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Antimicrobial drug resistance in India: Possible causes….. Dr Ron Thomas Varghese *, Dr Roby Das **. * Ron Thomas Varghese, MBBS is a Medical Officer, Karunya Vishranthi Bhavan ,Kattela, Sreekaryam, Trivandrum, Kerala ** Roby Das, MBBS is a Junior Resident, Department of T.B and Chest, SUT Medical College ,Vattapara, Trivandrum, Kerala Ron Thomas Varghese is the corresponding author: [email protected]

We have come a long way from Antony van Leeuwenhoek’s discovery of “animalcules” back in 1676. (1). Louis Pasteur introduced “germ theory of diseases” and Robert Koch in 1877 demonstrated that a specific bacterium could cause anthrax. In 1929 Alexander Fleming isolated Penicillium Notatum .It was not until 1940, however, that H.W.Florey , E.B.Chain, and their collaborators at Oxford University showed experimentally that penicillin was nontoxic and highly effective systemically in treating pyogenic infection , thus pioneering the antibiotic era. The war for survival between man and bacteria thus began. This resulted in the production of better antibiotics by man, which in turn culminated in the development of antibiotic resistant strains of bacteria. Antibiotic resistance was initially reported for gram positive organisms. Evidence is now mounting to the rapid emergence of antibiotic resistant gram negative strains. It has now reached alarming proportions, so much so that rate of acquisition of antibiotic resistance is faster than antibiotic discovery. So a stage could come in the near future wherein most antibiotics would be rendered redundant. Emergence of multidrug resistant strains of Klebsiella and E.Coli points to this direction. Until recently, Carbapenams had been the

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major antibiotic against ESBL (Extended Spectrum Beta Lactamase) producing gram negative organisms (2). Rapid emergence of Carbapenam resistance has resulted in limited antibiotic sensitivity, or even no antibiotic sensitivity as in the case of NDM-1 strain. Discovery of NDM-1 strain in India shows how vulnerable our health system is to the onslaught of multi drug resistant microbes, even though the origin of this strain is still a subject of debate. In this backdrop we would like to delve into the possible fallacies of healthcare system and delivery that contribute to the emergence of highly resistant organisms like those of NDM-1. India’s peculiar demographic, economic and political factors could have made a contribution to antibiotic resistance. Population density is an important determinant of antibiotic resistance (3).With the alarming population explosion, sanitation becomes a problem .This results in persistence of water and food borne infectious infections in the community, especially among those in the low socio-economic status .Lack of knowledge of modes of spread of infection, also contributes to spread of infectious diseases. The low literacy rate and poor access to genuine healthcare, results in both inadequate treatment of infectious diseases and poor

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response to public health campaigns. Monetary constraints often result in patients buying lesser amount of prescribed drug. They could also discontinue drug therapy when there is marginal improvement in symptoms. They need to be made aware of the necessity of taking drugs as per the prescription. Antibiotic abuse is also rampant, with notions that antibiotics need be taken for the slightest of illness. These socioeconomic factors coupled with injudicious use of antibiotics, may have contributed to the development of bacterial resistance. The problems posed by pharmaceutical companies , producing spurious substandard drugs, is also a major problem .Poor implementation of existing laws and rampant corruption could make India the hub of counterfeit substandard drugs. The lack of political will to curb this menace is appalling. This apathy results in widespread inadvertent suboptimal dosage of antibiotics resulting in resistance. In India the rampant multilevel misuse of antibiotics has contributed its part to development of antibiotic resistance (3). Use of antibiotics in agriculture results in entry of antibiotics into the food chain and thus result in emergence of antibiotic resistance (4,5,6). Household items like cleansers laced with antibiotics could also contribute to resistance (7). It occurs in the settings of medical practice, agriculture & aquaculture, households. Hospital effluents have also been found to contain antibiotics at sub lethal dose, contributing to antimicrobial drug resistance (8). In hospitals, rational drug prescription may not be practical due to a host of reasons ranging from patient expectations, maintaining

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‘reputation’ of hospitals, to pharmaceutical lobbying. Physician judgment in antibiotic prescription has been found to be largely affected by drug promotion by pharmaceutical industries (9,10). Various complementary gifts are given to doctors adhering to the whims and fancies of these companies. This could prove to be a calamity with regard to rational drug prescription. This calls for urgent steps to be taken to educate physicians about the importance of evidence based medicine, and to impose strict legislation and punishment to those found guilty of violating ethics. Hospitals must also be told to adhere to a strict antibiotic policy and take steps to reduce hospital borne infection. Irrational drug use is common in India (11). Errors in prescriptions like sub optimal doses, incorrect dosage schedule, dosing errors, are high, especially in the case of antibiotics (12,13). Use of antibiotics for nonbacterial infections is also common. Polypharmacy is a common practice in India (13,14). In many colleges, in India, the students are not taught about rational drug use. They thus lack knowledge about the same. (15) .These fresh doctors could then injudiciously prescribe drugs. To complicate matters, Continuing Medical Education about the recent evidence based drug prescription is not common in India. With a low Doctor-patient ratio, (1 per 1722 people) (16), especially in rural areas, the access to a doctor practicing modern medicine is abysmal. With 74% of the graduate doctors living in urban areas, serving only 28% of the national population, the rural population remains largely unserved (17). This often leaves the rural population at the mercy of practitioners of other forms of medicine and quacks. There is an unhealthy trend among

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doctors of other forms of medicine to prescribe allopathic drugs including antibiotics without having any knowledge about them, which may contribute to antibiotic resistance.

