ANTIBIOTICS: DEFINITION, BRIEF OVERVIEW OF ANTIBIOTIC RESISTANCE AND HISTORY OF ANTIBIOTICS DISCOVERY

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DEFINITION OF AN ANTIBIOTIC

There is no consensus to the definition of antibiotics. But it is very important that we do not displace the key points (“Killing and Inhibition”) that must be contained in any definition of an antibiotic. Abinitio, an antibiotic was originally defined as a substance produced by one microorganism, which inhibits the growth of other microorganisms. But due to the development of other synthetic or chemical methods by which drugs can be produced, there has been a modification to this definition. Today, an “antibiotic” can be defined as a substance produced by a microorganism (wholly or partly by chemical synthesis), which in low concentrations kill or inhibit the growth of other microorganisms in vivo or in vitro. The discovery of antibiotics and their subsequent application to clinical medicine is one of the outstanding scientific achievements of the twentieth century. Antibiotics – (“Magic Bullets” as fondly called by many) have been used for about 6 decades now to treat and cure variable series of diseases including tuberculosis (TB), pneumonia, gonorrhea, urinary tract infections (UTI’s), respiratory infections, syphilis, and other microbial related diseases, and they have been found to be very efficacious in this aspect.

Antimicrobial agents (antibiotics) has been the most effective of all medicines and their success is reflected by their continued use in clinical medicine and the decrease in morbidity and mortality from bacterial infections over the past 50 years. Today, it is very difficult to imagine a society without antibiotic despite the emergence of antibiotic resistant strains of bacteria that is gradually eroding the efficacy of our therapeutic regimens. Antibiotics cure disease by killing or injuring bacteria. Some antibiotics are ‘Bactericidal’, meaning that they work by killing bacteria. Other antibiotics are ‘Bacteriostatic’, meaning that they work by stopping bacteria multiplication. Each different type of antibiotic affects different bacteria in many different ways, thus stopping their deleterious effect to the host. Some antibiotics can be used to treat a wide range of infections and are known as ‘broadspectrum’ antibiotics. Others are only effective against a few types of bacteria and are called ‘narrow-spectrum’ antibiotics.

A NOTE ON RESISTANCE

In recent times, antibiotic resistance of pathogens to drugs (antibiotics) directed towards the degrading properties of microbes in vivo has been on the increase both in the community and in the hospital. Antibiotics are exceptionally vital in clinical medicine for the treatment of bacterial related infections, but unfortunately bacteria are capable of developing resistance to them. Antibiotic resistance is a global health problem that has bedeviled our health sector worldwide, affecting both the developed and developing countries of the world. They make infectious diseases very difficult to treat. The emergence of antibiotic resistance is a complex problem that is driven by many interconnected factors, of which the use and misuse of antimicrobial agents (antibiotics, antiseptics, disinfectants, and preservatives) amongst other factors, is the main driving force for the development of resistance. There is therefore need to step up the process of discovering and developing novel antibiotics that will be stable to the evolving resistance nature of microbes.

Antibiotic resistance occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals or agents designed to cure or prevent the infection. Thus, the bacteria survive and continue to multiply causing harm and havoc in the patient (host) taking the drug. There has been a very great concern that the “antibiotic era” might be coming to an end – firstly, because the rate of production of new drugs has diminished greatly and, secondly, because microbes (viruses, bacteria, fungi, protozoa) are showing great inventiveness in devising mechanisms for circumventing the inhibiting and killing properties of drugs (antibiotics) directed towards them. Deaths from acute respiratory infections, diarrheal diseases, measles, AIDS, malaria and tuberculosis account for more than 85% of the mortality from infection worldwide.

Resistance of microbes to first-line drugs causing these diseases according to the WHO ranges from zero to almost 100% and in some cases, resistance to both second – and third – line drugs is seriously compromising treatment outcome. A major example is extended spectrum β – lactamase (ESBL) – producing bacteria which is resistant to virtually all beta – lactam drugs and some non – beta lactam drugs. Antibiotic resistance though a natural biological phenomenon, has in no doubt lead to the loss in the efficacy of some important drugs (especially the beta-lactams) from our therapeutic armamentarium.  Nobody is to be blamed for this plethora of menace that is gradually eroding the efficacy of our drugs, since the introduction of every antimicrobial agent into clinical practice at one time or the other has been followed by the detection in the laboratory of strains of microorganisms that are resistant to these antimicrobial agents.

