Session 5 - Antibiotics Flashcards
How do antibiotics damage bacteria but not host cells?
By exploiting the differences that exist between the structure and physiology of the prokaryotic bacterial cells and the host eurkaryotic cells
What are two different overall mechanisms by which antibiotics effect bacteria
Bacteriostatic (inhibit bacterial growth)
Bacteriacidal (kill bacteria)
Give four sites on bacteria targeted by antibiotics
Peptidoglycan cell wall
Nucleic acids
Protein synthesis
Cytoplasmic membrane
Why can bacterial cell walls be targeted, and by which three main classes of AB?
Peptidoglycan cell wall only present in prokaryotic cell.
Penicillins
Cephalosporins
Glycopeptides
Why can nucleic acids be targeted, and by which three classes of AB?
Bacterial genome is a single, circular strand of DNA unenclosed by a nuclear envelope, in contrast to eukaryotic chromosomal arrangement within the nucleus Antifolates
Quinolones
Rifampicin
How can protein synthesis be targeted, and name three ABs which do thus
Bacterial ribosome (50s+30s subunits) is different to the mammalian ribosome (60s+40s subunits) Aminoglycosides Tetraclyclines Macrolides Chloramphenicol Fusidic acid
How can the cell membrane of bacteria be targeted, and give 1 AB that does thus
Bacterial plasma membrane does not contain any sterols, unlike mammalian. Polymyxins
Give four primary reasons for prophylaxis of bacterial infections
o Peri-operative (Prevention of surgical site infections) o Short term Meningitis contacts o Long term Asplenia (encapsulated bacteria) Immunodeficiency
Give two ways ABs can be used to treat significant bacterial iunfections
o Treatment of cultured, proven infection
o Empirical treatment of suspected infection
What is the ideal antibiotic? (2)
o Clean killing of infecting bacteria
Minimal impact on non-target commensal organisms
No resistance in any surviving pathogens
o No adverse effects on patient
Give 8 factors which help determine the likely infectious agent in an infection
o Anatomical Site o Duration of illness o Past medical history o Occupational history o Travel history o Time of year o Age o Personal background
Give four factors which determine which antibiotics are likely to be effective
o Community or healthcare onset? o Severity of infection o Baseline rate of resistance o Immune status of patient Immunocompromised patients will need IV Antibiotics immediately
What three factors do you need to consider when choosing best antibiotic?
o Efficacy
o Cost
o Administration Route
Give some common antibiotic adverse drug reactions
Pharmcological (toxicities, drug interactions)
Allergic reactions
Impact on normal flora (c.diff)
What is therapeutic drug monitoring?
Therapeutic drug monitoring is used to ensure and adequate, non-toxic dose.
Give two antibiotics which require therapeutic monitoring
Gentomicin
Vancomycin
What class of AB is gentomicin>
Aminoglycoside
What are the effects of gentomicin?
Dose related ototoxicity and nephrotoxicity at high plasma levels
What type of AB is vancomycin?
Glycopeptide
Give five side effects of vancomycin
Dose related ototoxicity and nephrotoxicity at high plasma levels
Fever, rashes
Local phlebitis at site of infection
Give two overarching methods via which bacteria develop AB resistance
Chromosomal gene mutation
Horizontal Gene transfer
What is chromosomal gene mutation and how does it pre-dispose to development of AB resistant pop of bacteria?
o Chromosomal gene mutates in one bacteria in a population, conferring a resistance to antibiotic
o Antibiotic kills all other bacteria, acting as a selection pressure, giving resistant bacteria an advantage
o Population of antibiotic resistant bacteria daughter cells
Give three types of horizontal gene transfer
Transformation
Transduction
Conjugation
What is transformation?
o Bacteria with antibiotic resistance gene releases DNA
o Uptake of DNA by recipient cell, conferring antibiotic resistance
What is transduction?
o Phage infected, antibiotic resistant Bacterial donor cell
o Phage passes the DNA conferring resistance to recipient cell
What is conjugation?
o Connection is made between antibiotic resistant donor cell, and recipient cell
o Plasmid containing resistance gene is replicated and passes from donor cell to recipient cell
o Plasmid may even become incorporated into recipient cell DNA
Give four methods of antibiotic resistance
- Antibiotic Inactivation
- Alteration of Drug Binding Site
- Alteration of Metabolic Pathways
- Reduced Intracellular Antibiotic Concentration
What is antibiotic inactivation?
o Production of enzyme that inactivate the drug
E.g. β-lactamase which inactivates Penicillins
What is alteration of drug binding site?
o Modified binding sites so drugs no longer have affinity for them
E.g. Bacterial ribosome alteration, meaning Aminoglycosides and Erythromycin cannot bind
What is alteration of metabolic pathways?
o Development of altered metabolic pathways
E.g. bacteria can become resistant to Trimethoprim due to acquired changes in their Dihydrofolate Redctase enzyme, which gives it very little affinity for the drug
What is reduced intracellular antibiotic concentration?
o Active Efflux Mechanisms
E.g. Active transport mechanisms used (e.g. p-glycoprotein) to pump a drug out of the bacterial cell because it accumulates to an effective level
o Decreased permeability
E.g. Some bacteria become resistant to Tetracycline because they alter their cell membrane to make it impermeable to the drug
Give three stages of the emergence of antibiotic resistnace
- Local selection (e.g. in a hospital)
- Clonal dissemination (e.g. around the country)
- Global spread
Give five main antibiotic resistant bacteria
o Methicillin Resistant Staphylococcus Aureus (MRSA)
o Glycopeptide Intermediate susceptibility Staphylococcus Aureus (GISA)
o Glycopeptide Resistant Enterococci (GRE)
o Extended Spectrum Beta Lactamase enterobacteriaceae (ESBLs)
o Extensively Drug Resistant Klebsiella Pneumoniae (XDR-KP)
- MDRTB
Give four parts of anti-microbial stewardship
o Right antibiotic
o Right time
o Right dose, frequency and duration (Pharmacokinetics – ADME)
o Right route
Give two stages of infection control
Prevent the spread of recognised resistant bacteria
Prevent bactrerial exposure to antiotics
How can we prevent the spread of recognised resistant bacteria?
Isolation or cohorting
Hand hygiene
Decolonisation of patients
How can we prevent bacterial exposure to antibiotics?
Minimise risk of infection
Monitor and control antibiotic prescribing
What are two different types of AB killing?
Time dependent killing
o Prolonged antibiotic presence at the site of infection, but not high concentration
Concentration dependent killing
o High antibiotic concentration at the site of infection, but short duration
What is MIC?
Minimum Inhibitory Concentration – MIC
The MIC is the lowest concentration of an antibiotic that will inhibit the visible growth of a microorganism after overnight incubation.
A MIC is generally regarded as the most basic laboratory measurement of the activity of a microbial agent against an organism.
