Beruflich Dokumente
Kultur Dokumente
Antibiotics
Dr Cathy Armstrong
SpR In Anaesthesia & Clinical Fellow in Undergraduate Medical Education
Manchester Royal Infirmary
March 2011
Objectives
Understand the classification of bacteria Discuss the broad mechanisms of action of antibiotics Consider important features of the main classes of antibiotic Understand penicillin allergy Understand the definitions of SIRS, sepsis & septic shock Be aware of some prescribing strategies & where to access help / information
Definitions
Antibiotic
Molecules that kills or stop the growth of microorganisms
Bactericidal
Antibiotics that kill bacteria
Bacteriostatic
Antibiotics that stop the growth of bacteria
Bacteria
Pili
Classification bacteria
Gram positive
Retain the original blue colour of Gram stain
Gram negative
Original blue colour washed away by acetone, counterstained red
Classification of bacteria
Gram Positive
Peptidoglycan cell wall
Plasma membrane
outer membrane
Gram negative
Classification of bacteria
Bacteria
Aerobic
Anaerobic
Gram +ive
Cocci Bacilli
Gram -ive
Cocci Bacilli
Gram +ive
Cocci
Bacilli
Staph aureus
Cellulitis, septic shock, endocarditis
Strep A
pharyngitis
Anaerobic
Clostridium
Tetanus Abdominal sepsis
Klebsiella
UTI, septic shock, pneumonia
Pseudomonas
UTI, pneumonia, septic shock
Anaerobic
Bacteroides
Abdo sepsis
Classification of antibiotics
Class by coverage
Gram negative Vs. Gram Positive Anaerobic vs aerobic atypical
Class by group
Beta lactams
penicillins Cephalosporins Carbapenems
Classification of antibiotics
Class by mechanism of action
Inhibit cell wall synthesis
Glycopeptides
All contain a beta lactam ring in chemical structure Target penicillin binding proteins (PBPs)
Peptidoglycan Cell wall synthesizing enzymes found in plasma membrane Not present in mammalian cells
Penicillins
Narrow spectrum
Benzylpencillin
Most Gram pos, anaerobes, some Gram neg Most S. Aureus resistant (-lactamase)
Flucloxacillin
Unaffected by staphylococcal -lactamase
Penicillins
Broad Spectrum
Amoxicillin
Gram pos & some Gram neg -lactamase resistance common
Piperacillin
Similar to amoxicillin + pseudomonas cover Destroyed by -lactamase
Penicillin allergy
Anaphylactic reactions are rare (0.05%) BUT - fatal in up to 10% of cases General hypersensitivity reaction (e.g. rashes) occurs in 1-10% of exposed patients Patients who have vague symptoms or GI upset are probably not allergic
Cephalosporins
Classified in generations 1st generation mainly Gram positive cover, successive generations increasing potency against Gram negative E.g.
1st - cephalexin 2nd - cefuroxime 3rd - cefotaxime / ceftriaxone Cefotaxime & ceftriaxone readily cross BBB - used in meningitis
Historically contraindicated in patients with severe immediate allergic reaction to penicillin (urticaria / anaphylaxis) Recent epidemiological studies
Suggest for 2nd generation - cross reactivity much less
Carbapenems
Similar mode of action to other -lactams Greater affinity for PBP-2
Faster bacterial death
Extremely broad spectrum E.g. imipenem / meropenem Used for severe hospital acquired infections
Glycopeptides
Prevent bacterial cell wall synthesis
Bind to amino acids in cell wall
Tetracyclines
Chloramphenicol
Aminoglycosides
Gentamicin
Good Gram neg cover, some Gram pos cover Used for serious Gram neg infections Synergistic action with -lactams Side effects
Nephrotoxic & ototoxic Toxicity directly related to plasma levels once daily dosing Caution in renal failure
Affect RNA
Rifampicin
Side effects
Common
GI disturbances
Less common
Anaphylaxis / hypersensitivity reactions Thrombocytopenia ARF Hepatotoxicity Photosensitivity
Drug interactions
OCP
When to Prescribe
Prophylaxis
Surgery Endocarditis
Treat infection
Which of the following is NOT considered as part of the criteria for SIRS?
1. RR > 20/min 2. Heart rate < 60 3. Temp <360C or >380C 4. PaCO2 < 32mmHg
25% 25% 25% 25%
SIRS
Systemic inflammatory response syndrome
2 or more of the following criteria:
Temperature < 36 0C or > 38 0C HR > 90 PaCO2< 32mmHg RR > 20 WBC > 12.0 < 4.0, or > 10% immature (band) forms
Associated definitions
Sepsis
Documented infection together with 2 or more SIRS criteria
Severe sepsis
Sepsis associated with organ dysfunction
Septic shock
Sepsis with refractory hypotension or hypoperfusion abnormalities in spite of adequate fluid resuscitation
Rationale
Ideally narrow spectrum Consider likely organisms Start broad spectrum then narrow with culture results
Other considerations
Route Length of course Appropriate dose
Renal failure
Information / guidelines
BNF Local guidelines Microbiologist
Summary
Classification of bacteria
Gram Negative Vs. Gram Positive
Discussed the broad mechanisms of action of antibiotics Consider important features of some of the main classes of antibiotic Discussed penicillin allergy Defined SIRS, sepsis & septic shock Discussed prescribing strategies & where to access help / information
All Figures were produced using Servier Medical Art - www.servier.com