Antimicrobial - Chemo Principles Flashcards
Prototype of antibiotics is from this source
Biological source
Prototype of antimicrobials is from this source
Synthetic source
5 factors that affect patient-drug-pathogen interactions
Pharmacokinetics
Pharmacodynamics (ideal is no response)
Immunity
Sepsis
Resistance
Factor that affects patient-drug-pathogen interactions:
Drug must be delivered to pathogen at clinically meaningful concentrations and durations with acceptable toxicity
Pharmacokinetics
Factor that affects patient-drug-pathogen interactions:
Ideal is no response
Selective toxicity
Toxic reactions from high doses, drug interactions, undesired effects, idiosyncratic reactions, allergic reactions
Pharmacodynamics
Ability of the antimicrobial agent to exploit some different between the bacteria and human cells to provide effective antibacterial action with minimal or tolerable toxicity
Selective toxicity
A systemic inflammatory response to microbial infection
Complex signaling leads to release of inflammatory mediators
Sepsis
Define sepsis
A systemic inflammatory response to microbial infection
3 Sepsis-associated pathologies can impact antibiotic pharmacokinetics
Hypotension
Edema endothelial injury
Organ damage
The ability of bacteria or other microbes to resist the effects of an antibiotic
Occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections
The microorganisms survive and continue to multiply causing more harm
Resistance
2 primary forms of resistance
Natural and acquired resistance
Form of resistance:
Inherent property of the microorganism to be unaffected by agent
For example, a microorganism with no cell wall would not be affected to by agent that interferes with cell wall synthesis
Natural resistance
Form of resistance:
Has 3 mechanisms: mutation, adaptation, and gene transfer
Acquired resistance
3 mechanisms of acquired resistance
Mutation
Adaptation
Gene transfer
Gene transfer (involved in acquired resistance) occurs via these extra chromosomal genetic elements
R(esistance) Plasmids
Two factors that affect resistance emergence
Evolution
Clinical/environmental practices
To acquire resistance, bacteria can develop fewer, none, or mutated _______, reducing drug entry into pathogen
Porins
5 major efflux systems
Multidrug and toxic compound extruder (MATE)
Major facilitator superfamily (MFS) transporters
Small multidrug resistance (SMR) systems
Resistance nodulation division (RND) exporters
ATP binding cassette (ABC) transporter
Refers to a subset of microbial population that is resistant when the majority is susceptible
Frequently associated with baseline chromosomal mutation rates
Essentially there is always a resistant microorganism
Hetero-resistance
Expected profile of activity against infectious organism
Imprecise reference
Spectrum of action
Spectrum of action that is therapeutically useful against one of the major groups of infectious agents easily characterized
Narrow spectrum of action
Spectrum of action that is more extensive compared to prototype of class
Extended spectrum of action
Agent that kills sensitive organisms
Cidal agents
2 typical cidal mechanisms of action
Disruption of cell wall or membrane activity
Inhibition of DNA or RNA structure or function
Agents that stop organism growth but may not kill sensitive organism
Typical action is reversible
Static agents
Disruption of cell wall or membrane activity and inhibition of DNA or RNA structure or function are examples of mechanisms of action of this type of agent
Cidal
Reversible inhibition of enzymatic processes or protein synthesis/function are examples of mechanisms of action of this type of agent
Static
2 static mechanisms of action
Inhibition of enzymatic processes
Inhibition of protein synthesis or function
Laboratory test for antimicrobial sensitivity used to identify which drugs inhibit bacterial growth and the drug concentrations required for that inhibition
Antimicrobial sensitivity test (AST)
What does MIC stand for in the context of antimicrobial sensitivity tests?
Minimal inhibitor concentration
3 reasons why earlier treatment is better
Rapidly dividing bacteria are more sensitive
Number of resistant organisms is low
Usually a single infectious agent
3 requirements for choosing a drug
Must be active against the microorganism
Must be able to reach effective levels
Must be safe
4 scenarios when to use combination therapy
Mixed bacterial infections requiring multiple drugs
Additional therapeutic benefits provided
Will result in enhanced antibacterial activity
Prevention of resistance
These two drugs are used in combination therapy because they have a synergistic effect against enterococci
Ampicillin and gentamycin
Predetermined change in empiric therapy (changing to a different drug)
Typically directed at preventing or reducing resistance
Proactive by design, reactive by need
Antimicrobial switching
A change in route of administration of the same agent
Antimicrobial switch therapy
Is short or long term fever usually viral?
Short term
Is short or long term fever usually bacterial?
Long term
Describes how during illness when host resistance is reduced, organisms of normally low virulence can become highly pathogenic
Increasingly common with some treatment regimens (cancer, inflammatory conditions, transplant rejection)
Opportunistic pathogens
During pregnancy, there is enhanced _______ and ______ clearance
Renal and hepatic clearance
Meds that have cardiac risk in geriatrics
Age must be considered when selecting a treatment
Quinolones
Quinolone, tetracycline, trimethoprim, and sulfonamides are avoided during pregnancy due to their _________ risk
Teratogenic
