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1

where do antibiotics come from from a historical perspective

• Plants
• Beer = Way to preserve liquids
• Salts = Can prevent micro-organisms from growing
○ Some micro-organisms like salt but most are sensitive to it
• Chemicals
• Moulds
○ Can create antimicrobials but can also become resistant to them

All, except moulds, are non selective

2

what is involved in microbial growth control

• Physical control
○ Heat sterilization
○ Radiation sterilization

• Chemical control
○ Antiseptics (biological) and disinfectants (inanimate - on surfaces)
○ Natural antimicrobials
○ Synthetic antimicrobials

3

what is the ideal scenario when dealing with microbials

The ideal way and our goal in patient care is the sterilization of all contaminated equipment and surfaces

This is not practical
Need to be cleaned and disinfected or
Covered with disposable barriers

4

what does PPE do

○ Protects yourself
○ Protects patients

5

name transmited pathogens

• Human Immunodeficiency Virus (HIV)
• Herpes simplex virus types 1 and 2
• Hepatitis B virus (HBV)
• Streptococci
• Staphylococci
• Mycobacterium tuberculosis
• Cytomegalovirus
• Some upper respiratory tract viruses

6

name resistant spores that can contaminate disinfectants and antiseptics

Pseudomonas aeruginosa and Serratia marcesnes
these may transmit infection

7

what is involved in infection control

• Disinfection of non-sterilizable surfaces and equipments
• Heat sterilization of all compatible equipment
• Handwashing techniques and appropriate antiseptics
• Combined with appropriate barrier techniques: masks, gloves and eye protection

8

define disinfectants

○ Are strong chemical agents that inhibit or kill micro-organisms
○ Ideally kill - don’t really want to just inhibit the micro-organisms as then they can return
Key word is strong

9

define antiseptics

○ Are disinfecting agents with sufficiently low toxicity for host cells
§ Can be used directly on skin, mucous membranes or wounds
○ Low toxicity as it is used on the human body
Like disinfectants but weaker

10

define sterilant

○ Kill both vegetative cells and spores when applied to materials for appropriate times and temperatures
○ Like disinfectant but has added value
§ Kills micro-organisms and spores (like c.difficile)

11

why are antiseptics low toxicity

want to kill the micro-organisms but don’t want to damage the patient

12

what is antisepsis

Use of chemicals to destroy most pathogenic organisms on animate surfaces

13

what is the most important property in an antiseptic

○ Selective toxicity
§ Toxicity to micro-organisms but not to human cells
§ Degree of selectivity depending on contacted tissues

14

what are the uses of antiseptics

• Treatment of skin infections
• Prevention of infections in cuts and wounds
○ Any trauma - antisepsis
• Cleaning the skin area of surgery from microorganisms
○ Prior to surgery
• Prophylaxis and treatment of infections in mucosal areas such as mouth, nose and vagina that are open to the environment
○ Never will completely get rid of all micro-organisms in an environment
• As a scrub for surgeons and the medical personnel

15

classify antiseptics

• Those that denature proteins (cidal)
○ Cidal is good

• Those that cause osmotic disruption of the cell (cidal)
○ Pops the cell open and they cannot re-inflate

• Those that interfere with specific metabolic processes (growth arrest / static)
○ Slows them down

[Ideally want to denature and lysis the cells
Slowing the cell down is okay but it leaves the potential for the micro-organism to return]

16

what are the mechanisms of action for antiseptics

• Phenols, iodine, alcohols, aldehydes and metallic compounds denature proteins and DNA bases

• Cationic detergents interfere with plasma membranes permeability and cause leakage of enzyme, co-enzyme and metabolites
○ Osmosis can lead to osmotic shock

• Oxidising compounds oxidize functional molecules in the micro-organism
○ Interfering with proteins
○ Slows things down, if not killing them

17

what are iodophors

One of the best
• Iodine and other free halogens oxidize the -SH groups of proteins and enzymes and produce -S-S- bonds and disrupts the structure and function of these

• Used either as an antiseptic or disinfectant
○ Difference is the concentration
§ Low concentration = not toxic
§ High concentration = toxic

• Povidone iodine - a complex of I with polyvinyl pyrrolidone-surface active agent (can be used as antiseptics or disinfectants)

