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Antibiotics Flashcards

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1
Q

Beta-lactam antibiotics

A
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2
Q

**Penicillins **- pharmocokinetics

A
  • Many IV and oral agents
  • Peak concentration in 1-2 hours
  • Distribution into body water - about 0.2L/kg
  • Little metabolism
  • Mainly urinary excretion
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3
Q

**Penicillin V/G **- indications

A
  • Beta-haemolytic streptococci
  • pneumococci
  • meningococci
  • gonococci
  • anerobes, gram-positive anaerobic cocci (GPAC) and clostridia
  • Resistance !
    • ​pneumococci
    • gonococci
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4
Q

**Flucloxacillin **- indications

A
  • S.aureus
    • ​NB MRSA
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5
Q

**Ampicillin/amoxicillin + clavulanate **- indications

A
  • otitis media
  • COAP
  • CAP
  • UTI
  • skin and soft tissue infection
  • surgical prophylaxis
  • intra-abdominal surgery
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6
Q

**Piperacillin/tazobactam **- indications

A
  • Hospital IV therapy - 2nd line
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7
Q

Carbapenem antibiotics

A
  • E.g. Meropenem
  • Very broad-spectrum
  • Injectable only
  • Used as 2nd/3rd line therapy in hospital
  • Typical Beta-lactam pharmacokinetics
  • Not active against:
    • MRSA
    • Stenotrophomas maltophilia
    • Some enterococci
  • Resistance remains rare
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8
Q

First generation cephalosporins

A
  • e.g. cefalexin
  • Active against gram positive cocci
    • Streptococci and Staphylococci
  • Active against gram negatives - cover UTIs
    • E.Coli
    • Klebsiella
    • Proteus species
  • Mainly oral
  • Mainly used in GP land
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9
Q

Second generation cephalosporin

A
  • e.g. cefuroxime
  • Effective as per first generation (Gram positive cocci and Gram negatives for UTI) + Gram negatives causing CAP and infective exacerbation of COPD:
    • H.influenzae
    • M.catarrhalis
  • ​Mainly given IV
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10
Q

Third generation cephalosporins

A
  • e.g. cefotaxime, ceftriaxone, ceftazidime
  • Poor activity against Gram positive cocci (especially ceftazidime)
  • Good against Gram negatives found in hospitals:
    • Citrobacter, Serratia species –> ceftriaxone/cefotaxime
    • Pseudomonas aeruginosa –> ceftazadime
  • ​Mainly given IV
  • Good CSF penetration
  • Only used sparingly in hospitals
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11
Q

Fourth generation cephalosporins

A
  • e.g. cefpirome
  • Similar spectrum to *ceftazidime + *good activity against some Gram positive cocci
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12
Q

Bacteria resistant to cephalosporins

A
  • MRSA
  • Enterococci
  • Listeria
  • Legionella
  • C.difficile
  • Camyobacter
  • ESBL producing E.Coli/Kleibsiella
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13
Q

Cephalosporins - Indications

A
  • Acute meningitis (cefotaxime/ceftriaxone)
  • Surgical prophylaxis (abdominal, orthopaedic, head and neck, obstetrical)
  • UTI/acute pyelonephritis
  • Chest infection
  • Community acquired sepsis of unknown site (ceftriaxone)
  • Hospital acquired sepsis of unkown site (ceftazidime + 2nd agent)
  • Skin/soft tissue infections
  • Intra-abdominal infections + metronidazole
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14
Q

Beta-lactamase inhibitors

A
  • e.g. co-amoxiclav (amoxicillin + clavulanic acid)
  • Clavulanic acid is an inhibitor of Betalactamase activity
  • S.aureus - penicillinase —> inhibited
  • E.coli, H.influenzae, Gonococcus, Salmonella - TEM 1/2 beta-lactamases –> inhibited
  • *Bacteriodes - *? –> inhibited
  • *Enterobacter - *AmpC beta-lactamase –> not inhibited
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15
Q

Fluoroquinolones

A
  • Mainly used in hospitals for Gram negative infections/LRTIs
  • Act by inhibiting DNA gyease
  • Resistance increaasingly common:
    • Efflux pumps to decrease intracellular concentration
    • Target site mutations
    • Proteins that bind to DNA gyrase
  • Pharmacokinetics:
    • Good oral bioavailability so PO = IV
    • Wide tissue distribution (2-3L/kg) - good for bone/soft tissue infections
    • Excretion by:
      • Metabolism - ciprofloxacin, moxifloxacin
      • Renal clearance - ciprofloxacin, moxifloxacin, levofloxacin**​
  • ​​Side effects (unusual):
    • Rashes/phototoxicity
    • Tendinitis and rupture
    • GI upset
    • QTC prolongation (moxifloxacin)
    • Hepatoxicity
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16
Q

Ciprofloxacin - spectrum

A
  • Effective against:
    • Aerobic Gram negative bacteria:
      • Coliforms
      • Pseudomonas
    • Neisseria gonorrhoeae ‘Gonococci’
    • H.influenzae
    • Atypical chest pathogens:
      • Legionella
      • Mycoplasma
      • Chlamydia
  • ​Borderline activity against *S.aureus *and Streptococci
  • Not active against anaerobes
  • Some activity against M.tuberculosis
17
Q

Moxifloxacin - spectrum

A
  • As for *ciprofloxacin *but much better activity versus *Staphylococci *and Streptococci
  • Poor activity against P.aeruginosa
  • Better activity against anaerobes
18
Q

Fluoroquinolones - Indications

A
  • Community acquired chest infections (moxifloxacin/levofloxacin)
  • UTI/acute pyelonephritis (ciprofloxacin/levofloxacin)
    • ​! resistance
  • Intra-abdominal infections (with metronidazole)
  • Bone/joint infections
  • Oral therapy for P.aeruginosa (ciprofloxacin)
19
Q

