Theme 3: Lecture 13 - antibacterials and antifungals Flashcards
What are antibiotics?
chemical products of microbes that inhibit or kill other organisms
What is bacteriostatic/ fungistatic killing?
- inhibit growth (as oppose to killing the organism)
- mainly protein synthesis inhibitors
What is bacteriocidal/fungicidal?
- cause cell death
- mainly cell wall-active agents
What is Minimum inhibitory concentration (MIC)?
- minimum concentration of antimicrobial agent at which visible growth is inhibited
- so the lower the MIC, the more sensitive the organism is to the antimicrobial
What is synergy?
a combination is considered to be synergistic when the effect observed with a combination is greater than the sum of the effects observed with the two drugs independently
What is antagonism?
activity of two antimicrobials given together is less than the activity if given separately
Whats the difference between broad spectrum and narrow spectrum antibiotics?
broad spectrum - kills most types of bacteria/fungi encountered
narrow spectrum - kills only a narrow range of organisms
Why does the spectrum of organisms covered by an antimicrobial agent become narrower during its clinical lifespan?
resistance develops in the target microbial population
Is penicillin broad spectrum or narrow spectrum?
was once broad spectrum but now considered to be narrow spectrum
What is peptidoglycan?
- murein
- major structural component of bacterial cell wall
What are PBPs?
- penicillin binding proteins
- enzymes involved in the synthesis and maintenance of peptidoglycan
What are the 2 groups of antibiotics that are cell wall synthesis inhibitors?
- B-lactams
- glycopeptides
What was the first true antibiotic in clinical practise?
- benzylpenicillin
- a B lactam
What do all B-lactams contain and what is their mechanism of action?
- all contain B-lactam ring
- mechanism of action is inhibition of PBPs
Give 4 groups of B-lactam antibiotics and some examples of each
- pencillins - narrow spectrum
- benzylpenicillin
- amoxicillin
- flucloxacillin - cephalosporins - broad spectrum
- cefuroxime - carbapenems - broad spectrum
- meropenem - monobactams - gram negative
- aztreonam
Give two examples of antibiotics that are glycopeptides?
vancomycin and teicoplanin
How do glycopeptides work?
- inhibit binding of transpeptidases and thus peptideoglycan cross linking
- gram +ve activity
- unable to penetrate gram negative outer membrane
Give the names of some antibacterials that inhibit the protein synthesis in bacteria?
-aminoglycosides e.g gentamicin
-macrolides e.g clarithromycin
-tetracyclin, doxycycline
-linezolid (gram +ve)
and some more
What are the 3 main groups of DNA synthesis inhibitors?
- trimethoprim
- sulfonamides
- fluoroquinolones
How do trimethoprim and sulfonamide work?
- both agents inhibit folate synthesis
- sulfonamides inhibit dihydropteroate synthetase
- trimethoprim inhibits dihydrofolate reductase
What are some examples of DNA synthesis inhibitors?
ciprofloxacin, levofloxacine
What is rifampicin? How does it work and what is it used for?
- RNA synthesis inhibitor
- inhibits RNA polymerase
- prevents synthesis of mRNA
- main use is to treat tuberculosis
Which antibiotics work on cell membranes?
gram negatives - colistin
gram positives - daptomycin
How are fungi classified and which fungi dosen’t fit into these categories
- fungi are classified as moulds/filamentous fungi or yeasts
- pneumocystis jiroveci dosen’t fit into these categories
What is a fungal cell wall made of?
-B-1,3-glucan
What is B-1,3-glucan synthesised by?
B-1,3-glucan synthase
Why is ergosterol in fungal cells a target for selective toxicity?
fufils the same function as cholesterol in animal cells but it is different in fungal cells so this can be manipulated
How do antifungal cell wall inhibitors work and what are some examples?
- echinocandins (antifungal)
- inhibit B-1,3-glucan synthase
- examples are caspofungin and anidulafungin
What are 3 classes of antifungal cell membrane agents
- azoles e.g clotrimazole, fluconazole, voriconazole
- terbafine
- amphotericin B
How does terbinafine and azoles work?
inhibit synthesis of ergosterol (a component of fungal cell membranes but not human or bacterial)
How does amphotericin B work?
binds to ergosterol causing physical damage to the membrane
Which antifungal agent is involved in RNA/DNA synthesis inhibition?
5-flurocytosine
What are the 3 types of antimicrobial therapy you can give patients?
- empiric therapy
- initial selection of antimicrobial agents of broad enough spectrum to cover the range of organisms likely to be causing the patients infection - targeted therapy
- use of narrowest-possible spectrum agents - susceptibility guided therapy
- based on susceptibility testing results
