Antimicrobial Chemotherapy 1 COPY Flashcards
Define ‘bactericidal’
An antimicrobial that kills bacteria (eg the penicillins)
Define bacteriostatic
An antimicrobial that inhibits growth of bacteria (eg. erythromycin)
Define ‘sensitive’
An organism is considered sensitive if it inhibited or killed by levels of the antimicrobial that are available at the site of infection
Define ‘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, either orally or parenterallyTopical
- Applied to the surface, usually skin or to mucous membranes e.g. conjunctiva Parenteral
- Administered either intra-venously (iv) or intra-muscularly (im), occasionally subcutaneously
What are the 3 mechanisms of action of antimicrobial agents
Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid synthesis
what two types of drugs are β-lactams
Penicillins and cephalosporins β-lactam antibiotics disrupt peptidoglycan synthesisby inhibiting the enzymes which are responsible for cross
-l inking the carbohydrate chains.(Peptidoglycan is an important structural component of the bacterial cell wall and the enzymesinvolved 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
They inhibit cell wall synthesis - but at a prior stage than B-lactamsthey act only on gram positive organisms
What route of administration must glycopeptides take (unless special circumstances)
Parenterally
What is one side effect of vancomycin
It is toxic
What are the 4 types of antimicrobial which inhibit protein syntehsis
- Aminoglycosides
- Macrolides and tetracyclines
- Oxazolidinones
- Cyclic lipopeptides
What type of bacteria are aninoglycosides useful for?
Serious gram negative Infection
What type of drug is getamicin and what is a common side effect of adminsitration
It is an Aminoglycoside and is toxic
- requiring a careful dosing regime and motoring of levels
What are the uses of macrolides and tatracyclines
Useful in treatment of gram positive infections in patients who are penicillin allergic
- however CANNOT BE USED WITHOUT LABORATORY TESTING
What class of drug is linezolid and what is it commonly used for?
It is an oxazolidonones (protein synthesis inhibitor). It has good activity against MRSA
- Typically held in reserve for the 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 of the drawbacks of the
Ciprofloxacin is a fluoroquinolone (nucleic acid inhibitor).
commonly used against gram negative organisms.
Can be taken orally
Not to be used in children
Describe inherent or intrinsic resistance
In some cases all strains of a given species are naturally resistant to an antibiotic.
This is usually due to inability of drug to penetrate the bacterial cell wall to exert its action
What are the 2 ways in which acquired resistance may be acquired?
- A spontaneous mutation during multiplication or bacterial DNA can result in a change in structure or function which no longer allows the antibiotic to act as its target may have changed
- The gene or genes that code for resistance can spread from organism to organism or indeed from species to species. This is by far the most common mode of the spread of resistance and genes can be carried on by plasmids (extra chromosomal packages for DNA) or on transposons (packets of DNA which insert themselves into the chromosome
What are the 2 mechanisms of resistance to β–lactam antibiotics?
β-lactamase production - β-lactamases are bacterial enzymes which cleave the β–lactam ring of the antibiotic and thusrender it inactiveAlteration of penicillin binding protein (PBP) target site
- Mutations in PBP genes result in amodified target site to which β–lactams will no longer bind
What drug is β-lactamase resistant
Flucloxacillin ( and hence can be used to treat β-lactamase producing staph. aureus
What are ESBL’s and what are the implications of their existence
Extended spectrum β–lactamases (ESBLs) are an increasing problem in hospitals and are producedby some Gram negative organisms.
These β–lactamases can break down third generationcephalosporins as well as penicillins and therefore render the organism resistant to all β–lactamantibiotics
What glycopeptide resistant bacteria has appeared recently and what are the implications of this mutation?
Vancomycin resistant enterococci (VREs) have appeared recently.
The major concern among microbiologists isthat this mechanism of resistance might spread from enterococci to Staph aureus, producingvancomycin resistant Staph aureus.
Staph aureus is a more significant pathogen than enterococciand this prospect is viewed with alarm
Describe the spectrum of Benzyl penicillin (penicillin G)
Best choice for intra-venous treatment of serious pneumococcal, meningococcal and step pyogens
Describe the spectrum of amoxicillin/ampicillin
Effective against streptococci and coliforms
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 peperacillin
Effective against Enterococcus faecalis and pseudomonas species
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
Generally not used as much anymore as they seem to encourage Ciff D infections
How must cephalosporins be taken?
Parenteral use only
Describe the specrum of aminoglycocides
Noted for action against Gram -‘ve organisms
Effective against staphlococci but not streptococci
Gentamicin cheapest and most common aminoglycocide
Describe the spectrum of glycopeptides
Only gram +’ve organisms are affected (anaerobic +aerobic)
Vancomycin most common example
Describe the spectrum of action of macrolides
Mainly used against gram +’ve organisms
- Used as an alternative to penicillin for patients with a penicillin allergy
Describe the spectrum of action of Quinolones
Nearly all gram -‘ve organisms are sensitive
Mainly used in treatment of community acquired pneumonia
Describe the spectrum of action of metronidazole
Effective against Gram +’ve and -‘ve anaerobes
Describe the spectrum of action of fusidic acid
Only used as staphylococcal drug
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
Effective against Gram +’ve organisms
What infection is linezolid used against
MRSA
What infection is fidoxmicin used against
C. diff
What infection is daptomycin used against?
MRSA
What are the 4 classes of anti-fungal drugs?
Polyenes
Echinocandins
Allymines
Azoles
Describe the mechanism of polyenes
They bind to the ergosterol which is present in the fungal cell wall but not in the bacterial cell wall resulting increased permeability of the cell wall.
HOWEVER this also binds to mammalian sterols making polyenes TOXIC
Describe the use of amphotericin B and Nystatin (Hint: they are Polyenes)
Amphotericin B is used intra-venously for serious yeast infections and other fungal infections.
Very toxic.
Nystatin is used topically or in oral suspension and is not an intra-venous agent for serious fungal infection
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
Describe the mechanism of allylamines
They suppress the ergosterol synthesis but act at a different stage of the synthetic pathway from azoles
Describe the use of Terbinafine
Used for fungal infections of the skin and nails
Describe the mechanism of echinocandinds
They inhibit the 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), eptein-barr virus (HBV), cytomegalovirus (CMV) and Varicella-Zoster Virus (VZV).
Describe the mechanism and function of Aciclovir
Nucleotide anologue. Converted into active form by an enzyme. It is specific for virus
- infected cells meaning it is not very toxicExtremely active againstHSV and active against VZVIV used for serious, Oral for less serious
Describe the use of valaciclovir and famciclovir
Related to aviclovir
- Used in oral treatment of HSV and shingles
Describe the use of valganciclovir
Pro drug of ganciclovir -> alternative treatment for CMV.
High levels of bone marrow toxicity
Describe the use of foscarnet
Used for HSV, VSV and CMVHighly nephrotoxic
Describe the use of Cidofovir
Used for CMV retinitis
