Antibiotics Flashcards
5 types of historic antibiotics
Plants
Beer
Salts
- Preserve food
- Hallophiles like salt - most are sensitive to salt
Chemicals
- exclusion of certain selective targets for some MO
- Dyes can penetrate into bacteria
Moulds
- Penicillin
what is the concept of repurposing
designed for something else but use them for something completely different
describe the penicillin discovery
Antibiotics
Zone of inhibition between bacteria and plate
- Fleming had insight to write down this - pass on information to people knowledgeable enough to purify it to be used
use of antibiotics in WWII
Antibiotics crucial
Die from open wounds from battle field get into wounds
- Gangrene
2 types of microbial growth control
physical
chemical
2 types of physical microbial growth
- heat sterilisation
- radiation sterilisation
3 types of chemical microbial growth control
antiseptics (biological) and disinfectants (inanimate/surfaces)
natural antimicrobials
synthetic antimicrobials
- antivirals or antifungals
what is the ideal clinical scenario
the ideal way and our goal in patient care is the sterilisation of all contaminated equipment and surfaces
this is not practical
- as you enter – no longer sterile
- need to be cleaned and disinfected or covered with disposable barriers
PPE – protect yourself and the pt
8 examples of transmitted 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
why is there a need for high level disinfectants over lower level ones and antiseptics
Disinfectants and antiseptics may be contaminated by resistant spores, Pseudomonas aeruginosa & Serretia marcesnes and may transmit infection.
Can be used partially – need high level disinfectants or antibiotics to prevent infection
4 basic methods of infection control
Disinfection of non-sterilizable surfaces and equipment
- Cannot put into autoclave
- Clean down chairs and handpieces
- Multi surfaces (plastics, metals, polymers) only some autoclavable
- Not all - need alternative methods
Heat sterilization of all compatible equipment
Handwashing techniques + appropriate antiseptics
Combined with appropriate barrier techniques:
- Masks, gloves and eye protection (PPE)
disinfectants
are strong chemical agents that inhibit or kill microorganisms
ideally kill
antiseptics
are disinfecting agents with sufficiently low toxicity for host cells→can be used directly on skin, mucous membranes, or wounds
similar to disinfectants but weaker
- low toxicity as need to be used in human body
some are quite potent
sterilants
kill both vegetative cells and spores when applied to materials for appropriate times and temperatures
disinfectants with added value can kill of spores
where are disinfectants used
Disinfecting agents with sufficiently low toxicity for host cells
Used directly on skin, mucous membranes or wounds (open sores, oral surgery)
- Don’t want to simulatenously harm pt when kill bacteria, fungi and viruses
E.g. chloroheidine
antisepsis is
use of chemicals to destroy most pathogenic organisms on animate surfaces (pre-surgical)
what are the properties of an ideal antiseptic
ideal antiseptic has to have similar properties as an ideal disinfectant
Primary importance is selective toxicity (unlike disinfectant)
- Toxicity to microorganisms but not to human cells
- Degree of selectivity depending on contacted tissues
5 examples of antiseptic use
Treatment of skin infections
Prevention of infections in cuts and wounds
- Any trauma – deliberate or accidental
Cleaning the skin area of surgery from microorganisms – pre-surgical
Prophylaxis and treatment of infections in mucosal areas such as mouth, nose and vagina that are open to environment
As a scrub for surgeons and the medical personnel
3 classifications of antiseptics
Those that denature proteins (cidal)
- Protein matter in most living organic orgnsims
Those that cause osmotic disruption of the cell (cidal)
- Pop; Burst balloon; Cannot reinflate
Those that interfere with specific metabolic processes (growth arrest/static
- Slows them down; Static
- Organisms can come back/grow again
what is the mechanism of action for phenols, iodine, alcohols, aldehydes and metallic compounds
dentaure proteins and DNA bases
- hand wash
- destroy protein/nucleic acid therefore destroy organism
what is the mechanism of action for cationic detergents
interfere with plasma membrane’s permeability and cause leakage of enzyme, coenzyme and metabolites
- osmotic shock
- slow it down to death
e.g. chlorohexidine
what is the mechanism of action for for oxidising compounds
oxidize functional molecules in the microorganisms
- Interfere with proteins – slow down – then kill
what are iodophores
Iodine and other free halogens oxidize the –SH groups of proteins and enzymes
- produce -S-S- bonds and disrupts the structure and function of these
- iodine containing molecules bind to sulphur groups on protein (many), disrupt the protein structure
Used either as an antiseptic or disinfectant
- Low concentrations are antiseptic
- High concentrations are disinfectant
one of the best
- surgical scrubs, ICU
what can iodophores kill
vegetative bacteria, mycobacteria, fungi, lipid containing viruses (spores on prolonged use)
one of the best
- surgical scrubs, ICU
what type of alcohols are effective antiseptics and disinfectant agents
Ethyl alcohol (70% [60-90]) and isopropyl alcohol - drying out of ethyl alcohol kills bacteria – destabilises the membrane
what is the decrease caused by ethyl alcohol on the skin in bacteria
90%
- cleaning surfaces
- preventative measure
what is the mechanism of action for ethyl alcohol and what can it kill
Denature proteins and disturb the membrane permeability of bacteria
- Limited antibacterial spectrum
Rapidly kill vegetative bacteria, fungi and inactivate lipophilic viruses
what is chlorohexidine used as
Water soluble chlorhexidine digluconate is used as an antiseptic
mechanism of action for chlorohexidine
Most effective against Gram- positive cocci and less active against Gram-positive and gram-negative rods
- Spore germination is also inhibited
- broad spectrum
Strongly adsorbs to bacterial membranes and causes leakage of small molecules and precipitation of cytoplasmic proteins
- Longevity – high protein bound
Can be toxic if too much lead to anaphylaxis
- Not broken down easily
- Stains teeth
- It is resistant to inhibition by blood or organic material
name common oxidising agent
Hydrogen peroxide (H2O2) is commonest oxidizing compounds that have been used as antiseptics
uses of oxidizing agents with concentration change
Concentrations potentially useful for antisepsis are effective against vegetative bacteria, higher concentrations are sporicidal
- Useful – not 100% kill, standard skin antiseptic
- Change concentration get disinfectant and sporicidal
- 10-25%
Disinfection of respirators, acrylic resin implants, plastic eating utensils, soft contact lenses, cartons for milk or juice
health warning of antiseptic, disinfectant and sterilant users (e.g. sodium hydrochloride, chlorohexidine)
short-term and long-term toxicity
general biocidal activity
accumulate in the environment OR in the patient’s/caregiver’s body – problematic
2 examples of bacteria antibiotics used against
streptomyces
bacillus
2 examples of moulds bacteria used against
penicillium
cephalosporium
what are antibiotics
Naturally occurring antimicrobials
- An antibiotic is a chemical substance produced by one organism that is destructive to another.
