Controlling the growth of the microorganism is critical for the treatment and prevention of infectious disease caused by bacteria. One of the important agents that are used to control microbial growth is antibiotics. The term antibiotic is derived from two Greek words, anti meaning against and bios meaning life. Antibiotics are the by-products that are synthesised within the microorganisms and are used to inhibit bacterial growth (bacterio-static) or to kill the micro-organisms (bactericidal) (Owen, Punt and Stranford 2013). The first ever antibiotic is Penicillin, from Penicillium notatum, discovered by Sir Alexander Fleming, a Scottish scientist in the year 1928. Fleming though contributed towards a path breaking discovery, but also stated an alarming prediction and that too, 80 years ahead of his time. After he was credited with a Nobel prize for his novel discovery in the year 1945, Fleming said that“The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism” (Calderone, 2015).
Figure 1: Properties of Antimicrobial Drugs
(Source: Owen, Punt and Stranford 2013)
Figure 2: Microbial Source of Antibiotics
(Source: Owen, Punt and Stranford 2013)
Threat Arising from Antimicrobial Resistance and over use of Antibiotics
Antimicrobial resistance is one of the greatest threats worldwide that is affecting human health. Methicillin-resistant Staphylococcus aureus (MRSA) has more annual mortality rate than HIV/AIDS, Parkinson’s disease and other homicidal activities. It is estimated that 20% of the previously treated cases of tuberculosis strain are now resistant to rifamcipin and isoniazid (Llor and Bjerrum 2014). For the last 10 years, the anti-tuberculosis agents are effective against tuberculosis but at present, that effect is insufficient. Today, more than half of the multi-drug resistant (MDR) tuberculosis is effectively treated along the application of other existing drugs (World Health Organization 2014). Extensively MDR tuberculosis strains have been detected in 84 different countries (World Health Organization 2013). Apart from tuberculosis, extended-spectrum beta-lactam producing Enteroacteriaceae and Carbapenem-resistant Enterobacteriaceae has been recently isolated (Society of Healthcare Epidemiology of America 2012). There is a huge dearth of development of new chemotherapeutic agents against the existing MDR bacteria with a special mention to those producing carbapenemases (Boucher et al. 2013). Moreover, none of the antibiotics, which are currently available, are effective against treating the disease. Antibiotic resistance is also a predominant problem under the clinical settings of the hospitals. According of the National collaborating Centre for Infectious Diseases (2010), MDR bacteria is also detected among the patients of the primary care. As per the report of the WHO, this scenario is not common in the poor or the third world countries; the situation is equally relevant throughout the world. However, the rate of antibiotic resistance among the bacteria varies between the countries. For example the of resistant Escherichia coli varies at a rate of 18% between Greece (18.2%) and Swede (1.0%) and for Klebsiella pneumoniae, the rate of variance is 0.7% in Sweden and 64.1% in Greece (European Centre for Disease Prevention and Control 2011). Asia accounts for the highest rate of antibiotic resistance with the Klebsiella pneumoniae showing resistance against the third generation cephalosporins, aminoglycosides and fluroquinolones. Most of these antibiotics are considered critical by WHO for the treatment of the bacterial infection.
The problem of antibiotic resistance not only hampers the community, but also affects at individual level. According to the recent reports patients who are treated with antibiotics for respiratory tract infection or urinary tract infection, reported the persistence of the individual resistance for up to 12 months after the treatment and thus generating need for the second-line of antibiotic treatment. Countries which have higher rate of antibiotic consumption have higher rate of antibiotic resistance. Infection caused by the antibiotic resistant bacteria generates severe illness along with increased risks of medical complications, increase rate of hospitalization and mortality rates (Livermore 2012). Antibiotic resistance leads to increase health-care costs, amounting to about €9 billion annually in Europe (Oxford and Kozlov 2013).
