Principles of antimicrobial use Flashcards
Systematic approach to antimicrobial use
1) Confirm presence of infection
- Risk factors
- Subjective evidence
- Objective evidence
- Site of infection
2) Identify pathogen
- Likely pathogen
- Any microbiological tests/results available
3) Selection of antimicrobial & regimen
- Empiric VS Definitive VS Prophylaxis
- Consider organism, host, drug factors
- Decide on choice of agent, route, dosing & duration
4) Monitor response
- Therapeutic response (treatment goals)
- ADR
Subjective evidence
Localized symptoms:
- Intra-abdominal: Diarrhoea, N/V, abdominal distension
- Respiratory tract: Cough, purulent sputum
- UTI: Frequency, urgency, dysuria
- Pain & inflammation (erythema, warmth, swelling) at site of infection
- Purulent discharge at site of infection
Systemic symptoms:
- Fever, chills, rigor
- Malaise, weakness
- Fast heart rate
- SOB
- Mental status changes
Objective evidence - Vital signs
1) Fever - Temperature ≥ 38 degC
- Non-infectious causes: Drug-induced (e.g. epileptic drugs), hyperthyroidism, cancer, stroke
2) Hypotension - SBP < 100 mmHg
3) Respiratory rate > 22 bpm
4) Heart rate > 90 bpm
5) Mental status changes
Objective evidence - Lab tests
1) TW > 10 x 10^9/L OR TW < 4 x 10^9/L
2) Increased neutrophils (normal: 45-75%)
3) Increased procalcitonin
4) Increased CRP
- Not specific, increases whenever there is inflammation
- Mild inflammation & viral infection: 10-40 mg/L
- Active inflammation & bacterial infection: 40-200 mg/L
- Severe bacterial infection & burns: > 200 mg/L
5) Increased ESR
- Not commonly used
Objective evidence - Radiology
1) X-ray
2) Ultrasound
3) CT scan
4) MRI
Using procalcitonin as a guide to start antibiotics
Initiation of antibiotics:
< 0.25 µg/L: Strongly discouraged
≥ 0.25 µg/L & < 0.5 µg/L: Discouraged
≥ 0.5 µg/L & < 1 µg/L: Encouraged
≥ 1 µg/L: Strongly encouraged
Overall: Procalcitonin must be at least ≥ 0.25 µg/L before considering antibiotics
Empiric therapy VS Culture-directed therapy VS Prophylaxis
Empiric therapy
- Microbiological results (culture / susceptibility test) not available
- Treatment is based on clinical presentation of likely site of infection, likely pathogen & likely resistance pattern (based on antibiogram)
Culture-directed
- Treatment based on microbiological results (culture / susceptibility test)
Prophylaxis
- Used to prevent an infection (e.g. surgical prophylaxis, post-exposure prophylaxis)
Selection of antibiotics - Organism factors
1) Identity of organism
- Fungus, bacteria, virus
- Genus, species
2) Susceptibility
- Based on susceptibility tests / antibiogram
Selection of antibiotics - Host factors
1) Age
- Children: Avoid Fluoroquinolones, Tetracyclines, Tigecycline
2) History of allergies & ADR
- Sulpha allergy: Avoid Sulphonamides, Cotrimoxazole
- Penicillin allergy: Avoid ß-lactams (except Aztreonam)
3) G6PD deficiency
- Avoid Sulphonamides, Cotrimoxazole, Nitrofurantoin
4) Renal/Hepatic impairment
- Renal impairment: Avoid Cotrimoxazole (CrCl < 15 mL/min), Nitrofurantoin (CrCl < 30 mL/min)
- Nephrotoxic: Vancomycin, Aminoglycosides, Polymyxin
- Hepatotoxic: Penicillins (e.g. Amoxicillin), Tetracyclines, Tigecycline, Macrolides, Nitrofurantoin
6) Pregnancy / Lactation
- Safe: ß-lactams, Macrolides
- Avoid: Tetracycline, Tigecycline, Aminoglycosides, Fluoroquinolones, Cotrimoxazole (1st & last trimester), Nitrofurantoin (at term - 38-42 weeks), Metronidazole (1st trimester)
6) Status of host immune function
- Immunocompromised - Use bactericidal drugs e.g. ß-lactams, Fluoroquinolones, Aminoglycosides, Vancomycin