However, in containing antibiotic resistance in both our community and the hospital, a good and adequate routine diagnostic antimicrobial susceptibility testing in the microbiology laboratory is paramount. Clinical microbiologists should be charged with the responsibility of detecting antibiotic resistant strains of microbes in the hospitals and in the community using internationally recognized protocol as outlined by the Clinical and Laboratory Standard Institute, CLSI (formerly, National Committee for Clinical Laboratory Standards) guideline. Data emanating from such studies should be made available and harnessed properly by all stakeholders in order to develop a road map for the proper control and eradication of antibiotic resistance from our world. Therefore, it is ripe for us to close the door on antibiotic resistant strains of bacteria before we wake up someday and find out that the only weapon (antibiotics) we have against bacterial related diseases have left us.

BRIEF HISTORY OF THE DISCOVERY AND DEVELOPMENT OF ANTIBIOTICS

Antibiotic history dates back to 1928 when Sir Alexander Fleming discovered the antibacterial effects of the yeast, Penicillium notatum, a Fungus in his laboratory. The “antibiotic era” was ushered in through the work of several pioneering scientists including Sir Alexander Fleming, Howard Florey, Ernest chain, Selman Waksman, Albert Schatz, Paul Ehrlich to mention but a few. Sir Alexander Fleming astutely recognized that a contaminated Petri dish of Staphylococcus aureus actually contained a bacterium – killing mould, which was later deciphered to be P. notatum. His work together with that of Ernest Chain and Howard Florey in 1939 lead to the isolation, purification, and commercial production of penicillin (a beta – lactam drug widely used in clinical medicine today) in 1940. Penicillin, a beta – lactam antibiotic is a cell wall inhibitor. Unlike other antibiotics, the penicillin does specifically affect the synthesis of peptidoglycan – which is very crucial in the synthesis of cell wall in bacterial cell. This jeopardizes the integrity and structure of bacterial cells, thereby exposing them to external pressure or harmful chemicals that finally destroy the bacterial cell. Just a few years later after the discovery of the antibacterial properties of the penicillins, the antibacterial properties of “Sulphonamides” were also noted by Paul Ehrlich in 1932.

Since then, a plethora of other antibiotics were also discovered and produced synthetically and semi – synthetically, thus giving hope to clinical medicine in the treatment of bacterial related infections. Antibiotics target different features of bacterial physiology, thus expanding the range of bacterial species that can be successfully treated with them. In the early 1940’s, the industrialization of penicillin production was quickly followed by the successful isolation and development of a large number of antibiotics that has led to most of the major classes of antibiotics in use even today, namely: tetracycline, chloramphenicol, glycopeptides, aminoglycosides, cephalosporins, and rifamycin. It is no doubt that the discovery and development of antibiotics and their introduction into clinical medicine, together with the introduction of such infection control measures like vaccination, use of clean water, and personal hygiene brought infectious diseases caused by bacterial species under control.

FURTHER READING

Ashutosh Kar (2008). Pharmaceutical Microbiology, 1st edition. New Age International Publishers: New Delhi, India. 

Block S.S (2001). Disinfection, sterilization and preservation. 5th edition. Lippincott Williams & Wilkins, Philadelphia and London.

Courvalin P, Leclercq R and Rice L.B (2010). Antibiogram. ESKA Publishing, ASM Press, Canada.

Denyer S.P., Hodges N.A and Gorman S.P (2004). Hugo & Russell’s Pharmaceutical Microbiology. 7th ed. Blackwell Publishing Company, USA. Pp.152-172.

Ejikeugwu Chika, Iroha Ifeanyichukwu, Adikwu Michael and Esimone Charles (2013). Susceptibility and Detection of Extended Spectrum β-Lactamase Enzymes from Otitis Media Pathogens. American Journal of Infectious Diseases. 9(1):24-29.

Finch R.G, Greenwood D, Norrby R and Whitley R (2002). Antibiotic and chemotherapy, 8th edition. Churchill Livingstone, London and Edinburg.

Russell A.D and Chopra I (1996). Understanding antibacterial action and resistance. 2nd edition. Ellis Horwood Publishers, New York, USA.

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