Figure 3: Risks associated with the overuse of antibiotics
(Source: Llor and Bjerrum 2014)
Apart from spreading disease resistance, the over-use of antibiotics is also associated with several complications as enlisted in figure 3. In United States, consumption of antibiotics causes drug-related emergency. Over-use of antibiotics also causes neurologic, gastrointestinal and psychiatric complications (Lode 2010). Although the majority of the adverse effects arising out of the AMR are mild but certain side-effects are fatal. Hepatotoxicity arising out of clavulanate and amoxicillin may generate sever life-threatening complications. Over-prescribe of antibiotics increase re-attendance of patient because it medicalizes the conditions that are self-limiting. While more attendance in hospitals signifies more administration of antibiotics.
Implications for health Professionals
At present, the human race is living in the dawn of the postantibiotic era. All the disease-causing bacteria have become resistant to antibiotics, which are commonly used to treat them. Without antibiotics, conducting minor injury to major transplants can become almost impossible and the cost burden of health-care is likely to spiral with longer hospital admission. Moreover, the mortality rates related to infection can excess to that of early 20th century.
Antibiotics are used across the world. It is mixed in animal feed and used as a non-prescription mode and at times, the sales of the antibiotics are incentivised, with half of revenues in some hospitals coming from antibiotic sales. Now, this over reliance over the antibiotics and the emergence of the multi-drug resistance bacteria is a global problem. Lack of surveillance system and policy methods have augmented the problem of over use of the antibiotics. An urgent need for antibiotic stewardship is important at this stage (Howard et al. 2013).
According to Légaré et al. 2012, prescribing nature of the doctors is influenced by several threats like demands coming from the patients for speedy recovery, threat coming from the competition or alternative healthcare system and lucrative nature of financial incentives. So a balance needs to be maintained between the restricting the availability of antibiotics while ensuring timely diagnosis of the chronic infection. Maintaining a balance between the use of the antibiotic is difficult in countries, which have a robust health-care systems and exponentially problematic in the countries, which have limited facilities in health care (Howard et al. 2013). However, the emergence of the antibiotic resistant Enterobacteriaceae, the principal reason behind the new born sepsis in the developing countries indicated that antibiotic resistance is a serious threat in these countries (Van Duin et al. 2013). Concretion actions and that too globally are required to handle this problem while ensuring equal access of the alternative effective treatments. Microbial diagnostic tests can assist in preventing the unwanted use of the antibiotic while narrowing down the spectrum of coverage that is required to treat microbial infection. However, microbial diagnostic tests are slow and delay the overall treatment, increasing the mortality rate and thus broad spectrum antibiotic therapy is prescribed (Sibley, Peirano and Church 2012). Generation of fast diagnostic test can help prevent this delay, promoting the treatment via targeted antibiotic from the very beginning (Caliendo et al. 2013). Proper education of the prescribers, about the importance of citing this test results while administrating antibiotics would help to prevent the overuse of broad-spectrum agents. It will in-turn prevent the development of antibiotic resistant bacteria (Kotwani et al. 2012). More research is required in the field of use of antibiotics in psisculture, agriculture and veterinary sectors. Reduction in the use of antibiotic in animal husbandry must be obtained via observing proper safety in food supply or the use of antibiotics in food. Further research is also required in the domain of non-human use of antibiotics and generation of antibiotic resistance in human being. Only two new classes of antibiotics have reached the pharmaceutical market since, 1970s (Howard et al. 2013). According to Llor and Bjerrum (2014), an instant need exist for the development of new generation antibiotics. However, there are certain economic challenges around the profitability of the newly discovered antibiotics. Innovative funding are required to influence research in the field while effective removal of incentive based salary structure of pharmaceutical companies, which they use to maximise their sales turn over (Llor and Bjerrum 2014). The innovative funding structure must include new models of collaboration encompassing research funders, including academia and non-profit organisations. Moreover, funding must also be raise against the development of the antibiotic alternative like vaccines and other antivirulence agents like antibiotic adjuvant and inhibitors of quorum sensing mediated by small diffusible molecule (Allen et al. 2013).