Metabolic products of bacteria and fungi
Reduce competition for nutrients and space
- Maximise what nutrients are made to modify
2 possible mechanisms of action for antibiotics
bacteriostatic
bacteriocidal
4 cellular targets of antibiotics
cell wall
cell membrane
nucleic acid
protein synthesis
8 characteristics of an ideal antimicrobial agent
selective toxicity against microbial target
minimal toxicity to the host
cidal activity (kills micro-organism)
long plasma half-life
- stick around in body for longer time
good tissue distribution
- ability to penetrate all of body – not compartmentalised
low binding to plasma proteins
oral and parental preparations
- IV – need to be day patient or in hospital for time period so not ideal
No adverse interaction with other drug
Difficult to get antibiotics that fits all
4 main antimicrobial targets
Inhibition of cell wall synthesis
- Osmotically unstable
Inhibition of protein synthesis
Inhibition of nucleic acid replication and transcription
- Unwinding DNA
Injury to plasma membrane polymyxin B
Inhibition of synthesis of essential metabolites
structural feature of peptidoglycan targeted by penecillin
Cross linked
- penicillin prevents cross link become unstable
Critical in terms of where antibiotics work
- Cause cell lysis
2 types of inhibitors of cell wall synthesis
beta- lactams
glycopeptides
beta-lactam inhibition of cell wall synthesis
Bind to ‘penicillin binding proteins’
Inhibition of cross-linking of cell wall
Accumulation of precursor cell wall units
Cell lysis
glycopeptides inhibition of cell wall synthesis
Examples: vancomycin, teicoplanin
Bind to terminal D-ala-D-ala residues
Prevent incorporation of sub-unit into growing peptidoglycan
how are different penicillin structures made
Different penicillin structures, Taken basic penicillin natural building block
Chemists have made semi synthetic versions by modifying branches to make different structures
how to antibiotics cause inhibition of protein synthesis
Antibiotics work on different subunits of ribosome leads to loss of function of protein
Specific Sites of Protein Inhibition
- Penicillin inhibit cell wall
- Protein inhibitors act on ribosomes
inhibit different aspects of translation
how do antibiotics cause nucleic acid inhibition
Super coiled DNA
- DNA gyrase unwinds specific section
Ciproflaxcin - stops this
3 basic points antibiotics attack on bacteria and fungi replication
cell wall
protein
nucleic acid
what drives the increase of Antimicrobial Resistance
Over use
- Ineffective empiric therapy
- Increase morbidity leads to More antibiotics prescribed
- Increased hospitalisation so even More antibiotics
- Increase health care resource use
Limited treatment alternatives thus more antibiotics and then mortality
what creates antibiotic resistance
missuse of antibiotics selects for resistance mutants
5 examples of antibiotic missuse
Using outdated or weakened antibiotics (no longer effective)
Using antibiotics for the common cold and other inappropriate conditions (viral)
Using antibiotics in animal feed
- respond to them in human gut
Failing complete the prescribed regimen
Using someone else’s leftover prescription
4 antibiotic resistance mechanisms
Blocking entry
Inactivating enzymes
- Chomp open beta lactam ring so ineffective
Alteration of target molecules
- Ribosome subtly change
Efflux of antibiotics
- Straight in and out
chemotherapeutic drug
any chemical used in the treatment, relief or prophylaxis of a disease
antimicrobial chemotherapy
the use of chemotherapeutic drugs to control infection
prophylaxis
use of a drug to prevent imminent infection of a person at risk
antimicrobials
all inclusive term for any antimicrobial drug, regardless of its origin
antibiotics
substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other micro-organisms
semisynthetic drugs
drugs which are chemically modified in the laboratory after being isolated from natural sources
synthetic drugs
the use of chemical reactions to synthesise antimicrobial compounds in the labratory
narrow (limited) spectrum
antimicrobials effective against a limited array of microbial types - e.g. drug effective mainly on gram-positive bacteria
broad (extended) spectrum
antimicrobials effective against a wide variety of microbial types - e.g. both gram positive and negative
