While attempting to stain bacteria without staining the surrounding tissue, he speculated about some “magic bullet” that would selectively find and destroy pathogens but not harm the host. This idea provided the basis for both selective toxicity and chemotherapy, a term he coined.
Antibiotic, a substance produced by microorganisms that in small amounts inhibits another microorganism.
The discovery and use of sulfa drugs made it clear that practical antimicrobials could be effective against systemic bacterial infections and resurrected interest in the earlier reports of penicillin
Most antibiotics in use today were discovered by methods that required identifying and growing colonies of antibiotic producing organisms, mostly by screening soil samples.
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These two cell types differ substantially in many ways, such as in the presence or absence of cell walls, the structure of their ribosomes, and details of their metabolism.
Some drugs have a narrow spectrum of microbial activity, or range of different microbial types they affect.
Antibiotics that affect a broad range of gram-positive or gram-negative bacteria are therefore called broad-spectrum antibiotics.
==A primary factor involved in the selective toxicity of antibacterial action lies in the lipopolysaccharide outer layer of gram-negative bacteria and the porins that form water-filled channels across this layer==
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Antimicrobial drugs are either bactericidal (they kill microbes directly) or bacteriostatic (they prevent microbes from growing)
The cell wall of a bacterium consists of a macromolecular network called peptidoglycan.
Penicillin, the first true antibiotic to be discovered and used if one does not also consider the sulfa drugs, is an example of an inhibitor of cell wall synthesis
==Ionophores are antibiotics produced by several soil bacteria and fungi.== They allow uncontrolled movement of cations across the plasma membrane.
A number of antibiotics interfere with the processes of DNA replication and transcription in microorganisms.
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The term penicillin refers to a group of over 50 chemically related antibiotics
Procaine penicillin, a combination of the drugs procaine and penicillin G, is retained at detectable concentrations for up to 24 hours; the concentration peaks at about 4 hours.
Penicillinases are enzymes produced by many bacteria, most notably Staphylococcus species, that cleave the β-lactam ring of the penicillin molecule
The carbapenems are a class of β-lactam antibiotics that substitute a carbon atom for a sulfur atom and add a double bond to the penicillin nucleus.
It’s a synthetic antibiotic that has only a single ring rather than the conventional β-lactam double ring, and it’s therefore known as a monobactam.
Isoniazid (INH) is a very effective synthetic antimicrobial drug against Mycobacterium tuberculosis. The primary effect of INH is to inhibit the synthesis of mycolic acids, which are components of cell walls only of the mycobacteria.
Chloramphenicol inhibits the formation of peptide bonds in the growing polypeptide chain by reacting with the 50S portion of the 70S prokaryotic ribosome.
The oxazolidinones are another class of antibiotics developed in response to vancomycin resistance.
==The synthesis of bacterial plasma membranes requires the synthesis of fatty acids as building blocks.==
Researchers in search of an attractive target for new antibiotics have focused their attention on this metabolic step, which is distinct from the fatty acid biosynthesis in humans.
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Several tests can be used to indicate which chemotherapeutic agent is most likely to combat a specific pathogen.
If the chemotherapeutic agent is effective, a zone of inhibition forms around the disk after a standardized incubation.
For a drug with poor solubility, however, the zone of inhibition indicating that the microbe is sensitive will be smaller than for another drug that is more soluble and has diffused more widely.
A more advanced diffusion method, the E test, enables a lab technician to estimate the minimal inhibitory concentration (MIC), the lowest antibiotic concentration that prevents visible bacterial growth.
A broth dilution test is often useful in determining the MIC and the minimal bactericidal concentration (MBC) of an antimicrobial drug.
After incubation, the turbidity may be read visually, although clinical laboratories with high workloads may read the trays with spectrophotometers that enter the data into a computer that provides a printout of the MIC
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When first exposed to a new antibiotic, the susceptibility of microbes tends to be high, and their mortality rate is also high; there may be only a handful of survivors from a population of billions.
Once acquired, however, the mutation is transmitted vertically by normal reproduction, and the progeny carry the genetic characteristics of the parent microbe.
Destruction or inactivation by enzymes mainly affects antibiotics that are natural products, such as the penicillins and cephalosporins.
Gram-negative bacteria are relatively more resistant to antibiotics because of the nature of their cell wall, which restricts absorption of many molecules to movements through openings called porins
Antibiotic resistance is costly in many ways beyond those that are apparent in higher rates of disease and mortality.
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Administering almost any drug involves assessing risks against benefits; this is called the therapeutic index.
Sometimes, the use of another drug can cause toxic effects that do not occur when the drug is taken alone.
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Other combinations of drugs can show antagonism. For example, the simultaneous use of penicillin and tetracycline is often less effective than when either drug is used alone.
The chemotherapeutic effect of two drugs given simultaneously is sometimes greater than the effect of either given alone which is called synergism.
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