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PA20319- Immunity, Infection and inflammation > Antibiotic modes of action and resistance > Flashcards

Antibiotic modes of action and resistance Flashcards

1
Q

Inhibitors of cell wall synthesis

A

B- lactams: penicillins, cephalosporins, carbapenems, monobactams

Glycopeptides: Vancomycin, teicoplenin

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2
Q

Synthesis of peptidoglycan

A

NAM/NAG alternatingly joined by glyosylase
Monomer join to PG via glycosylase
PG is x linked via aa side chains via transpeptidases

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3
Q

Beta-lactam mode of action

A

Bind to penicillin binding proteins (PBP’s-transpeptidase)

Prevents X linking from occuring leading to cell lysis

Also stimulates autolysins which breakdown the cell wall that also lead to cell lysis

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4
Q

Glycopeptide mode of action

A

Prevents glycosylase from adding PG monomers onto PG chain and prevents x-linking

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5
Q

Polymyxin (colistin) and lipopeptides

A

Act on cell membranes by binding to liposaccharides only on g-ve bacteria

Causes cell disruption leading to leakage

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6
Q

Fluoroquinolones

A

Ciprofloxacin, Levofloxacin

Binds to type 2 DNA gyrase (g-ve) and type 4 topoisomerase(g+ve)

Inhibits DNA replication and packaging and causes cell lysis

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7
Q

Aminoglycosides

A

Gentamycin, Bactericidal

Binds irreversibly to A site on 16s rRNA in 30s subunit

Causes misreading of codons along mRNA and interferes with translocation of tRNA from A to P site which disrupts membrane permeability

Inhibits protein synthesis

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8
Q

Tetracyclines

A

Doxycycline

Binds reversibly to A site on 16s rRNA in 30s subunit

Causes tRNA not to bind to A site. Selectivity through accumulating in cell and better binding to bacterial ribosome

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9
Q

Inhibitors of protein synthesis

A

50s: Macrolides, chloramphenicol, streptogramins, lincosamides, fusidic acid, oxazolidinones
30s: tetracyclines, aminoglycosides

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10
Q

Species of most concern?

A

MDR e.coli and TB

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11
Q

Aquiring resistance

A

Mutations and/or conjugation of plasmids

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12
Q

Beta lactam resistance

A

4 classes: A,C,D have serine at active site, B is a metallo lactamase requiring zinc

Beta lactamases can be produced which bind in peri plasmic space or medium

Or by altering Penicillin binding proteins through MecA gene. (causes methicillin resistence in s.aureus)

or reduce number/size of porins to decrease permeability and uptake

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13
Q

Beta lactamase inhibitors

A

Clavulanic acid (in co amoxiclav)

Tazobactam (in taxocin)

Sulbactam

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14
Q

Glycopeptide resistance (Vancomycin)

A

Change in aa sequeces reducing h bonds from 5 to 4 making it unstable

d-ala to d-lactate

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15
Q

Fluroquinolones (ciprofloxacin) resistance

A

Mutations alter structure of DNA gyrase or of topoisomerase 4 preventing binding

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16
Q

Tetracycline resistance

A

Efflux pumps

Actively pumps out drug molecules ensuring it never reaches the required concentration.

Basal rate is intrinsic resistance while upregulated is aquired

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17
Q

Multi drug efflux pumps

A

RND for g-ve, MFS for g+ve

AcrAB/TolC pump in e.coli
chromosomal RND pump
upregulation gives resistanc to fluoroquinilones, chloramphenicol etc

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18
Q

Main types of penicillins

A

Lactamase sensitive:benzypenicillin (pen g), benzythine benzylpenicillin, phenoxymethylpenicillin (pen v)

Lactamase resistant: Flucoxicillin, co-fluampicil, temocillin

Broad spectrum: amoxicillin, ampicillin, co-amoxiclav, augmentin

Antipseudomonal: piperacillin, tazocin, timentin

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19
Q

Benzypenicillin properties

A 
High blood conc achieved quick
non toxic
good diffusion into body tissues
low levels in CSF 
longpost antibiotic effect
20
Q

Uses of pen G

A 
Use immediately for meningitis
throat infection 
endocarditis
pneumonia
cellulitis 
osteomyelitis
21
Q

Meningitis causing microbes

A

Neisseria meningitidis
H.infuenzae
s.pneumoniae

22
Q

Side effects of penicillins

A

Hypersensitivity (rash/anaphylaxis)
Neurotoxicity (increase with renal failure)
Renal failure (High salt affects electrolyte balance)
Diarrhoea and pseudomembraneous colitis

