Prescription drugs overused and abused in the Mideast

It turns out that, in the Middle East, getting access to prescription medications for serious ailments, in the absence of supervision, can sometimes be as easy as picking up an over-the-counter medicine for a headache or the common cold, or so claims a new review published in Pharmacology Research & Perspectives.

In theory, the regulations separating access to either brand of medication is there. In practice, the review cites a “massive problem” of self-medication misuse in the region, particularly with prescription medication, one that eventually leads to greater health risks among patients, including drug dependency and addiction.

Drugs that are used recklessly or sometimes abused by Middle Eastern patients include codeine containing products, topical anesthetics, topical corticosteroids, antimalarial, and antibiotics. According to the review, which looked at 72 papers published on the subject between 1990 and 2015, self-medication medicine misuse cannot always be exactly quantified in the region but it seems widespread.

Some of the statistics that the review highlights are quite jarring.

For instance, 73.9% of the Sudanese population have reportedly used antibiotics or antimalarials without a prescription. Equally alarming trends have been observed in Syria, Yemen, Jordan, Tunisia, Egypt and the UAE, with drugs such as amoxicillin or ampicillin being dispensed freely. According to the review, most patients self-medicating on antibioitcs did not even follow through the full course of the medications and took them for less than three days.

Many of the patients follow the advice of relatives, or have a drug prescribed to them by a doctor over the phone. As well, some pharmacists play a role. “People tended to select medication based mainly on advice received from community pharmacists,” says one of the studies cited.

One study said that the majority of the 200 pharmacies under scrutiny in Syria had sold antibiotics without prescription, and in Saudi Arabia, only a single pharmacy had refused to release the medication without a doctor’s prescription.

As well as stacking prescription medications for future use, Middle Eastern patients often used them inappropriately; it’s not uncommon for many to pop antibiotics to treat illnesses unrelated to bacterial infections, for instance, or with incorrect dosages for inappropriate period of time, according to the review.

Bacterial methylomes and antibiotic potentiation

Cohen et al., Nature Genetics, 2016

Cohen et al., Nature Genetics, 2016

Antibiotics emerged as miracle drugs and “silver bullets” in the early 20th century, revolutionizing medicine and our ability to combat infectious disease while positively impacting health and lifespans on a large scale. This remarkable triumph held steady for many years, and consequently antibiotic research and development diminished as a priority due to the seeming defeat of bacterial infections. However, the selective pressure that came with antibiotic exposure led to the development of bacterial resistance to these compounds, motivating renewed interest in what is now an extremely important public health issue. Mechanisms of resistance are many and ever-evolving, and we know now that it is not a matter of IF bacteria will become resistant to a class of antibiotics, but when. The search for new and potentially exploitable bacterial vulnerabilities, then, becomes a constant enterprise in order for us to keep pace with the bacteria in the antibiotics/resistance arms race.

Cohen et al., Nature Genetics, 2016

Cohen et al., Nature Genetics, 2016

A new study this week in Nature Genetics describes how manipulating the bacterial DNA methylome affects susceptibility to multiple classes of antibiotics. The authors observed that deleting the dam gene, encoding a DNA methyltransferase, from E. coli causes increased susceptibility to sub-lethal doses of the β-lactam antibiotic ampicillin. Dam specifically methylates GATC sites, and deletion of any of the other three DNA methyltransferases found in E. coli had no effect on the level of antibiotic susceptibility. Using SMRT sequencing, the authors saw that genome-wide GATC methylation patterns did not change after exposure to ampicillin, so they sought alternative explanations for the observed phenotype. Continue reading

Antibiotics everywhere — in chicken, pork, fish, mutton

The ‘antibiotics in your chicken’ story was everywhere in the Indian media (1, 2, 3, 4)  today — studies by Delhi-based NGO Centre for Science and Environment (CSE) always manage to generate this level of interest — be it antibiotics in honey, toxic phthalates in toys, polluting car parks or pesticides in cola. These are studies that touch the common man’s  life directly and, many a time, help make policy changes by creating the necessary buzz. The peer review process follows the advocacy drive, I am told, “since publishing scientific findings could take time and the issue at hand might need urgent attention.”

Scientifically speaking, what do we know about the chicken-antibiotic story that we didn’t already? One, this is the biggest study done in India to test residues of antibiotics in chicken — 70 chicken samples from Delhi and the National Capital Region (NCR) were tested, 40 per cent samples tested positive, residues of more than one of six commonly used antibiotics were found in 17 per cent samples. All this “points to a large-scale unregulated use of antibiotics as growth promoters by the poultry industry and could be one of the reasons Indians might be developing antibiotic resistance.”

Antibiotics might creep into your plate from most commercially reared food animals

Antibiotics might creep into your plate from most commercially reared food animals{credit}S. Priyadarshini{/credit}

Getting back to the issue of humans developing antimicrobial resistance through use of antibiotics in food animals, way back in 2002, the World Health Organisation (WHO) raised an alarm over this “fast spreading, serious threat to global public health.” WHO  estimated that half of the antibiotics produced in the world are being used in farms and not to improve human health (WHO, 2002, Use of antimicrobials outside human medicine and resultant antimicrobial resistance in humans).  Antibiotics are administered eight times more for non-therapeutic purposes than for treatment. Antibiotics are given as prophylactics to prevent infections and also to promote growth.

