module two BIO 216

resistant mechanism

1.) drug inactivation

2.) target modification

3.) reduced permeability and efflux pumps

4.) bypassing metabolic mechanisms

drug inactivation

bacteria produces special enzymes that breakdown or change chemical structure of the antibiotic (physically destroying microbe before it does it’s job)

• aminoglycosidic-modifying; enzymes that attach chemical groups to antibiotic molecule that modify the target site preventing the drug from binding

• beta-lactamase destroys penicillin via hydrolysis

• genes can be passed from VGT or HGT

target modification

microbes alter specific cellular sites or protiens that the antibiotic is designated to attack

• typically done through genetic mutations

• target changes shape meaning drug can no longer bind or disrupt normal function

  • change in DNA, change in codon, change in amino acid, change in protein, change in function

reduced permeability and efflux pumps

bacteria limits the amount of drug that enters the body by altering or closing outer membrane channels (efflux pumps)

• efflux pumps are utilized to push antibiotics out before it can cause harm (remove the microbe)

bypassing metabolic pathway

bacteria develop alternative chemical pathway to achieve vital process

• Streptococcus stops utilizing biosynthetic pathway, instead utilize folate pathway

antimicrobial combinations

1.) synergist

2.) antagonist

3.) additive

synergist

activity of one medication enhance the activity of the other medication

trimethoprim and sulfamethozole

both inhibit different steps in bacterial folate synthesis producing a greater antibacterial effect

• example of synergist

antagonistic

medication interferes with the action of actively killing the dividing cells; one drug reduces or enhances the toxicity of the other drug

penicillin and tetracycline

penicillin works against actively growing or dividing bacteria, tetracycline reduces the effectiveness of penicillin in some aspects

additive

neither synergist or antagonistic

antimicrobial peptides

short chains of amino acids made by bacteria

• act as normal first defense against bacteria

• compromise cell membrane by leaking its insides

• can act synergistically with antibiotics to increase efficiency

selective toxicity

ability of an antimicrobial medication to effectively kill or inhibit the growth of the microorganism without causing little to no harm in the human body

• therapeutic index (the greater index the better the medication)

antimicrobial action

1.) bacteriostatic

2.) bactericidal

bacteriostatic

medication inhibits bacterial growth, must rely on the patient’s defense system to kill pathogen

• prevents growth of bacteria

• works with immune system to prevent it from growing

• action is reversible

  • examples: tetracycline, spectinomycin, sulfonamides

bactericidal

medication kills bacteria

• action is irreversible

• does NOT work with immune system

  • examples: betalactam antibiotics, cephalosporins, vanomycin

spectrum activity

1.) broad spectrum antibiotics

2.) narrow spectrum antibiotics

broad spectrum antibiotics

affects a wide range of bacteria (typically signifies one does not know the specific infection)

• disrupts microbiome

• gram-negative or gram-positive

narrow spectrum antibiotics

affects a limited range of bacteria (smaller subset, one has identified the specific infection)

• little to no disruption of microbiome

• gram-positive

drug penetration

some medication can cross from blood to cerebralspinal fluid

• blood brain barrier (meningitis)

route of admission

how it is introduced to the body

• orally, injected, topically

blood supply

antibiotics delivered through bloodstream may have difficulty reaching areas with poor circulation, damaged tissues, or abscess

local conditions

factors like pH levels, oxygen levels, presences of puss or dead tissue

• effect the effectiveness of antibiotics functions

bioavailability/tissue distribution

includes drug penetration, route of admission, blood supply, local conditions

half-life

time needed for serum concentration of that chemical to decrease by half

• depicts frequency of doses

adverse effects

patients must be closely monitored when taking medication with a low therapeutic index as it can have toxic effects on the patient

intrinsic resistance

innate resistance

• bacterial species lack a cell wall, therefore they are intrinsically resistant to penicillin and other antimicrobial that interfere with peptidoglycan synthesis

acquired resistance

development of resistance in previous sensitive organisms occurs through spontaneous mutation or horizontal gene transfer

• ongoing problem: microorganism continue to evolve and develop mechanisms to avoid drug effect

characteristics of microbial medication

1.) selective toxicity

2.) antimicrobial action

3.) spectrum activity

4.) antimicrobial combination

5.) bioavailability

6.) half-life

7.) adverse effects

8.) resistance