The World Antibiotic Awareness Week (Nov 18 - 24) is celebrated worldwide under the theme “Antibiotics: Handle with Care”. The key objective of this movement is to raise awareness and understanding of antimicrobial resistance through effective communication, education and training. In ancient societies people used molds to treat infections. In 1877, French biologist Louis Pasteur first observed that cultures of Anthrax bacilli, when contaminated with molds, were successfully inhibited. Some references say that Pasteur identified the strain as Penicillium notatum. However, the Scottish physician Alexander Fleming was the first to suggest that a Penicillium mold must secrete an antibacterial substance,which he extracted and named Penicillin in 1928. Penicillin became the first modern antibiotic, which began the era of antibiotics.It was one of the greatest advances in therapeutic medicine, but today their effectiveness is threatened by the ability of bacteria to adapt and resist treatment. In 1940, the first report came on antibiotic resistance (AR) when Escherichia coli (E.coli) produced an enzyme known as penicillinase/beta (β)-Lactamases enzyme, which was capable of breaking down penicillin and completely negating its antibacterial effect (Abraham E, 1940, Nature).
The surge in AR, mostly caused by high rates of antibiotic use and misuse, has become a matter of great concern as the rate of new antibiotic development is declining. AR poses a big risk in terms of mortality and economic burden worldwide. “If you develop an illness or an infection that cannot be treated in the traditional way with antibiotics, you can die. It’s as simple as that”, said World Health Organization (WHO). In the U.S. alone, it causes more than 2 million infections and 23,000 deaths per year (CDC: Centers for Disease Control, Atlanta, USA). A UK-commissioned report fears of 10 million deaths due to antimicrobial resistance by 2050. The misuse of antibiotics is putting us all at risk. Because of AR, standard treatments become ineffective; infections persist and may spread to others. A growing list of infections – such as pneumonia, tuberculosis, gonorrhea, and food-borne diseases – are becoming harder, and sometimes impossible to treat as antibiotics become less effective. WHO considers AR a high priority and matter of emergency.
In Bangladesh, 400 out of 900 patients admitted to the Intensive Care Unit of Bangabandhu Sheikh Mujib Medical University (BSMMUH) last year died due to resistance to antibiotics (bdnews24.com, April 25, 2019). Overall, a growing trend of AR has put the health of Bangladeshis under serious threats. It poses a regional and global threat. A systematic review analyzed 46 studies published between 2004 and 2018 on AR in Bangladesh (Ahmed I et al., 2019, Int J Infectious Disease). The review says, “AR is a worldwide problem and Bangladesh is a major contributor to this owing to its poor healthcare standards, along with the misuse and overuse of antibiotics..… and many of the common first-line drugs were mostly ineffective”. A high prevalence of resistance to most antibiotics has been detected in that study. The study found that bacteria which caused common ailments like urinary tract infection, pneumonia and ear infection were becoming resistant to most of the antibiotics in Bangladesh. Resistance to ampicillin, amoxiclav, ciprofloxacin and co-trimoxazole was 100%, 58% and 67.4% and 72.7%, respectively, in Klebsiella bacteria that cause pneumonia. Other reports also show that multidrug-resistant tuberculosis appeared to be a cause of concern in Bangladesh (Banu S et al., Int J Tuberc Lung Dis, 2017). A survey in Dhaka city revealed that 56% of antibiotics prescribed to patients in Dhaka failed to work (Poribesh Bachao Andolon, 2016). In a recent study at Rajshahi, Biswas et al (2014, BMC Public Health) showed that 347 [26.69%] out of 1300 participants experienced self medication with different types of antibiotics. In another study, highest resistance of Salmonella typhi was observed against nalidixic acid in Dhaka, Chittagong (40.0%) and Rajshahi (66.60%) division (Mannan A, 2014, Asian Pac J Trop Biomed).
In the late 1980s and early ‘90s, four bright postgraduate students in their Masters (Rezina Laz, now Professor of Zoology, RU, and Mariam Akhtar) and MPhil (Mofazzal Hossain and Nilufar Panna) dissertation/thesis-works devoted to their separate projects on AR in my lab at the Department of Zoology, University of Rajshahi, and found that bacteria (Salmonella, E. coli, Pseudomonas, and Proteus) collected from Rajshahi Medical College Hospital already developed resistance to different β-lactam antibiotics (of different generations/terms): the group of Penicillin and Cephalosporin.
