Antimicrobial AgentsActivity, Action and Resistance Flashcards
Aim of Treatment
To consider not only the outcome of the immediate infection but the effect of currently administered antibiotics on ………. that could precipitate ………………. infections”
Aim of Treatment
To consider not only the outcome of the immediate infection but the effect of currently administered antibiotics on flora that could precipitate future infections”
The goal of antimicrobial therapy
Achieve maximum eradication.
- Of the causative organism.
- From the site of the infection.
The goal of antimicrobial therapy
Achieve maximum eradication.
Of the causative organism.
From the site of the infection.
Considerations - Patient
Epidemiological considerations
- Ag…., se….., occu……….
- Location of infection
- Local knowledge about dis……… prev………
History of ove………… travel
Pre-existing me………. problems or treatments
Considerations - Patient
Epidemiological considerations
- Age, sex, occupation
- Location of infection
- Local knowledge about disease prevalence
History of overseas travel
Pre-existing medical problems or treatments
Laboratory Considerations
Confirmation of diagnosis
Identification of Organism
Selection of antimicrobial chem………………
Evidence of likely clinical response
Local epidemiological knowledge of bug-drug susceptibility patterns
M…… determination
Laboratory Considerations
Confirmation of diagnosis
Identification of Organism
Selection of antimicrobial chemotherapy
Evidence of likely clinical response
Local epidemiological knowledge of bug-drug susceptibility patterns
MIC determination
Antibiotic Considerations
Mode of Administration
- O……..
- Oi……………
- Intr………………
Target Site - Inhibitors of cell ........... synthesis - Protein synthesis .................. - Metabolic anta.................... - Nu....... acid synthesis inh. ............ When to use - Abso.............. - Distri.............. -Ex............... - Concentration at site of infection
Complications with treatment
- Resistan………
- Toxici………..
Antibiotic Considerations
Mode of Administration
- Oral
- Ointment
- Intravenous
Target Site
- Inhibitors of cell wall synthesis
- Protein synthesis inhibitors
- Metabolic antagonists
- Nucleic acid synthesis inhibitors
When to use
- Absorption
- Distribution
- Excretion
- Concentration at site of infection
Complications with treatment
- Resistance
- Toxicity
Methods of determining sensitivity/resistance to antimicrobial agents
Di……… tes…….
s………… me…………
B………….. Meth……….
Methods of determining sensitivity/resistance to antimicrobial agents
Disc testing
stoke method
BSAC Method
Stokes Method
Compares test s……… with c………. strain
Measure difference between test and control
2mm less than control strain = res…………
Very sub…………….
Requires accurate measurements
Prone to e…………..
Gives 3 results:
- Int…………….
- Se………………
- Resi…………….
Stokes
Compares test strain with control strain
Measure difference between test and control
2mm less than control strain = resistant
Very subjective
Requires accurate measurements
Prone to errors
Gives 3 results:
- Intermediate
- Sensitive
- Resistant
BSAC Method
L…….. prone to er…….
Compares zo…….. si……. to a st……….. set of
measurements of known se……… strains
Allows mo………… re………….. to be monitored
Need to spe………….. bacteria
E.coli sensitivity may be different from other G…… .negative bacilli
Can relate zone size to the min……… inhibi……….. concentration
BSAC Method
Less prone to error
Compares zone size to a standard set of measurements of known sensitive strains
Allows moving resistance to be monitored
Need to speciate bacteria
E.coli sensitivity may be different from other Gram negative bacilli
Can relate zone size to the minimum inhibitory concentration
Problems With Disc Diffusion Techniques
Depth of ……………
D………… concentration
Si……….. of an………………. molecule
Pre inc………….
Poor att………….. to zone measurements
Plate stacking
Variations in m……….. content (ca………. and mag…………..)
Disc storage
Problems With Disc Diffusion Techniques
Depth of media
Disc concentration
Size of antibiotic molecule
Pre incubation
Poor attention to zone measurements
Plate stacking
Variations in media content (calcium and magnesium)
Disc storage
Minimum inhibitory concentration (MIC)
Qua………………. methodology
L………….. concentration required to i…………. visible growth in v………
Serial dil………….. of test antibiotic prepared in broth or agar
Inoculate with bacterial sus…………..
Incubate overnight
MIC is the highest dil……….. showing no visible gr……………
Important for mana………….. of difficult infe……….
End……………..
Minimum inhibitory concentration (MIC)
Quantitative methodology
Lowest concentration required to inhibit visible growth in vitro
Serial dilutions of test antibiotic prepared in broth or agar
Inoculate with bacterial suspension
Incubate overnight
MIC is the highest dilution showing no visible growth
Important for management of difficult infections
Endocarditis
Minimum bacteriocidal concentration (MBC)
Extend the MIC test to determine the MBC
………….. concentration required to …………….. the organism
Sub culture the n……………. wells from the
MIC tubes onto an……………… free media
In…………………. overnight
MBC is the highest dil……….. where there is no vis………… gr………..
Minimum bacteriocidal concentration (MBC)
Extend the MIC test to determine the MBC
Lowest concentration required to kill the organism
Sub culture the negative wells from the MIC tubes onto antibiotic free media
Incubate overnight
MBC is the highest dilution where there is no visible growth
Inhibitors of cell wall synthesis
Primary structure of cell wall is peptidoglycan
Composed of repeating sugar molecules
- N-acetyl glucos………… (…….)
- N-acetyl muramic a…….. (………)
Meshwork is held together with small pe………. chains
Linking together of NAG and NAM subunits facilitated by several en……….
- Penicillin b……….. proteins (PBPs)
Inhibitors of cell wall synthesis
Primary structure of cell wall is peptidoglycan
Composed of repeating sugar molecules
- N-acetyl glucosamine (NAG)
- N-acetyl muramic acid (NAM)
Meshwork is held together with small peptide chains
Linking together of NAG and NAM subunits facilitated by several enzymes
- Penicillin binding proteins (PBPs)
Inhibitors of cell wall synthesis
b-lactams, vancomycin, daptomycin “crossbows”
b-lactams
- Penic……….
- Cepha…………..
- Carb……………
- Mono…………………
Inhibitors of cell wall synthesis
b-lactams, vancomycin, daptomycin “crossbows”
b-lactams
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
b-lactams – how they work
Essential core = b-lactam ring
Mechanism of action is same for ALL
- Inhibitors of PBPs
- b-lactam ring resembles D-alanyl-D- alanine portion of pe………….. side chains
- PBP binds with ri………. and not s………. chain
- Disruption of peptid……….. layer
- Lys……
b-lactams – how they work
b-lactams – how they work
Essential core = b-lactam ring
Mechanism of action is same for ALL
- Inhibitors of PBPs
- b-lactam ring resembles D-alanyl-D- alanine portion of peptide side chains
- PBP binds with ring and not side chain
- Disruption of peptidoglycan layer
- Lysis
b-lactams - resistance
Intrinsic resistance
- Resistance is int………. to structure or physiology of bacterial species
Acquired resistance
- A previously sensitive ba………….. acquires a mut………. or e……….. genetic material allowing it to resist activity of the a……..
b-lactams - resistance
Intrinsic resistance
- Resistance is intrinsic to structure or physiology of bacterial species
Acquired resistance
- A previously sensitive bacterium acquires a mutation or exogenous genetic material allowing it to resist activity of the agent
