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Applied Sciences Lecture Course. 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

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antibiotics

Applied Sciences Lecture Course

Antibiotics

Dr Cathy Armstrong

SpR In Anaesthesia & Clinical Fellow in Undergraduate Medical Education

Manchester Royal Infirmary

March 2011

objectives
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
Definitions
  • Antibiotic
    • Molecules that kills or stop the growth of microorgansims
  • Bactericidal
    • Antibiotics that kill bacteria
  • Bacteriostatic
    • Antibiotics that stop the growth of bacteria
bacteria
Bacteria

Pili

Ribosome

DNA

Flagella

classification bacteria
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
Classification of bacteria

Peptidoglycan cell wall

Gram Positive

Plasma membrane

outer membrane

Gram negative

Peptidoglycan cell wall

Periplasmic space

Plasma membrane

classification of bacteria1
Classification of bacteria

Bacteria

Aerobic

Anaerobic

Gram +ive

Gram -ive

Gram +ive

Gram -ive

Cocci

Cocci

Bacilli

Cocci

Bacilli

Bacilli

Bacilli

gram positive bacteria
Gram positive bacteria
  • Aerobic
    • Strep pneumoniae
      • CAP, septic shock, meningitis
    • Staph aureus
      • Cellulitis, septic shock, endocarditis
    • Strep A
      • pharyngitis
  • Anaerobic
    • Clostridium
      • Tetanus
      • Abdominal sepsis
gram negative bacteria
Gram negative bacteria
  • Aerobic
    • E. Coli
      • UTI, septic shock
    • Klebsiella
      • UTI, septic shock, pneumonia
    • Pseudomonas
      • UTI, pneumonia, septic shock
  • Anaerobic
    • Bacteroides
      • Abdo sepsis
classification of antibiotics
Classification of antibiotics
  • Class by coverage
    • Gram negative Vs. Gram Positive
    • Anaerobic vs aerobic
    • atypical
  • Class by group
    • Beta lactams
      • penicillins
      • Cephalosporins
      • Carbapenems
    • Glcopeptides
    • Aminoglycosides
    • Macrolides
    • Quinilones
    • Sulphonamides
    • tetracyclines
classification of antibiotics1
Classification of antibiotics
  • Class by mechanism of action
    • Inhibit cell wall synthesis
    • Inhibit protein synthesis
    • Inhibit nucleic acid synthesis
inhibition of cell wall synthesis
Inhibition of cell wall synthesis
  • Beta lactams
    • Penicillins
    • Cephalosporins
    • Carbapenems
  • Glycopeptides
which of these is the safest option in penicillin allergy
Which of these is the safest option in penicillin allergy?
  • Co-amoxiclav
  • teicoplanin
  • flucloxacillin
  • Tazocin
  • Cefuroxime
  • Meropenem
beta lactam antibiotics
Beta lactam antibiotics
  • Single largest group
    • Penicillins, Cephalosporins, Carbapenems, Monobactams
  • All contain a beta lactam ring in chemical structure
  • Target penicillin binding proteins (PDP’s)
    • Peptidoglycan Cell wall synthesizing enzymes found in plasma membrane
    • Not present in mamalian cells
  • Bacteriocidal
  • Synergistic action
beta lactam resistance
Beta lactam resistance
  • Enzymatic destruction of -lactam (-lacatamase or penicillinase)
  • Bacterial modification of PDP target (MRSA)
  • Impermeability of cell membrane to -lactam
  • Active excretion by bacteria (mainly Gram neg)
penicillins
Penicillins
  • Narrow spectrum
    • Benzylpencillin
      • Most Gram pos, anaerobes, some Gram neg
      • Most S. Aureus resistant (-lactamase)
    • Flucloxacillin
      • Unaffected by staphylococcal -lactamase

Classically given together in cellulitis

(staph / strep infections)

penicillins1
Penicillins
  • Broad Spectrum
    • Amoxicillin
      • Gram pos & some Gram neg
      • -lactamase resistance common
    • Piperacillin
      • Similar to amoxicillin + pseudomonas cover
      • Destroyed by -lactamase

Combined with -lactamase inhibitors

Amoxicillin + claulanic acid = co-amoxiclav

Piperacillin + Tazobactam = Tazocin

penicillin allergy
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
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

can cephalosporins be given in penicillin allergy
Can cephalosporins be given in penicillin allergy?
  • Traditionally 10% cross-reactivity stated
    • Based on 1975 study
  • Historically contraindicated in patients with severe immediate allergic reaction to penicillin (urticaria / anaphylaxis)
  • Recent epidemiological studies
    • Suggest for 2nd generation - cross reactivity much less
bnf 61 march 2011
“The principal side-effect of the cephalosporins is hypersensitivity and about 0.5-6.5% of penicillin-sensitive patients will also be allergic to the cephalosporins. Patients with a history of immediate hypersensitivity to penicillin should not receive a cephalosporin. If a cephalosporin is essential in these patients because a suitable alternative antibacterial is not available, then cefixime, cefotaxime, ceftazidime, ceftriaxone, or cefuroxime can be used with caution; cefaclor, cefadroxil, cefalexin, and cefradine should be avoided”.BNF 61 (March 2011)
carbapenems
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 aquired infections
glycopeptides
Glycopeptides
  • Prevent bacterial cell wall synthesis
    • Bind to amino acids in cell wall
  • Active against Gram positive bacteria.
    • Don’t penetrate outer membrane of Gram neg bacteria (polar molecules)
  • E.g. Teicoplanin, vancomycin
  • Used in severe Gram pos infection
  • Vancomycin
    • Needs levels monitoring (after 3-4 doses in normal renal function)
    • “red man syndrome”
inhibit protein synthesis
Inhibit protein synthesis
  • Affect 30s ribosome unit (bactericidal)
    • Aminoglycosides
      • gentamicin
    • Tetracyclines
  • Affect 50s ribosome unit (bacteriostatic)
    • Macrolides
      • Clarithromycin, erythromycin
    • Chloramphenicol
aminoglycosides
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
inhibit nucleic acid synthesis
Inhibit nucleic acid synthesis
  • Affect DNA
    • Quinolones
      • ciprofloxacin
    • Nitro-imidazoles (metronidazole)
    • Trimethoprim
    • Sulphonamides
  • Affect RNA
    • Rifampicin

Inhibit folate synthesis

side effects
Side effects
  • Common
    • GI disturbances
  • Less common
    • Anaphylaxis / hypersensitivity reactions
    • Thrombocytopenia
    • ARF
    • Hepatotoxicity
    • Photosensitivity
  • Drug interactions
    • OCP
which of the following is most likely to cause c diff
Which of the following is most likely to cause C. Diff?
  • Clindamycin
  • Metronidazole
  • Benylpenicillin
  • Vancomycin
when to prescribe
When to Prescribe
  • Prophylaxis
    • Surgery
    • Endocarditis
  • Treat infection
which of the following is not considered as part of the criteria for sirs
Which of the following is NOT considered as part of the criteria for SIRS?
  • RR > 20/min
  • Heart rate < 60
  • Temp <360C or >380C
  • PaCO2 < 32mmHg
slide32
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

(? Include change in mental state / hyperglycaemia in absence of diabetes)

associated definitions
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
Rationale
  • Ideally narrow spectrum
  • Consider likely organisms
  • Start broad spectrum then narrow with culture results
other considerations
Other considerations
  • Route
  • Length of course
  • Appropriate dose
    • Renal failure
information guidelines
Information / guidelines
  • BNF
  • Local guidelines
  • Microbiologist
summary
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