L7: Introduction to Antibiotics and Resistance Flashcards
What are the different classifications of antimicrobials?
Antibiotics–> bacteria
Antiviral–> Viruses
Antifungal–> Fungi
Antiprotazoal–> Parasites
What are the different classification of antibacterials?
Action–> Bactericidal (kill bacteria directly) or bacteriostatic (stop replication)
Spectrum–> Broad (works on wide range of bacteria) or Narrow (only works on a few bacteria)
Target site–> mechanism of action
Chemical structure–> antibacterial class
How do you choose an antibiotic?
1- Is it active against target organism?
2- Does it reach the target site? e.g. cross BBB
3- Is it available in the right form? - Oral vs IV
4- What is the half life- determines dosing frequency? - short T1/2 given frequently, long T1/2 given less often
5- Does it interact with other drugs?
6- Is there toxicity issues? -Low enough dose to kill infection, too high toxic
7- Does it require therapeutic drug monitoring?
How can antibiotic activity be measured?
Disc sensitivity testing
- spread bacteria over plate
- add discs soaked in antibiotics
- incubate 18hrs
- measure zonal clearance–> area around disc with no bacteria
Disc testing
- antibiotic diffuse out of disc across plate
- high conc close, low conc far
- bacteria grow
- reaches conc in agar where antibiotic too concentrated so bacteria stops growing
Broth microdilution
- increasing concentration of antibiotic placed in well
- add bacterial suspension
- leave overnight
- measure clearance
- MIC (minimum inhibitory clearance) –> minimum dose required to clear bacteria
E-test
- spread bacteria over plate
- add stripe with antibiotic at different grades
- leave overnight
- measure zonal clearance
What are clinical breakpoint tables?
Standardises antibiotic testing over Europe and the UK
Allows comparison between laboratories
Chosen concentration of antibiotic which determines whether a species of bacteria is susceptible or resistant to an antibiotic.
What are the different mechanisms of action of antibacterials?
Main target are to stop cell repair and replication 1- Cell wall synthesis--> inhibit 2- Cell membrane synthesis --> inhibit 3- Protein synthesis--> inhibit 4- Nucleic acid synthesis --> inhibit,
What are the different antibacterials that inhibit cell wall synthesis?
Beta-lactams (penicillin, cephalosporins, carbapenems and monobactams)
Glycopeptides (vancomycin and teicoplanin)
What are the differences in action between beta lactams and glycopeptides?
Beta lactams
- Beta lactam ring
- Binds to penicillin binding protein
- Prevents crosslinking gycopeptide
- Weakens cell wall
- Osmotic lysis–> water moves in cell swells, lysis, bacteria dies
Glycopeptides
- Bind directly to glycopeptides (peptide cell wall precurosors)
- Prevent crosslinking
What are the different types of resistance?
Intrinsic–> No target access for drug, resistance within the bacteria–> permanent
Acquired–> Acquires new genetic material or mutates–> permanent
Adaptive–> Stress response–> high levels of antibiotic–> becomes resistant–> remove antibiotic then re-add at later date no longer resistant
What are the mechanisms of resistance?
Enzymatic modification or destruction of antibiotics
Enzymatic alteration of antibiotic targets
Mutation of bacterial target sites
How does resistance come about?
Bacteria with chromosomal mutation
Antibiotic added–> all non-mutated killed
Mutated one survives and replicates
What is horizontal gene transfer?
Plasmid with resistant gene passed to new bacteria by conjugation
Can be passed between species
New resistant cells–> replicate–> daughter cells with resistance
What compounds are included in the B-lactam class?
Penicillins
Cephalosporins
Carbapenems
Monobactams
–> block cross linking of peptide chains during biosynthesis
What are some of the different types of penicillins? Which bacteria do they mainly target?
Penicillin –> mainly active against Gram +ve, e.g. streptococci
Amoxicillin–> Activity against Gram -ve
Flucoxacillin–> Against Gram +ve and Gram -ve e.g. staphylcocci and streptococci
B lactamase inhibitor combinations
- -> Co-amoxiclav
- -> Piperacillin/tazobactam
What are Beta-lactamase inhibitor combinations? Give a few example?
