CLINICAL USE OF ANTIBIOTICS

1
CLINICAL USE OF ANTIBIOTICS
2

• Broad-spectrum
• Justifiable in life-threatening disease, with
  unidentified organism
• In general more expensive more likely to ?
  resistance
• More adverse effects than narrow spectrum (inc.
  superinfection)
• Narrow spectrum
• Preferable if possible
• Dangerous choice in life-threatening disease
  unless organism (and sensitivities) known

3

• Principles for prescribing antibiotics
• Make a diagnosis of bacterial infection and
  consider likely organisms/sensitivities
• Take appropriate specimens for culture/sensitivity
  
• Are AB needed at all?
• ? Need for urgent therapy before culture data
  available?
• Seriously ill patients ? empirical AB
• This may prevent confirmation of diagnosis or the
  ID of the organism

4

• Major antibiotics
• Penicillins
• Cephalosporins
• Aminoglycosides
• Macrolides
• Quinolones
• Antifolates
• Metronidazole
• Mode of action in brief
• Spectrum in brief
• Clinical pharmacokinetics just the important
  bits
• Indications and modes of use
• Contraindications
• Adverse effects
• Drug interactions

5

• The most appropriate drug/dose/route
• organism AB sensitivities (often best guess)
• Age, allergy, renal or hepatic function,
  resistance to infection (e.g. immunosuppression),
  pregnancy
• Severity influences choice and route
• Site of infection e.g. aminoglycosides are
  inappropriate for meningitis
• Foreign bodies

6

• Monitor clinically, microbiologically, PK
• Combinations are occasionally used
• Mixed infections, e.g. in peritonitis
• To achieve synergism
• Organism unknown and serious illness
• To prevent the development of resistance

7
Penicillins

• Mode of action
• acts on the cell wall
• Spectrum in brief
• mainly Gram
• Benzyl penicillin narrow spectrum, Pneumococcus,
  Meningococcus
• Amoxycillin broader spectrum, including
  Haemophilus
• Flucloxacillin Staphylococcus aureus
• Clinical pharmacokinetics
• Benzyl pen acid labile
• Others many routes
• Cross BBB poorly except when inflamed
• Renal elimination
• Indications and modes of use
• No need for TDM

• Contraindications
• Hypersensitivity
• GIT upset
• (renal impairment)
• Adverse effects
• Gastrointestinal upsets (common)
• Drug interactions
• Only good ones

8
Macrolides

• Mode of action
• Protein synthesis
• Spectrum in brief
• Gram
• Atypical organisms (Chlamydia, Legionella)
• Clinical pharmacokinetics
• Erythromycin
• Acid labile (overcome by formulation) absorption
  can be erratic
• Poor BBB
• Metabolised in liver
• Indications and modes of use
• Penicillin allergy
• Oral and IV

• Contraindications
• Hypersens
• Adverse effects
• Gastrointestinal upsets (common)
• Rarely hypersensitivity, or cholestatic jaundice
• Interactions
• Enzyme inhibitor

9
Metronidazole

• Mode of action
• binds to DNA and blocks replication
• Spectrum in brief
• anaerobes
• Clinical pharmacokinetics
• well absorbed oral/rectal
• can also be given IV
• widely distributed (inc abscesses)
• metabolised by the liver
• Indications and modes of use
• abdominal surgery
• vaginal infections (pessaries)
• dental abscesses

• Adverse effects
• Nausea, anorexia and a metallic taste
• Peripheral neuropathy
• Disulfiram-like reaction
• Teratogenic
• Drug interactions
• Enzyme inhibitor

10
Antifolates

• Mode of action
• DHFR
• DHPS
• Spectrum in brief
• Gram and
• Pneumocystitis carinii
• Clinical pharmacokinetics
• Both trimethoprim and sulphonamides eliminated
  renally
• Indications and modes of use
• UTI
• URTI
• PCP

• Contraindications
• Sulphonamide allergy
• Adverse effects
• Allergy
• Megaloblastic anaemia
• Drug interactions
• Cotrimoxazole enzyme inhibition

11
Quinolones

• Mode of action
• DNA gyrase
• Spectrum in brief
• Mainly Gram
• Clinical pharmacokinetics
• Well absorbed
• Ciprofloxacin
• Renal and hepatic elimination
• Indications and modes of use
• UTI
• Life threatening bacteraemias (IV)

• Contraindications
• Bone damage in children
• Epilepsy
• Adverse effects
• Gastrointestinal upsets
• GABA confusion in the elderly and lower the
  fitting threshold
• Drug interactions
• Enzyme inhibitor

12
Aminoglycosides

• Mode of action
• Protein synthesis
• Spectrum in brief
• Need active transport, not done by anaerobes
• Mainly Gram
• Clinical pharmacokinetics
• Not absorbed from gut
• Parenteral
• Renal elimination
• Indications
• Life-threatening infections
• Parenteral admin in hospital
• TDM

• Contraindications
• Hypersens
• Renal failure
• Adverse effects
• Renal failure
• Ototoxicity
• Drug interactions
• Only good ones