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Year 5 Path Charis > Micro 1 - Antimicrobial agents 1 > Flashcards

Micro 1 - Antimicrobial agents 1 Flashcards

1
Q

Inhibitors of cell wall synthesis

A 
•	Β-lactam abx 
o	Penicillins
o	Cephalosporins
o	Carbapenems
o	Monobactams

• Glycopeptides
o Vancomycin
o Teicoplanin

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2
Q

• Β-lactam abx

A

o Penicillins
o Cephalosporins
o Carbapenems
o Monobactams

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3
Q

• Β-lactam abx MOA

A
  • Inactivate enzymes involved in the terminal stages of cell wall synthesis (no peptide cross-links) = transpeptidases/penicillin binding proteins (PBP)
  • Bactericidal

 These enzymes form peptide bonds between the peptidoglycan subunits of the cell wall NAM (N-acetylglucosamine) + NAG (N-acetylmuramic acid)
 Weak cell wall  bacteria lyse

renally excreted

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4
Q

B-lactam abx where are they ineffectiv?

A

o Ineffective against bacteria that lack peptidoglycan cell walls  Mycoplasma, Chlamydia
 Therefore in respiratory tract infections with these organisms (known as atypical organisms), different antibiotics are used

o Ineffective against bacteria that are in the stationary phase of the cell cycle/if the cell wall has already been formed

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5
Q

Flucloxacillin resistance

A

designed to be stable to b lactamases

o is alteration of the target – altered PBPs (peptide binding proteins)

Therefore flucloxacillin resistance is MRSA resistance  alteration of the target

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6
Q

o β lactamase inhibitors

A

• Clavulanic acid (+ amoxicillin = co-amoxiclav)

Tanzobactam ( + piperacillin = Tanzocin/Piptazobactam)

Avibactam

Staph. Aureus, Gram -ves (E.coli, Pseudomonas) and anaerobes

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7
Q

Intra-abdominal infections

A

Cefuroxime + Metronidazole
or
co-amoxiclav

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8
Q

Ceftriaxone

generation
use
associated with
paediatric version

A

3rd
sepsis, meningitis, meningococcal septicaemia,
associated with C. diff diarrhoea
paediatric versin cefotaxime

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9
Q

which abx is associated with c difficile

A

ceftriaxone

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10
Q

abx against pseudomonas

A

cefatizidime

aminoglycosides (gentamicin + tobramycin)

quinolones (ciprofloxacin)

piperacillin

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11
Q

abx against ESBLs (extended spectrum b lactamases) + why

A

Carabapenems

ESBLs are ENZYMES can break down penicilins + cephalosporins

therefore mechanism of resstance = enzymatic inactivation of the antibiotic

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12
Q

how to remember the generations of cephalosporins

A

1st gen have “fa” or “pha” in their name except cefalor (2nd gen)

3rd gen end in “ime”, “one”, “ten” excpet cefuoxime (2nd gen)

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13
Q

examples of carbapenems

A

• Meropenem, Imipenem, Ertapenem

v broad specturm

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14
Q

Glycopeptides

examples
use
MOA
SE

A
  • Vancomycin, Teicoplanin
  • Slowly bactericidal – inhibit cell wall synthesis

• Active against Gram +ve organisms
o Important in treating serious gram +ve infections
 MRSA infections (iv only) – Vancomycin, resistant to all β-lactam abx
o C. difficile  oral vancomycin

• Large molecules  unable to penetrate Gram -ve outer cell membrane

• Inhibit cell wall synthesis
o peptide at the end of the cell wall subunit will go on to form the peptidoglycan links
o this peptide is made up of amino acid subunits
o Vancomycin binds to D-Ala amino acid at the end of the peptide of the peptidoglycan precursor  stops transglycosidase (which forms glycosidic links) + prevents transpeptidase binding + stops the formation of the peptide bonds  osmotic lysis
o Stops formation of peptide bonds  weak peptidoglycan cell walls of daughter cells  bacteria lyse after dividing

• Nephrotoxic + to some extent ototoxic – monitor drug levels to prevent accumulation

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15
Q

Inhibitors of protein synthesis

A

Buy AT 30, CEL at 50

30s ribosome
• Aminoglycosides (e.g. gentamicin, amikacin, tobramycin)
• Tetracyclines (e.g. doxycline, tigecycline)

50s ribosome - chloramphenicol, erythromycin, linezolid
• The MLS group  Macrolides (e.g. erythromycin)/ Lincosamides (clindamycin) / Streptogramins (Synercid)
• Chloraphenicol
• Oxazolidinones (e.g. Linezolid)

All bacteriostatic except aminoglycosides (bacteriocidal)

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16
Q

Aminoglycosides MOA

A

inhibitor of protein synthesis

Inhibitor of protein synthesis

• Bind to amino-acyl site of the 30s ribosomal subunit
o Cause misreading of codons along the mRNA
o Prevent elongation of the polypeptide chain
• Bactericidal
• Require specific transport mechanism to enter cells
• Poor oral absorption – has to be given IV