There is also the burden of over the counter dispensation of prescription drugs in India (18). This is more common among low socioeconomic group who cannot afford the fees of a private practitioner, and thus turn to drug retail stores. Illegal dispensing of drugs by pharmacist without prescription has been found to be high even without the knowledge about these antibiotics (19). This calls for urgent measures to tackle this menace. All these factors call for a concerted effort from the part of the public, doctors and the law makers to tackle the menace of antibiotic resistance. It is already late, unless we act fast, we could be witnessing the death knell for antibiotics in India. REFERENCES 1) J. R. PORTER (1976), Antony van Leeuwenhoek: Tercentenary of His Discovery of Bacteria,BACTERIOLOGICAL REVIEWS, June 1976, p. 260-269 2) D. L. Paterson(2000),Recommendation for treatment of severe infections caused by Enterobacteriaceae producing extendedspectrum β-lactamases (ESBLs), Clinical Microbiology and Infection, Volume 6, Issue 9, pages 460–463, September 2000 3) N. Bruinsma, J. M. Hutchinson, A. E. van den Bogaard, H. Giamarellou, J. Degener and E. E. Stobberingh. (2003),Influence of population density on antibiotic resistance

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,Journal of Antimicrobial Chemotherapy (2003) 51, 385-390 4) Gustafson RH, Bowen RE (1997),Antibiotic use in animal agriculture. ,J Appl Microbiol 1997; 83 : 531-41. 5) Willis C, Booth H, Westacott S, Hawtin P (1999), Detection of antibacterial agents in warm water prawns. ,Commun Dis Public Health 1999; 2 : 210-4. 6) Willis C.(2000),Antibiotics in the food chain : their impact on the consumer.,Rev Med Microbiol 2000; 11 : 153-60. 7) Levy SB.(2001),Antibacterial household products: cause for concern,Emerg Infect Dis 2001; 7 (Suppl 3) : 512-5. 8) Masuder Rahman, Bahanur Rahman, Tanvir Rahman, Ferdousur Rahman Khan, Mohammad Jakir Hosen, M Mukhlesur Rahman, Bytul M Rahman. (2007),Patterns of Antimicrobial Resistance and Plasmid Profiles of Escherichia coli Isolates Obtained from Calf, Cattle and Diarrheic Children in Mymensingh, Journal of American Science, 3(3), 2007 9) Lal A.(2001),Pharmaceutical drug promotion: how it is being practiced in India?,J Assoc Physicians India. 2001 Feb;49:266-73 10) Anita Kotwani, Chand Wattal, Shashi Katewa, P C Joshi and Kathleen Holloway, Antibiotic use in the community: what factors influence primary care physicians to prescribe antibiotics in Delhi, India?,Family Practice, doi:10.1093/fampra/cmq059 11) Patel V, Vaidya R, Naik D, Borker P.(2005), Irrational drug use in India: A prescription survey from Goa., J Postgrad Med 2005;51:9-12

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12 ) Pote S, Tiwari P, D’Cruz S.(2007), Medication prescribing errors in a public teaching hospital in India: A prospective study. ,Pharmacy Practice 2007;5(1): 17-20. 13) Biswas, N. R., Jindal, S., Siddiquei, M. M. and Maini, R. (2001),Patterns of prescription and drug use in ophthalmology in a tertiary hospital in Delhi. British Journal of Clinical Pharmacology, 51: 267–269. 2001 14) Salman MT, Akram MF, Rahman S, Khan FA, Haseen MA, Khan SW(2008),Drug Prescribing Pattern in Surgical Wards of a Teaching Hospital in North India,Indian Journal for the Practising Doctor, 5, (2008-05 - 200806) (2). 15) Tejitider Singh, M.V. Natu, Effecting attitudinal change towards rational drug use, http://indianpediatrics.net/jan1995/43.pdf

16) Doctor: Patient Ratio, Government of India, Ministry of Health & Family Welfare 27.04.05, Available: http://164.100.24.208/lsq14/quest.asp?qref=1 4077 17) Report: Task Force on Medical Education for the National Rural Health Mission,Chapter I: Overview of the National Health System. p. 9,Ministry of Health and Family Welfare, Government of India. 18) Rema Devi Saradamma , Nick Higginbotham and Mark Nichter (2000),Social factors influencing the acquisition of antibiotics without prescription in Kerala State, south India, Social Science & Medicine, Volume 50, Issue 6, March 2000, Pages 891-903

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19 ) Vikram Dua, Calvin M. Kunin and Laura VanArsdale White(1994),The use of antimicrobial drugs in Nagpur, India. A window on medical care in a developing country Social Science & Medicine , Volume 38, Issue 5, March 1994, Pages 717-724