Antimicrobials and chemotherapy in clinical practice Flashcards
What antibiotics treat dental abscesses?
Amoxicillin 500mg tds x5/7
OR
Penicillin V 500mg qds x 5/7
How to consider if antibiotics are necessary?
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?
Primary management of dental abscesses?
Pulpectomy/incision and drainage
Analgesia
Antibiotics not recommended for a localised dental abscess
When are antibiotics indicated?
No possibility of immediate attention by a dental practitioner
Severity/increased risk
What are the features of severity or increased risk of complications?
Signs of severe infec - fever, lymphadenopathy, cellulitis, diffuse swelling
Systemic symptoms - fever/malaise
High risk = immunocompromised / diabetic / valvular heart disease
What is evidence of an infection?
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
Differential diagnosis of dental abscesses?
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
How do pharyngitis and dental abscesses differ?
Pharyngitis = streptococcus pyogenes, EBV
Abscesses = viridans group streptococci, anaerobes, gram neg rods
Bac associated with dental infec?
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
Why consider where the site of the infection is?
To ensure the antibiotic will penetrate the site
What is the organism sensitivity?
Primary resistance
- Innate property e.g. pseudomonas and penicillin
Acquired resistance;
- Due to mutation or gene transfer
- E.g chromosomal - M.tuberculosis
How do bacteria resist antibiotics?
Change antibiotic target
Destroy antibiotic
Prevent antibiotic access
Remove antibiotic from bacteria
How does antibiotic resistance develop?
Intrinsic - naturally resistant
Acquired
- Spontaneous gene mutation
- Horizontal gene transfer = conjugation, transduction, transformation
How do we detect antibiotic resistance/sensitivity?
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
Lowest MIC ≠ best antibiotic - also consider?
Pharmacokinetics
Protein binding
Distribution into the site of infec
Exposure of an organism to an antibiotic needed for its eradication
What are antimicrobials?
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
How does the antibiotic bind to its target site(s) in the bacterium?
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.
What are the 2 major determinants of bacteria killing?
Concentration and the time that the antibiotic remains on these binding sites
What to consider when treating a difficult infection with an antibiotic?
Peak/MIC, AUC/MIC, Time>MIC
What is the key parameter in concentration dependent killing?
How high the conc is above the MIC
Peak conc/MIC ratio;
- Aminogluycosides
- Quinolones
What is the key parameter in time dependent killing?
Time that serum concentrations remain above the MIC during the dosing interval
t>MIC;
- Beta-lactams (penicillins, cephalosporins)
- Clindamycin
- Macrolides (erythromycin)
Why consider what is the appropriate or available route of administration?
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
How to consider if the antibiotic is safe for the pt?
intolerance, allergy and anaphylaxis side effects age renal function liver function pregnancy and breast feeding drug interactions risk of Clostridium difficile (5 ‘C’s)
Risk of C.difficile?
Ciprofloxacin Clindamycin Cephalosporins Co-amoxiclav (augmentin) Carbapenems, e.g. meropenem
What does start smart mean? (What to follow when prescribing antimicrobials?)
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
What does then focus mean?
- 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
What to consider with antibiotics?
- Are antibiotics necessary?
- What is the site of infection?
- What is the organism sensitivity?
- What is the appropriate or available route of administration?
- What antibiotics are safe for the patient?
