Principles of Antimicrobial therapy_Pharmacology

Principles of Antimicrobial therapy_Pharmacology

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  Principles of Antimicrobialtherapy PHRM306 PHARMACOLOGY II
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  Principles of AntimicrobialTherapy 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.
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  II. Selection ofAntimicrobial 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
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  A. Identification ofthe 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.
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  B. Empiric therapyprior to identification of the organism 1. The acutely ill patient with infections of unknown origin 2. Selection a Drug
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  C. Determination ofantimicrobial 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
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  • 2. Minimuminhibitory 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.
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  D. Effect ofthe 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:
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  1. Lipid solubledrug, 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
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  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
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  III. Route ofAdministration • 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.
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  IV. Determinants ofRational Dosing • Two important pharmacodynamic properties that have a significant influence on the frequency dosing are: 1.Concentration-depending Killing 2.Post-antibiotic effect
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  V. Agents usedbacterial infections • Penicillin • Cephalosporin's • Tetracycline's • Aminoglycosides • Macrolides • Fluoroquinolones • Others
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  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
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  VII. Combinations ofantimicrobial 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.
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  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
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  IX. Prophylactic Antibiotics X.Complications of Antibiotics Therapy 1.Hypersensitivity 2.Direct toxicity 3.Superinfections XI. Sites of Antimicrobial Actions