Flashcards in Antimicrobials Deck (120):
What can antimicrobials be classified into?
How can antibacterials be classified?
Bactericidal or bacteriostatic
Broad or narrow
What do bactericidal antibacterials do?
What do bacteriostatic antibacterials do?
What does the target site of an antibacterial depend on?
The mechanism of action
What are the ideal features of an antimicrobial agent?
Few adverse effects
Reach site of infection
Oral and IV formulation
No interference with other drugs
Why should an antimicrobial be selectively toxic?
So it is minimally toxic
Why should an antimicrobial have a long half life?
Allows for infrequent dosing
What are the classes of mechanism of action of antibacterials?
Affect cell wall synthesis
Affect protein synthesis
Affect cell membrane function
Affect nucleic acid synthesis
Give two examples of classes of antimicrobials that affect cell wall synthesis
Give three examples of classes of antimicrobials that affect protein synthesis
Give an example of a class of antimicrobial that affects cell membrane function?
Give an example of a polymixin
Give an example of a class of antimicrobial that affects nucleic acid synthesis
Give two examples of quinolones
What are the most important classes of antibacterials?
Those that affect cell wall synthesis and those that interfere with protein synthesis
What class of antibacterial is penicillin?
What is penicillin binding protein?
A bacterial protein that physiologically cross-links the cell walls in bacteria
What is the mechanism of action of penicillin?
It binds to penicillin binding protein and inhibits it from cross-link the cell wall
What class of antimicrobial is vancomycin?
What is the mechanism of action of vancomycin?
It sits on the cross-links of the forming cell wall and stops penicillin binding protein from attaching, preventing cross-links from being attached to each other by the cell wall cross-linking enzyme
What class of antimicrobial are fluoroquinolones?
What is the mechanism of action of fluoroquinolones?
Interferes with the action of DNA gyrase during bacterial growth
What does DNA gyrase do?
Physiologically catalyses the supercoiling of DNA
How do fluoroquinolones interfere with the action of DNA gyrase?
Binds to both the enzyme and DNA to form a ternary (three molecule) complex, inhibiting the rejoining step and thus causes cell death
What are the mechanisms of antimicrobial resistance?
Drug inactivating enzymes
Give two examples of antimicrobials affected by drug inactivating enzymes
What happens in the altered target mechanism of antimicrobial resistance?
Target enzyme has a lowered affinity for antibacterial
Give three examples of antimicrobials affected by the altered target mechanism of resistance
What is caused by antibiotic resistance to methicillin?
How can altered uptake be achieved in antibiotic resistance?
Give an example of an antimicrobial affected by the decreased permeability mechanism of resistance
Give an example of an antimicrobial affected by the increased efflux mechanism of resistance
How can antibiotic resistance be genetically obtained?
Chromosomal gene mutation
Horizontal gene transfer
How does a chromosomal gene mutation result in antimicrobial resistance?
A chromosome mutates to contain a gene that confers resistance.
An antibiotic is then applied and the resistant gene is selected for, as only the resistant bacteria will survive.
The surviving bacteria can then replicate to produce large numbers of bacteria the now carry the mutated resistance gene
What can antibiotic resistance genes be carried on?
How can antibiotic resistance genes be transferred?
How does antimicrobial resistance transfer by conjugation?
Resistant cell carries the gene on a plasmid or transposon that passes it on to another cell via pili
How does antimicrobial resistance transfer by transduction?
Resistant cell is infected by bacteriophage virus.
During replication of bacteriophages within resistant cell, bacterial DNA containing resistant gene is packaged into one of the phages
The bacteriophage then goes on to transfer the resistant gene to a non-resistant cell that incorporates it into its genes via recombination
How does antimicrobial resistance transfer by transformation?
Resistant cell carries the gene on a chromosome of plasmid
The resistant cell dies, and releases its DNA
The free DNA is picked up by the competent non-resistant cell, that has now acquired resistance
What happens once antimicrobial resistant is acquired by another cell?
It can go on to replicate so that it's off-spring now possess the resistance gene
How can antibiotic activity be measured?
Disc sensitivity tests
Minimum inhibitory concentration
What happens in disc sensitivity tests?
Discs of antimicrobials are placed in a petri-dish containing clear agar, where a culture of bacteria is to be grown
How are the results of a disc sensitivity test interpreted?
The size of the clear agar around each disc correlates with its effectiveness
What happens in a minimum inhibitory concentration test?
There are two control test tubes, one with no antibacterials and bacteria, and one with no antibacterials and no bacteria.
