Antimicrobial chemotherapy Flashcards
Define ‘bactericidal’
antimicrobial that kills bacteria (eg penicillins)
Define bacteriostatic
antimicrobial that inhibits growth of bacteria (eg. erythromycin)
Define a ‘sensitive’ organism
Organism that is inhibited or killed by levels of antimicrobial at site of infection
Define a ‘resistant’
An organism is considered resistant if it is not killed or inhibited by levels of the antimicrobial that are available at the site of infection
Define ‘MIC’
Minimal inhibitory concentration - The minimum conc. of an antimicrobial needed to inhibit visible growth of a given organism
Define ‘MBC’
Minimal bactericidal conc. - The minimum conc. of the antimicrobial needed to kill a given organism
What are the 3 routes of administration
Systemic - taken internally, orally or parenterally
Topical - Applied to surface, skin or mucous membranes e.g. conjunctiva
Parenteral - intra-venously (iv), intra-muscularly (im), subcutaneously
What are the 3 mechanisms of action of antimicrobial agents
Inhibition of:
cell wall synthesis
protein synthesis
nucleic acid synthesis
What two types of drugs are β-lactams
Penicillins and cephalosporins
β-lactam antibiotics disrupt peptidoglycan synthesis by inhibiting enzymes responsible for cross-linking carbohydrate chains
(Peptidoglycan is important structural component of bacterial cell wall and enzymes involved in its synthesis)
What are the two types of antimicrobials which inhibit cell wall synthesis
Glycopeptides and β-lactams
What are two common glycopeptides
Vancomycin and teicoplanin
Describe the mechanism and range of action of glycopeptides
Inhibit cell wall synthesis - at a prior stage than B-lactams
only act on gram positive organisms
What route of administration must glycopeptides take (unless special circumstances)
Parenterally
What is one side effect of vancomycin
Toxic
What are the 4 types of antimicrobial which inhibit protein syntehsis
- Aminoglycosides
- Macrolides and tetracyclines
- Oxazolidinones
- Cyclic lipopeptides
What type of bacteria are aminoglycosides useful for?
Serious gram negative Infection
What type of drug is getamicin and what is a common side effect of adminsitration
Aminoglycoside, toxic - requires careful dosing regime and motoring of levels
What are the uses of macrolides and tatracyclines
Treatment of gram positive infections in patients with penicillin allergy
Cannot be used without lab testing
What class of drug is linezolid and what is it commonly used for?
Oxazolidonones (protein synthesis inhibitor)
Good activity against MRSA
Typically in reserve for treatment of serious infection
What class of drug is daptomycin and what it is commonly used for?
Cylic lipopeptide (protein synthesis inhibitor)
Activity against gram positives in general and MRSA in particular
What are the 2 classes of drug which inhibit nucleic acid synthesis
- Trimethoprim and sulphamethoxazole
- Fluoroquinolone’s
What type of drug is ciprofloxacin?
What it is commonly used for?
What are some drawbacks?
Fluoroquinolone (nucleic acid inhibitor)
Against gram negative organisms
Can be taken orally
Not used in children
Describe inherent/intrinsic resistance
Some cases all strains of a species are naturally resistant to antibiotic
Inability of drug to penetrate bacterial cell wall to exert its action
What is the first way in which acquired resistance can be acquired in bacteria
- Spontaneous mutation during multiplication of bacterial DNA can result in change in structure or function which no longer allows antibiotic to act, target may have changed
What is the second way in which acquired resistance may be acquired?
- resistance genes can spread from organism to organism or species to species
Most common mode by plasmids (extra chromosomal packages for DNA) or on transposons (packets of DNA which insert themselves into chromosome)
What are the 2 mechanisms of resistance to β–lactam antibiotics?
β-lactamase production - bacterial enzymes cleave β–lactam ring of antibiotic and inactive it
Alteration of penicillin binding protein (PBP) target site - Mutations in PBP genes modifies target site and β–lactams will no longer bind
What drug is β-lactamase resistant
Flucloxacillin - can be used to treat β-lactamase producing staph. aureus
(staph.aureus produce β-lactamase)
What are ESBL’s and what are the implications of their existence
Extended spectrum β–lactamases (ESBLs) - increasing problem in hospitals
Produced by some Gram negative organisms and can break down third generation cephalosporins and penicillins
Render organism resistant to all β–lactam
antibiotics
What glycopeptide resistant bacteria has appeared recently and what are the implications of this mutation?
