and the mammoth. We have failed to take into account the consequences of this primeval biological tendency. We would happily defer to what competent professionals know about whether the Trematodes (liver flukes) and Cestodes (tape worms) have developed resistance to drugs used against them. These are considerable health problems in South East Asia and Africa respectively.
Going over to protozoan pathogens, it is well known that Plasmodium sp., (Malaria), Trypanasoma sp., (Sleeping sickness) etc., have developed resistance to some of the commonest substances used against them. Further, Leishmania sp., have been difficult and expensive to treat while global warming has triggered its entry into previously cooler northern areas like Southern Europe and the upper regions of the United States. These and several more pathogens will remain, and we cannot ignore the threat they pose.
Bacterial pathogens resistant to antimicrobials are legion, and need no elaboration. A large number of them for instance, Staph. Aureus, Esch. Coli, Psd. Aëruginosa, Kleb. Aërogenes, Proteus sp., Vibrio cholarae etc., can live in a moist ambience outside the human body. And they will multiply outside as long as sufficient nutrients are available to them. Human and animal waste is quite adequate for this purpose.
Thus, while the protozoans resistant to antimicrobials will remain and multiply at a relatively slow rate, similar bacteria will not only multiply more quickly, but will continue to spread owing to international travel and trade. We maintain that every rational and practical effort to deal with the problem should take this into account, and the communicators should bear this in mind.
Now a few facts which may ruffle quite a few feathers soon. As any competent medical microbiologist with an adequate knowledge of basic facts would testify, a bacterium exposed to anything equal or lesser than the so-called minimal inhibitory concentration of an antimicrobial may develop a resistance to it. This amount is very small, no more than a few micrograms of it per millilitre. At the same time, any competent pharmacologist would tell one most antimicrobials are excreted in urine and faeces whether the patient follows the most prudent regimen of treatment or not. Since the use of Penicillin became wide-spread, antimicrobials have been in use for over 70 years.
Now even in the most affluent countries, sewage including domestic waste has been discharged into the sea and rivers in its raw state even as late as in the 1980’ies. This included a considerable quantity of human excretion products containing antimicrobials at low concentrations in an environment containing many a potential pathogen.
This provided those microbes a nutrient environment where they could develop resistance to the antimicrobials involved. One does not need further elaboration of the point to grasp the simple fact that this has done much to spread microbes resistant to antimicrobials.
True, it has been done unwittingly, but it makes placing the onus of responsibility for the current situation entirely on physicians unjust and contrary to basic biological facts. Furthermore, in the sewage mentioned here, the microbes that have developed resistance to an antimicrobial could transfer it not only to others of the same species, but also to some others through plasmid transfer of such resistance.
Moreover, according to statistics from the UN, 2 billions of people in the world do not have access to a sanitary latrine. It is unlikely that none among them have been on an antimicrobial therapy when they relived themselves out of doors. This provides the faecal bacterial flora an ideal opportunity to develop antimicrobial resistance and remain in nature. In this case, ‘prudent’ use of an antimicrobial by a physician or a patient becomes academic with no practical significance.
The perceptive reader who has persisted in reading this far, would have now realised that this applies with equal force to the veterinary use of antimicrobials. There are no provisions in animal husbandry to prevent the development of resistance to antimicrobials in waste from animals on them. Further, Tetracycline derivative has been used as a ‘growth accelerator’ for many years, and this has rendered it almost useless owing to many species of bacteria developing resistance to it. These bacteria remain with us.
As the space at our disposal is limited, we have not dealt in depth with the subject. However, a clear thinking person with no vested interests will freely admit to points; the balance sheet is grim indeed and the experts have overlooked the importance of human and animal waste disposal as a major cause of the problem which could not have been avoided by the so-called prudent use of antimicrobials. Nor yet can we expect microbes not to evolve a counter strategy to deal with antimicrobials.
Both the competent medical microbiologists and the pharmacologists understood this when they observed the emergence of the so-called L-forms of bacteria in response to Penicillin and its derivatives. As Penicillins act by interfering with bacterial cell wall synthesis prior to cell division, the bacterial simply evolved into a cell wall-less organisms known as L-forms, making Penicillins useless against them.
