Antibiotic development

Antibiotic development
An ideal antibiotic is one which inhibits the growth or kills all harmful bacteria within a patient’s body and at the same time sparing the normal body flora while not causing any toxicity to the host body tissues. Unfortunately, such an antibiotic does not exist but when manufacturing antibiotics such factors must be considered so that even if not perfect, a drug close to such features is made amongst other factors. Firstly, the spectrum of coverage offered is a key factor to be considered, an antibiotic covering both gram-positive and gram-negative bacteria effectively is more efficient than a drug acting on one group of bacteria as it even reduces incidences of antibiotic resistance (Palomino & Palomino 2011). For example, Cefepime, a fourth-generation is potent against gram +ve and –ve bacteria making it a preferred drug.

Secondly, having more than one target as a site of action is a key factor that I would consider. Having one site of action helps abolish resistance, for example, a drug that acts would act by inhibiting both the synthesis of the 30s and 50s subunit proteins would be more effective because its action is additive, additionally, if the bacteria resist one mode of action (MOA), then the other MOA covers up for the deficit thus avoiding drug resistance. Moreover, having the structure of the bacteria in mind is vital, determine the strengths and weaknesses of its structure then one can easily determine the target of your drug in that microorganism ( Kaye & Pogue 2015). For example, when one understands the structure of the wall of the bacteria, manufacturing an antibiotic against cell wall synthesis is easy. For example, penicillin act by inhibiting bacterial peptidoglycan synthesis have been effective against a wide spectrum of bacteria.

Additionally, the antibiotic should not over adversely affect the host, some antibiotics cause teratogenic effects when used by pregnant women (Khadka et al., 2014). The disease process is an important factor in terms of the organs affected by the bacteria with respect to the bioavailability of the drug. Some drugs bind strongly to bloodstream proteins such as globulins, and proteins thus inadequate amounts are available at sites of action. Therefore while manufacturing these drugs, bioavailability is an important factor for the drug to be effective.

Various hypotheses have been established and proved as causes of drug resistance. Some bacteria express enzymes that can resist the mechanism of action of some antibiotics. For example, beta-lactamases are some enzymes acting against beta-lactam ring containing drugs thus rendering them ineffective, such drugs affected by beta-lactamases include penicillins, cephalosporins, carbapenems etc. In such incidences, such drugs are given alongside other drugs that protect the initial drugs against beta-lactamases, for example, Amoxicillin is administered alongside clavulanic acid which offers Amoxicillin protection against beta-lactamases (Richter & Hergenrother 2019). Moreover, some bacteria encode genes that synthesize efflux pumps, they can pump out drugs thus not having growth inhibition or killing impact on the organism.

Some bacteria have porins which regulate the molecules that enter the bacteria’s internal environment. Porins have therefore blocked some antibiotics from accessing the organism’s interior environment therefore culminating in resistance against the drug. Mutations of drug targets is also a key contributor to resistance to antibiotics (D’Costa et al., 2011). For example, some quinolones act by inhibiting topoisomerase IV and DNA gyrase, mutation of genes that encode these enzymes means that the enzymes encoded will be abnormal and antibiotics may not be effective against the newly encoded enzymes thus leading to resistance against antibiotics.

References

Almeida Da Silva, P. E., & Palomino, J. C. (2011). Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. Journal of antimicrobial chemotherapy, 66(7), 1417-1430.

D’Costa, V. M., King, C. E., Kalan, L., Morar, M., Sung, W. W., Schwarz, C., … & Golding, G. B. (2011). Antibiotic resistance is ancient. Nature, 477(7365), 457-461.

Kaye, K. S., & Pogue, J. M. (2015). Infections caused by resistant gram‐negative bacteria: epidemiology and management. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 35(10), 949-962.

Khadka, P., Ro, J., Kim, H., Kim, I., Kim, J. T., Kim, H., … & Lee, J. (2014). Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability. Asian journal of pharmaceutical sciences, 9(6), 304-316.

Richter, M. F., & Hergenrother, P. J. (2019). The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics. Annals of the New York Academy of Sciences, 1435(1), 18.

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