Contains a beta lactamase enzyme–> inactivates beta-lactmases released by bacteria–> prevents them being resistance
Co-amoxiclav–> Amoxicillin with clavulanic acid–> as well as others mentioned also targets anaerobes and gram negative bacteria
Piperacillin/tazobactam–> also targets gram negative and pseudomonas bacteria (go on to cause lung infections)
What are the cephalosporins?
Gram +ve and -ve
Broad spectrum activity with no anaeobe activity
Increased targeting of -ve bacteria
Generations of antibiotics 1st, 2nd, 3rd, 4th…
Cetriaxone–> good activity in CSF (Neisseria meningitides)
Concern–> associated with C.difficile–> colitis types of infection
What are some of the carbapenems? What are the key points about them?
Mostly Gram -ve Broad spectrum (including anaerobes) Generally safe in penicillin allergy 'Reserve' antibiotic Meropenem, ertapenem and imipenem
What are the glycopeptides?
Vancomycin
- -> most against gram +ve
- -> IV formulations–> not absorbed by gut (oral no use)
- -> Therapeutic drug monitoring required
- -> Resistance to Staph rare
- -> Some Enterococci resistant
Teicoplanin --> Gram +ve --> Similar activity to vanomycin --> easier to administer Monitoring required but only needs administering once a day
What are the difference classes of antibiotics that target proteins synthesis?
Tetracyclines + Doxycycline
Aminoglycosides
Macrolides
What do tetracyclines and doxycyclines do, target and key characteristics?
Inhibit proteins synthesis Gram +ve Broad spectrum (penicillin allergy) Both oral Shouldn't be given to <12yrs or breastfeeding women (staining of developing teeth)
Active in atypical pathogens in pneumonia (colourless upon gram +ve and -ve staining)
Active against chlamydia and some protozoa
What are the characteristic of aminoglycosides?
Inhibit protein synthesis Most common--> gentamicin Activity against gram -ve--> Reserved for severe gram -ve sepsis Good activity in blood/urine Potentially nephrotoxic or ototocix Therapeutic drug monitoring required
What are the characteristics of macrolides?
Inhibit protein synthesis Mild gram +ve infection- alternative to penicillin Intracellular penetration Atypical respiratory pathogens Erythromycin and clarithromycin
What are the different classes of antibiotics that target nucleic acid synthesis?
Quinolones
Trimethoprim
Rifampicin
What are the characterisitics of Quinolones?
Inhibit nucleic acid synthesis
Active against gram -ve
Atypical pathogens
Inhibit DNA gyrase
Commonest–> ciprofloxacin
Increased resistance and risk of C.difficile
Side effects–> tendinitis, rupture, aortic dissection, CNS defects
What are the characterisitics of trimethopim and sulphonamides?
Inhibit nucleic acid synthesis \+ve and -ve Inhibitors of folic acid synthesis Treat UTI Trimethopim combined with sulphamethoxazole --> co-trimoxazole --> treat pneumocystis jirovecii (disease of immunocompromised patients) --> activity against MRSA
What is a class of antifungals? How do they work?
Azoles–> active against yeast (+/- mold)
Inhibit cell membrane synthesis
Polyenes–> disrupt cell membrane
What are some of the specific types of Azoles?
FUNGUS Inhibits cell membrane synthesis Yeast and moulds Fluconazole--> treat Candida (thursh) Itra/vori/posaconazole--> treat fungal infections in immunocomprimised patients and Aspergillus (mold) in patients in hospital
What are some of the specific types of Polyenes?
Nystain and amphotericin
- Inhibit cell membrane function
- Nsytain–> topical treatment of thrush
- Amphotericin–> IV treatment of systemic fungal infections
What are two drugs that are used to treat viral infections?
Aciclovir–> Phosphorylated inhibits viral DNA polymerase
Treatment of Herpes simplex and Varicella zoster (chicken pox and shingles)
Oseltamivir–> Tamiflu
–> inhibits viral neuroaminidase
–> Influenza A and B –> Within 2-3 days of symptoms presenting
What is metronidazole?
Antibacterial and antiprotozoal agent
Anaerobic bacteria
Protazoa: Amoebae (dysentery (diarrhoea lasting 14 days or systemic), Giardia (diarrhoea) and trichomonas (vaginitis- inflammation)
