Antibiotics Flashcards
ESCaPeM
Which microorganisms produce large amounts of chromosomal β-lactamases?
Enterobacter, Serratia, Citrobacter, Pseudomonas and Morganella
What are the two mechanisms of action for antimicrobial drugs?
Label A and B.
A- bactericidal
B- bacteriostatic
In an immunocompromised patient, would bactericidal or bacteriostatic antimicorbial txt be better?
Bacteriocidal
Describe the spectrum of Penicillin G and V
GPC, GPR, GNC
What is the route of administration for penicllin G and penicillin V? What are their oral efficacies?
Penicillin G- intravenous (injected; poor oral efficacy)
Penicillin V- orally (good oral efficacy)
List examples 6 penicillins (from the lecture)
Penicillin G
Penicillin V
Ampicillin
Methicillin
Flucloxacillin
Carbenicillin
What do the penicillins ampicillin, methicillin, flucloxacillin and carbenicillin all derive from?
6-APA from the microorganism Penicilium chrysogenum
Put these in order of toxicity (most to least): methicillin, flucloxacillin and carbenicillin
Methicillin (moderate toxicity)
flucloxacilin (low toxicity)
carbenicillin (v. low toxicity)
What spectrum (GNR, GPR, GNC & GNR) do methicillin and flucloxacillin target? Why would you prescribe one over the other?
They both target GPC (Staphyloccocus) but methicillin has a weak oral efficacy and a moderate toxicity, so flucloxacilin would generally be preferred.
What is MRSA?
Methicillin resistant Staphyloccus aureus; multi-resistant staphylococcus aureus
What specific bacteria do methicillin, flucloxacillin and carbenicillin target?
Methicillin- GPC (Staphylococus)
Flucloxacillin- GPC (Staphylococcus
Carbenicillin- GNR (Pseudomonas; especially Pseudomonas aeringinosa)
Am poo
What antibiotic would you generally prescribe for a patient with an E. coli infection?
Ampicillin (GNR spectrum)
Salmonella causes food poisoning, which makes you poo….
What antibiotic would you generally prescribe for a patient with an Salmonella typhi infection?
Ampicillin (GNR spectrum)
Ampicillin is generally considered the same as ______
Amoxycillin
Which penicillin would you use to detect MRSA?
Methicillin
What antibiotic would you generally prescribe for a patient with an Pseudomonas aeringinosa infection?
Carbenicillin
Dan’s: Car runs into a fake Mona Lisa
Bella: Car runs into a pond
Which penicillin have good oral efficacy?
FAPv;
Flucloxacillin, amplicillin, penicillin V
Common causes of gas gangrene
Most commonly caused by clostridium perfringens bacterium.
Less commonly by Group A Streptococcus.
Common cause of gonorrhea
Neisseria gonorrhoea
What is meant by selective toxicity from antimicrobial agents?
The drugs target bacterial components that are absent from our own cells;
E.g.
What do beta lactams and glycopeptides target in the bacterial cell?
Cell wall
What do polymyxins and polyenes target in their target cells?
What are the microorganisms eah of these drugs target?
Cytoplasmic membrane
Polymyxins- bacteria
Polyenes- fungi (best anti-fungal agent)
What do aminoglycosides and chloramphenicol target in the bacterial cell?
Ribosomes
What are the antimicrobial agents which target nucleic acid?
Which one is also used as a txt for Tb?
quinolones and rifamycins
Rifamycin is used as a txt for tb
mnemonic: DNA looks like a train rail; Queensland Rail
Jon is shooting his rifle (rifamycin) at the train’s back (Tb)
True or false:
Unlike us, bacteria synthesis their own folate?
True.
Sulphonamide and trimethoprim target what bacterial components?
Folic acid pathways
Mnemonic: Three meth heads in their prime (trimethoprim) who are pregnant (folic acid) and stink like sulphur armpits (sulphonamide)
What component in bacteria determines their shape as rod or cocci?
The peptidoglycan in the cell wall
True or false; bacteria only contain D amino acids in their cell walls, which we target with trimethoprim and sulphonamide.
False; they have alternating D and L amino acids, and as humans only contain L a.a’s, we can target the D a.a’s as an antimicrobial therapy.
What is the mechanism of action of Vancomycin?
Vancomycin binds to the C terminal a.a’s (D-ala & D-ala) in a peptidoglycan precursor molecule; thereby blocking the formation of peptidoglycan used in cell wall synthesis.
What is the basis of Vancomycin resistance in Enterococci (VRE)?
Vancomycin works by binding to the C terminal amino acids (D-ala and D-ala) however, when a mutation (which requires 9 genes) occurs in the enterococci, the terminal amino acid changes to D-lac and vancomycin no longer binds to inhibit peptidoglycan synthesis.
What is the name of the enzyme which catalyses this reaction?
What drug inhibits its action?
Transpeptidases or penicillin binding proteins
β-lactams bind to this enzyme and inhibit its action; resulting in inhibition in cell wall synthesis in the bacteria.
β-lactams have a bactericidal or bacteriostatic mechanism of action?
Bactericidal;
binds to the transpeptidases catalyses the reaction which forms cross bridges in peptidoglycan. When peptidoglycan is unable to be synthesised, the bacteria die from osmotic lysis.
Why can’t you give bacteriostatic and bactericidal drugs together?
