Antimicrobial Chemotherapy Flashcards
MIC
Minimum inhibitory conc. of antimicrobial able to inhibit organism growth
MBC
Minimum antimicrobial conc. required to kill an organism
Sensitive
Organism inhibited or killed by antimicrobial
Resistant
Organism not affected by antimicrobial
Bacteriocidal
Antimicrobial that kills bacteria - penicillin
Bacteriostatic
Antimicrobial that inhibits bacteria growth - erythromycin
Synergy
Combination of antimicrobials effect is greater than the sum of individual effects
Antagonism
Combination of antimicrobials effect is less than the sum of individual effects - work against each other
Action of Antibiotics and examples
Inhibit cell wall synthesis - penicillin and cephalosporin
Inhibit protein synthesis - gentamicin and erythromycin
Inhibit nucleic acid synthesis - Trimethoprim and ciprofloxacin
Mechanism of inhibition of cell wall synthesis
B-lactams - inhibit peptidoglycan synthesis by inhibiting enzymes penicillin bind proteins (PBPs)
Glycopeptides - inhibit assembly of a peptidoglycan precursor - act only on gram positive
Mechanism of inhibition of protein synthesis
Structural difference of mammalian and bacterial ribosomes allow antimicrobial attach and alter function
Aminoglycosides - treatment of gram negative - coliform and Staph. are sensitive but strep. are not - gentamicin
Macrolide and tetracycline - treatment of gram positive if patient allergic to penicillin - erythromycin, clarithromycin (low MIC).
Staph. aureus, strep progenies, strep. pneumonia resistant
Mechanism of the inhibition of nucleic acid synthesis
Inhibit DNA directly or indirectly by disrupting precursors
Trimethoprim (treats UTI infect.) and sulphamethoxazole - used as a combo (co-trimoxazole) - chest infections
Fluroquinolones - ciprofloxacin treats gram negative and cannot be used in children (no cart. growth) and levoflaxocin treats gram positives
Polyene use and examples
Anti-fungal drugs that bind to ergosterol in fungal cell wall in yeasts and filamentous fungi. Bind to sterol in mammalian cell walls so toxic
Amphothericin B
- IV treatment for serious yeast and fungal infections (use when necessary)
- Very toxic - side effect: renal, hepatitis and cardiac toxicity
Nystatin
- Regular use
- Topical treatment or in oral suspension
Azole and examples
Anti-fungal drugs that inhibit ergosterol synthesis
Fluconazole - only treats yeast infections and Candida albican sensitive but Candida krusei / glabrata are resistant
Intraconazole - yeast and filamentous fungi treats aspergillosis and dermatophytes
Vorinconazole - treats aspergillosis
Characteristic and mechanism of anti-viral drugs
There are no virucidal drug (able to kill virus) but they are virustatic (inhibit growth and replication
Many are nucleoside analogues which disrupt nucleic acid synthesis
Anti-Herpes drugs
Aciclovir - treats HSV and VZV and low toxicity
Famciclovir and Valaciclovir - HSV and shingles
Ganciclovir - CMW and toxic to bone marrow, given by IV (valganciclovir is a prodrug)
Foscarnet - treats HSV, VZV and CMW when they’re resistant to nucleoside analogues. High nephrotoxic and given by IV
Cidofovir - treat CMW
Mechanism of anti-HIV drugs
Nucleoside analogue which disrupts reverse transcriptase - shows down replication
3 drug combo - two reverse transcriptase inhibitor and either non-one or protease inhibitor
Example of a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor
Non - nevirapine and efavirenze
Prot - saquinavir, duranavir
Drugs for Hep B and C
Hep B andC - interferon-a - forms host immune system and attaches to PEG so excretion is slowed and treatment is reduced
Subcutaneous injection of interferon a and oral ribacvarin treats hep C
Hep B - lamivudine given orally
Drugs for Viral Respiratory Infection
Zanamavir and oseltamivir - treats influenza A or B with 48hrs of symptoms and post-exposure prophylaxis
Ribavarin - nucleoside analogue treats severe Respiratory Syncytial Virus (RSV)
Allylamines and examples
Anti-fungal drug which suppress ergosterol but at different stage to azoles
Terbinafrine - dermatophyte infections; fungal infection of skin and nail
Echinocandins and examples
Anti-fungal drug that inhibit synthesis of glucan polysaccharides in fungi
Caspogungin, micafungin and anidulafungin are fungicidal agents against serious candida and aspergillus infections
Action of Benzyl Penicillin
- B-lactam
- Gram positive or meningococci
- IV
- Treats pneumococcal, meningococcal and strep. pyogenes
Actions of Amoxicillin and Ampicillin
- B-lactam
- Gram negative
- 30% coliforms resistant
- Streptococci and some coliforms
Action of Flucloxacillin (methicillin in lab)
- B-lactam
- Staphlococcal infections: resistant to staph. B-lactamase
- MRSA is resistant
Action of Piperacillin
- B-lactam
- Broad spectrum
- Gram negative
- Activity against enterococcus faecalis and pseudomonas species
- Intra-adominal infection as anti-anaerobic activity
- Combined with tazobactam = tazocin (B- lactamase inhibitor)
Action of Imipenem and Meropenem
- B-lactam
- Pen. subgroup Carbapenem
- Widest spectrum
- All bacteria, includ. anaerobes
Action of Ceftriaxone
- Cephalosporin
- 3rd gen with increased activity against gram neg
- Active Pseudomonas spp.
