Diese Präsentation wurde erfolgreich gemeldet.
Wir verwenden Ihre LinkedIn Profilangaben und Informationen zu Ihren Aktivitäten, um Anzeigen zu personalisieren und Ihnen relevantere Inhalte anzuzeigen. Sie können Ihre Anzeigeneinstellungen jederzeit ändern.

Antimicrobial chemotherapy

Antimicrobial chemotherapy

  • Loggen Sie sich ein, um Kommentare anzuzeigen.

Antimicrobial chemotherapy

  1. 1. 1 Chapter N0 # 03 1 ANTIMICROBIAL CHEMOTHERAPY A. Antimicrobial Agents B. Chemotherapeutic Agents C. Antibiotics A) ANTIBIOTICS Natural substances produced by various species of microorganisms  bacteria  fungi  actinomycetes suppress growth / kill other microorganisms B) ANTIMICROBIAL AGENTS Synthetic analogues includes synthetic as well as naturally obtained drugs that attenuate microorganisms C) CHEMOTHERAPEUTIC AGENTS  Drugs in this class differ from all others in that they are  Designed to inhibit/kill the infecting organism and have no/minimal effect on the recipient.  The drugs also known as agents that are known to be used in chemotherapy for cancer (wikipedia)-most specifically any how they also includes drugs used as antibiotics. Microorganisms of medical improtance fall into four categories  Bacteria  Viruses  Fungi  Parasites Antimicrobial chemotherapy Use of drugs to combat infectious agents  Anti-bacterial  Anti-viral  Anti-fungal  Anti-parasitic agents
  2. 2. 2 Chapter N0 # 03 2 Antimicrobial Chemotherapy  Differential ( Selective) toxicity: Based on the concept that the drug is more toxic to the infecting organism than to the host.  Majority of antibiotics are based on naturally occurring compounds.  Or may be semi-synthetic or synthetic. What is the ideal antibiotic?  Have the appropriate spectrum of activity for the clinical setting.  Have no toxicity to the host, be well tolerated.  Low propensity for development of resistance.  Not induce hypersensitivities. In the host.  Have rapid and extensive tissue distribution.  Have a relatively long life.  Be free of interactions with other drugs.  Be convenient for administration.  Be relatively inexpensive. Principles / Definitions. Spectrum of Activity:  Narrow spectrum -Drug is effective against a limited number of species.  Broad Spectrum – Drug is effective against a wide variety of species.  Gram negative agent.  Gram positive agent  Anti-anaerobic activity.  Minimum in hibitory concentration ( MIC)  Minimum concentration of antibiotic required to inhibit the growth of the test organisms.  Minimum Bacterial Concentration ( MBC)  Minimum Concentration of antibiotic required to kiss the test organisms.  Bacteriostatic.  Bactericidal.  Time dependent killing.  Concentration dependent killing.  Treatment and Prophylaxis  Prophylaxis- Antimicrobial agent are administered to prevent infection.  Treatment - Antimicrobial agents are administered to cure existing or suspected infections. Combination Therapy  To prevent the emergence of resistance .  Mycobacterium tuberculosis
  3. 3. 3 Chapter N0 # 03 3  To treat polymicrobial infections.  Initial empiric therapy.  Synergy. Why not use 2 antibiotics all the time?  Antagonism.  Cost .  Increased risk of side effects.  May actually enhance development of resistance inducible resistance.  Interactions between drugs of different classes.  Often unnecessary for maximal efficacy. How do antimicrobial agents work?  Must bind or interfere with an essential target.  May inhibit or interfere with essential metabolic process.  May cause irreparable damage to cell. Target of antimicrobial agents.  Inhibit cell wall production.  Penicillin binding proteins.  Inhibit protein synthesis .  Bind 30s Or 50s ribosomal subunits.  Inhibit nucleic acid synthesis.  Binding topoisomerases / RNA polymerase.  Block biosynthetic pathways.  Interfere with folate metabolism.  Disrupt bacterial membrane.  Polymixins.
  4. 4. 4 Chapter N0 # 03 4
