Irresponsibility with Penicillin Treatment: A Moral Responsibility

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. I hope this evil can be averted " Sir Alexander Fleming.HISTORYThe discovery of antibiotics remains to be one of the marvelous events in medical history till date. The accidental discovery of penicillin in the dawn of 1928 by Sir Alexander Fleming, changed the entire course of medical history. He was often described as a careless lab technician, and on that day he had just returned from a two week vacation, to find a mould that had developed over an accidentally contaminated staphylococcus culture plate, which on examination was found to result in the lysis of staphylococcus.

An article published by Fleming in 1929 says I certainly didn't plan to revolutionize all medicine by discovering the world's first antibiotic, or bacteria killer. But I guess that was exactly what I did. The first patient was successfully treated with penicillin in 1942 for streptococcal septicemia.

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Penicillin created a dramatic reduction in the number of infection related deaths. Since World War 2, till date, penicillin remains as the most widely used antibiotic in the world which has saved many lives from fatal conditions. It is very interesting to learn that usage of penicillin in pneumococcal pneumonia and bacterial endocarditits never underwent any randomized controlled trial, as the results were so apparent that nobody ever thought or wanted to conduct a research trial for the usage of the drug. 1The discovery of the miracle drug was soon available to the public and other population ,with the war going on, and many pharmaceutical companies had come forward to take up the manufacture and distribution of the same.