- Consider broader spectrum, combination therapy
7) Severity of illness
- Consider broader spectrum, combination therapy
8) Recent antimicrobial use
- Avoid antimicrobials used recently if treatment failed
9) Healthcare-associated risk factors
- Consider broader spectrum, combination therapy
Healthcare risk factors
1) Hospitalization in past 90 days
2) Current hospitalization ≥ 2 days
3) Residence in nursing home
4) Antimicrobial use in last 90 days
5) Home infusion therapy
6) Chronic dialysis
Selection of antibiotics - Drug factors
1) Spectrum of activity
2) Ability to reach site of infection
3) PK/PD characteristics
4) Route of administration
5) Side effects
6) DDI
7) Cost
Antibiotics that cover MRSA
5th generation Cephalosporin (Ceftaroline) Vancomycin Doxycycline Tigecycline Clindamycin Linezolid Cotrimoxazole Daptomycin
Antibiotics that cover P. aeruginosa
Piperacillin-Tazobactam Ceftazidime, Cefepime Carbapenem (except Ertapenem) Aztreonam Aminoglycosides Fluoroquinolones Polymyxins
Antibiotics that cover ESBL-producing strains
Carbapenems (1st line)
Aminoglycosides
Tigecycline
Antibiotics that cover anaerobes
Bacteroides: Metronidazole Clindamycin Amoxicillin-Clavulanate Piperacillin-Tazobactam Carbapenems
C. difficile:
Vancomycin
Metronidazole
Choice of antibiotics based on site of infection:
1) CNS
2) Lungs
3) Abscesses
4) Urinary tract
5) Prostate
CNS:
Penicillins
3rd - 4th generation Cephalosporins (Ceftriaxone, Ceftazidime, Cefepime)
Meropenem
Vancomycin
Avoid: 1st - 2nd generation Cephalosporins, Aminoglycosides, Macrolides, Clindamycin
Lungs:
Avoid: Daptomycin
Abscesses:
ß-lactams
Clindamycin
Avoid: Aminoglycosides
Urinary tract: Nitrofurantoin Fosfomycin Cotrimoxazole Ciprofloxacin
Prostate:
Cotrimoxazole
Ciprofloxacin
PK-PD characteristics
1) Concentration dependent killing
2) Time-dependent killing with:
- No persistent effect (short half-life)
- Persistent effect (long half-life, post-antibiotic effect)
Antibiotics that exhibit concentration dependent killing
Aminoglycosides, Fluoroquinolones
Antibiotics that exhibit time dependent killing (no persistent effect)
Penicillins, Cephalosporins, Carbapenems
Antibiotics that exhibit time dependent killing (persistent effect)
Vancomycin
Dosing strategy for concentration dependent killing
Optimise peak:MIC ratio
Peak is 8-10x above MIC
Larger doses at extended intervals
Dosing strategy for time dependent killing (no persistent effect)
Optimize % time concentration > MIC
40-70% of dosing interval above MIC
More frequent administration IV infusion/Prolonged intermittent infusion Block excretion (e.g. Probenecid)
Dosing strategy for time dependent killing (persistent effect)
Optimize AUC:MIC ratio
E.g. Vancomycin - 400-600 for MRSA
Depends on total daily dose
Choice of route of administration
Oral route often preferred
Advantages & disadvantages of IV administration
Advantages:
1) Can achieve higher antibiotic concentrations
2) More reliable levels
3) Can be used in patients who cannot absorb orally
Disadvantages:
1) Need IV access, hospital admission
2) Phelbitis
3) More costly (requires syringes, needles etc. for administration)
IV administration often used in
1) Hospitalized patients
2) Severe infections
3) High blood concentrations needed
Oral administration NOT used if
1) Absorption problems (GI pathology)
2) No suitable oral form available
3) High tissue concentrations needed (especially in severe/difficult to treat infections e.g. endocarditis, meningitis, bone/joint infections)
