Drugs used for treating infectious diseases are called antibiotics, anti-infectious agents, and anti-microbial or chemotherapeutic drugs. Despite the fact that all of these terms are basically interchangeable, the first three—antibiotics, anti-infectious agents, and antimicrobial drugs—are generally used to describe drugs used for treating infectious diseases, while the term chemotherapeutic drugs is more associated with drugs used for treating cancer.
Antibiotics are essentially natural compounds produced by microorganisms that are capable of inhibiting growth of pathogenic microbes, bacteria, and a few of the more simple microorganisms.
Semisynthetic antibiotics generally are products that are a partially chemically altered versions of antibiotics that are isolated from natural sources.
Thus, antibiotics are compounds produced by microorganisms and that are able to kill or inhibit growth of bacteria and other microorganisms. This definition makes a specific distinction between antimicrobial drugs produced by microorganisms and completely synthetic compounds. The difference is of a completely academic nature, and today the word antibiotic is used quite often for specifying antimicrobial drugs in general. It should be noted that there are compounds produced by microorganisms with antifungal and antitumor action, which also are classified as antibiotics.
The general concept of antimicrobial action is called selective toxicity, which entails that the growth of the infected organism is inhibited or destroyed by certain drugs without harming host cells. All of the antimicrobial drugs used in clinical practice are selectively toxic with respect to microorgansisms. High selective toxicity of antibiotics to microorganisms is explained by the unique qualities of the organization of microbial cells, which are principally different from mammalian cells. The nature and degree of this selectivity determines whether the given antimicrobial drug is generally non-toxic in its relationship with mammalian cells or if it just exhibits certain toxicity on certain mammalian tissues. Antimicrobial drugs exhibit antibacterial effect using one or all of the following mechanisms:
1. Inhibition of cell membranes synthesis in microorganisms (beta-lactam antibiotics, vancomycin, cycloserine).
2. Inhibition of protein synthesis in microorganisms (aminoglycosides, erythromycin, clindamycin, chloramphenicol, and tetracyclines).
3. Inhibition of nucleic acid synthesis or their function in microorganisms (sulfonamides, trimethoprim, metronidazole, quinolones, and rifampicin).
4. Inhibition or alteration of function of external or cytoplasmic membranes of microorganisms (polymixin).
An effective approach of antimicrobial therapy of an infection is based on the isolation and identification of the infected organism and determining its sensitivity to antimicrobial drugs. In vitro tests, such as diffusion in agar and determining the minimally inhibitory concentration in a liquid medium are the most widely used tests.
In the method of diffusion in agar, a paper disc containing a certain amount of antimicrobial drug is placed on the top of the plate covered by agar containing a standard amount of bacteria. After incubating it for a certain amount of time, the diameter of clean zones around the disc are measured, which indicates the absence of bacterial growth. The diameters are interpreted as sensitive, intermediate, and resistant to the specific drug after comparing it with the standard. A drawback of this method is that it only shows the possible qualitative inhibitory activity.
Qualitative sensitivity is also determined by a method of determining the minimal inhibitory concentration in a liquid medium. A series of two-fold dilutions of a drug in a solution containing a standardized amount of microorganisms are observed. The results are expressed by an index of minimal inhibitory concentration (MIC), which is the minimal concentration of drug that inhibits visible growth after overnight incubation. Minimal bactericidal concentration (MBC) is determined by the absence of bacterial growth on agar plates that have been reincubated for one more night. This is the lowest concentration of drug that destroys a minimum of 99.9% of the bacterial contents of the test. The MIC and MBC must be correlated with the concentration of drug attainable in the plasma and in other tissues and fluids in the body.
Antimicrobial drugs can be classified as bacteriostatic (for example, tetracyclines, sul-fonamides) and as bactericidal (for example, penicillin). Bacteriostatic drugs inhibit bacterial growth, but do not destroy these organisms in clinically attainable concentrations. It should be expected that the MBC of such drugs will be significantly higher than the MIC.
Bactericidal drugs cause death of microbial cells and their lysis at clinically attainable concentrations. For such drugs, the MBC is close or equal to the MIC. Treatment with bacteriostatics stops bacterial growth, thus allowing neutrophils and other protective powers of the body to remove the pathogen.
Resistance can be observed during the process of antibiotic use. Resistance of bacteria to antimicrobial drugs can be characterized and classified by two signs: internal resistance and acquired resistance. Internal resistance of a microorganism is the genetic ability of a microorganism that is coded in the chromosomes and spread to all lines of the given type of microorganisms. Acquired resistance means that the given line of a type of bacteria acquired the ability to oppose the given antimicrobial drug.
Acquired resistance implies a change in the DNA of the bacteria that results in the appearance of new characteristic features. Such resistance is achieved in two ways: mutation of chromosomes in bacteria or acquisition of new pieces of DNA (plasmid) that code for a function of resistance.
The biochemical mechanisms of internal and acquired resistances are identical and can be explained as the result of one of the following four reasons:
1. Inactivation or modification of drugs by bacterial enzymes.
2. Formation of a impermeable barrier, so that the drug cannot reach the desired region of action.
3. Changing the target itself so that the drug cannot bind or have an effect on it.
4. Development of altered metabolic pathways, which permits the effect of the drug to be bypassed.
If the organism undergoes simultaneous action of two antimicrobial drugs, it can result in an additive effect, synergism, or antagonism.
Drugs are considered to act additively when the activity of drugs in combination are equal to the sum of their independent activity. The overall effect of two antimicrobial drugs can be less (antagonism) or more (synergism) than the sum effect.
Synergism can occur as a result of various mechanisms of action, such as subsequent blockage of the general metabolic pathway or increasing the permeability of bacterial cells.
There are several ways to classify antibiotics and they are determined primarily by the professional interests of researchers.
In particular, antibiotics are classified according to their principal biological origin (for example, antibiotics developed by certain microorganisms), mechanism of their biological action (for example, antibiotics that inhibit synthesis of nucleic acids), their spectrum of biological use (for example, antibacterial antibiotics with a narrow spectrum of use, active mainly with respect to Gram-positive organisms, antibacterial antibiotics with a broad spectrum of use, antituberculosis antibiotics, antifungal antibiotics, antitumor antibiotics, and antiamebic antibiotics), and finally, according to their chemical structure, for example, beta-lactam antibiotics, tetracyclines, aminoglycosides, macrolids, and so on.
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