They all played a deaf ear to Sir Alexander Fleming when he tried to warn that the over usage of the drug could result in mutant bacteria. They were unaware of the fact that bacteria can transfer genes horizontally, from one to another immediately and become resistant over the drug. Humans have just overused the antibiotics for each and every disease, from sore throat to pneumonia, for a longer duration. This may be because of the human nature to have it in the complete and best way or that was the kind of awareness given to them, by pharmaceutical companies for the promotion of their drugs and for the benefit of their companies. Later on this overuse has extended to its usage in our agricultural systems, animals and animal products, food products etc. The microbes are considered to have extraordinary genetic features which has been found to be evolving with every new antibiotic introduced clinically, agriculturally, or otherwise to eliminate drug resistance. The microbes continue to do what they are good at " finding ways to survive. Bacterial resistance have always existed alongside antibiotics, but not on a large scale as in present scenario. Its high time, that we have to make desperate changes in order to prevent drug resistant cases and related deaths, in the coming decades.2FACTORS LEADING TO DRUG RESISTANCEEpidemological studies have proved direct relationship between the consumption of antibiotics and the emergence of drug resistance. In developing countries like India, strict regulations regarding drug dispatch is not formulated or imposed, leading to easy availability of prescription only drugs, over the counter without prescription leading to irrational and over usage of antimicrobial drugs. This is one of the important causes of drug resistance. Incorrect prescription of antibiotics is another important contributor to the growth of resistant bacteria. In most of the cases, the choice of drug and the duration of antibiotic therapy varies greatly from the treatment indication. The changes in gene expression increases the virulence of the bacteria which promotes its growth and spread.The environmental microbiome is affected largely by the agricultural use of antibiotics. The antibiotics given to the livestock are excreted through urine and feces which widely affects the natural micro biome. In addition, antibiotics are dispersed through fertilizer which eventually affects the ground and groundwater along with it.Newer development of antibiotics is no longer considered as an economic investment by the pharmaceutical companies as antibiotics are taken for a short duration as part of curative therapy, unlike other drugs for chronic conditions such as diabetes mellitus, hypertension where patients take life long drug therapy. The newer drugs available are usually considered as restraint ones and are used as last-line therapy in conditions irresponsive to other drugs. Thereby older agents are continued to be prescribed and used normally widely which contributes to drug resistance.Lack of strict regulatory measures from the manufacturing of the drug, through the trial, marketing and dispatch of drug has totally altered the system resulting in a dramatic rise of drug resistant cases. Strict regulatory measures to be adopted to reduce the prevalence of this global burden.3CLINICAL OUTCOMEAnti-microbial resistance affects patient outcome in a great way. The development of resistance genes alters the microbe to be weak or stronger. Most of the mutations results in weakness of the organism following which there is compensated mutation that results in regained fitness rise. The resistant strains in clinical set ups survive and effectively multiply in a antibiotic dense environment making them highly resistant and fitter than a random group of resistant strains. This can lead to a delay in the administration of appropriate antibiotic therapy which when given, will be toxic or inadequate and can result in adverse outcomes. The use of colistin in the treatment of highly resistant Pseudomonas is associated with high risk of renal dysfunction. The increase in resistance to common pathogens has resulted in the wide usage of broad spectrum agents for many common infections. These broad spectrum agents are found to be more expensive, with more toxic effects on the normal bacterial flora and considered to be more toxic than effective. The usage of these agents have exemplified the usage of narrow spectrum agents, such as penicillin, for common infections.As a final resolution for patients infected with such organisms, surgical procedure is done to remove the nidus of infection, and patients not amenable to surgical debridement, have high mortality rates. In short, with increasing resistance against anti- microbial therapy, will result in a complete failure of anti-microbial drugs or anti-microbial drugs may not work at all.The understanding and awareness regarding antibiotic resistance in society, as a whole is limited. The population demand for effective drug therapy, majority of whom believe that maximum antibiotic coverage protects them from illness. This is resulting in the exhaustion of effective drugs and a multi drug resistance society is alarmingly on the rise.4PREVENTIVE MEASURESA complete approach across various segments to be adopted for reducing the prevalence of anti-microbial resistance. The Central Pollution Control Board (CPCB), in March 2018 has prepared a set of draft demands for antibiotic discharge in pharmaceutical industry effluents which is being awaited for approval by the Environment ministry. It is important to accomplish stringent standards to eliminate environmental pollution with antibiotics.The priorities as per NAP-AMR (National Action Plan " Antimicrobial Resistance) are: 1. Adopting effective communication, education and training measures to improve understanding of AMR and to raise awareness general public and farmers 2.Appropriate education to improve knowledge of professionals 3.Strict regulations in human, animal, food and environment sectors 4. Surveillance of antimicrobial resistance. 5. Effective infection control and prevention.6.Effective healthcare to reduce spread of AMR and antimicrobials through animals and food. 7.To reduce the spread of AMR and antimicrobials in the community and environment .5RECENT ADVANCES1)Micro-organisms in recent drug discovery " There has been lot of recent research activities happening with drug discovery utilizing environmental microbes which has now become one of the leading source of drug discovery. These are the large number of microbes which were not targeted for drug discovery. With emerging technologies, novel drugs are harvested from these uncultivable microbes, which is assumed to be more promising than other group of drugs.2)Newer drug " Discovery of a newer drug Teixobactin, was announced in January this year. It is considered to be one of the most significant antibiotic discovered in the last thirty years, which is considered to combat multi drug resistant bacteria. 3)Alternative to antibiotic " The utilization of enzymes of bacteriophage is considered to be a newer alternative method to usage of antibiotics. Bacteriophages are small virus that infect the bacteria, following which they make copies of themselves, and then leave the bacteria. They release an enzyme before leaving the bacteria, which dissolves the bacterial cell membrane. It is this mechanism that is being utilized for the development of antibiotic alternative.4)Proteomics " Proteomics is one of the recent advances that has helped us to understand beyond genomics. Proteomic studies have been used for understanding mechanism of bacterial virulence and important aspects of interaction of bacteria with human cells, which has helped in newer revelations.5)Antibiotic stewardship/ policy- This refers to a set of coordinated strategies to improve the usage of anti-microbial medications by reducing adverse outcomes and drug resistance. Various online course regarding antibiotic stewardship have been launched for the easy access of medical personnel. WHO also have implemented educational course of the same for medical personnels mainly targeting medical students and physicians.6