23
Q

Cephalosporins

A

Made from cephalosporium acremonium, cephalosporin C

Specificty, selectivity determined by R groups 1 and 2

24
Q

Properties of cephalosporins

A

resistant to b-lactamases

good drugs but limited by c.difficle risk

affinity for pbp’s in g+ve
outer membrane penetration in g-ve

25
Side effects of cephalosporins
Hypersensitivity (rash/anaphylaxis/inflammation) Diarrhoea, nausea, c.difficile super infection Vomiting, headaches, dizziness, renal toxicity, hemorrhage (rare)
26
2nd gen cephalosporins
cefuroxime , cefaclor, cefadroxil ceftriaxone, cefotaxime is 3rd gen
27
Carbapenems
Imipenem, meropenem v resistant to b lactamase broad spectrum for p.aeruginosa and ESBL
28
Glycopeptides
Vancomycin oral for c.difficile teicoplanin injection for systemic infections Active against g+ve not g-ve
29
PK of glycopeptides
High CSF penetration Renal excretion Side effects: pain, thrombophlebitis, renal toxicity, ototoxicity, blood disorders, anaphylactoid reactions
30
Polymyxins
Colistin Active on g-ve bacteria, last resort iv Highly nephro and neurotoxic
31
Lipopeptides
daptomycin Active on g+ve bacteria causes depolarisation of membrane Used for skin/soft tissue infections, endocarditis caused by resistant g+ve bacteria Side effects: nephrotoxicity, myopathy, peripheral neuropathy, colitis
32
Fluoroquinolones
ciprofloxacin, levofloxacin, Synthetic, broad spectrum, bactericidal Active against g-ve and intracellular pathogens. ltd use against streptococci and enterococci Side effects: gi disturbance,cns, tendon damage, rash, photosensitivity, renal impairment. Interacts with CYP450
33
Rifamycins
Rifampicin Bactericidal, inhibits rna polymerase, given in combo to reduce resistance Treats tb, meningitis, prosthetic infections
34
Rifamycin PK
well distributed, >90% metabolised side effects are hepatotoxicity, fever, rash, hypersensitivity, GI disturbance, orange/red secretion increased metab of warfarin, OCP's
35
Nitroimidazoles
Metronidazole Anaerobic infections, GI + genital +abdominal+dental infections
36
Nitroimidazole PK
Well distributed including CSF, hepatic metabolism, renal excretion Side effects are nausea, vomiting, diarrhoea/constipation, taste, candida super infection neuropathy, hives, rash, red/brown urine Makes people more sensitive to urine
37
Nitrofurantoin
Targets fucking everything Used for non catheterised UTI caused by g+ve and g-ve aerobic bacteria
38
Aminoglycosides
For serious aerobic bacteria infections Eg. septacaemia, complicated UTI, nosocomial RTI Active mostly against g-ve psuedomonas Streptomycin for TB, mycoplasma
39
Aminoglycoside PK
Can be given orally for gut decontamination as it is not absorbed Poor penetration for cells and CSF Renally excreted Side effects:Reversible nephro/ototoxicity
40
Tetracyclines
Broad spectrum Oral for acne, rti, ssti's Staphylococci and streptococci now resistant
41
Tetracycline PK
60-80% absorption but well distributed including foetal. No CSF penetration Renal and bile excretion Side effects:GI superinfections, teeth discolouring, headache, vertigo, hepatotoxicity, phototoxicity
42
Macrolides
Erytromycin, clarithromycin Alternative to penicillin for treating strep infection Oral for rti, sti, gi,ssti
43
Macrolide PK
Acid labile so given as enteric coated Rapid absorption, well distributed except CSF Bile excretion Side effects are gi superinfections, cholestatic jaundice, ototoxicity, allergy, arrythmia
44
Fusidic acid
Narrow spectrum for staph infections Effects EF-G which supply energy for translocation
45
Chloramphenicol
Broad spectrum Topical use in eye infection Oral for meningitis or typhoid fever
46
Chloramphenicol PK
Well absorbed everywhere, metab in liver, renal excretion Side effects: bone marrow suppression, grey baby syndrome, gi flora disturbed, neuritis, aplastic anaemia

PA20319- Immunity, Infection and inflammation (13 decks)

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