Implications for Patients
In dodging the threat against the antibiotic resistance, the observance of the hygiene cannot be overlooked. The effect of reimplementation of effective hand hygiene protocol in health-care clinics are found in reducing the incidence of emergence of methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficle (Calfee et al. 2014). Moreover, the implementation of proper sanitization methods in the rural areas can help in reduction of the burden of infection caused but bacteria which are spread via faeces like Salmonella typhimurium (Narváez-Bravo et al. 2013). It will reduce the burden of both infection and spread of antibiotic resistance micro-organism. Proper education of the public about the increase in the incidence of the multi drug resistant bacteria (MDR) will act as a mode of awareness. In, UK, a cross-government antimicrobial strategy has been initiated. The main factors of this strategy include, overall improvement in prevention of infection, specialised control practise in animal and human health, proper standardisation of the antibiotic prescribing practise, overall improvement of professional education, effective training, public engagement and development of new age drugs or antibiotics (Kessel and Sharland 2013). The government of UK is also working in collaboration with the other governmental bodies under the banner of WHO to improve the antimicrobial stewardship globally along with proper surveillance (Ashiru-Oredope et al. 2016).
Other steps that must be undertaken include, use of less antibiotics, proper enforcement of government laws that prohibits over-the-counter sales of antibiotics for the sake of incentives, proper campaigns and audits of the antimicrobial stewardship programs, derivation of more evidence from the pragmatic studies that are being carried with the primary care patients, promotion of the use of the valid-of-care tests among the patients, promotion of delayed use of antibiotics and proper communication among the patients (Llor and Bjerrum 2014).
Figure: Communication tips with patients to reduce overuse of antibiotics
(Source: Llor and Bjerrum 2014)
The communication tips will also help in the generation of awareness among the patients. Majority of the patients who are residing in the third world countries treat antibiotics like any other drugs. They start consuming it after been asked to do so by the doctors but as soon as the disease symptoms fade, they stop the intake of the medicine altogether, without even completing the dose. This incomplete dosage increase the emergence of the MDR bacteria which are fatal and thus promoting second time recurrent infection. But when they try of reuse the left over antibiotics for the treatment of the recurrent infection, they get no results and the outcome is increase in the mortality rates. So, effective communication regarding the use of antibiotics is a must need. Here not only the doctors, but the governmental bodies must come forward to generate the awareness via organizing campaigns. In the campaigns can be audio visual like in the form of television advertisements or audio ode, circulated in radio or live stage show. Here the patients will be made to understand that how antibiotics are different from other analgesic and how the completion of the dose is a must in order to prevent recurrent infection (Farag et al., 2014).
Thus from the above discussion it can be concluded that there lies no basis behind explaining the use of antibiotics behind treating respiratory tract infection among the primary care patient. Doctors need to serve the patient for the betterment of health while abiding by the ethical principles of justice and autonomy. However, ethical conflicts breach in under the domain of non-maleficence and justice during the overuse of the antibiotics. By reducing the use to antibiotics in treating mild infection can reduce the incidence of generation of antibiotic resistance among the bacteria. The use of the strategies as, discussed above will help the doctors to reduce the over-use of the antibiotics.
Allen, H.K., Levine, U.Y., Looft, T., Bandrick, M. and Casey, T.A., 2013. Treatment, promotion, commotion: antibiotic alternatives in food-producing animals. Trends in microbiology, 21(3), pp.114-119.
Ashiru-Oredope, D., Budd, E.L., Bhattacharya, A., Din, N., McNulty, C.A.M., Micallef, C., Ladenheim, D., Beech, E., Murdan, S., Hopkins, S. and English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR), 2016. Implementation of antimicrobial stewardship interventions recommended by national toolkits in primary and secondary healthcare sectors in England: TARGET and Start Smart Then Focus. Journal of Antimicrobial Chemotherapy, 71(5), pp.1408-1414.
Boucher, H.W., Talbot, G.H., Benjamin Jr, D.K., Bradley, J., Guidos, R.J., Jones, R.N., Murray, B.E., Bonomo, R.A., Gilbert, D. and Infectious Diseases Society of America, 2013. 10×'20 progress—development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clinical infectious diseases, 56(12), pp.1685-1694.
Calfee, D.P., Salgado, C.D., Milstone, A.M., Harris, A.D., Kuhar, D.T., Moody, J., Aureden, K., Huang, S.S., Maragakis, L.L. and Yokoe, D.S., 2014. Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute care hospitals: 2014 update. Infection Control & Hospital Epidemiology, 35(S2), pp.S108-S132.