- Less activity to gram positive form first gen
- Encourage C. Difficile
Action of Aminoglycosides and give example
- Inhibit protein synthesis
- Gentamicin - toxic
- Parenteral use only
- Gram negative includ. pseudomonas
- Staph sensitive but not strep.
Two examples glycopeptides and action
- Inhibits cell wall synthesis
- Vancomycin and Teicoplanin
- Gram positive
- Aerobic and anaerobic
- Van. = toxic
- Vancomycin resistent enterococci (VRE) - in enterococcus faecalis - precursor for peptidoglycan that it binds to have altered structure
Action of Macrolides
- Inhibits protein synthesis
- Gram positives
- Alternative to penicillin to patients with pen. allergy
- Activity against atypical pneumonia (legionella pneumophila)
Examples of macrolides
Clarithromycin and Erythromycin
-Azithromycin treats chlamydia
Action of Ciprofloxacin (Fluoroquinolone)
- Inhibits nucleic acid synthesis by targeting enzymes involved in coiling DNA
- Wide spectrum
- Gram negative includ. pseudomonas
- Second choice for staph infections
Action of Levofloxacin (Quinolone)
- Inhibits nucleic acid synthesis
- Pneumococci
- Atypical pneumonia
Action of Metronidazole (miscellaneous)
- Anaerobes
- Gram pos and neg
- Anaerobic infection; intra-abdominal sepsis
- Treat MRSA
Action of Fusidic acid (miscellaneous)
- Anti-staphylococcal drug
- Use in combo with flucloxacillin to prevent resistance
- Diffuses well into bone and tissue - staph pneumonia
Action of Trimethoprim (miscellaneous)
- Inhibits nucleic acid synthesis by inhibiting purine synthesis
- Treats UTIs
Action of Tetracyclines (miscellaneous)
- Broad spectrum which inhibit bacterial protein synthesis
- Genital and respiratory tract infection
- No to pregnant w. and -12yrs as deposited in teeth and bone
Action of Clinamycin (miscellaneous)
- Gram postive
- Anaerobes
- Good tissue penetration
- Oral
- Causes pseudo-membranous colitis
Action of Linezolid (oxazolidinone)
- Inhibits protein synthesis
- Active against MRSA
- Oral
- Cause bone marrow suppression
Action of Daptomycin (cyclic lipopeptide)
- Inhibits protein synthesis
- Gram positive only
- Treats serious MRSA infection
Action of Fidaxomicin
- Macrocyclic antibiotic
- Bactericidal against C. difficile and reduces recurrence
Name agents for urinary tract infection (cystitis)
- Nalidixic acid
- Nitrofurantoin
Action of Nalidixic acid
- Quilones
- Treats coliform urinary tract infect.
- only gram neg. aerobes (coliform)
- All excreted in urine
Action of Nitrofurantoin
- Urinary antiseptic - UTI treatment
- Gram neg. - except Proteus and Pseudomonas spp.
- Also some gram pos.