Aminoglycosides

A
  • e.g. *Gentamycin * (most common), tobramycin, amikacin
  • Act by inhibition of protein synthesis at ribosome
  • Resistance by enzymes (aminoglycosides monitoring enzymes) - rare
  • Pharmacokinetics
    • Poor oral absorption - IV/IM only
    • Modest tissue distribution
    • Concentrates in kidneys and ears –> toxicity
    • Renal excretion only not metabolises –> accumulation in renal failure
    • Reduced use due to toxicity - requires therapeutic drug monitoring and dosa adjustment
  • Side effects:
    • Nephrotoxicity (reversible)
    • Ototoxicity (irreversible)
20
Q

Aminoglycosides - spectrum

A
  • Broad Gram negative activity - coliforms, P.aeruginosa
  • No anaerobic activity
21
Q

Aminoglycosides - indications

A
  • All in combination therapies for:
    • intra-abdominal infection
    • infective endocarditis
    • neutropaenic sepsis
    • neonatal sepsis (penicillin + flucloxacillin)
    • *P.aeuginosa *infection (cystic fibrosis)
    • *S.aureus *infection
22
Q

Glycopeptides

A
  • IV hospital use only
  • Wide use to treat multi-resistant Gram positive infection especially MRSA
  • Acts by inhibiting cross-linking of bacterial cell wall
  • Resistance rare except in enterococci
    • ​Altered target site - enterococci, staphylococci
    • Altered permeability - staphylococci
  • ​Pharmacokinetics
    • IV use only
    • Renal excretion, not metabolised
  • Side effects
    • Nephrotoxicity (10%) increased by use of other nephrotoxic agents e.g. gentamycin, furosemide
    • Ototoxicity very rarely
    • Red man syndrome (vancomycin)
    • Thrombocytopenia (teicoplanin large doses)
  • Requires therapeutic drug monitoring
23
Q

Glycopeptides - spectrum

A
  • Active against nearly all Gram positive bacteria - especially multi-resistant strains
  • Not active against Gram negative bacteria
24
Q

Glycopeptides - indications

A
  • *MRSA *infection
  • *Clostridium difficile *associated diarrhoea (CDAD) as a second line treatment
  • Multi-resistant Gram positive infections:
    • Coagulase negative staphylococci
    • Corynebacteria
    • Enterococci
  • ​Prosthetic infection (line, joint etc.)
  • Penicillin allergy
25
Q

Macrolides

A
  • IV and PO agents widely used in hospital and community to treat LRTIs and in penicillin allergy
  • Mode of action by inhibition of protein synthesis at ribosome
  • Resistance common due to target side modification
  • Pharmacokinetics:
    • Reasonable bioavailability
    • Good oral absorption
    • Good tissue penetration
    • Renal and biliary excretion
  • Side effects:
    • Nausea and GI upset (especially erythromycin) - due to pharmacological effect on stomach motility
26
Q

Macrolides - spectrum

A
  • Active against Gram positive oranganisms i.e. *S.aureus *(not MRSA) and Streptococci
    • Resistance 10-20%
  • Active against atypical respiratory pathogens:
    • Legionella
    • Mycoplasma
    • Chlamydia
  • ​No activity against Gram negatives except for campylobacter
27
Q

Macrolides - Indications

A
  • Skin/soft tissue infections if allergic to penicillin
  • Community acquired pneumonia
  • *Campylobacter *infections
28
Q

Tetracyclines

A
  • Used in primary care to treat acne
  • Used in hospitals to treat MRSA
  • Acts by inhibitng protein synthesis at the ribosome
  • Resistance common due to:
    • Efflux pumps
    • Target site modification
  • Contraindicated in children as concentrates in bone/teeth where it binds to calcium
  • Only oral availability
29
Q

Metronidazole

A
  • Available IV/PO
  • Widely used to treat anaerobic infections
  • Resistance very rare
  • Acts by disrupting DNA
  • Pharmacokinetics:
    • Well absorbed PO and PR
    • Wide tissue distribution
  • Side effects:
    • Safety concerns in early pregnancy
    • Disulphiram-like reaction with alcohol
    • Rare peripheral neuropathy on long-term therapy
30
Q

Trimethoprin

A
  • Available PO only
  • Used to treat uncomplicated UTI
  • Used in combination with *sulphamethoxazole (co-trimoxazole) *to treat p**neumocystis pneumonia (PCP) - PO/IV
  • Acts by inhibiting dihydrofolate resuctase to impair folate metabolism
  • Resistance due to:
    • Overproduction of enzyme
    • Target site modification
  • 20% of E.coli resistant
  • Renal excretion
31
Q

Linezolid

A
  • Only oxazolidinase available for clinical use
  • Active against a wide range of Gram positive bacteria including multi-resistant strains (MRSA, VRE)
  • Used as a second line agent in serious Gram positive infection
  • Pharmacokinetics:
    • Good bioavailability
    • Moderate/good tissue distribution
    • Non-enzymatic degradation
    • Breakdown products renally excreted
  • Side effects:
    • Thrombocytopenia
    • Neuropathy with long term use
32
Q

Daptomycin

A
  • Only lipopeptide antibiotic available
  • Active against a wide range of Gram positive bacteria including multi-resistant strains (MRSA, VRE)
  • Used as a second line therapy against serious Gram positive infection
  • Not suitable for use in lung infections
  • Pharmacokinetics:
    • Poor oral absorption - IV only
    • Renal excretion
    • Poor lung penetration
  • Side effects:
    • Muscle toxicity

Microbiology (10 decks)

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