The growth of pathogenic microorganisms is usually accompanied by the synthesis of new molecules including DNA, RNA and proteins. Microorganisms also acquire nutrient molecules from their surrounding environment or growth medium as their cells multiply and divide either in vivo or in vitro. Every drug has particular target site on pathogenic microorganisms when administered; and the antimicrobial agent is mainly programmed or designed to disrupt and destabilize these target sites especially those that has to do with the growth of the invading pathogen (inclusive of bacteria, viruses, fungi and protozoa). To be more effective, antimicrobial agents also target different metabolic processes in the invading organism such as the inhibition of cell wall development and the synthesis of important macromolecules such as DNA and proteins. Antimicrobial agents have different spectrum of activity or action; and this is usually taken into consideration when selecting drugs for a particular infection or disease.
The spectrum of an antimicrobial agent refers to the range of pathogenic microorganisms to which a particular drug is active against. It is a description of the general activity of an antimicrobial agent against particular micro-organisms. Antimicrobial agents are usually divided into two groups based on their spectrum of activity as narrow spectrum drugs and broad spectrum drugs.
Narrow spectrum antibiotics are antimicrobial agents that have activity against a few groups of pathogenic microorganisms. Such agents can target either Gram-positive bacteria or only Gram-negative bacteria; and narrow spectrum drugs only have antimicrobial activity against a limited number of microorganism.
Broad spectrum antibiotics are antimicrobial agents that have activity against a wide variety of pathogenic microorganisms. They are active against both Gram-positive and Gram-negative bacteria. Antimicrobial agents can also be categorized as cidal agents or static agents in terms of whether they kill or inhibit the growth of microorganisms. And the cidal- or static- nature of antimicrobial agents inclusive of antibiotics is usually summarized as the activity of the drug.
The activity of an antimicrobial agents thus describes the nature of the effect of the antimicrobial agent against particular microorganisms. For example, bactericidal agents are antibiotics that can kill bacteria while bacteriostatic agents are antibiotics that only inhibit the growth of bacteria. The term “cidal” and “static” is also applicable to antifungal agents, antiviral agents and antiprotozoal agents. To be effective for therapeutic purposes, antimicrobial agents must generally be able to reach their target site on the invading pathogen (Figure 1), and they must remain stable when administered, and resist all forms of modification by the host cells or target organisms until their antimicrobial activity must have been released.
Figure 1. Target sites of antibiotics and/or antimicrobial agents on bacteria. Photo source: medschool
They must also have little or no untoward effect (i.e., side effects) when used for therapeutic purposes. Antimicrobial agents only target pathogenic microorganisms that invaded the host cells or tissues, and it is critical that these drugs are selectively toxic in their action. All drugs used for systemic or topical usage including those that target bacteria, viruses, fungi and protozoa must be designed in such a way that they leave no adverse effect on the recipient host cells.
Selective toxicity is the ability of an antimicrobial agent to be injurious to a pathogenic microorganism (i.e. kill or inhibit the growth of the microbe) without being detrimental to the recipient host. It is generally the ability of drugs or chemotherapeutic agents to kill or inhibit the growth of pathogens when used for topical or systemic applications without leaving any serious untoward effect on the host cells. Normally, the selective toxicity of an antimicrobial agent could be determined by looking for specific targets on the pathogenic microorganism(s) which are actually lacking in the recipient host cell. For example, some drugs (e.g. penicillins) only target bacterial cell walls, and such antibiotics are selectively toxic in action because human cells (eukaryotic cells) do not have cell walls like bacteria (prokaryotic cells).
Most antimicrobial agents (particularly drugs) target specific metabolic processes of microbial cells (inclusive of fungi, bacteria, viruses and protozoa) which are not available or obtainable in the normal metabolic activities of the recipient host cells; and such phenomenon makes the agent to be selectively toxic and thus useful for clinical and other therapeutic purposes in humans and/or animals. Chemotherapeutic agents must be able to disrupt a microbial function that is lacking in the recipient host taking the drug; and this makes the agent to have a greater selective toxicity than the drug that simultaneously targets a microbial function as well as a host cell’s function.
Selective toxicity differentiates antibacterial drugs, antifungal agents, antiprotozoal and antiviral drugs from disinfectants which is also an example of antimicrobial agents because disinfectants (which are used mainly on inanimate objects to control microbial growth) are not selectively toxic in action, and may be harmful when used on the human body. An understanding of the physiological and metabolic differences between microbial cells and the cells of humans (who are the recipients of these drugs or antimicrobial agents) is critical in the development of drugs with selective toxicity. A good antimicrobial agent (inclusive of antibacterial, antifungal, antiprotozoal and antiviral agent) must have higher therapeutic index to be clinically effective for treating infectious diseases. Therapeutic index is the ratio of the toxic dosage of an antimicrobial agent compared to its therapeutic dosage. The toxic dosage of a drug is the concentration at which the agent becomes too poisonous to the recipient host, while the therapeutic dosage is the concentration of antimicrobial agent that is clinically relevant for treating a particular microbial disease.
Both the therapeutic dosage and the toxic dosage of an antimicrobial agent determine the selective toxicity of a drug; and antibiotics with better selective toxicity always have higher therapeutic dosage than toxic dosage.
All drugs are potential poisons! The use of antimicrobial agents (orally, topically or systemically) for the treatment of microbial infections should always be guided by proper medical procedures especially based on the results of prior antimicrobial susceptibility testing (AST) in the microbiology laboratory. This practice is important because it will help to contain the emergence and spread of resistance strains of microorganisms as well as preserve the efficacy of available drugs. Since all drugs are potential poisons, there clinical usage for medical treatment, prophylactic or chemoprophylactic measures should be well informed so that the best course of therapy will always be administered.
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