Antimicrobial agents 1 Flashcards
What is the broad mechanism of action of beta lactams?
Inhibition of cell wall synthesis
What is the broad mechanism of action of glycopeptide antibiotics?
Inhibition of cell wall synthesis
Bind to peptide crosslink sticking out of pep glycol precursor, prevent bond formation
What 3 groups of antibiotics are classified as beta lactams?
Penicillins
Cephalosporins
Carbapenems
Name 2 glycopeptide antibiotics
Vancomycin
Teicoplanin
Describe the mechanism of action of beta lactams
Inactivates transpeptidase enzyme that forms X-links during cell wall synth.
Resulting cell wall is weak, so bacteria lyse because of osmotic pressure.
What bacteria is penicillin active against?
+ve
What bacteria is amoxicillin active against?
BS: +ve, enterococci + gm -ve
Is streptococci gram pos or neg?
+ve
Which beta lactam antibiotic is effective against pseudomonas?
Piperacillin-Tazobactam
(Tazocin)
How can beta lactam resistance be overcome?
Include a B-lactamase inhibitor
E.g. Amoxicllin + Clavulanic acid (co-amoxiclav)
Piperacillin + Tazobactam (Tazocin)
Is pseudomonas gram pos or gram neg?
-ve bacilli
(Pseudo”moan”as ‘moan’ = negative)
Is neisseria meningitis gram pos or gram neg?
-ve cocci
(Neisseria starts with N = negative)
Recall 3 antibiotics associated with C. difficile
Ceftriaxone (cephalosporin)
Clindamycin (lincomycin)
Ciprofloxacin (fluoroquinolone)
Which beta lactam antibiotics are stable to ESBL organisms?
Carbapenems
Recall 3 cautions of beta lactam antibiotic
Excreted renally: reduce dose if renal impairment
Short half life: multiple doses spaced equally required
Cross-allergenic (penicillins 10% X-reactivity with cephalosporins/ carbapenems)
What type of bacteria are glycopeptides effective against?
+ve only
Are large molecules so can’t penetrate -ve outer cell wall
What infection are glycopeptides particularly useful for?
MRSA
What is a caution of glycopeptide antibiotics?
Nephrotoxic
Monitor levels to prevent accumulation
Recall the broad mechanism of action of glycopeptide antibiotics
Prevent peptide X-links in cell wall
What type of bacteria are aminoglycoside antibiotics effective against?
Recall MOA of aminoglycosides
-ve
Bind to 30s ribosomal subunit, preventing elongation of polypeptide chain
No anaerobic activity
Recall 2 examples of aminoglycoside antibiotics
Gentamicin (effective in P. aeruginosa)
Amikacin
Recall 2 toxicities of aminoglycosides
Ototoxicity
Nephrotoxicity
What type of bacteria are macrolides effective against?
+ve
Bind to 50s subunit of ribosomes
What are macrolides particularly useful for? What else are they active against?
Mild staph or strep infections in penicillin allergic
Campylobacter sp + legionella pneumophila
Recall 3 macrolide antibiotics
Azithromycin
Clarithromycin
Erythromycin
What type of bacteria are tetracylines effective against?
BS
Intracellular pathogens e.g. Chalmydiae, Rickettsiae, Mycoplasma
Recall a class of antibiotic you should never give to children or pregnant women
Tetracyclines
as
TERATOGENIC, deposit in growing bones
Recall one side effect of tetracycline antibiotics
Light-sensitive rash
Avoid sun
Recall the broad mechanism of action of tetracyclines
Bind to 30s subunit of ribosomes
What type of bacteria is chloramphenicol effective against? What may chloramphenicol be used for?
V Broad Spectrum
Eye drops
Why is chloramphenicol rarely used?
Risk of aplastic anaemia + grey baby syndrome in neonates due to inability to metabolise drug
Recall the broad mechanism of action of chloramphenicol
Binds 50s subunit of ribosomes
Inhibits formation of peptide bonds during translation
Recall the broad mechanism of action of oxazolidinones
Binds 23s + 50s subunit of ribosomes to prevent 70s subunit formation
Recall two types of bacteria that oxazolidinones are particularly active against
Highly active against gram +ve, inc:
MRSA + VRE
Recall an example of oxazolidinones
Linezolid
Recall one potential side effect of oxazolidinones
Thrombocytopaenia
(+ expensive)
(+ can cause serotonin syndrome)
Recall the MOA of fluoroquinolones
Act on alpha subunit of DNA gyrase
Broad activity, esp. vs -ve inc. P aeruginosa
Levo + Moxi have activity against +ve and intracellular e.g. Chlamydia
Recall 4 uses of fluoroquinolones
UTI
Pneumonia
Atypical pneumonia
Bacterial gastroenteritis
Recall 3 examples of fluoroquinolone antibiotics
Ciprofloxacin
Levofloxacin
Moxifloxacin
Give an example of a nitromidazole antibiotic
Metronidazole
Recall types of organisms that metronidazole is effective against
Anaerobes
Protozoa e.g. Giardia
When should metronidazole be taken?
