Antibiotics Flashcards
Beta-lactam antibiotics
**Penicillins **- pharmocokinetics
- Many IV and oral agents
- Peak concentration in 1-2 hours
- Distribution into body water - about 0.2L/kg
- Little metabolism
- Mainly urinary excretion
**Penicillin V/G **- indications
- Beta-haemolytic streptococci
- pneumococci
- meningococci
- gonococci
- anerobes, gram-positive anaerobic cocci (GPAC) and clostridia
-
Resistance !
- pneumococci
- gonococci
**Flucloxacillin **- indications
-
S.aureus
- NB MRSA
**Ampicillin/amoxicillin + clavulanate **- indications
- otitis media
- COAP
- CAP
- UTI
- skin and soft tissue infection
- surgical prophylaxis
- intra-abdominal surgery
**Piperacillin/tazobactam **- indications
- Hospital IV therapy - 2nd line
Carbapenem antibiotics
- 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
First generation cephalosporins
- 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
Second generation cephalosporin
- 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
Third generation cephalosporins
- 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
Fourth generation cephalosporins
- e.g. cefpirome
- Similar spectrum to *ceftazidime + *good activity against some Gram positive cocci
Bacteria resistant to cephalosporins
- MRSA
- Enterococci
- Listeria
- Legionella
- C.difficile
- Camyobacter
- ESBL producing E.Coli/Kleibsiella
Cephalosporins - Indications
- 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
Beta-lactamase inhibitors
- 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
Fluoroquinolones
- 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
Ciprofloxacin - spectrum
- Effective against:
- Aerobic Gram negative bacteria:
- Coliforms
- Pseudomonas
- Neisseria gonorrhoeae ‘Gonococci’
- H.influenzae
- Atypical chest pathogens:
- Legionella
- Mycoplasma
- Chlamydia
- Aerobic Gram negative bacteria:
- Borderline activity against *S.aureus *and Streptococci
- Not active against anaerobes
- Some activity against M.tuberculosis
Moxifloxacin - spectrum
- As for *ciprofloxacin *but much better activity versus *Staphylococci *and Streptococci
- Poor activity against P.aeruginosa
- Better activity against anaerobes
Fluoroquinolones - Indications
- 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)
Aminoglycosides
- 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)
Aminoglycosides - spectrum
- Broad Gram negative activity - coliforms, P.aeruginosa
- No anaerobic activity
Aminoglycosides - indications
- All in combination therapies for:
- intra-abdominal infection
- infective endocarditis
- neutropaenic sepsis
- neonatal sepsis (penicillin + flucloxacillin)
- *P.aeuginosa *infection (cystic fibrosis)
- *S.aureus *infection
Glycopeptides
- 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
Glycopeptides - spectrum
- Active against nearly all Gram positive bacteria - especially multi-resistant strains
- Not active against Gram negative bacteria
Glycopeptides - indications
- *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
Macrolides
- 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
Macrolides - spectrum
- 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
Macrolides - Indications
- Skin/soft tissue infections if allergic to penicillin
- Community acquired pneumonia
- *Campylobacter *infections
Tetracyclines
- 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
Metronidazole
- 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
Trimethoprin
- 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
Linezolid
- 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
Daptomycin
- 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