Microbiology Flashcards
What is the difference between gram positive and gram negative bacteria
- Gram-positives have a THICK peptidoglycan cell wall
- Gram-negatives have an outer membrane (which is part of the reason why some antibiotics don’t work on Gram-negatives)
What are the inhibitors of cell wall synthesis ?
Beta lactams and glycopeptides (work only against gram positives)
List the classes of beta-lactam containing antimicrobials.
Penicillins
Cephalosporins
Carbapenems
Monobactams
How do beta lactams work?
- inactivate enzymes that are involved in cell wall synthesis (transpeptidases also known as penicillin binding proteins) which gives the cell walls their rigidity
so daughter cells have weka peptidoglycan cells so they lyse and die - it is a structural analogue of the enzyme substrate
-bactericidal
-works against rapidly dividing bacteria so it is not useful in biofilm or abscesses
How is resistance to penicillin overcome?
adding both beta-lactamase inhibitors such as clavulanic acid and tazobactam
However caution due to its pharmacokinetics
Outline the different generations of cephalosporins.
1st: Cephalexin
2nd: Cefuroxime
3rd: Ceftriaxone, Cefotaxime, Ceftazidime
As you go up the generations you get increasing activity against gram negative and decreasing gram positive
What problems did cephalosporins start developing and what was introduced as a result?
ESBL ( extended spectrum beta lactamase )
- * These are a type of beta-lactamase that also breakdown cephalosporins as penicillins
* This was a big problem because cephalosporins were the mainstay of treatment for a lot of severe infections
carbapenems which are resistant ESBL
what other type of antibiotic can be used for gram -positive only?
Glycopeptides. They are very large so cannot pass the gram negative outer membrane because of their size.
also inhibit cell wall synthesis like beta lactams
examples: vancomycin and teicoplanin
important for treating serious MRSA infections
it is nephrotoxic
MOA: glycopeptide bind to the amino chain and prevents glycosidic bone. they bind to the binding sited of the enzymes
What is the difference between glycopeptides and beta lactams in terms of MOA
Beta lactams work by blockign transpeptidases directly
Gylcopeptide bind to the binding sites of the enzyme
What are the classes of protein synthesis inhibitors and their MOA?
Aminoglycosides ( gentamicin, amikacin)
- binds to amino-acyl site of the 30S ribosomal subunit
Tetracyclines ( Doxycycline)
-works against intracellular pathogens/gram negative bacteria
-binds to ribosomal 30S subunit
Macrolides ( erythmycin, clindamycin, clarithromycin)
- bind to 50S subunit of the ribosome
Chloramphenicol
- binds to peptidyl transferase of the 50S ribosomes
-used for eye infection
Oxazolidinones (Linezolid)
- binds to 23S compononent of 50 S subunit
-used for MRSA and VRE
Examples of DNA synthesis inhibitors and MOA?
Quinolones:
Ciprofloxacin
Levofloxacin
MOA: alpha subunit of DNA gyrase
good for gram negative like pseudomonas
UTIs
Nitroimidazoles:
Metronidazole
Break DNA strands
good against anaerobic bacteria and protozoa
Nitrofurantoin
Mechanism of rifampicin and MOA?
Inhibits protein synthesis by binding to DNA-dependant RNA polymerase
mycobactertia and chlymadia
Monitor LFTS
What are the mechanism of resistance for different type of infection in beta lactams
Beta lactams : beta lactamases production for staph A and gram negative bacilli such as e.coli and pseudomonas
For MRSA and pneumococci (causing community acquire pneumonia) –> altered target
Methicillin/flucloxacillin
has a mecA gene which encodes PBP 2a, which encodes another transpeptidase that does not bind to penicillin so is resistant
Strep pneumonia and haemophilius influenza?
b-lactamase never detected.
MOA: slight changes to the PBP which can be overcome by increasing dose
Can beta lactamase inhibitors be used in extended-spectrum beta-lactamases?
No
ESBL can break down cephalosporins and penicillin
-Amp C beta lactamses are not inhibited by clavulonic acid
What is the mechanism of resistance for macrolides?
ribosomal methylation
ribosomes altered so macrolide cannot bind
caution to use clindamycin as lab results can be hard to find this
