Principles of Antibiotic Use Flashcards
Describe the systemic approach to using & monitoring antimicrobial therapy in patients
- Confirming presence of infection
- Identification of pathogen
- Selection of antimicrobials & regimen
- Monitor response
What is subjective evidence?
- Localised symptoms
- Diarrhoea, N/V, Abdominal distention (GIT)
- Cough, purulent sputum (RTI)
- Dysuria, freq, urgency (UTI) - Systemic symptoms
- Feverish, chills, rigors, malaise, palpitations
- SOB, Mental status changes, weakness
What is objective evidence?
- Vital signs
- Fever** (>38.0)
- Hypotension (SBP < 100mmHg)
- Tachypnea ( RR > 22bpm)
- HR ( > 90bpm)
- Mental status (drop in Glasglow coma scale) - Lab test
- Elevated/depressed total WBC
- Increased neutrophils (Normal: 45-75%)
- Increased CRP
- Increased ESR
- Increased procalcitonin (>0.5 encouraged) - Radiological Imaging
- look for tissue changes, collections, abscess, obstructions
Difference between empiric, culture-directed & prophylaxis therapy?
Empiric
- Microbiological results not available
- Choice based on: Likely pathogen, site of infection, susceptibility
Culture-directed
- Pt’s specific microbiological results
Prophylaxis
- Given to prevent infection (eg. surgical/post-exposure prophylaxis)
Host factors affecting selection of antimicrobial agent
- Age
- Hx of allergies & ADR
- Pregnancy/lactation
- Renal/Hepatic impairment
- Status of host immune function
- Severity of illness
- Recent antimicrobial use
Rationale for combination therapy
- Extended spectrum of activity
- Synergistic batericidal effect
- Prevent development of resistance
Disadvantages of combination therapy
- Increased risk of toxicity & allergy
- Increased risk of DDI
- $$$
- Selection of MDR bacteria
- Increased risk of superinfections
- Concern for antagonistic effect?
Possible reasons for unsatisfactory response
- Inappropriate diagnosis
- Inappropriate agent
- Subtherapeutic conc
- Collections of abscess (need surgery/drainage)
- Impaired host defense
- Superinfection
- Toxicity
Types of dosing principles based on PK-PD characteristics
1) Concentration-dependent (High Cmax/MIC ratio)
- Larger dose at extended interval
2) Time-dependent (No persistent effect)
- Optimize time [antibiotic] > MIC
- More frequent dosing interval
3) Time-dependent (Persistent effect)
- Long half-life/ Post-antibiotic effect
- Overall drug exposure (AUC)/MIC
- Total daily dose
Risk factors for infection
1) Disruption of natural protective barriers
2) Age
3) Immunosuppression
4) Alterations in normal flora of host with conditions that might promote overgrowth of microorganisms
Why is oral route of administration prefered?
- Won’t introduce infection/irritation to vein
- Reduce nursing load
- Cost
- Patient tend to be > fearful of needles
In what situations would we NOT give by oral route?
- High tissue conc required
- Urgent treatment required
- Patient non-compliant
- Absorption problem
- No suitable oral antibiotic
Which antibiotics have good oral F?
- Fluoruquinolone
- Metronidazole
- Linezolid
- Cotrimoxazole
Drug factors to consider
- Spectrum of activity
- Ability to reach site of infection
(Eg. CNS - Penicillins, Cefepime, Ceftazidime, Ceftriaxone, Meropenem, Vancomycin) - PK-PD characteristics
- Route of administration
- SE profiles
- Drug interactions
- Cost
What do we look out for when monitoring response?
- Therapeutic response achieved?
- -> Resolution of signs & symptoms, microbiological clearance
- Adverse drug reactions/complications
- -> All new antibiotics: Rash, itch, angioedema