What antimicrobials are associated with allergic reactions
Commonly B-lactam drugs
Example of immediate hypersensitivity
Anaphylactic shock
Mechanism of anaphylactic shock
- After parenteral administration of drugs
- IgE mediated
- Itching, nausea, vomiting
Symptoms of delayed hypersensitivity
- Drug rashes
- Uncommon: drug fever, serum sickness and erythema nodosum
- Maculopapular and restricted to skin
Gastrointestinal side effects
- Nausea and vomiting
- Clostridium difficile
What type of organism in C. difficile?
Anaerobic gram positive bacillus - spore forming
How is C. difficile detected?
Detection of toxin in stool by an enzyme immunoassay (EIA)
Steps taken when patient diagnosed with C. difficile?
- Isolated until asymptomatic for 48hr
- Stop drugs if possible
What is C. difficile treated with?
Oral metronidazole or vancomycin and fidaxomicin
How do antimicrobials cause thrush?
Broad spectrum drugs suppress normal flora allowing overgrowth of Candida albicans causing oral/vaginal candidiasis (thrush)
What side effect do antimicrobials have on the liver?
- Cause hepatotoxicity
- Elevation of enzymes
- Hepatitis
What drugs cause liver toxicity?
- Tetracyclin
- Rifampicin
- Flucloxacillin
What drugs cause nephrotoxicity (renal toxicity)?
- Aminoglycoside (gentamicin, netilmicin, amikacin)
- Vancomycin
What drugs cause Ototoxicity (neuro tox)
Aminoglycosides or vancomycin
What can ethambutol (anti-tuberculous drug) cause?
Optic nerve damage
What types of drugs cause encephalopathy and convulsions?
High dose penicillin and cephalosporin
What drugs cause peripheral neuropathy?
- Metronidazole
- Nitrofurantoin
Neutropenia effect on haematological toxicity
Selective depression of one cell line in bone marrow
Pancytopenia effect on haematological toxicity
Unselective depression of all bone marrow elements
Linezolid effect on haematological toxicity
- Bone marrow suppression
- Lowers platelet counts
How to prevent adverse reactions
- Use minimum dose and duration
- Care with pregnant w., age and patients with liver or renal insufficiency
- Monitor toxicity of drugs with small therapeutic margins
Importance of age when choosing an antimicrobial agent?
Some not suitable for children - ciprofloxacin
Importance of renal function when choosing an antimicrobial agent?
Doses to be decreased proportional to degree of renal insufficiency
Importance of liver function when choosing an antimicrobial agent?
Doses decreased in hepatic insufficiency or use alternate drug
Importance of pregnancy when choosing an antimicrobial agent?
Some drugs not used as mutagenic (in foetus) or teratogenic (cogenital abnormalities)
Unknown effect of foetus
What are safe drugs to use in pregnancy?
Penicillins, cephalosporins and urinary antiseptic nitrofurantoin
What drugs cause teratogenic and mutagenic effects?
Metronidazole and trimethoprim
What is prophylaxis?
Administration of drugs to prevent the future occurrence of infection
When is prophylaxis used?
- Exposure to highly communicable disease
- About to undergo surgery that has high post-op infection rates
What is a principle of prophylaxis?
Dosage should cover the period of risk only - beyond could develop resistant organisms
What is empirical antimicrobial therapy?
Treating infection by guessing likely causative organisms and common drug susceptibility patterns
What is important to carry out after empirical antimicrobials therapy?
Treatment to be reviewed once results of culture and antibiotic sensitivity tests are available
Describe drug related considerations
- Be effective against organism
- Choice based on results of sensitivity tests
When should drugs be used in combination?
- Cover mixed infections by more than one organisms
- Synergistic effect
- Minimise development of resistant strains to one agent
Action of Co-amoxiclav
- B-lactamase inhibitor
- Covers B-lactamase producing conforms (gram negative)
Why monitor serum levels?
To ensure therapeutic levels have been achieved and to check it is not toxic
What is the E test?
Way to measure MIC of drug against organism - can be read from the point where the growth of organism intersects strip
What drugs treat C. difficile?
Oral metronidazole and vancomycin and fidaxomicin
What drugs treat MRSA?
Vancomycin, teicoplanin, linezolid and daptomycin
