Antibiotics: Wonder drugs or a threat to public health?

What are antibiotics?

Antibiotics, also known as antibacterials, are category of medications which kills or slow down the bacterial growth. Penicillin was the first antibiotic, discovered by Sir Alexander Fleming in 1928, but it was not until the early 1940s that its true potential was recognized before it came into widespread use. In 1942, the term antibiotic was first used by Selman Waksman. In earlier days, antibiotics were often referred as “wonder drugs” because they cured several bacterial diseases that were once fatal. With antibiotic use, the number of deaths caused by bacterial infections like meningitis, pneumonia, tuberculosis, and scarlet fever were drastically reduced.  Discovery of antibiotics have revolutionized human development in a highly significant way. Other than vaccines, few medical discoveries had such a huge impact on healthcare delivery. Major complicated surgeries, transplants, advances in neonatal medicine, and advances in chemotherapy for cancer patients would not be possible without antibiotics.

Antibiotics classification:

Antibiotics are broadly classified based on their mechanism of action, structure, source or origin of the antibacterial agent or their biological activity. With the recent advances in medicinal chemistry, most antibiotics available nowadays are semisynthetic derivative of various natural compounds (penicillins, Cephalosporins and Ampicillin). Very few antibiotics like aminoglycosides (Streptomycin, Gentamicin, and Neomycin) are isolated from living organisms while many other antibiotics, Sulfonamides,Quinolones, Moxifloxacin and Norfloxacin are chemically synthesized. Based on the biological activity of the microorganisms, antibiotics are classified as bactericidal agents (which kill bacteria) and bacteriostatic agents (which slow down or impede bacterial growth). Microorganisms are known to develop resistance faster to the natural antimicrobials since they have been pre-exposed to these compounds in nature. Therefore semisynthetic drugs were developed for increased efficacy and less toxicity. Synthetic drugs possess an added advantage that bacteria are not exposed to these compounds until they are released systemically. They are designed to have even improved effectiveness with decreased toxicity.

Antibiotics are also classified based upon their range of effectiveness. Broad-spectrum drugs are effective against many types of microbes (gram-positive and gram-negative) and tend to have higher toxicity to the host. Narrow-spectrum drugs are effective against a limited group of microbes (either gram-positive or gram-negative) and exhibit lower toxicity to the host. Based on the chemical structure, antibiotics are classified into two categories: β-lactams and aminoglycosides. All the above mentioned classes of antibiotics are further divided according to their targets or mode of action in the bacteria. Following are the five important antibiotic targets in bacteria.

1. Inhibitors of cell wall synthesis (-cillins)

2. Inhibitors of protein synthesis (-mycins)

3. Inhibitors of membrane function (Polymyxin)

4. Anti-metabolites (Sulfa drugs)

5. Inhibitors of nucleic acid synthesis (Nalidixic acid, Rifampicin)

 The deluge of antibiotic resistance bacteria:

“The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them”, a quote by Paul L. Marino. Well, after an era of plentiful antibiotics, presently, the situation is alarming due to the ever increasing number of antibiotic resistant strains. In early years, new antibiotics were developed faster than bacteria developed resistance to them. But the bugs have caught up fast now. In the 1950s and 60s, many new classes of antibiotics were discovered. However, in 1980s and 1990s, scientists have only managed to make improvements within different classes of antibiotics.

 The emerging resistance of bacteria to antibacterial drugs is becoming a continuous threat to human health. Bacterial resistance to penicillin was observed within 2 years of its introduction in mid 1940s. Rapidly emerging resistance to ciprofloxacin and various anti-tuberculosis drugs indicates that it is microbe’s world and they are ready to adapt. Since, microbes congregate in large numbers to induce infection, generate rapidly and mutate efficiently, developing resistance is not a matter of “if” but of ‘when”. To overcome any assault, bacteria possess efficient defense system present within DNA or chromosomes or extrachromosomal elements called plasmid. The bacteria have advantage that these plasmids carrying resistance gene with them can easily shuttle between bacterial cells and humans.

Now, no longer limited to the hospitals, antibiotic resistance with Neisseria gonorrhea and Streptococcus pneumoniae is becoming a household and a community setting phenomenon. The use of surface antibacterials in common households, self-medication and unregulated sales of antibiotic in many countries are further aggravating the problem. According to a CDC report by the end of 20th century, approximately 30 % of S. pneumoniae (causative agent of meningitis, otitis media and pneumonia) were no longer found to be sensitive against penicillin. Similarly, treatment failures were observed in patients because of the resistant strains of, Shigella, Salmonella typhi, Staphylococcus, Mycobacteria tuberculosis, Klebsiella pneumoniae, Clostridium difficle and S. pneumoniae. Drug-resistant bacteria can be acquired in community settings like, daycares, schools and other crowded places. Other risk factors are antibiotic use and consumption of food products treated with antibiotics. Increased use of quinolones in poultry and farm animals has been associated with the increased prevalence of human infection with quinolone-resistant Salmonella and Campylobacter.  Besides, the established pathogens, relatively recent appearance of opportunistic organisms, intrinsically resistant to many drugs are making the matter worse. With a larger number of immunocompromised patients, these organisms have become ‘specialized’ pathogens—typically attacking only the most vulnerable patients. Examples of such opportunistic pathogens are Enterococci, the coagulase-negative Staphylococci, Pseudomonas aeruginosa and Acinetobacter baumanii. Therefore, it is the high time to think and act to reverse this trend of antibiotic resistance by medical professionals by creating awareness among communities on the proper use of antibiotics and discouraging self-medications. In the next series, I will discuss the factors responsible for antibiotic resistance and its detailed mechanism.

 


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