Antimicrobials and chemotherapy in clinical practice

Question 1

What antibiotics treat dental abscesses?

Answer 1

Amoxicillin 500mg tds x5/7
OR
Penicillin V 500mg qds x 5/7

Question 2

How to consider if antibiotics are necessary?

Answer 2

Is there a non antibiotic option?
Is there evidence of infection?
Is there evidence of a bacterial infection?
Is the bacteria colonising or actually causing disease?

Question 3

Primary management of dental abscesses?

Answer 3

Pulpectomy/incision and drainage
Analgesia
Antibiotics not recommended for a localised dental abscess

Question 4

When are antibiotics indicated?

Answer 4

No possibility of immediate attention by a dental practitioner
Severity/increased risk

Question 5

What are the features of severity or increased risk of complications?

Answer 5

Signs of severe infec - fever, lymphadenopathy, cellulitis, diffuse swelling
Systemic symptoms - fever/malaise
High risk = immunocompromised / diabetic / valvular heart disease

Question 6

What is evidence of an infection?

Answer 6

Find evidence of the causative organism
Obtain a blood culture - before initiating parental antibiotics
Needle aspirate - is indicated for gram stain and aerobic / anaerobic cultures

Question 7

Differential diagnosis of dental abscesses?

Answer 7

Non-infectious;

• Localised lymphadenopathy due to other infec or neoplasm
• Salivary gland problem due to stone, infec (parotitis) or dehydration/dry mouth

Neoplasm;

• Intraoral
• Salivary gland

Unerupted teeth
Viral - mumps

Question 8

How do pharyngitis and dental abscesses differ?

Answer 8

Pharyngitis = streptococcus pyogenes, EBV

Abscesses = viridans group streptococci, anaerobes, gram neg rods

Question 9

Bac associated with dental infec?

Answer 9

Bacteroides - gram neg, anaerobic
Fusobacterium - gram neg, anaerobic
Actinomyces - gram pos, , , faculatively anaerobic
Pepostreptococcus - Gram pos, anaerobic
Prevotella melaninogenica - gram neg, aerobic
Streptococcus viridans - gram pos, facultatively anaerobic
Haemophilus - gram neg, aerobic or facultatively anaerobic

Question 10

Why consider where the site of the infection is?

Answer 10

To ensure the antibiotic will penetrate the site

Question 11

What is the organism sensitivity?

Answer 11

Primary resistance
- Innate property e.g. pseudomonas and penicillin

Acquired resistance;

• Due to mutation or gene transfer
• E.g chromosomal - M.tuberculosis

Question 12

How do bacteria resist antibiotics?

Answer 12

Change antibiotic target
Destroy antibiotic
Prevent antibiotic access
Remove antibiotic from bacteria

Question 13

How does antibiotic resistance develop?

Answer 13

Intrinsic - naturally resistant
Acquired
- Spontaneous gene mutation
- Horizontal gene transfer = conjugation, transduction, transformation

Question 14

How do we detect antibiotic resistance/sensitivity?

Answer 14

Antibiotic sensitivity testing;

• Dilutional liquid culture MIC and MBC
• Antibiotic discs
• e-tests

Breakdown plates;
- Plates with specific breakpoint concentration of antibiotic in and see if a given inoculum grows or not

Chromogenic plates
Mechanism-specific tests
Genotypic methods e.g. PCR for known resistance conferring genes

Question 15

Lowest MIC ≠ best antibiotic - also consider?

Answer 15

Pharmacokinetics
Protein binding
Distribution into the site of infec
Exposure of an organism to an antibiotic needed for its eradication

Question 16

What are antimicrobials?

Answer 16

Molecules that work by binding to a target site on a bacteria
Defined as points of biochemical rxn crucial to the survival of the bacterium;
- Penicilin-binding proteins in cell wall
- Cell membrane
- DNA
- Ribosomes
- Topoisomerase IV or DNA gyrase

The crucial binding site will vary with antibiotic class

Question 17

How does the antibiotic bind to its target site(s) in the bacterium?

Answer 17

Penetrate the outer membrane (penetration resistance),
Avoid being pumped out of the membrane (efflux pump resistance),
Binding site can change its molecular configuration
and remain intact as a molecule (e.g., avoid hydrolysis by beta-lactamases)
Drug must not only attach to its binding target but also must occupy an adequate number of binding sites, which is related to its concentration within the microorganism.
To work effectively, the antibiotic should remain at the binding site for a sufficient period of time in order for the metabolic processes of the bacteria to be sufficiently inhibited.

Question 18

What are the 2 major determinants of bacteria killing?

Answer 18

Concentration and the time that the antibiotic remains on these binding sites

Question 19

What to consider when treating a difficult infection with an antibiotic?

Answer 19

Peak/MIC, AUC/MIC, Time>MIC

Question 20

What is the key parameter in concentration dependent killing?

Answer 20

How high the conc is above the MIC
Peak conc/MIC ratio;
- Aminogluycosides
- Quinolones

Question 21

What is the key parameter in time dependent killing?

Answer 21

Time that serum concentrations remain above the MIC during the dosing interval
t>MIC;
- Beta-lactams (penicillins, cephalosporins)
- Clindamycin
- Macrolides (erythromycin)

Question 22

Why consider what is the appropriate or available route of administration?

Answer 22

And dose interval/duration

Strep pharyngitis - penicillin V, oral 6hrly, 10 days

Odontogenic neck space infec - severe, IV cerfuroxime 8hrly plus oral metronidazole 8 hrly
- Mild/out pt. - oral amoxicillin 8hrly and oral metronidazole 8 hrly

MRSA bacteraemia;

• Vancomycin
• Intravenous
• 2X daily 2 weeks

Question 23

How to consider if the antibiotic is safe for the pt?

Answer 23

intolerance, allergy and anaphylaxis
side effects
age 
renal function
liver function
pregnancy and breast feeding
drug interactions
risk of Clostridium difficile (5 ‘C’s)

Question 24

Risk of C.difficile?

Answer 24

Ciprofloxacin
Clindamycin
Cephalosporins
Co-amoxiclav (augmentin)
Carbapenems, e.g. meropenem

Question 25

What does start smart mean? (What to follow when prescribing antimicrobials?)

Answer 25

Do not give if not evidence of infec
Avoid inappropriate use of broad spectrum antibiotics
Drug allergy history
Follow prescription guidelines
Document indication, drug name, dose and route on drug chart and notes
Review/stop date and duration
Obtain cultures before therapy if possible

Question 26

What does then focus mean?

Answer 26

• Reviewing the clinical diagnosis and the continuing need for antibiotics at 48*-72 hours and documenting a clear plan of action
• The ‘antimicrobial prescribing decision’ options are:
  1. Stop antibiotics if there is no evidence of infection
  2. Switch antibiotics from intravenous to oral
  3. Change antibiotics – ideally to a narrower spectrum – or broader if required
  4. Continue and document next review date or stop date
  5. Outpatient Parenteral Antibiotic Therapy (OPAT)

Record in notes

Question 27

What to consider with antibiotics?

Answer 27

1. Are antibiotics necessary?
2. What is the site of infection?
3. What is the organism sensitivity?
4. What is the appropriate or available route of administration?
5. What antibiotics are safe for the patient?