Antimicrobial Chemotherapy Flashcards
Indications of antivirals
- Therapy: empiric, directed
- Prophylaxis: primary, secondary
Diagnosis
- Diagnosis: clinical, lab
- Severity: sepsis, septic shock
Patient characteristics
- Age
- Renal function
- Liver function
- Immunocompromised
- Pregnancy
- Known allergies
Antimicrobial selection
- Guideline/”individualised” therapy
- Likely organisms
- Empirical or result-based
- Bactericidal vs bacteriostatic
- Single agent/combination
- Potential adverse effects
Bactericidal
E.g. beta-lactams
- Act on cell wall
- Kill organisms
- Indications: neutropenia, meningitis, endocarditis
Bacteriostatic
E.g. macrolides
- Inhibit protein synthesis
- Prevent colony growth
- Require host immune system to “mop up” residual infection
- Useful in toxin-mediated illness
Prescribing
- Route of administration
- Dose
- Adverse effects
- Duration
- IV to oral switch therapy
- Inpatient or outpatient therapy
- Therapeutic drug monitoring
IV to oral switch
Oral bioavailability
- Ratio of drug level when given orally compared to IV
- Oral: not vomiting, normal GI, no shock, no organ dysfunction
- IV: severe infection, when oral not available
Antibiotic resistance
- Bacteria adapt and rapidly (generate resistance) rapidly
- 4 mechanism
enzymatic inactivation of drug, modified drug targets, reduced permeability to drug, efflux of drug - Genetics: chromosomal and plasmid mediated
Chromosomal mediated resistance
- Mutation in gene coding for drug target or membrane transport system
- Frequency of spontaneous
- < frequency of acquisition of plasmids
- Basis for using multi-drug therapy
Plasmid mediated resistance
- Replicate independent of cell chromosome
- Carry 1 or more resistance genes for enzymes which degrade antibiotics/modify membrane transport systems
- Bacteria conjugate, transfer resistance genes to other species
- Certain bacteria can take up plasmids by transformation
Antibiotic Intolerances and Adverse Effects of Beta-Lactams
Mostly with penicillin and cephalosporin.
Immediate and delayed hypersensitivity
- Type I: IgE mediated specific immunoglobulin, stimulates pro-inflammatory. (Anaphylaxis)
- Type II: IgG or IgM, haematological reactions or interstitial nephritis
- Type III: IgG or IgM, lodging results in serum sickness, drug-related fever
- Type IV: T-cell causes localised inflammation
All drugs particularly tetracyclines and TB drugs
- Liver toxicity particularly pre-existing liver disease
Ethambutol (TB) side effects
Optic neuropathy
Isoniazid (TB)
Peripheral neuropathy
Resistance
Inability of antibiotic to kill bacteria
- Measured using MIC (minimum inhibitory concentration) levels
Reasons for resistance
- Inadequate dose
- Inappropriate route
- Non-compliance
- Bacteria walled off in abscess cavity
- Foreign bodies
- Poor penetration of drug to site of infection
Important Resistant Organisms
- MRSA
- VRE
- ESBL
- CPE
- C. diff
Antibiotic stewardship
- Right antibiotic, right indication, right duration
- Use only suspected/proven bacteria
- Use as per guidelines and review results
- Review prescriptions regularly and stop soon as possible
- Limit broad-spectrum use to seriously ill
Single or combination
Single - Simple - Fewer side effects/drug interactions Combination - HIV/TB, severe sepsis, mixed organisms
Penicillins (beta-lactams)
- illin/clav
Inhibition of cell wall synthesis
- Benzylpenicillin
- Penicillin V
- Amoxicillin
- Flucloxacillin
- Co-amoxiclav
- Piperacillin
- Tazobactam
Side effects:
Candida, convulsions, encephalopathy
Benzylpenicillin
Penicillin V
- Streptococci, Neisseria, Spirochetes
- Soft tissue, pneumococcal, meningococcal, gonorrhoea, syphilis
- IV/IM
- Cheap
Amoxicillin
- Broad spectrum
- Resistance common
- UTI, RTI
- Cheap
Flucloxacillin
- Staphylococcal e.g.
S. aureus - Cheap
Co-amoxiclav (4C’s)
- Broad spectrum
- Anaerobes
- UTI, RTI, soft tissue, surgical wounds
- C. diff (4C’s)
Piperacillin/tazobactam
- Broad spectrum
- Pseudomonas, anaerobes
- Neutropenic sepsis
- IV only
Cephalosporins (4C’s) (beta-lactams)
- ime
Inhibition of cell wall synthesis
- Cefradine (1)
- Cefuroxime (2)
- Ceftriaxone/Cefotaxime (3)
- Ceftazidime (3)
- Ceftaroline/Ceftobiprole (4)
Side effects: Candida, convulsions and thrush
Cefradine
- Broad spectrum
- UTI, soft tissue
- Oral, cheap but resistance +
Cefuroxime
- Broad spectrum
- UTI, RTI, surgical prophylaxis
Ceftriaxone/ceftaxime
- Broad spectrum
- Especially good against Gram -ve bacilli
- Hospital infections e.g. bacteraemia, pneumonia, sepsis
- Risk for: MRSA, C.diff, VRE
- IV/IM only
Ceftazidime
- Broad spectrum
- Especially good against gram -ve bacilli
- Pseudomonas (Hospital and CF)
- Risk for: MRSA, C. diff, VRE
- IV only
Ceftaroline/Ceftabiprole
- Broad spectrum
- Less gram -ve
- Anti-MRSA
- Good biofilm activity
- Skin and soft tissue
- Endocarditis
- Resistant to other treatment
- Risk factor for C. diff, VRE
- Expensive
- IV only
Aminoglycoside
-cin
Inhibition of protein synthesis
- Gentamicin
- Amikacin
IV? IM only
Renal and ototoxicity
Gentamicin and Amikacin
- Serious gram -ve bacilli
e. g. bacteraemia, endocarditis, neutropenic sepsis
Macrolide
-mycin
Inhibition of protein synthesis
- Clarithromycin
- Erythromycin
- Azithromycin
Clarithromycin
- Streptococci, staphylococci, mycoplasma, chlamydia, legionella
- RTI, soft tissue, STD
Erythromycin
- Streptococci, staphylococci, mycoplasma, chlamydia, legionella
- RTI, soft tissue, STD
- GI intolerance
Azithromycin
- Better for gram -ve e.g. haemophilus, chlamydia
- Once daily or stat
Quinolones
- floxacin
Inhibition of nucleic acid synthesis
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
Associated with C. diff, MRSA
May affect growing cartilage
Ciprofloxacin
- Gram -ve bacilli