Right after visiting the toilet as it sits in bladder
Recall the broad mechanism of action of rifampicin
Inhibits RNA polymerase
Recall the main use of rifampicin
TB
Recall one side effect of rifampicin
Turns secretions orange
Recall one condition of rifampicin prescription
Never prescribe alone as resistance develops very quickly
Name 2 cell membrane toxins. How do their activity differ from other antibiotics?
Daptomycin. +ve. Limited by surfactant, not good in lungs.
Colistin. -ve. Nephrotoxic, reserved for MR bacteria
Work when bacteria are NOT active.
What is daptomycin licensed for the treatment of?
MRSA
VRE
Recall the 2 classes of antibiotic that inhibit folate metabolism
Sulphonamides
Diaminopyrimidines e.g. Trimethoprim
What does Trimethoprim combined with sulfamethoxazole form? What is this used for?
Septrin (co-trimazole)
PCP
Elderly- doesn’t exacerbate C diff
What is the main use of trimethoprim alone?
Uncomplicated UTI
What are the 4 main mechanisms of resistance
- Inactivation- B latamases
- Altered target (abx no longer binds - important in MRSA where bacteria change PBP, + in protein-synthesis inhibitors where binding of ribosome subunit is prevented)
- Reduced accumulation
(most important in gram -ve: either due to efflux or to reduced uptake) - Bypass
(important for folate inhibitors: bacteria can change the enzyme they use)
Name 2 classes of abx that inhibit DNA synthesis
Fluoroquinolones
Nirtromidazoles
Which bacteria typically forms “gram pos cocci in clusters”?
Staphylococcus
Which bacteria typically forms “gram pos cocci in chains”?
Streptococcus
Strep sounds like ‘stripe’ = chain
What gram stain status are enterococci?
+ve
(“Enter-o-coccus” = like letting someone in, +ve thing to do)
Is haemophilus gram pos or neg?
-ve
Ha”emo”philus - emo = -ve
Is listeria gram pos or neg?
+ve
Lister = good man = +ve
How do gram positive and negative bacteria differ in their cell walls?
+ve: THICK peptidoglycan
-ve: THIN peptidoglycan, have outer membrane
Against which cells are b-lactams ineffective against?
Those lacking pep wall: Chlamydia + Mycoplasma
Those not metabolically active/ dividing: biofilms/ abscesses/ prostheses
What is transpeptidase also known as?
Penicillin binding protein
Which penicillin is penicillinase stable? Against which bacteria does this allow use for compared to other penicillins?
Flucloxacillin
Use against S aureus
Describe the components of Co-amoxiclav
Clauvanic acid is a b-lactamase inhibitor allows Amoxicillin to retain activity
Give examples of each generation of cephalosporin. How do they differ?
Increasing activity against -ve bacilli
1: Cephalexin
2: Cefuroxime
3: Cefotaxime, Ceftriaxone, Ceftazidime
What is ceftazidime most commonly used for?
Anti-pseudomonas
Which enzymes confer resistance to Cephalosporins? What drug may be used instead?
ESBL
Rx: Carbapenem e.g. Meropenem
Give 3 examples of Carbapenems
Meropenem
Imipenem
Ertapenem
Which emerging enzymes would confer resistance to Meropenem?
Carbapenemase
How do B lactase interact with the blood brain barrier?
Intact: DONT cross (non-inflamed meninges)
Meningitis: cross BBB as high dose used + inflamed meninges
Why are B lactams more preferable to glycopeptides?
Glycopeptides are slowly bactericidal
What can Vancomycin PO be used to treat?
Serious C. difficile
2 examples of glycopeptides
Vancomycin
Teicoplanin
Give 5 classes of protein synthesis inhibitor antibiotics
Aminoglycosides
Tetracyclines
Macrolides
Chloramphenicol
Oxazolidinones
2 side effects of fluoroquinolones
Tendonitis
Lowers seizure threshold
What is a related class of compounds to Nitroimidazoles?
Nitrofurans- Nitrofurantoin used in simple UTIs
Why does DH need to be considered when prescribing Rifampicin?
Enzyme inducer
Increases rate of metabolism of drugs metabolised by liver
How can Streptococcus pneumoniae resistance be overcome?
Mutation: Becomes step-wise resistant with altered PBP
Overcome with high dose if low level resistance
Why has there been tx failure reported with B lactamase inhibitors?
In ESBL +ve bacteria
Traditional inhibitors don’t work against all enzymes
What is the mechanism of resistance to macrolides?
Altered target: ribosomal methylation encoded by ERM gene
Ribosome which macrolide binds to is altered, no longer binds
What antibiotic should you avoid if you see macrolide resistance?
Clindamycin
(related to macrolides, so may be resistance)