Bacteria, not humans or animals, become antibiotic-resistant. As AR rises, so do research and development of new antibiotics. Bacteria have a remarkable genetic plasticity that allows them to respond to a wide array of environmental threats, including the presence of antibiotic molecules that may jeopardize their existence. The three fundamental mechanisms of AR are: 1) enzymatic degradation of antibacterial drugs; 2) alteration of bacterial proteins that are antimicrobial targets; and 3) Changes in membrane permeability to antibiotics. Bacteria use two major genetic strategies to adapt to the antibiotic attack, i) mutations in gene(s) often associated with the mechanism of action of the compound (bacteria such as E.coli can alter their genetic makeup with astonishing rapidity), and ii) acquisition of foreign DNA coding for resistance determinants through horizontal gene transfer (i.e., bacterial cell-to-cell contact through conjugation or bacterial sex). The major mechanism of resistance to β-lactams in Gram-negative pathogens is the production of β-lactamases, enzymes capable of hydrolyzing the four-membered β-lactam ring of antibiotics, rendering them inactive. It’s a matter of great concern that more than 1,000 individual β-lactamases have been reported and their number is steadily growing (Nuno T, Antimicrobial agents, and Chemotherapy, 2014). The gene (bla) encodes for β- lactamases is located in either the bacterial DNA or in the Plasmid (a small circular DNA in the cytoplasm of a bacterium or protozoan), i.e., AR can be either plasmid-mediated or maintained on the bacterial chromosome. The number of new AR genes has dramatically increased over the last decade, as part of the adaptation ability of bacteria facing new antibiotics.
Responding to a call of WHO and also, being a member of the “Global AR Partnership (GARP)” project, Bangladesh has seriously addressed to antimicrobial resistance by preparing a National Strategy and Action Plan to preserve antibiotic effectiveness, slowing down the spread of resistance, and establish national capacity for antibiotic policy and access. Also, the Directorate General of Drug Administration (DGDA), as a National Regulatory Authority, is implementing drug regulations at all stages of productions, including the dispenses of medicines in Bangladesh. In spite of serious measures taken by the Government of Bangladesh, different studies show that the widespread misuse of antibiotics, non-human antibiotic use, availability of poor quality of drugs in the market, and inadequate surveillance still remain a big threat to further development of AR in Bangladesh. Also, self-medication with antibiotics is highly prevalent in Bangladesh, with most medicines being purchased from the pharmacy stores without prescription from a physician. In order to stop indiscriminate use of antibiotic drugs, the High Court of Bangladesh has recently directed the government to take measures to prevent the sale of antibiotics without proper supervision and prescription (The daily Observer, April 26, 2019). If these directives are properly followed, the use of antibiotics will be reduced significantly.
Another important aspect is that the antibiotic business is most profitable one, which is the second best-selling drug in Bangladesh. According to a review on the pharmaceutical industry business in Bangladesh by LankaBangla, the sale of antibiotic was Tk 1,687.61 crore in 2018, the second most sold medicines after acidity drugs. Public knowledge on appropriate use of antibiotics tends to be low. The key objective of ‘Antibiotic Awareness Week 2019’ is to increase cognizance about AR and promote the correct use of antibiotics across all sectors to avoid further emergence and spread of AR. In order to prevent antibacterial resistance, the following major contributing factors to AR need to be controlled and regulated in all the districts of Bangladesh: over-prescription of antibiotics, unnecessary use of antibiotics in viral infections (such as flu, common cold, a runny nose condition, etc), unregulated pharmacies and quacks, self-medication among patients, irrational antibiotic prescribing by some physicians, overuse of antibiotics in livestock and fish farming, maintenance of hygiene and sanitation. Also, not skipping doses, the full course of antibiotic, even if you feel better, should be completed. Preventing infections prevents the spread of resistant bacteria.
I wish this upcoming Antibiotic Awareness Week campaign by the Department of Pharmacy, Varendra University, a great success.
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*Pro-Vice Chancellor and Director of “Center for Interdisciplinary Research (CIR)”, Varendra University (VU), Rajshahi, Bangladesh.