Principles of Antimicrobial therapy _Pharmacology


Published on

Principles of Antimicrobial therapy

Published in: Health & Medicine, Technology

Principles of Antimicrobial therapy _Pharmacology

  1. 1. Principles of Antimicrobial therapy PHRM306 PHARMACOLOGY II
  2. 2. Principles of Antimicrobial Therapy I. Overview:  Antimicrobial therapy takes advantage of the biochemical differences that exist between microorganisms are human beings.  Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity.  That is, they have the ability to injure kill an invading microorganism without harming the cells of the host.
  3. 3. II. Selection of Antimicrobial Agents 1. The organism’s identity 2. Its susceptibility to a particular agent 3. The site of the infection 4. Patient factors 5. The safety of the agent 6. The cost of the therapy
  4. 4. A. Identification of the infecting organism • Characterization of the organism is central to selection of the proper drug. • A rapid assessment of the nature of the pathogen can sometimes be made on the basis of the Gram stain, which is particularly useful in identifying the presence and morphologic features of microorganisms in body fluids that are normally sterile.
  5. 5. B. Empiric therapy prior to identification of the organism 1. The acutely ill patient with infections of unknown origin 2. Selection a Drug
  6. 6. C. Determination of antimicrobial susceptibility of infective organisms 1. Bacteriostatic drugs: Which arrest the growth & replication of bacteria at serum levels achievable in the patient. Bactericidal agents: Which kills bacteria at serum levels achievable in patients. • Cholarmphenicol is static against gram negative rods and is cidal against other organisms such as S. pneumoniae
  7. 7. • 2. Minimum inhibitory concentration: Minimum Inhibitory Concentration (MIC) is the lowest concentration of antibiotics that inhibits bacterial growth. • To provide effective antimicrobial therapy, the clinically obtainable antibiotic concentration in body fluid should be greater then the MIC. • 3. Minimum Bactericidal concentration: the minimum bactericidal concentration (MBC) is the lowest concentration of antimicrobial agent that results in a 99.9 percent decline in colony count after overnight broth dilution incubations.
  8. 8. D. Effect of the site of injection on therapy • The blood Brain Barrier: this barrier is formed by the single layer of tail-like endothelial cells fused by tight junctions that impede entry from the blood to the brain of virtually all molecules, except those that are small and lipophilic. • The penetration and concentration of an antibacterial agent in the CSF is particularly influenced by the following:
  9. 9. 1. Lipid soluble drug, such as quinolones and metronidazole, have significant penetration into the CNS. • In contrast, β-lactum antibiotics, such as penicillin, are ionized at physiologic PH and have low solubility in lipids. • They therefore have limited penetration through the intact blood brain barrier under normal circumstances. 2. Molecular Weight of the drug 3. Protein binding of the drug
  10. 10. E. Patient factors 1. Immune System 2. Renal Dysfunction: serum creatinine levels are frequently used as an index of renal function for adjustment of drug regimens. 3. Hepatic dysfunction 4. Poor perfusion 5. Age 6. Pregnancy 7. Lactation F. Safety of the agent G. Cost of the therapy
  11. 11. III. Route of Administration • Some antibiotics, such as Vancomycin, the aminoglycosides and amphotericin are so poorly absorbed from gastrointestinal tract that adequate serum levels can not be obtained by oral administration. • Parenteral administration is used for drugs that are poorly absorbed from the gastrointestinal tract and for the treatment of the patients with serious infections.
  12. 12. IV. Determinants of Rational Dosing • Two important pharmacodynamic properties that have a significant influence on the frequency dosing are: 1.Concentration-depending Killing 2.Post-antibiotic effect
  13. 13. V. Agents used bacterial infections • Penicillin • Cephalosporin's • Tetracycline's • Aminoglycosides • Macrolides • Fluoroquinolones • Others
  14. 14. VI. Chemotherapeutic Spectra A. Narrow-Spectrum antibiotics: Isoniazid is active only against mycobacteria B. Extended-Spectrum: Ampicillin acts against gram positive and some gram negative bacteria C. Broad-Spectrum Antibiotics: Tetracycline and chloramphenicol affect a wide variety of microbial species
  15. 15. VII. Combinations of antimicrobial drugs • Treatment of tuberculosis • Advantages of drug combinations: When infection is of unknown origin. Beta lactums and aminoglycosides show synergism • Disadvatages of drug combinations: A number of antibotics act only when organisms are multiplying. Thus co administration of an agent that causes bacteriostasis plus a second agent that is bactericidal may result in the first drug interferring with the action of second.
  16. 16. VIII. Drug Resistance A. Genetic alterations leading to drug resistance 1. Spontaneous mutations of DNA: Emergence of rifampin-resistant Mycobacterial tuberculosis when rifampin is used as a single antibitotic. 2. DNA transfer of drug resistance B. Altered expression of proteins in drug-resistant organisms 1. Modification of target site 2. Decreased accumulation 3. Enzymic Inactivation
  17. 17. IX. Prophylactic Antibiotics X. Complications of Antibiotics Therapy 1.Hypersensitivity 2.Direct toxicity 3.Superinfections XI. Sites of Antimicrobial Actions