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17
Q

tetracyclines MOA

A

Inhibitor of protein synthesis
30s ribosome

  • Bacteriostatic (stops bacteria from reproducing)
  • Reversibly bind to the ribosomal 30s subunit  prevent binding of aminoacyl-tRNA to the ribosomal acceptor site  inhibit protein synthesis
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18
Q

Tetracyclines

Use
SE

A

30s ribosome
• Broad-spectrum agents with activity against
o Bacteria with no peptidoglycan cell wall (e.g. chlamydiae, rickettsiae + mycoplasmas – atypical pneumonia)
o Intracellular pathogens (e.g. legionella, chlamydiae, rickettsiae & mycoplasmas)
o Most conventional bacteria

• Used as cover in
o Atypical pneumonia
o Skin infections
o Soft tissue infections

  • Low levels in blood so not useful for bacteraemia
  • Light-sensitive rash – particularly with doxycycline – warn patients to stay out of sunlight
  • Can discolour growing teeth
  • Can be deposited in growing bones  Do not give to children, pregnant or breastfeeding women
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19
Q

Macrolides

examples
MOA
use

A

Inhibitor of protein synthesis
• Erythromycin (QDS), clarithromycin (BD), azithromycin (OD)
• Bacteriostatic
• Binds to peptidyl transferase of the 50s ribosomal subunit + inhibits peptide bond formation during translocation
o Stimulate dissociation of the peptidyl-tRNA

• In general, limited utility against gram -ve – do not use for E. Coli, Pseudomonas etc
• Newer agents (e.g. clarithromycin, azithromycin)  can be used in some situations for treating gram -ves
o Azithromycin  used to treat Salmonella typhae and in CF
o Azithromycin – long half-life, used in paediatrics

• Useful for treating Staphylococcal or Streptococcal infections in penicillin-allergic patients
• Also active against Campylobacter sp , Legionella pneumophilia, mycoplasma, pneumophilia
o Campylobacter enteritis  long duration of symptoms, bloody diarrhoea

• Can be used in pregnancy + childhood

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20
Q

Chloramphenicol

MOA
Indications
SE

A

Inhibitor of protein synthesis
• Bacteriostatic
• Binds to peptidyl transferase of the 50s ribosomal subunit + inhibits peptide bond formation during translocation

  • Eye drops – bacterial conjunctivitis
  • Big indication  meningococcal + pneumococcal meningitis in patients who are penicillin anaphylactic

o Risk of aplastic anaemia
o Risk of grey baby syndrome in neonates – inability to metabolise the drug

21
Q

Oxazolidinones

example
MOA
Use
SE

A

Inhibitor of protein synthesis
Linezolid

  • Can be both bacteriostatic (enterococci, staphylococci) and bactericidal (streptococci)
  • Binds to the 23s component of the 50s subunit – prevents the formation of a functional 70s initiation complex (required for the translation process to occur)
  • Highly active against Gram +ve organisms – MRSA (methicillin resistant staph aureus), VRE (vancomycin resistant enterococci)
  • Not active against Gram -ves

• May cause thrombocytopenia (common, reversible) + >4 weeks of treatment may cause optic neuritis (may not be reversible)

22
Q

Fluoroquinolones

example
MOA
Use
SE

A

ciprofloxacin, levofloxacin, moxifloxacin

Inhibitors of DNA synthesis
• Act on α-subunit of DNA gyrase predominantly
• Bactericidal

• Ciprofloxacin  gram -ve organisms incl. Pseudomonas aeruginosa
• Newer agents (e.g. levofloxacine, moxifloxacin)  gram +ve + intracellular (e.g. Chlamydia spp)
o Levofloxacine, moxifloxacin  Used for atypical pneumonia treatment

•	Used for
o	UTIs
o	Pneumonia
o	Atypical pneumonia
o	Bacterial gastroenteritis

• Side effects
o Lower seizure threshold – not used in epileptics or pt w a hx of seizure
o Tendonitis – particularly achilles tendonitis, not used in the elderly or pt on steroids

23
Q

Nitroimidazoles

example
use
MOA

A

metronidazole, tinidazole
Inhibitors of DNA synthesis
• Bactericidal
• Used exclusively for anaerobes  anaerobic bacteria (GI infections) + protozoa (e.g. Giardia, amoeba)
o Under anaerobic conditions an active intermediate is produced  DNA strand breakage

24
Q

Inhibitors of RNA synthesis

MOA
Use
SE
Resistance

A

Rifamycins, e.g. rifampicin & rifabutin

  • Bactericidal
  • Inhibits protein synthesis by binding to DNA-dependent RNA polymerase  inhibits RNA polymerase  inhibits initiation

• Active against Mycobacteria + Chalmydiae
o Main use  TB (but always used in combination to prevent the development of resistance while on treatment)
o Other uses: other mycobacteria, chlamydia, prosthetic joint infections (can disrupt biofilms)

