substance! GENERAL PROPERTIES OF ANTIMICROBIAL AGENTS Selective Toxicity For internal use, an antimicrobial drug must have selective toxicitythat is, it must harm the microbes without causing significant damage to the host. toxic dosage level VS therapeutic dosage level chemotherapeutic index is defined as the maximum tolerable dose per kilogram of body weight, divided by the minimum dose per kilogram of body weight, that will cure the disease. The Spectrum of Activity The range of different microbes against which an antimicrobial agent acts is called its spectrum of activity. Broad Narrow
if the identity of the organism
is known, a narrows pectrum A broad-spectrum drug is drug should be used especially useful when a patient such a drug minimizes the is seriously ill with an infection destruction of the hosts caused by an unidentified microflora organism narrow-spectrum drugs also decreases the likelihood that organisms will develop drug resistance. Modes of Action INHIBITION OF CELL WALL SYNTHESIS Antibiotics such as penicillin and cephalosporin contain a chemical structure called a b-lactam ring, which attaches to the enzymes that cross- link peptidoglycans. By interfering with the cross- linking of tetrapeptides, these antibiotics prevent cell wall synthesis
Fungi and Archaea, whose cell walls lack
peptidoglycan, are unaffected by these antibiotics DISRUPTION OF CELL MEMBRANE FUNCTION
Certain polypeptide antibiotics, such as
polymyxins, act as detergents and distort bacterial cell membranes, probably by binding to phospholipids in the membrane
These antibiotics are especially effective
against Gramnegative bacteria, which have an outer membrane rich in phospholipids INHIBITION OF NUCLEIC ACID SYNTHESIS
Differences between the enzymes used by
bacterial and animal cells to synthesize nucleic acids provide a means for selective action of antimicrobial agents. Antibiotics of the rifamycin family bind to a bacterial RNA polymerase and inhibit RNA synthesis ACTION AS ANTIMETABOLITES
Antimetabolites are substances that affect the
utilization of metabolites and therefore prevent a cell from carrying out necessary metabolic reactions. Antimetabolites function in two ways: (1)by competitively inhibiting enzymes and (2) by being erroneously incorporated into important molecules such as nucleic acids. PENICILLIN-FAMILY ANTIBIOTICS All penicillin-family antibiotics have a beta-lactam ring. For this reason they are also called the betalactam antibiotics. Mechanism of Action To be effective the beta-lactam penicillin must: 1) Penetrate the cell layers. 2) Keep its beta-lactam ring intact. 3) Bind to the transpeptidase (penicillin-binding protein). Types of Penicillin 1) Penicillin G: This is the original penicillin discovered by Fleming,
2) Aminopenicillins: These penicillins offer better coverage of
gram-negative bacteria
3) Penicillinase-resistant penicillins: This group is useful
against beta-lactamase
4) Anti-Pseudomonal penicillins (including the
carboxypemcillins, ureidopenicillins, and monobactams): This group offers even wider coverage against gram negative bacteria
5) Cephalosporins: This is a widely used group of antibiotics
that have a beta-lactam ring, are resistant to beta-lactamase, and cover a broad spectrum of grampositive and gram-negative bacteria. The Resistance of Microorganisms The Resistance of Microorganisms 1. Alteration of Targets. 2. Alteration of Membrane Permeability. 3. Development of Enzymes. 4. Alteration of an Enzyme. 5. Alteration of a Metabolic Pathway.