DDT 16 - Antibiotics Flashcards
New antibiotic
An antibiotic not used clinically before, but belonging to an existing class of antibiotics
novel antibiotics
An antibiotic with a mechanism of action that has never been used against bacteria before - less likeliness of resistance
name the 4 enzymes S. aureus normally produces
Penicillin Binding Proteins 1-4
how can antibiotics react to PBPs
PBP can be modified by B-lactam antibiotics and leads to inhibition and bacterial death
How does MRSA react to PBP inhibition from beta-lactam antibiotics
MRSA produces an altered PBP (PBP2a), which is not inhibited by b-lactam antibiotics and can perform the functions of the 4 PBPs of S. aureus.
last resort drug for MRSA
Vancomycin - resistance soon began
treatment of MRSA
linezolid
synercid
daptomycin
what class does linezolid belong in
oxazolidinone class novel antibiotics
linezolid is effective against disease
MRSA and VRE infections
Mechanism in which linezolid is used to stop infection
inhibition of protein synthesis
synercid has what 2 variations
quinupristin
dalfopristin
what illness does synercid treat
intravenous treatment of VRE caused infections and skin infections of staphylococcus aureus and streptococcus pyogenes
how does synercid treat infection
inhibit protein synthesis by binding to 70S ribosome both agents bind at same place in ribosome
synercid bacteriostatic or bactericidal
Bacteriostatic when administrated individually, but act synergistically in combination (bactericidal).
daptomycin is used for what kind of infections
gram positive infections particularly in the skin
how does daptomycin treat infection
Binds to cell membranes and causes their depolarisation
interrupts protein, DNA and RNA synthesis
why does daptomycin have slow emergence of resistance
is novel antibiotic
enterococci
Antibiotic resistant opportunistic pathogens commonly found in patients hospitalized for prolonged periods and receiving multiple courses of antibiotics.
what enterococci are most difficult to treat
Enterococcus faecium
2 enterococci
Enterococcus faecalis and Enterococcus faecium
how many years were for emergence resistance against vancomycin to occur
32 years it took 5 genes
how many years were for emergence resistance against penicillin to occur
2-3 years 1 gene
what kind of antibiotic is vancomycin
glycopeptide antibiotic
how does vancomycin treat infection
inhibit cell wall biosynthesis
blocks substrate
must interact with peptide chain with 5 hydrogen bonds
how does bacteria for vancomycin occur?
Loss of a single hydrogen bond when vancomycin binds to substrate = 1,000-fold
drop in drug-binding affinity:
enough for the bacteria to become resistant
clostridium difficile Associated Disease
Clostridium difficile is a Gram-positive, spore-forming, obligate anaerobic bacterium.
what does clostridium difficile mainly cause
nosocomial diarrhoea
toxins A and B can cause extensive damage to colonic mucosa
when does clostridium difficile Associated Disease occur
90 of CDAD occur after or during antibiotic treatment
treatment of CDAD
- medical therapy - discontinuation of the inciting antibiotics
- specific antibiotic treatment
metronidazole = first line antibiotic agent
- vancomycin as alternate agent for second line therapy
spores can still stay in colon of patient
metronidazole is what kind of compound
prodrug
Nitroaryl compound
how is metronidazole activated
Prodrug activated by anaerobic organisms by reduction of the nitro group to hydroxylamine group
During reduction, reactive derivative/species produced that can damage bacterial cell components such as DNA, proteins, membranes
advantages of metronidazole as first line agent
Prevent selection of vancomycin-resistant enterococci
Reserve vancomycin use for the treatment of MRSA infections
when is vancomycin prescribed instead of metronidazole
Failure to respond to metronidazole after 3-5 days of treatment
Pregnancy & lactation
Intolerance to metronidazole
Metronidazole-resistant infecting organism
Critically ill patients
what percentage of gram negative bacteria are responsible for HAI
30%
main HAIs caused by gram negative bacteria
pneumonia
bloodstream infection
urinary tract infection
how does bloodstream infection occur
Most commonly caused by central vascular catheter.
Can be associated with an initial infection of the lung, genitourinary tract, or abdomen.
how is UTI caused
Associated almost exclusively with urethral catheterization.
Risk of infection increases by 5 to 10% per day.
bacterial resistant against penicillin
beta-lactamases
reisstance against cephalosporins
Extended Spectrum
b-Lactamases (ESBLs)
resistance against Carbapenems
Carbapenemases
what does carbapenemases inactivate and what is it inhibited by?
Carbapenemases can inactivate all types of b-lactam antibiotics and are not inhibited by inhibitors of b-lactamases (clavulanic acid).
Represent one of the main clinical challenges.
antibiotic treatment of HAI in response to resistance
Gram-negative pathogen expressing ESBLs:
Carbapenems (eg. meropenem Gram-negative pathogen expressing carbapenemases:
- Colistin or tigeclycine.
what kind of antibiotic is meropenem
Carbapenem, b-lactam antibiotic
describe how strcuture of meropenem is similar to penicillin
Structure similar to penicillins:
bicyclic structure, with 1 b-lactam ring and a 5-membered ring
how does meropenem different to pencillin
however, sulfur atom not in the 5-membered ring, but attached on that ring as part of a functional side-chain
1 carbon-carbon double bond in the 5-membered ring
what type of antibiotic is colistin
Polymyxin antibiotic.
Peptide antibiotic
describe structure of colistin and from what process is it produced?
Mixture of 2 cyclic peptides (colistins A and B) produced by fermentation of Bacillus polymyxa.
colistin is used as a last resort for what infection and why
‘last resort’ antibiotic against
MDR Gram-negative bacteria.
last resort because of nephrotoxicity
how does colistin attack bacteria
Binds to phosphate groups in lipids on the cell cytoplasmic membrane. Disrupts its integrity
describe type of tigecycline
Novel tetracycline class: glycylcyclines
Broad spectrum antibiotic.
how is tigecycline characterised
Characterised by additional glycylamido substituent.
how does tigecycline treat infection
Inhibitor of bacterial protein synthesis by binding to the 30S ribosomal subunit blocks entry of amino-acyl tRNAs into the ribosome.