• Should never be used as a single agent  resistance develops rapidly
• Monitor LFTs
• Enzyme inducer  Interactions with other drugs that are metabolised in the liver (e.g. COCP, warfarin)
• May turn urine, contact lenses, sputum, tears orange
o Resistance due to chromosomal mutation  causes a single amino acid change in the β subunit of RNA polymerase  fails to bind to rifampicin

25
Q

Abx against MRSA, VRE

A

Linezolid (oxazolidinones) (inhibitor of protein synthesis)
Daptomycin (cell membrane toxin)

o Daptomycin is inhibited by surfactants – not used in pneumonia
o Linezolid is easier to use – used in MRSA pneumonia
o Daptomycin can only be used as IV, Linezolid can be used orally
o In general daptomycin isn’t used very commonly, linezolid is used more

26
Q

Cell membrane toxins

A

Daptomycin
against gram +ve
MRSA, VRE

Colistin
against gram -ve
Pseudomonas aeruginosa, multi-drug resistant Acinetobacter baumannii and Klebsiella pneumoniae
nephrotoxic

only IV

27
Q

Inhibitors of folate metabolism

examples
use
MOA

A

Sulfonamides - Sulfamethoxazole
o Only used in combination with trimethoprim as co-trimoxazole

• Diaminopyrimidines – trimethoprim

o Co-tramoxizole  HAP, skin + soft tissue infections, PCP (pneumocystitis jiroveci pneumonia) in HIV/immunocompromised patients (prophylaxis + treatment)

  • Act indirectly on DNA through interference with folic acid metabolism
  • Synergistic action between the 2 drug classes  act on sequential stages in the same pathway
  • Sulphonamide resistance is common  combine with trimethoprim (co-trimoxazole)
28
Q

list the 4 mechanisms of drug resistance

A

BEAT

Bypass antibiotic sensitive step in pathway
Enzyme mediated drug inactivation
Impaired accumulation of drug
Modification or replacement of the drug’s target in the microbiome

29
Q

Enzyme mediated drug inactivation

abx

A

b lactams
aminoglycosides
chlorampenicol

30
Q

• Modification or replacement of the drug’s target in the microbiome

A 
b lactams
macrolides
quinolones
rifampicin
chloramphenicol
linezolid
glycopeptides
31
Q

reduced acuumulation

A 
tetracyclines
b lactams
aminoglycosides
quinolones
chloramphenicol
32
Q

bypass

A

trimethoprim

sulphonamides

33
Q

cause of resistance in b lactam abx vs cause of resistance in penicillin resistance

A

• B lactamases are a major mechanism of resistance to β lactam abx in
o Staphylococcus aureus
o Gram negative bacilli (coliforms) – Pseudomonas, E.coli, Citrobacter, Enterobacter

 Penicillin resistance is the result of the acquisition of a series of stepwise mutations in PBP genes
 Penicillin resistance mediated by altered transpeptidases/penicillin binding proteins
e.g. MRSA

34
Q

MRSA mechanism of resistance

A

o MRSA – altered transpeptidase/penicillin binding protein (PBP)
 Resistant to all the β lactam abx
 mecA gene encodes a novel PBP (2a)
 low affinity for binding β lactams abx
 Substitutes for the essential functions of high affinity PBPs at otherwise lethal concentrations of abx

35
Q

Streptococcus pneumoniae mechanism of resistance

A

• Penicillin resistance is the result of the
acquisition of a series of stepwise mutations
in PBP genes.
• Lower level resistance can be overcome by
increasing the dose of penicillin used

36
Q

Macrolides mechanism of resistance

A

altered target
• Enzyme adenine-N6 methyltransferase modifies 23S rRNA
o Encoded by erm (erythromycin ribosome methylation) genes
o UK  erm is the commonest macrolide resistance mechanism

o Clindamycin is not an inducer of this mechanism  therefore this looks sensitive in vitro

• Modification  reduces the binding of MLS abx and results in resistance
o The MLS group  Macrolides (e.g. erythromycin)/ Lincosamides (clindamycin) / Streptogramins (Synercid)

37
Q

Staph aureus resistance

A

Staph. aureus resistance can be either enzymatic or altered binding (MRSA)

38
Q

Which 2 bacteria dont have a cell wall

A

Mycobacterium

Chlamydia

39
Q

As generations of cephalosporins increase…

A

Abx becomes less active against gram +ves and more active against gram -ve bacilli

40
Q

Piperacillin

A

Gram positive organisms
Streptococci
Clostridia

41
Q

amoxicillin

A

Enterococci

Gram negative organisms

42
Q

flucloxacillin

A

MRSA

43
Q

piperacillin

A

Pseudomonas

other non-enteric Gram negatives

44
Q

clavulanic acid and tazobactam

A

S. aureus, Gram negatives and anaerobes

45
Q

ceftazidime

A

anti-Pseudomona

46
Q

cefuroxime

A

Gram

negatives

47
Q

• Oral vancomycin can be used to treat

A

serious C. difficile infection

48
Q

Gentamicin & tobramycin

A

particularly active vs. Ps.

aeruginosa

Year 5 Path Charis (44 decks)

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