Lecture 10 Flashcards
What is Colistin?
- It is a last-resort antibiotic
- It is increasingly used as a ‘last-line’ therapy to treat infections caused by multi-drug resistant Gram-negative bacteria
Antimicrobial Chemotherapy
- Antimicrobial drugs must be administered in the proper dose and at the correct dosing intervals
- Immune system competence of host body is critical
What are potential issues with therapy?
- Drug delivery and retention
- Correct activity spectrum
- Toxic side effects
- Development of resistance
What is Antimicrobial Chemotherapy? What are the types of parasites?
Drug treatment of parasitic infections in which the parasites are destroyed or removed without injuring the host.
Parasites: bacteria, viruses, protozoa, fungi and worms
Who developed the concept of antimicrobial chemotherapy?
Paul Ehrlich in 1906
What are the important microorganisms involved in infectious diseases?
Bacteria
Viruses
Fungi
Protazoa
Helminths
(look at slide 11 for examples)
What is the proper use of antimicrobial drugs?
- Diagnosis
- Removal of barriers to cure
- Necessity of chemotherapy
- Selection of appropriate drug
- Combinations of antimicrobials
- Chemoprophylaxis and preemptive suppressive therapy
(look at slide 12)
What are the general problems with antimicrobial drugs?
- Opportunistic infection
- Allergic reactions
- Treatment failure
(look at slide 13)
The relationship between humans and microorganisms is affected by factors such as?
- Natural distribution of microorganisms
- Microbial pathogenicity
- Susceptibility to infection
(look at slide 15)
What is the classification of antimicrobial drugs?
- Mode of action in target organism
- Site of action in target organism
- Type of organism against which they are active
- Spectrum of antimicrobial activity
What is a bacteriostatic and bactericidal?
- Bacteriostatic: the arrest of bacterial growth. kills pathogens, if at all, only at much higher conc.
- Bactericidal: killing of bacteria
at high conc. some bacteriostatic drugs become bactericidal. Kills pathogens at levels 2-4 times the MIC
What are some types of antimicrobial drugs?
- Antibacterial drugs
- Antiviral drugs
- Antifungal drugs
- Antiprotozoal drugs
- Anthelminthic drugs
What are the different sites in a target organism?
- Cell wall
- Cytoplasmic membrane
- Protein synthesis
- Nucleic acid metabolism
What is the spectrum of antimicrobial drugs?
- Narrow-spectrum drugs
- Broad-spectrum durgs
What are some examples of cell wall synthesis inhibitors?
- Penicillins
- cephalosporins
- bacitracin
- vancomycin
What agents are highly suitable since human host cells lack a cell wall?
Anti-bacterial agents that inhibit cell wall synthesis are highly suitable. Cell wall synthesis inhibitors, bactericidal on growing or multiplying bacteria.
What is the Inhibition of peptidoglycan synthesis?
Penicillins
- Inhibition of transpeptidation and thus no proper cross-linking of peptidoglycan via binding and inhibition
of penicillin-binding proteins (PBP)
Cephalosporins
- Inhibition of transpeptidation and thus no proper cross-linking of peptidoglycan
Bacitracin
- Inhibition of regeneration of lipid carrier due to blocking its de-phosphorylation
Vancomycin
- Inhibition of transport and release of peptidoglycan building blocks through the plasma membrane
What are penicillins?
- They are beta-lactam antibiotics
- Their parent substance in Penicillin G (benzyl-penicillin)
- Obtained from cultures of mold fungi Penicillium notatum
- Disrupts cell wall synthesis by inhibiting transpeptidase
- Bactericidal effect: since cell wall prevents rupture of the bacterial plasma membrane from a high internal osmotic pressure, cell wall defects cause bacterial cells to swell and burst
- It requires injection
- Has potential adverse effects such as hypersensitivity, neurotoxic effects, anaphylactic shock
What are the disadvantages of Penicillin G?
- Cleavage of beta-lactam ring by gastric acid
- Cleavage of beta-lactam ring by bacterial enzymes (beta-lactamases)
- Narrow anti-bacterial spectrum (mostly against gram+ bacteria)
What are penicillin derivatives?
- Penicillin V
- Oxacillin
- Amoxicillin
- Amoxicillin plus clavulanic acid
What are the advantages of penicillin derivatives?
Penicillin V
- Acid resistance (permits oral administration)
Oxacillin
- Penicillinase resistance (suitable for therapy of penicillinase-producing staphylococci)
Amoxicillin
- Extended activity spectrum, also including many gram-negative bacteria
Amoxicillin in combination with Clavulanic Acid
- Protection against destruction by penicillinase
Estimation of antimicrobial activity levels is a crucial procedure to what?
- Determine which agents are most effective against a particular pathogen of interest
- Estimate the proper therapeutic dose
Some idea of the effectiveness of a chemotherapeutic agent against a pathogen can be obtained from determining what? need to know
- MIC - Minimal Inhibitory Conc.
- lowest conc of a drug that prevents the growth of a particular pathogen
- MLC - Minimum Letal conc.
- lowest conc of drug that kills the pathogen
What are the two established methods that are often used to determine the level of antimicrobial activity?
- Mueller-Hinton broth dilution susceptibility assay
- Kirby-Bauer disk diffusion assay
Dilution susceptibility test
look at slide 25
What is the Kirby Bauer method?
- The antibiotic-impregnated disk is placed on agar previously inoculated with a test bacterium.
- Disk picks up moisture, and the antibiotic diffuses radially outward through the agar
- Production of an antibiotic concentration gradient
(look at slide 26)
