ANTIBIOTIC RESISTANCE IN MICROBES AND CAUSES: BRIEF HISTORY AND EXPLANATION

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Antibiotic resistant bacteria were first discovered soon after the first introduction of the first antibiotic and medicinal use of drugs particularly penicillin in clinical medicine for the treatment and management of infectious diseases. The first signs of antibiotic resistance were observed in the early 1940s, some few years before penicillin became commercially available to the general public for use in infectious disease management and control. The first observed bacterial enzyme (beta-lactamase) that destroyed penicillin antibiotic was first described during this period. Beta-lactamases are enzymes that hydrolyze and render inefficacious antibiotics that contain a 4-membered beta lactam ring such as penicillin’s and cephalosporins. These enzymes are usually secreted by microbes particularly bacteria in vivo or in vitro in response to an antimicrobial action, and as a way of surviving the onslaught of the antimicrobial agent or antibiotic targeted towards it. Today, there are plethora of beta-lactamase enzymes and even some mutated forms of these enzymes such as extended spectrum beta-lactamases (ESBLs) and metallo beta lactamases (MBLs) that confer on bacteria the ability to become multidrug resistant in nature.

The discovery of bacterial enzymes (i.e., the beta lactamase enzymes) was indeed the first observed evidence of bacterial resistance to an antibiotic action. Therefore, it would not be far-fetched from the truth that the history of antibiotic resistance coincided with the history of antibiotic discovery. The number of antibiotics belonging to various families, their varied mode of action and the number of bacteria in which antibiotic resistance has been documented suggests that, in principle, any microbe could develop resistance to any antibiotic. It is also noteworthy that most microorganisms that are antibiotic producers are resistant to their own antibiotic. This phenomenon gives impetus to the school of taught that microbial resistance is a natural process of microbial adaptation in their environment. Antibiotic resistance is one of the biggest challenges that bedevil our health sector worldwide, and this medical quagmire threatens our ability to effectively manage and treat some infectious diseases. Microbial resistance to antibiotics and/or antimicrobial agents has been documented not only against antibiotics of natural and semi-synthetic origin such as the penicillins, but also against some purely synthetic compounds (such as the fluoroquinolones) or those which do not even enter the cells (such as vancomycin). And unfortunately, the slow pace in the discovery and development of novel antibiotics have not actually kept pace with the emergence and rate at which bacteria develops and mount resistance to some available antibiotics.

Penicillin (the first commercialized antibiotic) was serendipitously discovered by Alexander Fleming in 1928.  It was not until 1945 that penicillin was distributed for use among the public. This antibiotic was widely used in World War II to treat wounded soldiers of their surgical and wound infections. Penicillin was hailed as a “miracle drug or magic bullet due to its potent action in containing the excesses of bacterial infections as at the time. This set the stage for the discovery and development of several other antibiotics and/or antimicrobial agents including but not limited to streptomycin, tetracycline and chloramphenicol capable of treating and bringing under control the excesses of some infectious diseases.  When Alexander Fleming won the Nobel Prize for his discovery of the first commercialized antibiotic, penicillin, he foresaw a future of medicine with microbial resistance and warned of bacteria becoming resistant to penicillin in his acceptance speech. It was not until long that the world discovered the actual threat of microbial resistance to antimicrobial agents and/or antibiotics. Antimicrobial agents particularly antibiotics have been critical in the fight against infectious diseases caused by pathogenic microorganisms including bacteria, fungi, viruses, and protozoa.

There usage in clinical medicine for treating infectious diseases has drastically leads to increase in the life expectancy of humans over the past six (6) decades. This is because the discovery and usage of antibiotics in infectious disease management has helped to reduce the rate of morbidity and mortality caused by infectious disease pathogens in human population. Nevertheless, some infectious diseases including but not limited to tuberculosis (TB), bacterial pneumonia, septicaemia, gonorrhea, wound infections, and otitis media are now becoming recalcitrant to treat with some available antibiotics because the causative agents of these diseases are fast becoming resistant to some available antibiotic therapy. These antibiotic resistant organisms have developed several novel ways and mechanisms that allow them to ward-off the antimicrobial onslaught of potent antimicrobial agents and/or antibiotics targeted towards them. Some available antimicrobial agents have been underused or misused in human medicine, agriculture, and veterinary practice; and this development have allowed these microbes to develop resistance to these agents through selective pressure.

Antibiotic selective pressure is simply defined as the impact of antibiotic usage on a population of microorganisms in which the microbes that are resistant to the antibiotic gain (or acquire) a survival advantage over those bacteria that are susceptible to the antimicrobial onslaught of the drug. The advantage gained by the resistant microbes is so unique because it allows them to take over the niche or habitat left by the antibiotic-susceptible bacteria (which were all killed by the antibiotic). The resistant bacteria begin to spread in that environment even as it proliferates and ensures a continued reservoir of antibiotic-resistant bacteria. This kind of development allows some chronic infections caused by drug-resistant microbes to persist and cause more harm to the individual. Microbial strains that harbour antibiotic resistance genes are usually more likely to clonally disseminate under some environmental conditions such as antibiotic selective pressure that encourages their dissemination within a given community.

Clonal dissemination of microbes refers to the spread of specific clones of an organism throughout a particular community. To prevent antibiotic selective pressure amongst bacterial populations and other microbes, it is critical to restrict and limit as much as possible antimicrobial usage especially for non-clinical purposes such as is obtainable in agricultural practices. Maintaining proper personal and environmental hygiene as well as good infection control practices in both the hospital and community settings are all important for the containment of antibiotic-resistant bacteria. Antibiotic resistance in microbial pathogens should be timely and accurately detected as they emerge to avoid there spread within a given locality. And it is vital to also take necessary concerted efforts to contain their nefarious activities both within a hospital environment and in the community. However, the prevention of the problem through the rational use of available drugs vital as to the detection of these organisms. While the development of resistant strains of microorganisms is inevitable (since the process is part of microbial adaptation in the environment), the slack ways that antibiotics are administered and used in the hospitals and outside the hospital environment (especially in veterinary practice, livestock production and poultry production) has no doubt greatly exacerbated the rate at which drug resistant microbes emerge and spread.

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.

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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