“The prolonged use of low doses of antibiotics in animal feed can create ideal environment for production of antibiotic resistant bacterial strains. The resistant bacteria can be transmitted from animals to humans via contact, food and environment. Infections caused by resistant microorganisms do not respond to the standard drugs, leading to prolonged illness, higher cost of health care and more risk of death.”

So, if you thought your mutton, fish and pork are exempt from the antibiotic-fed category, here’s a rude shocker, by WHO:

antibiotics-WHO

{credit}WHO{/credit}

 

This year WHO mentioned in its global surveillance report on antimicrobial resistance :

The use of antibiotics in animal husbandry – including  in livestock, poultry and fish farming – are leading to increasing recognition that urgent action is needed to avoid inappropriate use, and to reduce antibiotic usage in animal husbandry and aquaculture, as well as in humans. More data are needed on antibiotic consumption in food-producing animals worldwide, and on the occurrence of antimicrobial resistance in diff‚erent countries and di‚fferent production systems, in order to make comparisons between countries and identify priority areas for intervention.

Food-producing animals are reservoirs of pathogens with the potential to transfer resistance to humans. The magnitude of such transmission from animal reservoirs to humans remains unknown, and will probably vary for di‚fferent bacterial species. The spread of resistance genes from animal bacteria to human pathogens is another potential danger which adds complexity.

The report rang alarm bells saying antibiotic resistance was sweeping the developing world. India also has the dubious distinction of being the hotbed of many drug-defying bugs.

So, earlier this month, at the International Conference on Host Pathogen Interactions (ICHPI) in Hyderabad, the issue of antimicrobial resistance raised some sharp reactions. Scientists attending the meet recognised how microbes are constantly fighting back by gaining new resistance mechanisms against drugs. The need for novel and effective antimicrobial drugs was felt, not only to treat emerging infections but also for the success of medical procedures such as organ transplantation, cancer chemotherapy and major surgeries that are commonly preceded by infections especially in developing nations like India.

Scientists at the meet said it was unfortunate to see ‘lack of data’ for India in the recent WHO report on global surveillance on antimicrobial resistance. A brainstorming, therefore, intended to identify international and national organizations and funding agencies for addressing antimicrobial resistance. The scientists and policy makers participating in the brainstorming were looking at existing Indian policies on antimicrobial resistance and their strengths and weaknesses to spot areas that need immediate amendment.

Some key recommendations that came out of the session (and have been sent to India’s Department of Biotechnology and the Indian Council of Medical Research)  were:  (i) creating awareness about the growing antimicrobial resistance and its impact on animal and human health to the public, doctors and other stakeholders – lobbying with the politicians for this, (ii) regulation of the prescription / sale of antibiotics and standardisation of antibiotic treatment regimen, (iii) collection of epidemiological and surveillance data and maintenance of a nationwide database to monitor and record developing antimicrobial resistance in hospitals, fields and among public, (iv) research to identify novel growth promoters, novel targets to kill microbes, novel combination of approved drugs and alternatives to antibiotics such as probiotics, immunomodulators, anti-virulence drugs, anti-toxins, vaccines and improved sanitary managements, (v) development of community level, rapid, point of care diagnostics/screening tools, (vi) understanding the molecular mechanisms involved in the development of antimicrobial resistance and development of strategies to overcome it, (vii) strict regulation of antibiotic withdrawal period in animal produce and need to monitor food borne illnesses, (viii) development of alternatives to the use of antibiotics in the poultry/aquaculture/veterinary practices, as growth promoters and (ix) as large pharma is not interested in the development of new antibiotics, there is need for enhanced public funding and incentives for small and medium companies.

The scientists have also recommended establishment of a National network for antimicrobial resistance, a coordinating centre for molecular epidemiology, genomics and control of drug resistant pathogens with multiple regional monitoring and surveillance centres. The centre is proposed to give emphasis on hospital and community acquired infections.

Lets hope some of these recommendations get some attention — the near absence of global scientific data in this field means taking the first step would be avant-garde.

The CSE study, therefore, comes at the right time as a pioneering effort to generate public discourse on this very significant threat to public health in India.

Group urges speedier approvals for badly needed antibiotics

Infectious-disease doctors have proposed a speedier, easier approval process for drug companies developing antibiotics against untreatable illnesses.

The Infectious Diseases Society of America (IDSA) made the proposal today at a hearing of a subcommittee of the US House of Representatives Committee on Energy and Commerce. The hearing focused on reauthorization of the Prescription Drug User Fee Act, which funds the US Food and Drug Administration (FDA).

According to IDSA, only two or three drug companies are still conducting research on antibiotics in the United States, even as antibiotic-resistant strains of bacteria are becoming an ever more urgent health problem. A bill proposed by Rep. Phil Gingrey (R-GA) called the Generating Antibiotic Incentives Now Act (GAIN), would grant incentives to companies that develop antibiotics against drug-resistant bacteria. IDSA is proposing that lawmakers also create a ‘Special Population Limited Medical Use’ (SPLMU) mechanism that would allow companies to conduct clinical trials in fewer patients and obtain more streamlined approvals for the drugs if they are intended to treat patients for which no other drugs are available.

The new mechanism would also reserve these drugs specifically for use in patients harboring pathogens resistant to all other treatments. That provision is designed to address a major concern among doctors and the FDA that new antibiotics will quickly lose their effectiveness if they are overused.

“We need antibiotics to be used for life-threatening infections that lack medical treatments … and not for your kid’s ear infection,” Janet Woodcock, head of the FDA’s drugs center, told reporters on Wednesday, according to Reuters.