ANTIBIOTIC RESISTANCE: DEFINITION AND HISTORY

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Antibiotic resistance is a phenomenon that occurs when bacteria are not killed or inhibited by usually achievable systemic concentration of an antibiotic (drug) with normal dosage schedule. It occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs or other agents designed to cure or prevent the infection. Thus, the bacteria survive and continue to multiply causing more harm in the host taking the drug. Pathogenic bacterial strains that are resistant to some available conventional antibiotics are constantly emerging in both the community and hospital settings. And this has been greatly attributed to the misuse of these agents both for human and non-human purposes. Antibiotic resistance is a natural phenomenon and it is exacerbated following the prior administration of an antibiotic. According to the World Health Organization (WHO), the introduction of every antimicrobial agent into clinical practice has been followed by the detection in the laboratory of strains of microorganisms that are resistant, i.e. able to multiply in the presence of drug concentrations higher than the concentrations in humans receiving therapeutic doses.

Microorganisms harbour resistance genes which encode various mechanisms that allow them to resist the killing or inhibitory effects of specific antibiotics directed towards them. These mechanisms also offer resistance to other antibiotics or antimicrobial agents of the same class and sometimes to several different antimicrobial classes. Microbial infections involving resistant strains of microbes usually result in treatment failure. Antibiotic options in such scenarios of multidrug resistant infections are limited because it takes time to decipher the resistant profile of the infecting organism. Also, the organism is able to thrive even in the face of agents capable of inhibiting its growth and survival. The possibility of the resistant microbe causing infection in a susceptible human host through transmission is also feasible. The problem of antibiotic resistance is a vital topic and a global health problem that has received increasing attention over the last two decades. It is certainly not a new topic neither was it unpredictable. When antibiotic resistance occurs, it is the microbe (bacterium) that is resistant, not the antibiotic nor the patient or host taking it.

Species of bacteria that are normally resistant to penicillin for example, can develop resistance to these drugs either through mutation (vertical transmission) or through acquisition from other bacteria of resistance genes (horizontal transmission). This dual means of acquiring resistance explains why the resistance trait can spread rapidly and replace a previously drug – susceptible population of bacteria. Antibiotic resistance is on the rise threatening our ability to treat infectious diseases and even some of those infections that cause most deaths in the past (e.g. tuberculosis). Diseases such as tuberculosis, which once thought to be under control, are now becoming increasingly difficult to treat. This is because available medicines become less effective following the emergence of resistance forms of microbes that steadily depletes the arsenal of drugs available for therapy.

BRIEF HISTORY OF ANTIBIOTIC RESISTANCE

There has probably been a gene pool in nature for resistance to antibiotic as long as there has been for antibiotic production. This is because most microorganisms that are known to be antibiotic producers are resistant to even their own antibiotic. Antibiotic resistance in microorganisms is therefore a natural biological phenomenon, and it is spurred in microbes through selective pressure posed on pathogens by these agents (i.e. antimicrobials). Antibiotics no doubt have been able to stop the growth and kill many pathogenic microorganisms. But microorganisms including bacteria, fungi, protozoa, and viruses have proven to be much more ingenious and adaptive to a pool of antimicrobial agents. They have developed resistance to some available antibiotics at an ever increasing pace than was previously imagined.

Part of what have contributed to the dreaded increase in the emergence and spread of antibiotic resistant forms of microorganisms include bad practices on the part of some health practitioners when it comes to antibiotic prescription. The mismanagement of some available antibiotics (especially the extended spectrum drugs) by both the health care practitioners and the general public have only helped in exacerbating the status quo. The history of antibiotic resistance is as old as the historical discovery and development of antimicrobial agents (antibiotic in particular) – since most cases of antibiotic resistance were discovered soon after the discovery and development of these antimicrobial agents. Antibiotic resistant bacteria were first discovered soon after the medicinal use of penicillin began. The first signs of antibiotic resistance were actually observed in 1940, five years before penicillin became commercially available to the public. In that year, the first observed bacterial enzyme (beta-lactamase) that destroyed penicillin was described. This was the first observed evidence of bacterial resistance to an antibiotic action.

Therefore, the history of antibiotic resistance coincided with the history of antibiotics themselves. 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. Antibiotic resistance is one of the biggest challenges that bedevil our health sector worldwide. Resistance of microbes to antibiotics has been documented not only against antibiotics of natural and semi – synthetic origin, but also against purely synthetic compounds (such as the fluoroquinolones) or those which do not even enter the cells (such as vancomycin). And unfortunately, the discovery and development of newer antibiotics have not kept pace with the emergence and rate at which bacteria develops and mount resistance to antibiotics. Thus, the rate at which microbes are developing resistance to antibiotics is much faster than the rate at which the drugs are developed to curb the problem.

Pathogenic bacteria express a variety of mechanisms with which it evades the activity of potent antimicrobial agents including antibiotics, antifungal agents and antiviral agents. They use these mechanisms to remain active even in the face of antimicrobial onslaught. This allows pathogenic organisms to acquire resistance genes which they propagate and transfer to susceptible microbes. Efflux pump mechanism, production of beta-lactamase enzymes and other antibiotic degrading-enzymes are some of the notable means with which pathogenic microorganisms uses to ward-off the action of antimicrobial agents directed towards them. 

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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