23. Polypeptides and other antibiotics (glycopeptides, rifamycins) Flashcards
1
Q
Peptide ABs. Drug lists
A
Polypeptide ABs:
- bacitracin
- polymyxin B
- colistin (= polymixin E)
Glycopeptide ABs:
- vancomycin
- teicoplanin
2
Q
Bacitracin. Mechanism of action
A
- blocks bactoprenol phosphate (transmembrane transporter embedded within bacterial cell membrane which lets NAG and NAM from inside of the cell membrane to outside where they are needed for synthesis of peptidoglycan) -> new peptidoglycan can’t be made anymore
- narrow spectrum - few Gram+ bacteria
- only works topically
- highly nephrotoxic and can lead to kidney failure if used systemically
3
Q
Glycopeptide ABs. Mechanism of action
A
- Latch onto tetrapeptide chains, preventing linking by PBP-enzymes
- Do not act on PBPs so it helpt it to avoid resistance caused by PBP mutations, though some Staphyloccoccus aureus have changed tetrapeptide structure -> resistance VRSA
- Gram+ bacteria
- can’t be be absorbed fro GIT -> given IV
- SE thrombophlebitis, ototoxicity, nephrotoxicity, diffuse flashing
4
Q
Polymixins. Drugs, route of adm, mechanism, mode, PK)
A
- polymixin B, colistin
- topically and PO
- interact strongly with phospholipids in bacterial cell membranes (detergent-like activity) and disrupt their permeability and function, primarily against gram—
- also reduce the activity of endotoxins /9secondary drug effect)
- concentration-dependent bactericidal
- poorly absorbed and poorly distributed, cationic (+) basic molecules that are attracted to negatively charged LPS in bacteria
5
Q
Polymyxins. Toxicity, spectrum, resistance
A
- effect all cell membranes -> toxicity by systemic usage
- little to no effect on gram+, proteoglycan level is too thick, no outer cell membrane
- spectrum is rather narrow: Enterobacter, Klebsiella, Salmonella, Pasteurella, Bordetella, Shigella, Escheria coli, Pseudomonas)
- higher doses -> Staph aureus, S. pseudointermedius
- chromosome-dep. resistance: relatively uncommon
- plasmid-mediated: mcr-1 gene Escheria coli, Klebsiella pneumoniae and mcr-2 - mobilised cohosting resistance
6
Q
Polymyxins. PK
A
- not absorbed after PO or topical administration
- blood conc is usually low because Polymyxins bind to cell membranes as well as tissue debris and purulent exudates
- renal elimination mostly as degradation products, plasma half-life is 3-6h
- cross BBB
- activity is decreased by divalent cations, unsaturated FAs and quarterly ammonium compounds
7
Q
Polymyxins. Toxicity
A
- low TI
- nephrotoxic (tubular necrosis) and neurotoxic after infection
- neuromuscular blockade can be seen at higher concentrations
- pain at site of injection and hypersensitivity can be expected.
- Polymyxin B is a potent histamine releaser
- not toxic after oral, ophthalmic, optic or topical use
8
Q
Polymyxins. Clinical use
A
- main indication for parenteral use of polymixins is *life-threatening infection due to gram— bacilli or Pseudomonas species that are resistant to other drugs
- act synergetically when combined with SAs, TCs, penicillins, FQs, and AGs. Use of lower dose is safe
- polymyxin /b is often applied as topical ointment in combination with bacitracin or neomycin or both
- PO against intestinal infections. E.g. E. coli diarrhoea treatment
- topical application is common, e.g. pyoderma, otitis externa
- intramammary application (in comb with bacitracin, penicillins, and AGs)
9
Q
Bacitracin. Mode, mechanism of action, spectrum
A
- concentration dependent bactericidal
- inhibits bacterial cell wall synthesis
- antibacterial spectrum is very small: most active against gram+ bacteria: Staphylococcus, Streptococcus, Clostridia, Haemophilus)
10
Q
Bacitracin. PK
A
- absorption rate after oral and topical use is almost 0
- elimination via kidneys (prohibited in kidney failure)
11
Q
Bacitracin. Toxicity
A
- nephrotoxic
- IM adm only in critically ill patients (staphylococcal pneumonia, empyenemia)
- hypersensitivity reactions including allergic dermatitis and/or anaphylaxis
- in vet medicine is not used systematically
12
Q
Bacitracin. Indications
A
- topical and local infections of mouth, nose, eye, skin and mammary gland
- topical formulations e.g. ointments (often combined with polymyxins or neomycin) for suppression of mixed bacterial flora in skin, wounds or mucous membranes
- oral premixes: epizootic rabbit enteropathy (ERE) (f.n. Mucous enteritis) and necrotic enteritis (Cl. perfringens) in rabbits
13
Q
Rifampicin. Main use, mode of action
A
- major use is the treatment of tuberculosis and other mycobacterial infections
- also can be used for profylaxis of meningococcal disease
- bactericidal concentration-dependent for intracellular as well as extra cellular bacteria
14
Q
Rifampicin. Mechanism of action
A
Inhibits bacterial DNA-dependent RNA polymerase -> inhibition of RNA synthesis
15
Q
Rifampicin. Spectrum. Resistance
A
- relatively broad
- most Gram+ organisms (Rhodococcus equi, Neisseria spp (meningococcus), Haemophylus spp, Mycobacteria
- some non-enteric gram—
- Enterobacteriacceae, Acinobacter, Pseudomonas are intrinsically resistant
- resistance develops rapidly
