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Monday, March 9, 2015

South Asia's terrible record of Antibiotic abuse comes at a huge price

It is not only the doctors; from the people buying and taking antibiotics on their own and rural health workers using the 'wonder drug' to cure the patients at the earliest, to regulatory bodies doing everything but their job, everybody is to blame for a mess that is likely to threaten the health of, don't gasp, people across the world.

I, along with a number of people with a deeper understanding of the problem of anti-microbial resistance (AMR), doubt even a number of measures outlined here will substantially help the region and the world to prolong the antibiotic era. But if nothing is done, we may be already approaching the threshold to post-antibiotic era, with South Asia regrettably leading the world's march to abyss. 

Less than nine decades from discovery of penicillin—the first antibiotic to be recognized and used as such—there are dire but credible warnings about the onset of a post-antibiotic era. For a health system dependent on the use of antimicrobials in an increasingly critical and diverse ways, the likelihood of extensive resistance of microbes to these magic drugs is the ultimate nightmare.

When the worst fears of people closely watching the resistance patterns of microbes come to be unavoidable realities, a patient with a modest open wound may stare at death and an oncologist will counsel a cancer patient awaiting chemotherapy and organ transplantation like this: there is a very real risk of untreatable infections during the treatment and that is often uniformly fatal, though the scenario was much more different two decades ago or so.

For those still skeptical about the seriousness of the problem, this is how the latest report by WHO titled 'Antimicrobial resistance: Global report on surveillance' opens: "A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century."

Amid the effort of the scientists, doctors and public health workers to somehow prolong the ongoing 'antibiotic era' by delaying the inevitable and saving millions of lives in the meanwhile, it is being realized that the problem goes much deeper than simply infections not responding to antimicrobials. Here is one sentence from the first chapter of the book 'Antimicrobial resistance in developing countries':

If other elements and genes, such as the horizontally transferable mutS gene, that accelerate the mutation rate of bacteria (Brown et al. 2001) are also being co-selected by antibiotics, the legacy of this ‘‘antibiotic era" would be not only resistant bacteria but also bacteria that are much more competent to face environmental threats, by means of increased prevalence of determinants that increase genomic plasticity.

For their complexity and diversity, delving deeper into the mechanisms of antimicrobial resistance is beyond the scope of this article but suffice here to say that there are both microbe-dependent—mostly non-modifiable—and host-dependent—mostly modifiable—factors and it is the latter about which something can be done. Data from many studies appear to suggest that, among the modifiable ones, antimicrobial misuse, prophylactic use, diagnostic imprecision, and interpersonal spread are key factors in the selection and dissemination of resistant strains.

Impossibility of a piecemeal solution

The worst part of the problem is that, as in the efforts to eradicate some of the formidable infections like polio from the world, combating Antimicrobial Resistance (AMR) demands a globally coordinated effort and a single pocket of failure can jeopardize the achievements from rest of the planet. In this era of globalized world, it is the matter of hours to days in which a menacing microbe can travel across the continents.

Different geographical regions in the world with different determinants of resistance to antimicrobials have to tailor the strategy to combat the problem after a thorough study of the latter. Many of the developed countries with established surveillance programs for patterns of AMR appear on way to tackling the crisis relatively better by minimizing the modifiable causes of resistance like misuse and improper use of antimicrobials. Even in these countries the threat posed by rampant and unsupervised use of these drugs in livestock is a source of great concern.

Compared to that, however, the problems in the developing countries are just overwhelming and risk making any gains made in the other parts of the world towards fighting AMR irrelevant. That, in turn, forms the recipe for a potentially devastating public health disaster in the world.

The basic argument of this article is that while the factors like the excessive use of antibiotic use in livestock continue to be an emerging problem in developing countries as in the developed ones, a fundamentally flawed practice around antibiotic prescription among the practicing clinicians here poses a unique challenge to the global efforts at tackling AMR. With observations based on Nepal and to some extent India, I will try to elucidate why the misuse and overuse of antibiotics continues unfettered and how the problem is worsening by the day. 

Why South Asian doctors misuse antimicrobials

A sensible doctor should have in mind both the short term considerations like curing a patient and the long term considerations like maintaining the viability of antimicrobials in their rapidly depleting arsenal. Indeed they should imbibe the value and ethics of a sound clinical practice while getting the degree itself of a course in medicine. 

But that is not the case in most parts of South Asia. While it is possible that some of the doctors graduating from here will have awareness and sense of urgency towards the long term problems faced by the mankind in the form of multiple and emerging diseases and conditions—and there are quite a few of them—the medical education here plays little pro-active role towards instilling such an awareness in every doctor it produces.

Here, the orientation towards research activities during the study period is nil and with very few exceptions, the mandatory theses for the postgraduate programs are mockery of research as there is little element of research in its true sense. It is thus impossible for these doctors to effectively understand the scopes and challenges of scientific experiments and researches involving human life. Even if they rote-learn how such experiments are done, they cannot truly comprehend the cost and complexity of a process like development of a new class of antibiotic or any other drug. Zero engagement with the research activities both during the student life and professional life reduces the total activity of a practicing clinician to prescribing medicines and doing surgeries.

As a result, the average practicing clinicians are utterly disconnected from the larger issues governing the health of people in the entire society, country and the world.  As soon as they get a degree, the paltry pay at government or private institutions where they work full time forces the doctors to engage with so called 'private practice' in the clinics and nursing homes. With most of the day already consumed in the practice, they can little afford to study the recent advances in the realm of diagnosis and treatment.  