Pathogenic fungi like Candida sp., Cryptococcus sp., etc also have developed resistance to several antimicrobials used against them. Nor have we tried here to give a complete list of protozoan, fungal, bacterial and viral pathogens that have already developed resistance to the medicines commonly used to deal with them. What is important here is to understand clearly the influence of the following biological and social facts on resistance to antimicrobials.:
- There is a considerable load of protozoan, fungal, bacterial and viral pathogens that already possess resistance to antimicrobials used against them. Their number will continue to increase and spread as global temperatures rise, international trade and travel continues and population density increases in inhabited areas.
- Defective and non-existing human waste disposal will continue to introduce into the environment pathogens resistant to antimicrobials.
- The types of pathogens we have discussed will continue to develop strategies to meet the threat antimicrobials pose to them.
- In view of the foregoing, over the counter sale of antimicrobials and hawking of their adulterated variant only play a limited role.
- The highly publicised ‘prudent use’ of antimicrobials has no effect whatsoever on the first three influences listed above.
One may now ask, “Do you maintain that what has been done so far is futile? Do you say that all the recognised experts who have been working on the problem are incompetent?” And it is a short step from such question to the well-known ploy, “ah, you think you are the only one who knows what to do!” Perhaps, such candid statements will remain unspoken.
We would like the impartial reader to consider the three facts listed above. Their factual soundness is obvious to anyone versed in biology, medical microbiology and social conditions in less affluent countries. True, lack of proper latrines and their biological consequences may be beneath the dignity of academic debate, but it is nevertheless a real world problem.
It is in this light we propose to outline a set of strategies to address the problem of resistance to antimicrobials. We do not use the common abbreviation AMr in deference to Standard English grammar and semantic correctness. It will be noted that we do not ignore any one of the above facts and understand the enormous difficulties one would have to overcome to resolve the present problem.
- Discovery/invention of antimicrobials will have to be a continuous endeavour in order to deal with the already resistant pathogens and those that might emerge in the future.
- This will require non-commercial, reliably peer reviewed basic research which is best carried out on an international cooperative basis with a view to developing, rigorously testing, manufacturing and distributing the new antimicrobials.
- Research and development is needed to devise an effective method to rapidly break down the excreted antimicrobials in order to minimise the development of resistance to them.
- Rapid incorporation into medical and veterinary syllabi extensive theoretical and practical instructions on the use of antimicrobials. When appropriate, such may be included in agriculture syllabus.
- International and national efforts to deploy adequate primary health care especially where none exists or the existing units are inadequate.
- Redouble the efforts of the UN to provide adequate latrines to those 2 billions.
- Comprehensive school and public education of the importance of personal hygiene.
- Although difficult, it would repay to halt the global increase in population with a view to reducing it.
- A new approach to animal husbandry is required, for large populations of a single species in a confined area promotes the development of resistance to antimicrobials as well as the emergence of New pathogens.
We do not claim that this list of strategic steps is exhaustive, but they represent the essential practical things we can do to address a problem that has not received the attention it deserves until now. The other virtue of the proposed approach is that it openly admits two biological facts; living pathogens will continue to develop counter measures against the chemicals we use against them and it is impossible to eradicate from the world those pathogens that have succeeded in doing so.
We shall next describe some of the ways and means we may use to implement those strategies. These can be placed in two broad categories. In the first, we have the real world actions various groups should undertake while the second contains the acts of communication that would prod the decision-makers to respond rapidly and appropriately. Moreover, it would inform the public of the seriousness of the problem with a view to inducing it to encourage the authorities to act promptly.
Naturally, the decision to undertake the requisite strategic actions will have to be taken at the cabinet level, and they should seek advice only from the professional groups mentioned below. Authorities should understand the problem in terms of misery that accompanies infectious disease. It would be irresponsible to view the problem primarily in monetary or sociological terms, for it would be putting the cart before the horse. Obviously, potential financial loss or social disruption comes as a consequence of pain, discomfort and dysfunction from infection. So, let us deal with the cause rather than drowning in secondary issues.
A note of caution must be sounded at this point. On implementing the strategies listed here, one requires tactical/field support on an inter-disciplinary basis. But, this coordinated support only involves competent medical microbiologist, pharmacologists, surgeons, physicians and teachers in medical, veterinary and the agriculture schools. In communication, personnel with competence in medical and biological sciences are to be preferred.
