6. Miscallaenous antibiotics Flashcards
1
Q
Glycopeptides
- structure and mechanism of action
A
- it has structures containing either glycosylated cyclic or polycyclic nonribosomal peptide
- these antibiotics inhibit the cell wall structure Gram + cocci by inhibiting peptidoglycan synthesis
2
Q
Glycopeptides
- first and second generation
A
First generation glycopeptide:
- Vancomycin (Amycolatopsis /f. Streptomyces)
- Teicoplanin
- Ramoplanin
Second generation semisynthetic glycopeptide:
- Oritavancin/Orbactive
- Dalbavancin/Dalvance
- Telavancin
3
Q
How does Vancomycin and Teicoplanin inhibit cell wall synthesis
A
They interrupt cell wall synthesis by binding tightly to the D-Ala-D-Ala terminus of the murein monomer unit, inhibit transglycosidase and thereby blocking the addition of murein units to the growing polymer chain.
4
Q
Oral vancomycin is used to treat?
A
antibiotica associated enterocolitis, especially if it is caused by C. difficile
5
Q
When is Glycopeptides used?
A
due to their toxicity, their use is restricted to those patients who are critically ill (eg. nosocomial infections) or who have a demonstrated hyperensitivity to the B-lactams
6
Q
Glycopeptides
- spectrum of action
A
they have a narrow spectrum of action
- principally effective against Gram + rods and cocci
- gram - rods are resistant to the action of these drugs
- they are bactericidal aganist most species
- they are only bacteriostatic against the enterococci
- some tissues are not penetrated very well by glycopeptides, and they dont penetrate into the CSF
7
Q
Treatment of MRSA
A
- Glycopeptide is the last effective
- Linezolid of the oxazolidinone class and daptomycin of the lipopeptide class have proven to have activity against MRSA
8
Q
Glycopeptides
Teicoplanin vs Vancomycin
A
- Teicoplanin is more lipophilic than vancomycin, as it has more fatty acid chains.
- it is considered to be 50-100 times more lipophilic than vancomycin
- Teicoplanin has an increased half life compared to vancomycin, as well as having better tissue penetration.
- it can be 2-4 times more active than vancomycin, but it does depend upon the organism.
- Teicoplanin is more acidic, forming water soluble salts, so it can be given IM
- Teicoplanin is much better at penetrating into leucocytes and phagocytes than Vancomycin
9
Q
Glycopeptides
- Side effects
A
- Vancomycin:
- can cause tissue necrosis and phlebitis at the injection site if given too rapidly IV
- nephrotoxicity including renal failure and interstitial nephritis, and blood disorders (reversible once therapy is stopped)
- pain at site of injection
- Idiosynchratic reaction to bolus, caused by Histamine release
- risk of accumulation in patiens with renal impairment because 90% of the dose is excreted in the urine. Therapeutic drug monitoring (TDM) is recommended!
10
Q
Glycopeptides:
Route of administration
A
- Vancomycin is usually given IV as an infusion
- oral preparations are available (eg. solution powder)
- however, they arent absorbed from the lumen of the gut, so are on no use in treatment of systemic infections
- but they are formulated for the treatment of infection in the GI tract, eg: C. difficile
11
Q
Glycopeptides
- What is “VISA”?
A
- Vancomycin and Teicoplanin are used to treat MRSA infections.
- They must be given IV or IM (because of low oral absorption) (Vancomycin only IV)
- Several newly discovered strains of MRSA show antibiotic resistance to Vancomycin and Teicoplanin.
- these new evolutions of the MRSA bacterium are called Vancomycin intermediate-resistant Spaohylococcus aureus (VISA)
- VISA has a thicker murein layer in which increased amounts of free D-Ala-D-Ala act as decoy target for vancomycin
12
Q
Glycopeptides
- what confers vancomycin resistance?
A
- the VanA gene
13
Q
Glycopeptides
- Vancomycin compared to Second generation glycopeptides
A
- Several derivatives of vancomycin are being developed (second generation), including: Oritavancin, Dalbavancin, Telavancin
- they process longer half-lives than vancomycin, and demonstrate improvements over vancomycin due to less frequent dosing and activity against vancomycin-resistant bacteria.
- they are las resort antibiotics, used for treatment of:
- Acute bacterial skin and skin structure infections caused by Staphylo - and Streptococci
- IV, SID for 7-10 days
14
Q
Rifamycins
- structure and use
A
- Rifampicin and its structural relative, Rifabutin, are two semisynthetic derivatives of the naturally occuring antibiotic Rifamycin B.
- Rifampin and Rifabutin inhibit bacterial DNA-dependent RNA polymerase
- Rifampin can be used for:
- prophylaxis of meningococcal disease and treatment of some bacterial infections
- its major use is treatment of Tuberculosis and other Mycobacterial infections
- particularly effective agianst phagosome-dwelling mycobacteria because it is bactericidal for intracellular as well as extracellular bacteria
15
Q
Rifamycins
- Rifampin mode of action
A
- Rifampin inhibits bacterial DNA-dependent RNA polymerase by binding to the beta-subunit of the polymerase
- Rifampin exerts its bactericidal activity by forming a stable complex with bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis
- Rifampin displays high selectivity for bacteria, as mammalian polymerases (even those of mitochondria) are inhibited by rifampin only at far higher concentrations
- Hence, Rifampin is well tolerated, ant he incidence of adverse effects (typically: rash, fever, nausea, vomitting and jaundice) is low
16
Q
Rifamycins
- spectrum
A
- Rifampin is widely distributed, including CSF
- Active against most Gram + organisms
- R. equi, Neisseria spp., Mycobacteria (incl. M. tuerculosis)
- Rifampin is also used prophylactically for meningitis
17
Q
Mupirocin (Bactroban)
- mechanism of action, mode of action, usage
A
- category A: prohibited in food producing animals
- Fermentation product of Pseudomonas fluorescens (pseudomonic acid A)
- Bacteriostatic (in eight-times higher dose bactericidal)
- Reversibly inhibits the isoleucyl tRNA synthetase enzyme, the protein synhtesis decreases in the sensitive bacteria (G+ cocci)
- Usage only topically against S. aureus infections
- Other indication of use: intranasal use against MRSA strains (eg. after operations)
18
Q
Polymixins
- mechanism and mode of action
A
- Polymyxins (Bacillus polymyxa) are cationic basic polypeptides that acts as a detergent to disrupt the cell membrane functions of Gram - bacteria
- They are positively charged molecules attracted to negatively charged bacteria (LPS)
- they act like a cationic detergent: rapid killing, but effect all membranes similarly –> toxicity
- little or no effect on Gram + as PG cell wall is too thick
- they neutralize LPS, preventing its pathological action
- They are concentration dependent bactericidal
- they interact strongly with phospholipids in bacterial cell membranes and radically disrupt their permeability and function
- they are poorly absorbed and are poorly distributed to tissues
19
Q
Polymyxins
- route of admin,
A
of this group of polypeptide antibiotics:
- Polymyxin B, polymyxin E = colistin
- Polymyxin M = mattacin
- –> they are most commonly used topically and PO
- Colistimethate is a form of colistin intended for parenteral administration
20
Q
Polymyxins
- spectrum
A
- more effective against Gram - than Gram +
- their narrow spectrum includes:
- Enterobacter, klebsiella, salmonella, pasteurella, bordetella, shigella spp., E. coli and Pseudomonas spp. (incl resistant strains)
- higher levels (topical formulation) S. aureus
- most Proteus spp. are not susceptible