  5. 5. 5 Chapter N0 # 03 5 Antimicrobial Resistance  Factors which may accelerate the development of resistance.  Inadequate levels of antibiotics at the site of infections.  During of treatment too short.  Overwhelming numbers of organisms.  Overuse / misuse of antibiotics. Antimicrobial Resistance  General mechanisms of resistance.  Altered permeability .  Inactivation / destruction of antibiotic.  Altered binding site.  Novel ( new) binding site.  Efflux ( pumps) mechanisms.  Bypass of metabolic pathways. Bacterial Resistance to ANTIMICROBIAL AGENTS 3 general categories  Drug does not reach its target  Drug is not active  Target is altered Drug does not reach its target Porins  Absence/mutation  Reduce drug entry  Reduced effective drug concentration at the target site. Efflux pumps  Transport drugs out of the cell  Resistance to tetracyclines & β-lactam antib Inactivation of Drug Second general mechanism of drug resistance β-lactam antibiotics - β-lactamase Aminoglycosides - Aminoglycoside modifying enzymes
  6. 6. 6 Chapter N0 # 03 6 Variant: failure of bacterial cell to convert an inactive drug to its active metabolite. Resistance to INH (isoniazed) in mycobacterium TB. Alteration of the Target  Mutation of natural target  Target modification The new target does not bind the drug for native target Resulting in resistance to antibiotic. Components mediating resistance to β –lactam antibiotics in Psuedomonas aeruginosa  β –lactam antibiotics hydrophilic  Must cross outer membrane barrier of the cell via outer membrane protein (Omp) channel or porins  Mutation/missing/deleted
  7. 7. 7 Chapter N0 # 03 7  Drug entry slow or prevented.  β - lactamase concentrated between the inner & outer membrane in the periplasmic space  constitutes an enzymatic barrier  Drug destroyed  Effective concentration not achieved  Target: PBP penicillin binding protein  Low affinity for drug  Altered  Efflux transporter  Mex A, Mex B & Opr F  Pumps the antibiotic across the outer membrane  Reduced intracellular concentration of active drug Resistance. Mutations  May occur in  Target protein  Drug transport protein  Protein important for drug activation  Random events  Survival advantage upon re-exposure to the drug. Resistance is acquired by horizontal transfer of resistance determinants from a donor cell, often of another bacterial species by  Transduction  Transformation  Conjugation Insatiable need for new antibiotics  Emergence of antibiotic resistance in bacterial pathogens both nosocomially & in the community setting is a very serious development that threatens the end of antibiotic era.  Responsible approach to the use of antibiotics  That are now available & new agents that might be developed in future  Is essential  If the end of antibiotic era is to be averted. CROSS RESISTANCE  Acquisition of resistance to one AMA conferring resistance to another antimicrobial agent to which the organism has not been exposed,is called cross resistance  Seen b/w chemically or mechanistically related drugs.  Resistance to one sulphonamide means resistance to all others  Resistance to one tetracyclines means insenstivity to all others
  8. 8. 8 Chapter N0 # 03 8 Complete cross resistance Resistance to one aminoglycoside may not extend to others, Gentamycin resistant strains may respond to amikacin. partial cross resistance  Sometimes unrelated drugs show partial cross resistance, o e.g. Tetracyclines o & Chloramphenicol Prevention Drug Resistance  Use of AMAs should not be:  indiscriminate  inadequate  unduly prolonged  Use rapidly acting & narrow spectrum (Selective) AMA whenever possible.  Combination AMA  whenever prolonged therapy is undertaken. Tuberculosis, SABE  Infection by organism notorious for developing resistance Staph, E. Coli, M. Tuberculosis must be treated intensively. Prepared By ; Amjad Khan Afridi Date: 18March, 2017

×