Basic Principles of Antimicrobials PDF

Basic Principles of Antimicrobials Dr. Zainab zaki zakaraya Al-Ahliyya Amman University Faculty of Pharmacy  Charactestics of the antimicrobials Selective Toxicity The ability of an antibiotic to kill or suppress microbial pathogens with...

Basic Principles of Antimicrobials Dr. Zainab zaki zakaraya Al-Ahliyya Amman University Faculty of Pharmacy  Charactestics of the antimicrobials Selective Toxicity The ability of an antibiotic to kill or suppress microbial pathogens without causing injury to the host. This can be done due to differences in the cellular chemistry and biochemical processes of mammals and microbes. Disruption of the bacterial cell wall: bacteria are encased in a rigid cell wall while mammalian cells have no cell wall (penicillins, cephalosporins) Inhibition of an enzyme unique to bacteria: inhibit an enzyme critical to bacterial survival but not to our survival. Sulfonamides block the conversion of para-aminobenzoic acid (PABA) to folic acid Disruption of bacterial protein synthesis: bacterial and mammalian ribosomes (synthesis of proteins) are not identical  Classification Of Antimicrobial Drugs Classification by Susceptible Organism Narrow-spectrum antibiotics, are active against only a few species of microorganisms (preferred) Broad-spectrum antibiotics are active against a wide variety of microbes. Antimicrobial drugs can be classified according to susceptible organisms into three major groups: antibacterial drugs, antifungal drugs, and antiviral drugs.  Classification by Mechanism of Action Drugs that inhibit bacterial cell wall synthesis or activate enzymes that disrupt the cell wall (penicillins, cephalosporins) Drugs that increase cell membrane permeability—Drugs in this group (e.g., amphotericin B) increase the permeability of cell membranes, causing leakage of intracellular material Drugs that cause lethal inhibition of bacterial protein synthesis—The aminoglycosides (e.g., gentamicin) Drugs that cause non-lethal inhibition of protein synthesis- these drugs (e.g., tetracyclines-30S ribosomal subunit) inhibit bacterial protein synthesis, only slow microbial growth; they do not kill bacteria  Classification by Mechanism of Action Drugs that inhibit bacterial synthesis of DNA and RNA or disrupt DNA function. Rifampin, metronidazole, and the fluoroquinolones (Ciprofloxacin) Antimetabolites—These drugs disrupt specific biochemical reactions. The result is either a decrease in the synthesis of essential cell constituents or synthesis of nonfunctional analogs of normal metabolites. Trimethoprim and the sulfonamides. Classification by Mechanism of Action  Classification by Mechanism of Action Bactericidal drugs are directly lethal to bacteria at clinically achievable concentrations. Bacteriostatic drugs can slow bacterial growth but do not cause cell death. When a bacteriostatic drug is used, elimination of bacteria must ultimately be accomplished by host defenses (The immune system and phagocytic cells)  Innate Or Acquired Resistance To Antimicrobial Drugs 1. Innate (natural, inborn) 2. Acquired over time: over time, an organism that had once been highly sensitive to an antibiotic may become less susceptible, or it may lose drug sensitivity entirely Antibiotic resistance is associated with extended hospitalization, significant morbidity, and excess mortality. Organisms for which drug resistance is now a serious problem include Methicillin Resistant staphylococcus aureus (MRSA), enterobacter species, pseudomonas aeruginosa, acinetobacter baumannii, klebsiella species, and clostridium difficile  Microbial Mechanisms of Drug Resistance 1. Stop active uptake of certain drugs—tetracyclines and gentamicin 2. Increase active export of certain drugs—tetracyclines, fluoroquinolones, and macrolides 3. Alteration of drug target molecules: resistance to streptomycin because of structural changes in bacterial ribosomes 4. Drug inactivation: by producing drug-metabolizing enzymes. Bacteria are resistant to penicillin G because of increased production of penicillinase, an enzyme that inactivates penicillin. Other antibiotics that are inactivated by enzymes include: cephalosporins, carbapenems, and fluoroquinolones  The Influence of Increased Antibiotic Use on the Emergence of Resistance The more that antibiotics are used, the faster drug-resistant organisms will emerge Promote the overgrowth of normal flora that possesses mechanisms for resistance and normal flora can transfer resistance to pathogens How to prevent resistance Avoid the use of antibiotics by individuals who don’t actually need them ( Individuals who don’t have a bacterial infection)  Superinfection A superinfection is defined as a new infection that appears during the course of treatment for a primary infection. New infections develop when antibiotics eliminate the inhibitory influence of normal flora, thereby allowing a second infectious agent to flourish. Because broad-spectrum antibiotics kill off more normal flora than do narrow-spectrum drugs, superinfections are more likely in patients receiving broad-spectrum agents. Because superinfections are caused by drug-resistant microbes, these infections are often difficult to treat. Clostridium difficile, Candida or other fungi  SELECTION OF ANTIBIOTICS When choosing an antibiotic, three principal factors must be considered: 1. The identity of the infecting organism 2. Drug sensitivity of the infecting organism 3. Host factors, such as the site of infection and the status of host defenses. For most infections, there is usually one drug that is superior to the alternatives. This drug of first choice may be preferred for several reasons, such as greater efficacy, lower toxicity, or more narrow spectrum. Conditions that might rule out a first-choice agent include 1. Allergy to the drug of choice 2. Inability of the drug of choice to penetrate to the site of infection 3. Increased susceptibility of the patient to toxicity of the first-choice drug