Caliendo, A.M., Gilbert, D.N., Ginocchio, C.C., Hanson, K.E., May, L., Quinn, T.C., Tenover, F.C., Alland, D., Blaschke, A.J., Bonomo, R.A. and Carroll, K.C., 2013. Better tests, better care: improved diagnostics for infectious diseases. Clinical Infectious Diseases, 57(suppl_3), pp.S139-S170.
European Centre for Disease Prevention and Control (2011) Antimicrobial resistance surveillance in Europe. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). Available at: https://www.ecdc.europa.eu/en/ publications/Publications/antimicrobial-resistancesurveillance-europe-2011.pdf (Accessed: November 2017).
Farag, A., Garg, A.X., Li, L. and Jain, A.K., 2014. Dosing errors in prescribed antibiotics for older persons with CKD: a retrospective time series analysis. American Journal of Kidney Diseases, 63(3), pp.422-428.
Howard, S.J., Catchpole, M., Watson, J. and Davies, S.C., 2013. Antibiotic resistance: global response needed. The Lancet Infectious Diseases, 13(12), pp.1001-1003.
Kessel, A.S. and Sharland, M., 2013. The new UK antimicrobial resistance strategy and action plan. BMJ (Clinical research ed), 346, p.f1601.
Kotwani, A., Wattal, C., Joshi, P.C. and Holloway, K., 2012. Irrational use of antibiotics and role of the pharmacist: an insight from a qualitative study in New Delhi, India. Journal of clinical pharmacy and therapeutics, 37(3), pp.308-312.
Légaré, F., Labrecque, M., Cauchon, M., Castel, J., Turcotte, S. and Grimshaw, J., 2012. Training family physicians in shared decision-making to reduce the overuse of antibiotics in acute respiratory infections: a cluster randomized trial. Canadian Medical Association Journal, 184(13), pp.E726-E734.
Livermore, D.M., 2012. Current epidemiology and growing resistance of gram-negative pathogens. The Korean journal of internal medicine, 27(2), p.128.
Llor, C. and Bjerrum, L., 2014. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Therapeutic advances in drug safety, 5(6), pp.229-241.
Narváez-Bravo, C., Rodas-González, A., Fuenmayor, Y., Flores-Rondon, C., Carruyo, G., Moreno, M., Perozo-Mena, A. and Hoet, A.E., 2013. Salmonella on feces, hides and carcasses in beef slaughter facilities in Venezuela. International journal of food microbiology, 166(2), pp.226-230.
National Collaborating Centre for Infectious Diseases (2010) Proceedings of Community-Acquired Antimicrobial Resistance Consultation Notes, Winnipeg, MB, Canada, 10–11 February 2010. Available at: https:// www.nccid.ca/files/caAMR_ConsultationNotes_final.pdf (Accessed: November 2017).
Owen, J.A., Punt, J. and Stranford, S.A., 2013. Kuby immunology(pp. 427-444). New York: WH Freeman.
Oxford, J. and Kozlov, R., 2013. Antibiotic resistance–a call to arms for primary healthcare providers. International Journal of Clinical Practice, 67(s180), pp.1-3.
Sibley, C.D., Peirano, G. and Church, D.L., 2012. Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology. Infection, Genetics and Evolution, 12(3), pp.505-521.
Society for Healthcare Epidemiology of America, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society (2012) Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America, the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society. Infect Control Hosp Epidemiol 33: 322–327.
Van Duin, D., Kaye, K.S., Neuner, E.A. and Bonomo, R.A., 2013. Carbapenem-resistant Enterobacteriaceae: a review of treatment and outcomes. Diagnostic microbiology and infectious disease, 75(2), pp.115-120.
World Health Organization (2013) Antimicrobial resistance. Fact sheet n°194. Updated May 2013. Available at: https://www.who.int/mediacentre/ factsheets/fs194/en/.(Accessed: November 2017)
World Health Organization (2014) WHO’S first global report on antibiotic resistance reveals serious, worldwide threat to public health. Antimicrobial resistance – global surveillance report. Virtual Press Conference. 30 April 2014. Available at:https://www. who.int/mediacentre/multimedia/amr-transcript. pdf?ua=1 (Accessed: November 2017)