The concentration of antibacterial is halved each test tube, and observe to see when no bacterial growth is observed- when the broth is not turbid
What are the types of beta-lactams?
Give 5 examples of penicillins
What is co-amoxiclav?
Amox and clavulanate
What is tazocin?
Piperacillin + tazobactam
Give an example of a cephalosporin?
Give an example of a carbapenum
Give an example of a monobactam
What is penicillin mainly active against?
What is amoxicillin active against?
Gram +ve, some gram -ve
What is flucloxacillin active against?
Staphylococci and streptococci
Give two beta-lactamase inhibitor combinations
What is co-amoxiclav active against?
More gram -ve than other penicillins
What is Tazocin active against?
Same as co-amoxiclav, and even more gram negative, including pseudomonas
How are cephalosporins organised?
How do each generation of cephalosporin differ?
Each generation has increased activity against gram -ve and decreased activity against gram +ve
What is the advantage of cephalosporins over penicillin?
More broad spectrum drug
What is the disadvantage of cephalosporins over penicillins?
No anaerobes activity
Where does ceftriaxone have good activity?
In the CSF
What are there concerns over regarding cephalosporins?
Association with C. Difficile
What are the advantages of meropenum?
Very broad spectrum, including anaerobes
Active against most Gram -ve
Generally safe in penicillin allergy
When are meropenum not safe in penicillin allergy?
What is vancomycin active against?
Most gram +ve
What is the resistance situation regarding vancomycin?
Some enterococci are resistant
Resistance in staphs is rare
What is the problem with vancomycin?
Therapeutic drug monitoring
When is vancomycin given orally?
C. Difficle only
Why is therapeutic drug monitoring required for vancomycin?
Narrow therapeutic window
What is the activity of teicoplanin similar to?
What is the advantage of teicoplanin over vancomycin?
Easier to administer
What are the similarities between tetracyclines and doxycycline?
Where are tetracycline and doxycycline used?
Broad-spectrum, but specific use in penicillin allergy, usually from gram +ve
Atypical pathogens in pneumonia
Chlamydia and some protozoa
Who shouldn't tetracycline and doxycycline be given to?
Children under 12 years
Why shouldn't tetracycline and doxycycline be given to children under 12 years?
Stains teeth and bones
What is the most common aminoglycoside?
What is gentamicin active against?
Profound activity against gram negatives
Where does gentamycin have good activity?
In the blood and urine
What is the problem with gentamicin?
What is required with gentamicin?
Therapeutic drug monitoring
What is gentamicin generally reserved for?
Severe gram -ve sepsi
Give two macrolides
What is good about erythromycin?
Well distributed, including intracellular penetration
Where is erythromycin used?
Alternative to penicillin for mild gram +ve infections
Active against atypical respiratory pathogens
What is the most common example of quinolone?
What is the mechanism of action of ciprofloxacin?
Inhibit DNA gyrase
What is ciprofloxacin active against?
Very active against atypical pathogens
What is the problem with ciprofloxacin?
Risk of C. Difficile
What is the mechanism of action of trimethoprim and sulphonamides?
Inhibitors of folic acid synthesis
When is trimethoprim used alone in the UK?
What is co-trimoxazole?
Sulphamethoxazole and trimethoprim
What is co-trimoxazole used for?
Has activity against malaria
What are the classes of antifungals?
What are azoles active against?
Yeasts, and sometimes molds
What is the mechanism of action of azoles?
Inhibits cell membrane synthesis
Give an example of an azole?
What is fluconzole used for?
What is itra/vori/posaconazole active against?
Give two polyenes
What is the mechanism of action polyenes?
Inhibit cell membrane function
What is nystatin used for?
Topical treatment of Candida
What is amphotericin used for?
IV treatment of systemic fungal infection, e.g. Aspergillus
Give two antivirals
What is the mechanism of action of aciclovir?
When phosphorylated, it inhibits viral DNA polymerase
What is aciclovir active against?
Give two things caused by herpes simplex
Give two things caused by varicella zoster
What is the commercial name for oseltamivir?
What is the mechanism of action of tamiflu?
Inhibits viral neuraminidase
What does tamiflu treat?
Influenza A and B
What conditions require specialist antivirals for treatment?
What kind of antimicrobial is metronidazole?
Antibacterial and antiprotozotal
What bacteria is metronidazole active against?
What protozoa is metronidazole active against?
What does amoebae cause?
What does giardia cause?
What does trichomonas cause?