We have not gone into the tactical implementation of the strategy suggested here because it has little to do with communication. We have discussed the problem somewhat at length in order to illustrate two important points:
- The purpose of communication is to encourage a target audience to behave in a desirable way. If people just learn about a problem and remain indifferent to it, communication would be pointless.
- But, if we just inform the people that resistance to antimicrobials exists, does that mean that they would know what to do about it?
- We have pointed out that two relevant, basic biological facts, and the social issue of adequate latrines have been overlooked in the current expert debate on the problem.
- We have demonstrated with reference to the real world that it has been unfair to place the onus of responsibility for the problem on the medical profession. We have emphasised that we are dealing with a biological issue, and its correct description does not depend on consensus or a majority of votes.
- So, what are we to communicate and to whom?
- Obviously, we need to communicate to the right target audience what would make them to do one of the two things:
- Implement the proposed strategies;
- Compel those able to implement them to act quickly and appropriately.
- The target audience capable of implementing the strategies are the authorities. As they may not be familiar with the scientific reasoning presented here, the communicators should prepare a simple presentation in consultation with the professional groups described here. Its content should be neither technical nor yet a tabloid type simplification. It must underline the seriousness of the problem as well as its inevitability even if we had taken greater care in the use of antimicrobials.
- Moreover, as it is a universal problem with the potential to cause a great deal of human and animal misery, it must be emphasised that research and development of new antimicrobial should be an international effort anchored in a sense of common decency and good will rather than financial gain from pain and suffering.
- Communicators should encourage the public to demand from their governments the type of research and development described above.
- Likewise the public should be informed of the biological facts and the pointlessness in blaming any group, because we generally do not consider the consequences when we solve a problem. History can provide countless examples of this.
- Communicators should stress the importance of personal hygiene as a very effective way of avoiding infection and parasitic infestation.
- Communicators in countries where primary health care is sketchy and/or poorly distributed and where adequate latrines are the exception, should inform the public of their importance with a view to creating a wide-spread demand for them.
At the outset, we were aware of two critical issues the present forum discussion appears to have overlooked, viz., why one should communicate to the public information on the problem and for what purpose. Unless the public acted on such information in a suitable way that would facilitate its resolution, such communication would serve no purpose. Therefore, it becomes necessary to understand not only the full implications of resistance to antimicrobials, but also what biological and social factors that influences it.
An understanding of those factors is crucial for determining what we need to communicate and to whom it should be directed. In this submission, we were compelled to identify those factors in order to distinguish between our principal target audiences i.e., the decision-makers, relevant advisors and the general public. As their contributions to the resolution of the current problem are very different in kind, information that would motivate them to act appropriately would also differ significantly.
We have given a general description of the information each target group ought to consider carefully. How it may be most effectively disseminated remains a problem. We do not believe that a few disjointed sentences widely publicised will have greater effect than a shrug and an expletive or two. We believe public meetings where articulate speakers who have a thorough understanding of the problem would be of greater use. Their speeches can be followed by the distribution of lucid explanations of the problem adopted for lay readers but not deviating from the facts.
Our approach here has been pragmatic, but we have always kept in mind that it is vital that the decision-makers respond appropriately and speedily while the general public can only demand such action. Every realistic communicator should bear these two things in mind. We can easily deceive ourselves into thinking that we have done a great deal even if we have achieved very little.
Another great danger is the belief that inter-disciplinary action is a panacea for all our ills. Nothing can be farther from the truth. Yes, it is a must, but only when it involves disciplines relevant to the issue under discussion. We do not believe anyone would propose to include a famous literary critic, a well-known novelist, archaeologist, an actor, a barber, or a linguist in a committee to decide on what to say to the public about resistance to antimicrobials. Let us never forget the relevance at all times.
We have not touched on the consequences of not responding to the problem in a timely manner because they are well established. Competent relevant professionals involved have known about them, and have issued many unheeded warnings. We hope the actions stemming from this discussion would make the authorities and the public to shake off their tendency to indulge in masterly inaction.
Best wishes!
Lal Manavado.
Sr. Lal Manavado