Antimicrobialsl Flashcards
What are the classifications of antimicrobials?
• Antibacterial, antifungal, antiviral &
antiprotozoal (against parasites) agents
• Antibacterial agents can be classified:
– Bactericidal (kill bacteria) or bacteriostatic (stop replication so they eventually die)
– Spectrum – ‘broad’ (eg gram pos only) v. ‘narrow’ (eg certain types of gram pos only)
– Target site (mechanism of action)
– Chemical structure (antibacterial class)
What are the ideal features of antimicrobial agents?
- Selectively toxic - to bacteria but not to host
- Few adverse effects - dont want patient to experience side effects
- Reach site of infection - need to know where site is
- Oral/IV formulation - ideal want both but some only exist in one form
- Long half-life (infrequent dosing)
- No interference with other drugs
Name some classes of antibacterials and their mechanism of action
Cell wall synthesis:
- beta-lactams
- glycopeptides
Cell membrane function
- polymixins e.g. colistin
Protein synthesis
- tetracyclines
- aminoglycosides
- macrolides
Nucleic acid synthesis
- quinolones - trimethoprim, riampicin
Explain the mechanism of action of penicillin
Penicillin binding protein helps to build bacterial cell walls
Penicillin binds to this which prevents it from building/maintaining the bacterial cell wall
Explain the action of vancomycin
Vancomycin sits on gly-ala residues - the cell wall cross-linking enzyme cannot link them together so cell wall synthesis is disrupted
What is the mechanism of action of fluoroquinolones
They bind to 2 nuclear enzymes (DNA gyrase and Topoisomerase IV) which inhibits DNA replication)
What are 3 types of antimicrobial resistance?
• Intrinsic
– No target or access for the drug - drug doesnt have access to bacteria
– Usually permanent
• Acquired
– acquires new genetic material or mutates
– Usually permanent
• Adaptive - some bacteria only have gene which is expressed in the presence of antimicrobial, e.g. codes for an enzyme that breaks down the antibiotic
– The organism responds to a stress (e.g. sub-inhibitory level of antibiotic)
– Usually reversible
What are mechanism of antimicrobial resistance?
• Drug inactivating enzymes
– e.g. Β-lactamases, aminoglycoside enzymes
• Altered target
– Target enzyme has lowered affinity for antibacterial e.g. resistance to meticillin, macrolides & trimethoprim
- target changed via mutation - antibiotic cant bind to the site
• Altered uptake
– ↓permeability (e.g. Β-lactams) – or ↑efflux (e.g. tetracyclines)
- antibiotic cant get in, or if they do get in, upreglte the efflux pump
What is teh genetic basis for antibiotic resistance?
Resistance can be passed on in 2 ways
- chromosomal gene mutation
- horizontal gene transfer
What is chromosomal gene mutation?
- one bacterial cell may have a mutated gene conferring resistance
- in the presence of antibiotics cells without the gene will die
- the gene is an evolutionary advantage - bacteria with it will survive and replicate so subsequent generations all have the resistance
What is horizontal gene transfer?
Mutation can be in chromosome or plasmid 0 it can be transferred by
- conjugation of 2 bacteria cells
- phages
- can be free bits of DNA taken up and integrated
Then when these replicate the subsequent generations have the gene
How can antibiotic activity be measured using disc sensitivity testing?
Resistance = smaller zone size
sensitive = larger zone size
vary for different bacteria against different antibiotic
zone sizes nee to be measured - compared to a preset table
Antibiotic disc placed on agar - antibiotic diffuses through agar
How can antibiotic activity be measured using the minimum inhibitory concentration method?
Wells on a dish - each contain different concentration of antibiotic
No organism = negativecontrol
Organism in positive control
Various concs of antibiotic going up in doubles each with a set amount of bacteria
Minimum inhibitory concentration is the first well where antibiotic growth is inhibited
What are beta lactams
Inhibition of cell wall synthesis. This particular group is characterized by its four-membered, nitrogen-containing beta-lactam ring at the core of their structure, which is key to the mode of action of this group of antibiotics.
These include penicillins, cephalosporins, carbapenams, and monobactams
What are penicillins? Give some examples
Penicillins
Penicillin v, benzylpenicillin, amoxicillin, flucloxacillin, co-amoxiclav (amoxicillin + clavulanate), tazocin (piperacillin + tazobactam)
• Penicillin
– Mainly active against streptococci
• Amoxicillin
– Also some activity against Gram-negatives
- slightly wider spec than penicillin
• Flucloxacillin
– Active against staphylococci & streptococci
- choice for cellulitis
• Β-lactamase inhibitor combinations - prevent beta lactamase enzymes from breakin it down (acts as protection)
– Co-amoxiclav (all of above +anaerobes + ↑Gneg
– Piperacillin/tazobactam (as above + ↑↑ Gneg incl
pseudomonas)
What are cephalosporins?
1st - cefalexin, 2nd - cefuroxime, 3rd - cefotaxime ceftriaxone and ceftazidime
- ‘Generations’ with ↑Gneg and ↓Gpos (increasing generations - increasing Gneg)
- ↑broad-spectrum but no anaerobe activity
- Cetriaxone has good activity in the CSF
- Concern over association with C. difficile
What are carbapenams?
Carbapenems - meropenam, imipenam
• Carbapenems: Meropenem (& imipenem)
– Very broad spectrum (incl anaerobes)
– Active against most (not all) Gram negs, also work against Gpos
– Generally safe in penicillin allergy
- cover big range of infections
- penetrate rly well to skin
Give an example of a monobactam
Monobactams e.g. aztreonam
What are glycopeptides?
• Vancomycin
– Active against most Gram pos (not Gnegs)
– Some enterococci resistant (VRE)
– Resistance in staphs rare
– Not absorbed (oral for C. difficile only)
– Therapeutic drug monitoring (TDM) required (narrow therapeutic window)
• Teicoplanin
– Similar activity to vancomycin
– Easier to administer
What are tetracyclines?
Tetracyclines
• Tetracycline & doxycycline
– Similar spectrum, both oral only
– Broad-spectrum but specific use in penicillin allergy, usually for Gram pos
- very versatile - active against atypical pathogens
– Active in atypical pathogens in pneumonia
– Active against chlamydia & some protozoa
– Shouldn’t be given to children <12 years bc irreversible staining of teeth and boens
What are aminoglycosides?
- Most common agent is gentamicin
- Profound activity against Gram negs But not active against Gpos
- Good activity in the blood/urine
- Potentially nephrotoxic/ototoxic - toxic to kidneys at high levels
- Therapeutic drug monitoring (TDM) required - if levels too high increase interval length
- Generally reserved for severe Gram neg sepsis
- Can lead to autotoxicity
What are macrolides?
Macrolides
• e.g. erythromycin (& clarithromycin)
• Well distributed including intracelleluar penetration
• Alternative to penicillin for mild Gram pos infections
• Also active against atypical respiratory pathogens
Gets into cells very well - work against atypical organisms and organisms what survive very well in host cells
What are quinolones?
Quinolones
• Commonest example ciprofloxacin
• Inhibit DNA gyrase so inhibit DNA replication
• Very active against Gram negs
• Also active against atypical pathogens
• Increasing resistance and risk of C. difficile
• penetrates bones and other tissues well - bioavailability about 70%
• can cause tendinitous or tendon rupture during several month treatment - try not to give long term
What are trimethoprim and sulphonamides?
Trimethoprim & sulphonamides
• Inhibitors of folic acid synthesis • Trimethoprim used alone in the UK for UTI • When combined with sulphamethoxazole – Co-trimoxazole – Used to treat PCP – Has activity against MRSA
