Antimicrobial agents, particularly antibiotics are the most significant class of pharmaceuticals and are one of the most influential medical inventions of the twentieth century. They have undeniably been a boon to human society in the fight against bacteria, saving millions of lives. Nonetheless, the number of infections caused by multidrug-resistant (MDR) bacteria is increasing across the world, and the threat of untreatable infections has been looming since the beginning of the 21st century. This is of serious public health importance because antibiotic resistance if allowed to continue may lunch the world into a post-antibiotic era – where no antibiotics will work or be efficacious against infectious diseases or their causative agents.

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 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; and the mismanagement of some available antibiotics (especially the extended spectrum drugs) by both the health care practitioners and the general public have only help 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 amongst others. They use these mechanisms to remain active even in the face of antimicrobial onslaught; and 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 (Figure 1; Table 1). 

Figure 1. Schematic illustration of mechanisms of resistance in pathogenic bacteria.

Table 1. Modes of action and resistance mechanisms of commonly used antibiotics

Antibiotic classExample(s)TargetMode(s) of resistance
β-LactamsPenicillins (ampicillin), cephalosporins (cephamycin), penems (meropenem), monobactams (aztreonam)Peptidoglycan biosynthesisHydrolysis, efflux, altered target
AminoglycosidesGentamicin, streptomycin, spectinomycinTranslationPhosphorylation, acetylation, nucleotidylation, efflux, altered target
GlycopeptidesVancomycin, teicoplaninPeptidoglycan biosynthesisReprogramming peptidoglycan biosynthesis
TetracyclinesMinocycline, tigecyclineTranslationMonooxygenation, efflux, altered target
MacrolidesErythromycin, azithromicinTranslationHydrolysis, glycosylation, phosphorylation, efflux, altered target
LincosamidesClindamycinTranslationNucleotidylation, efflux, altered target
StreptograminsSynercidTranslationC-O lyase (type B streptogramins), acetylation (type A streptogramins), efflux, altered target
OxazolidinonesLinezolidTranslationEfflux, altered target
PhenicolsChloramphenicolTranslationAcetylation, efflux, altered target
QuinolonesCiprofloxacinDNA replicationAcetylation, efflux, altered target
PyrimidinesTrimethoprimC1 metabolismEfflux, altered target
SulfonamidesSulfamethoxazoleC1 metabolismEfflux, altered target
RifamycinsRifampinTranscriptionADP-ribosylation, efflux, altered target
LipopeptidesDaptomycinCell membraneAltered target
Cationic peptidesColistinCell membraneAltered target, efflux


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