• Kill vegetative bacteria, mycobacteria, fungi, lipid containing viruses (spores on prolonged use)

• Used frequently with surgical scrubs

18

how do alcohols work as antiseptics

About membrane permeability
• Ethyl alcohol (70% [60-90]) and isopropyl alcohol are effective antiseptic and disinfectant agents
• Reduce bacterial numbers 90% when applied to the skin
• Rapidly kill vegetative bacteria, fungi and inactive lipophilic viruses
• Denature proteins and disturb the membrane permeability of bacteria
• Limited antibacterial spectrum
• More preventative rather than as an absolute way to treat an infection

19

how does chlorhexidine work as an antiseptic

• Water soluble chlorhexidine digluconate is used as an antiseptic

• Most effective against gram positive cocci and less active against gram positive and gram negative rods
○ Broad spectrum of activity

• Spore germination is also inhibited

• Strongly adsorbs to bacterial membranes and causes leakage of small molecules and precipitation of cytoplasmic proteins
○ Highly protein bound
○ Sticks around - longevity

• It is resistant to inhibition by blood or organic material

• Good compound but can be toxic with too much of it

• There has been a couple of clinical cases where there are anaphylaxis reports with chlorhexidine

• Standard 0.2% solution can only be used for 2 week periods

20

how are oxidising agents used as antiseptics

• Hydrogen peroxide (H2O2) is commonest oxidising compounds that have been used as antiseptics
○ 2 oxygens
○ Binds with everything about

• Concentrations potentially useful for antisepsis are effective against vegetative bacteria, higher concentrations are sporicidal
○ Useful agent
○ Doesn’t 100% kill everything that you want it to
○ Useful as a standard skin antiseptic and used in a range of things
○ Can change concentration to go from disinfectant to an antiseptic

• Disinfection of respirators, acrylic resin implants, plastic eating utensils, soft contact lenses, cartons for milk or juice

• 10-25% concentration is sporicidal

21

what is the health warning associated with antiseptis, disinfectants and sterilant users

○ Short term and long term toxicity
○ General biocidal activity
○ Accumulate in the environment OR in the patient's / caregiver's body

22

what are antibiotics

• Naturally occurring antimicrobials
○ Metabolic products of bacteria and fungi
○ Reduce competition for nutrients and space
○ Micro-organisms don’t produce antibiotics to kill one another, more like sensing molecules to say this is my space don’t come too close

• Antibiotics can be
○ Bacteriostatic
○ Bacteriocidal

• Cellular targets - cell wall, cell membrane, nucleic acid, protein synthesis

23

what bacteria make antibiotics

Streptomyces
bacillus

24

what moulds make antibiotics

Penicillium
cephalosporium

25

define antibiotics

a chemical substance produced by one organism that is destructive to another organism

26

what is the ideal antimicrobial agent

• Selective toxicity against microbial target
• Minimal toxicity to the host
○ Don’t want it to kill human cells
• Cidal activity (kill micro-organisms)
• Long plasma half life
○ Ability to stick around in the body for a longer time
• Good tissue distribution
○ Ability to penetrate all over the body
• Low binding to plasma proteins
○ Don’t want it to be captured by other proteins
• Oral and parenteral preparations
○ Ideally taken orally
○ If it has to be taken intravenously then the patient must be in hospital for the period of time
• No adverse interactions with other drugs
○ Not always the case
• Difficult to get an antibiotic to fit all the criteria

27

what are antimicrobial targets

1. inhibition of cell wall synthesis: penicillins, cephalosporins, bacitracin, vancomycin

2. inhibition of protein synthesis: chloramphenicol, erythromycin, tetracyclines, streptomycin

3. inhibition of nucleic acid replication and transcription: quinolones, rifampin

4. injury to plasma membrane: polymyxin B

5. inhibition of synthesis of essential metabolites: sufanilamide, trimethoprim

28

where does penicillin work

on peptide cross links
without this cross link the cell is unstable

29

explain how penicillin inhibits cell wall synthesis

bind to penicillin binding proteins

inhibition of cross-linking of cell wall

accumulation of precursor cell wall units

cell lysis

30

what is the key concept of penicillin structures

there are different structures
chemists take the basic building blocks and create slight changes to the structure
helps with antibiotic resistance