Vancomycin resistant enterococci (VREs)
Mechanism of resistance might spread from enterococci to Staph aureus, producing
vancomycin resistant Staph aureus
Staph aureus more significant pathogen than enterococci
Describe the spectrum of Benzyl penicillin (penicillin G)
Best choice for IV treatment of serious pneumococcal, meningococcal and strep pyogenes
Gram +ve
Describe the spectrum of amoxicillin/ampicillin
Streptococci and coliforms
Gram -ve
Describe the spectrum of co-amoxiclov
Effective against B-lactamase producing coliforms
Describe the spectrum of flucloxacillin
Effective against staph infections
Describe the spectrum of piperacillin
Enterococcus faecalis
Pseudomonas species
Extended Gram -ve cover
Describe the spectrum of cephalosporins
Activity against Gram -‘ve organisms increases from 1st through 3rd generation
Activity against Gram +’ve organisms decreases from 1st through 3rd generation
Not used as much now, may encourage Ciff D infections
How must cephalosporins be taken?
Parenteral use only
Describe the specrum of aminoglycocides
Gram -‘ve organisms
Effective against staphlococci but not streptococci
Gentamicin cheapest and most common aminoglycocide
Describe the spectrum of glycopeptides
Only gram +’ve organisms - anaerobic + aerobic
Vancomycin most common example
Describe the spectrum of action of macrolides
Mainly against gram +’ve organisms
Alternative to penicillin for patients with penicillin allergy
Describe the spectrum of action of Quinolones
Active against nearly all gram -‘ve organisms
Mainly used in treatment of community acquired pneumonia
Describe the spectrum of action of metronidazole
Gram +’ve and -‘ve anaerobes
Describe the spectrum of action of fusidic acid
Disrupts bacterial protein synthesis
Anti-Staphyloccocal
In combo with flucloxacillin
Describe the spectrum of action of trimethoprim
Used in urinary infections
Describe the spectrum of action of tetracyclines
Used in genital tract and urinary tract infections
Describe the spectrum of action of clindamycin
Gram +’ve organisms
What infection is linezolid used against
MRSA
What infection is fidaxomicin used against
C. diff
What infection is daptomycin used against?
MRSA
Vancomycin Resistant Enterococci
What are the 4 classes of anti-fungal drugs?
Polyenes
Echinocandins
Allyamines
Azoles
Describe the mechanism of polyenes
Bind to ergosterol
Present in fungal cell wall but not bacterial
Increases permeability of cell wall
Binds to mammalian sterols making polyenes toxic
Describe the use of amphotericin B and Nystatin
Amphotericin B - IV for serious yeast infections and other fungal infections
Very toxic
Nystatin - topically or in oral suspension for serious fungal infection
Not intra-venous agent
Describe the mechanism of Azoles
Inhibit ergesterol synthesis
What is fluconazole used to treat?
Yeast infections
What are voriconazole and intraconazole used to treat?
Aspergillosis
(fungal infection caused by aspergillus, affects airways)
Describe the mechanism of allylamines
Suppress ergosterol synthesis but act at different stage of synthetic pathway from azoles
Describe the use of Terbinafine
Fungal infections of skin and nails
Describe the mechanism of echinocandins
Inhibit synthesis of glucan polysaccharide in several types of fungi
What are echinocandins used for?
Serious candida and aspergillus infections
Describe anti-herpes virus drugs
All become latent and include:
Herpes simplex virus (HSV)
Epstein-barr virus (EBV)
Cytomegalovirus (CMV)
Varicella-Zoster Virus (VZV).
Describe the mechanism and function of Aciclovir
Nucleotide analogue
Converted into active form by enzyme
Specific for virus-infected cells
Not very toxic
Extremely active against HSV and VZV
IV used for serious, Oral for less serious
Describe the use of valaciclovir and famciclovir
Related to aciclovir - Used in oral treatment of HSV and shingles
Describe the use of valganciclovir
Prodrug of ganciclovir -> alternative treatment for CMV
High levels of bone marrow toxicity
(prodrug is a medication or compound that, after intake, is metabolised into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolised, and excreted)
Describe the use of foscarnet (Foscavir)
Used for HSV, VZV and CMV
Highly nephrotoxic (toxic to kidneys)
Describe the use of Cidofovir
Used for CMV retinitis (retinal eye disease)