4) Urgent treatment needed (emergency) (especially for severely ill patients)
5) Non-compliance
Advantages & disadvantages of IM administration
Advantages:
1) Community based
Disadvantages:
2) Painful
Nephrotoxic agents
Vancomycin, Aminoglycosides, Cotrimoxazole, Polymyxins
Hepatotoxic agents
Penicillins, Tetracyclines, Tigecycline, Macrolides, Nitrofurantoin
Antibiotics that can cause superinfections (CDAD)
Penicillins, Cephalosporins, Tetracyclines, Tigecycline, Fluoroquinolones, Clindamycin, Daptomycin
Antibiotics that can cause photosensitivity
Tetracyclines, Tigecycline, Fluoroquinolone, Cotrimoxazole
Antibiotics that can cause QT prolongation / arrhythmia
Macrolides, Fluoroquinolones
What is collateral damage
Antibiotic exerts selection pressure –> selects for drug-resistant pathogen –> increased risk of infection by drug-resistant pathogen
Benefits of combination
1) Extend spectrum of activity
- Empirical / Culture-directed therapy of polymicrobial infections
- Cover all resistant strains of the same organism
- Important in severely ill patients (appropriate antibiotics decreases mortality)
2) Synergistic bactericidal effect
- E.g. Gentamicin + Ampicillin to achieve bactericidal effect & faster clearance in Enterococcus endocarditis
3) Prevent development of resistance
- E.g. In M. tuberculosis, HIV infections
Disadvantages of combination therapy
1) Increased risk of toxicity & allergic reactions
2) Increased risk of DDI
3) Increased risk of superinfections
4) Increased cost
5) Selection of multi-drug resistant bacteria
6) Antagonistic effects (when bactericidal & bacteriostatic agents are used together)
- Less of a concern clinically
Duration of treatment for:
1) Surgical prophylaxis, chlamydia cervicitis
2) UTI, respiratory, skin infections
3) Endocarditis, osteomyelitis
4) Tuberculosis, chronic suppression
5) HIV
1) Single dose / 24h
2) 5 - 14 days
3) 4 - 6 weeks
4) Months
5) Life-long
Monitoring parameters
1) Therapeutic response
- Should see improvement within 48-72h after initiation of antibiotics
- Resolution of S/Sx
- Microbiological clearance
- Absence of complications/progression
2) ADR
- Allergies: Rash, itches, angioedema
- Vancomycin: Flushing, itch, hypotension (red man syndrome)
- Aminoglycosides: SCr, urine output (nephrotoxicity)
When to modify therapy
1) Culture / Susceptibility results available
- Escalate / De-escalate therapy according to results
2) Satisfactory response (therapeutic response)
- Switch from IV to oral
- De-escalate / Streamline therapy (switch to narrower spectrum)
- Stop if completed adequate duration
3) Unsatisfactory response (lack of therapeutic response, ADR)
- Modify therapy depending on cause of unsatisfactory response
Reasons for unsatisfactory response
1) Inappropriate diagnosis
2) Inappropriate choice of agent
3) Subtherapeutic concentrations
- Due to non-compliance, improved renal function, DDI
4) Collections / Abscesses (require drainage / surgery)
5) Weakened immune system
6) Toxicity
7) Superinfection
Patient counselling
Indication of antibiotics
Take __ tabs/caps __ times a day, for __ days
Take with/without food
Avoid taking with ___
- E.g. Tetracyclines / Fluoroquinolones - avoid taking with dairy products/products containing divalent/trivalent cations (Al/Mg antacids, Fe supplements) - take 2h before / 6h after
Complete the whole course even if you feel better (ensure infection is completely cleared)
Side effects may include ___
Stop if signs of allergy (rashes, itch, swollen eyes) or intolerable side effects occur. See a doctor immediately