This background now makes it easier to look into why the irrational prescription of antibiotics is so rampant in this part of the world. Totally blind to the larger picture of the country and the world, these doctors have the only priority in clinical practice: getting the patient cured at the earliest. Even this goal is distorted by unethical practices like collusion with the agents of drug companies, to be elaborated later. This concoction of ignorance and greed forms the mainstay of outrageous overuse and misuse of antibiotics in South Asia.

When I personally observed the practice in two tertiary hospitals in Nepal and asked some of the practicing clinicians and students of post-graduate courses in Nepal and India as to why qualified doctors were so blatantly misusing and overusing antibiotics, they made the following points:
  • Peer pressure: Nobody is really aware of how it all started but what they find in day-to-day practice is that every clinician around them is prescribing a newer generation and powerful antibiotic with faster and more satisfactory results for an illness that should have been rationally treated with simpler antibiotic or no antibiotic at all. If you resort to rational treatment in the case with simpler antibiotic or if you wait for a culture and sensitivity report to start an antibiotic, the patient will be likely disappointed and go to another clinician looking for quick relief and you risk simply being counted as the less efficient among the clinicians.
  • Influence of the drug-peddlers: Among the many ways the drug companies use to boost the sales of their drugs and maximize the profits, the most effective and the one most directly leading to antibiotic misuse and overuse is the system in which they incentivize both the peddlers (euphemistically termed 'Medical Representatives') and the doctors, of course, for both rational and irrational prescriptions. In case of particularly rogue doctors practicing grossly unethically, they set a daily target for a particular drug—often the new generation antibiotic—and prescribe the required number regardless of the total number of patients they see on a particular day and the number of patients genuinely needing the drug among them. Most egregious of these doctors often prescribe multiple antibiotics with overlapping spectrum for a patient at the same time. 
  • Poor support from the laboratory: Many doctors cite the poor sensitivity and reliability of the microbiology labs that perform the microbial culture and sensitivity as the cause behind some of the apparently irrational prescriptions.
  • Abuse and overuse of antibiotics at the community level: Given the availability of an increasing range of antimicrobials at the dispensaries even in small villages, the paramedics practicing there often use the newer generation and reserve antibiotics to start with, in a zeal to cure the patient at the earliest. Often, a patient from a remote part of the country lands in a hospital in Kathmandu with an infection sensitive to only one antibiotic for which the oral form is not available. 
  • Patient factors: Some of the advocates of rational drug prescription have frequently faced strange situations. Their adherence to simpler and cheaper antibiotics makes the patients think that they are the less capable ones among the doctors in places like Kathmandu because the very drugs were earlier prescribed by the paramedics back home. There is a fair proportion of patients who take on their own a repeat course of an antibiotic that was earlier prescribed by the doctor for a purportedly similar illness. And a large number of patients tend to stop taking antibiotics as soon as the symptoms are relieved and without completing the course. 
These problems, however, are a mere sideshow in face of some larger and more systematic problems plaguing the health care delivery system and medical education in the region:
·        As the medical students doing a MBBS course see their professors regularly using the antibiotics of last resort like vancomycin or imipenem regularly in the wards, they start thinking that this is indeed the rational use of antibiotic. Only exceptionally bright ones among them can see through the practice and be worried about the larger problems like antimicrobial resistance. Majority will never doubt the professors and start prescribing the antibiotics recklessly as soon as they get the degree and for their entire professional life. 
·        As the regulatory bodies of the state meant for preventing the malpractice are incompetent, corrupt or even non-existent, it is commonplace to gap the holes in antisepsis and sterilization processes in operation theaters and intensive care units with the blanket cover of new generation antibiotics. Over the time, the guidelines for asepsis and antisepsis have been forgotten and the antibiotic use has been routine. And nobody is ever uneasy about the situation.

The way ahead

If the governments in the region are left alone to deal with the problem, they are likely to take a whole decade to merely understand its gravity, by which time all of the available antibiotics in the planet will have developed substantial resistance in the region. And there will be left pretty nothing to do with.

What can potentially make a difference is a comprehensive action to be started immediately for both the short term and the long term. 

In the short term, an empirical study of the problem involving the entire region followed by a taskforce of specialists from a body like WHO with the following responsibilities can make a difference to start with: 1) educate the doctors about the dire status of AMR and a need to salvage potency of antimicrobials through rational practices, 2) instruct the regulatory bodies to monitor the situation and to take corrective steps, and 3) declare a public health emergency in pockets of particularly high degree of malpractice and resistance and take emergency measures in those pockets.

In the longer term, overhauling of the entire medical education and health care delivery system in the region is long overdue to bring to end the archaic clinical practice in the region totally detached from the evidence-based medicine in the advanced countries. A few concrete steps can be summarized as:
  • The process has to start with the medical school with timely update of the curricula emphasizing the research component of medical education. 
  • Uplifting the laboratory services (microbiology labs in particular) is also a must as the even the clinicians in cities like Kathmandu complain of poor laboratory support. 
  • A detailed analysis of aseptic and antiseptic practices in hospitals with a mandatory protocol to ensure asepsis can help reduce the reliance on antibiotics during and after surgeries. 
  • Punishing the mischievous doctors with unethical behaviors like taking commissions from drug companies for prescriptions 
  • Finally, a public drive to 
    • discourage antibiotic abuse by people by educating them about the hazards, 
    • abolish the over-the-counter sale of antibiotics by pharmacies and 
    • a strict policy to discourage use of higher end antibiotics in the communities.

I, along with a number of people with a deeper understanding of the problem, doubt even that will substantially help the region and the world to prolong the antibiotic era. But if nothing is done, we may be already approaching the threshold to post-antibiotic era, with South Asia regrettably leading the world's march to abyss. 

Read more on the issue in the official blog of Nepalese Initiative for Prevention of Antimircobial Resistance (NIPAR). 

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