Bacteria have to be growing/dividing in order for antibiotics (β-lactams) to work; bacteriocidal requires growth whereas bacteriostatic inhibits growth.
This bond here is hydrolysed by ____, which leads to ____ resistance
Beta lactamase –> beta lactam resistance.
Two methods of resistance to β-lactams:
- β-lactamase
Cell synthesises an enzyme to hydrolyse and destroy the β-lactams
- Altered penicillin-binding proteins
The enzyme which penicillin (and beta-lactams) bind to is altered and beta-lactams can no longer inhibit it.
Pseudomonas aeringosa is intrinsically resistant against ______. Why? and intrinsically susceptible to ______
It can get an acquired resistance through _____
Resistant: Penicillin G, V and amoxycillin (ampicillin) due to the action of chromosomal β-lactamase.
Suscpetible to: Carbenicillin
Acquired resistance: plasmid encoded β-lactamase
What is clavulanic acid used for?
E.g.?
Clavulanic acid in iteself is poorly anti-bacterial as it poorly binds to well (β-lactam effect) however, it can bind to β-lactamases (particularly plasmid derived) and inhibits their activity, allowing for other antibiotics (β-lactams) to them act on the bacteria; requires another antibiotic for anti-bacterial effect.
Amoxycillin + clavulanic acid = augmentum/co-amoxyclav.
What is the required antibiotic treatment for Pseudomonas aeringinosa infections with acquired β-lactamase?
Timentin; ticarcillin (β-lactam action –> prevents cross linking of peptidoglycan) + clavulanic acid (inhibits β-lactamase)
Protein:
aminoglycosides and tetracyclines
Gentamicin, tobramycin, amikacin (only for emergencies)
Mechanism of action of aminoglycosides and tetracyclines
They inhibit the recognition phase of protein synthesis in the bacterial cell.
Firstly, they bind to the ribosome and distort the reading frame, causing mistakes in translation –> abnormal proteins –> weakened structure in bacteria –> influx of aminoglycosides into permeable cell –> complete stop of protein synthesis
What are the 4 mechanisms to resistance against aminoglycosides?
- Enzymatic modification of the drug –> reduced entry into cell
- Modified outer membrane leading to reduced entry (G - bacteria)–> prevents ALL aminoglycoside entry
- Efflux
- Ribosomal mutuation (ribosomal protein or rRNA)
True or false: aminoglycosides are inactivated via covalent modification, not vua hydrolysis.
True.
True or false: β-lactams are inactivated via covalent modification, not via hydrolysis.
False; they are inactivated via hydrolysis (through β-lactamases)
Specific examples of altering the target of drug action
VISA –> increased peptidoglycan synthesis –> overproducing target
mnemoic: fuzzy, Dan’s lenient VISA card
modified PBP in pneumococcus and MRSA –> modification of the target to a less sensitive form –> binds penicillin less avidly
ribosomal mutations–> modification of the target to a less sensitive form –> aminoglycoside no longer binds –> aminoglycoside resistance
Describe a txt against anaerobes which utilises an inactive precursor.
Metronidazole;
Inactivated drug is activated via pathogenic nitroreductase enzyme. Active drug then affects a.a synthesis, nucleotise synethesis etc.
Describe the mechanism of resistance against Metronidazole.
Pathogen loses activity of nitroreductase enzyme –> drug is not activated –> resistance against Metronidazole.
What do the following acronyms stand for:
MRSA, PRP, VRE, VISA, MDR-TB, XDR-TB
MRSA- methicillin-resistant Staph. aureus
PRP- penicillin-resistant pneumococci
VRE- vancomycin resistant enterococci
VISA- Vancomycin-intermediate Staph. aureus
MDR-TB- Multi-drug resistant Mycobacterium tb
XDR-TB- Extensively drug resistant M. tb
Common microorganism of infection post-op in hip joint replacement?
Staphylococcus epidermidis
Vancomycin is unable to penetrate the membrane of gram __ cells?
Negative
What are the three mechanisms for the transfer of genes between bacteria?
- Transformation
- uptake of naked DNA released from another, closely related bacterium
- homologous recombination; incorporates DNA fragment into its own genome - Transduction
- phage mediated DNA recombination
- Phages are spp. specific, but can occur just between genus (less specific than transformation) - Conjugation
- plasmid-mediated
- can occur between completely unrelated bacteria
Three factors which favour the development of resistance?
- Vast numbers
- Rapid growth
- Promiscuity
The MIC/MBC measures the bacteriostatic property of the antibiotic?
The MIC/MBC measures the bacterialcidal property of the antibiotic?
MIC (min. inhib, concentration)
MBC (min. bacterialcidal concentration)
Which serious infections would illicit the use of intravenous penicillin?
Pneumococcal pneumonia, streptococcal cellulitis and syphilis.
Jawetz’s Laws
Bacteriostatic + Bacteriostatic=
Bacteriostatic + bacteriocidal=
Bacteriocidal + bacteriocidal=
Bacteriostatic + Bacteriostatic= additive (or indifferent)
Bacteriostatic + bacteriocidal= antagonistic
Bacteriocidal + bacteriocidal= synergistic
What should you not prescribe in the txt of meningitis?
Bacteriostatic + bactericidal drugs which give antagonistic effects; inhibits the action of the bactericidal drug via the bacteriostatic
e.g. tetracycline + β-lactams
What does chloramphenicol target in the bacterial cell?
Ribosome
