Anti-microbials Flashcards
ILO 1.14a: have knowledge of the causes of infection, mechanisms and routes of spread of infection and principles of treatment
what do beta-lactams do? how do they work?
inhibit cell wall synthesis or function
- acts against the peptidoglycan layer especially on gram positive bacteria
- penecillin binding proteins (PBP) assemble the cross-linked chains of peptidoglycan
- beta-lactmas interfere with the PBPs by blocking the active site so it cannot function properly
what are different beta-lactams?
- penicillin
- cephalosporins
- carbapenems
- monobactams
what are beta-lactamases? which species produce them?
produced by gram negative bateria commonly so they can resist beta-lactam activity
* Prevotella and Fusobacterium species
what are beta-lactamase inhibitors? what is an example of this? what do bacteria do in response?
beta-lactamase inhibitors block the active site of beta-lactamases
* clavulanic acid is a beta-lactamase inhibitor which, when added to amoxixillin creates augmentin (protects the amoxacilin)
* bacteria produce more beta-lactamase to overcome the bet-lactamase inhibitors
what are carbapenems? what do bacteria do in response?
- different and newer class of beta-lactams
- prove a protective layer
- bacteria produce carbapenemase to break down carbapenems - carbapenemase producing enterobacteriales (CPEs)
describe enterobacteriaceae
- gram negative bateria
- small rods
what typical infections do carbapenemase producing enterobacteriales (CPEs) cause? why are they important to control?
- pneumonia
- UTI
- wound infections
- bacteraemia
important to control because:
* can be efficiently transmitted in healthcare facilities
* plasmids can transfer resistance to other strains and species
how can you screen for CPE? what should you do if it comes back positive?
- rectal swab - 3-4cm beyond anal sphincter
- isolate patient
- apply SICPs
what is the mechanism of action for macrolides and lincosamides? give examples of them
both target the 50S subunit of ribosomes to inhibit protein synthesis
* macrolides - erythromycin, clarithromycin
* lincosamides - clindamycin
what is the mechanism of action of tetracyclines? give an example
target the 30S subunit of ribosomes to inhibit protein synthesis
* e.g. deoxycycline
what is metronidazole effective against? how is it useful clinically? what is the mechanism of action?
- only effective against strict anaerobes and some parasites
- useful clinically to know which pathogens are strict anaerobes
- PFOR enzyme reacts with metronidazole and adds an electron which creates a reactive anion species that destroys anaerobe DNA
how does metronidazole resistance come about?
the Nim gene (nitro-inidazole-reducases gene) adds two electrons and hydrogen to metronidazole to inactivate it
when does antibiotic resistance occur?
occurs when microorganisms change in ways that render the medications used to cure infections they cause ineffective
what are the different ways that you can test antibacterial activity of antibiotics?
- E-test strip
- disc diffusion testing
- automated susceptibility testing
what is a breakpoint?
a chosen concentration of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic
* depends on type of antibiotic, dosing, dose frequency, concentration at site of infection
what is clinical resistance?
when infection is highly unlikely to respond even to maximum doses of antibiotic
what is the definition of susceptible?
when there is a high likelihood of therapeutic success using a standard dosing regimen of the agent
what is the definition of susceptible with increased exposure?
when there is a high likelihood of therapeutic success because exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection
what are the laboratory co-founding variables affecting whether bacteria will be sensitive or resistant to antibiotics?
- inoculum size
- pH
- planktonic size
- atmosphere
- biofilm
what are the clinical co-founding variables affecting whether bacteria will be sensitive or resistant to antibiotics?
- co-morbidities
- pus collections
- foreign bodies
- site of infection
- biofilm
what is the definition of pharmacokinetics? what is it affected by?
the absorption, distribution, and elimination of a drug
affected by:
* physiological factors (site of infection)
* drug factors (protein binding)
what is the definition of pharmacodynamics? what does the 1. Cmax 2. area under the curve and 3. when T>MIC show?
the relationship between concentration of drug and the microbial effect
1. larger doses less frequently inprove success
2. the effect is concentration and time dependent for success
3. increasing the dose to achieve a higher concentration does NOT increase efficacy once it is above MIC
describe the pharmacokinetics of Pen V. vs amoxyl
- both exert their killing effect dependent on the time above the MIC and is independent of concentration
- both peak serum levels 1-2 hours after administration
- Pen V approx 60% absorption following oral administration
- amoxyl approx 75% absorption following oral administration
- Pen V 500mg fasting dose = 4ug/ml
- amoxyl 500mg fasting dose = 7.5ug/ml
why is Pen V used as first line therapy over amoxicillin? what dose should be prescribed?
- key principle is to limit unintended consequences of antimicrobial use
- amoxicillin has a broader spectrum and a greater impact on selection of resistance in host micro-flora but has greater interference with the commensal flora (more harmful)
- Pen V: 500mg 6 hourly for 5 days
