Antibiotics and Resistance - Part 2 Flashcards
Name the first streptogramin antibiotic to be released
Synercid
Describe the structure of the first streptogramin antibiotic synercid
A combination of two cyclic peptides - quinupristin and dalforpristin
Streptogramin antibiotics are distantly related to which antibiotic group?
The macrolides
How do streptogramin antibiotics such as Synercid act?
They block protein synthesis by attaching to the 50S portion of the ribosome
Against which bacteria are streptogramins effective against?
A broad range of gram-positive bacteria
The oxazolidinones are a new class of antibiotics developed in response to…
Vancomycin resistance
How do oxazolidinones act?
They act on the ribosome, inhibiting protein synthesis
What is different in the way oxazolidinones act on the 50S ribosome compared to other antibiotics discussed?
They act close to the point where it interfaces with the 30S subunit
The oxazolidinones are totally synthetic which may
make resistance slower to develop
Give an example of an oxazolidinone and its function
Linezolid - used mainly to combat MRSA
What is the mode of action of pleuromutilin antibiotics?
Interfere with protein synthesis
What is the first pleuromutilin antibiotic to be approved?
Retapamulin
What is a limitation of Retapamulin which is a pleuromutilin antibiotic?
It is limited to topical use
What is pleuromutilin effective against?
Gram positive bacteria including MRSA
A new class of antibiotics developed in recent years…
Lipopeptides
Give an example of a lipopeptide that is effective against gram positive bacteria including MRSA infections
Daptomycin
Daptomycin is produced by a…
Streptomycete
Daptomycin is approved for what?
For certain skin infections
What is the apparent mechanism of daptomycin which is a lipopeptide antibiotic
To attack the membrane of the bacterial cell
Give an example of a lipopeptide antibiotic which is used for gram negative bacteria
Polymyxin B
Infections caused by Pseudomonas Bacteria can be treated with
Polymyxin B which is a lipopeptide
By attacking the membrane of the bacterial cell
Give an example of a rifamycin antibiotic
Rifampin
How do the rifamycin class of antibiotics such as rifampin work?
They are nucleic acid synthesis inhibitors - work by inhibiting the synthesis of mRNA
Rifampin are structurally related to…
The macrolides
What is a valuable characteristic of rifampin?
The ability to penetrate and reach therapeutic levels in cerebrospinal fluid and abscesses
What is the most important use of rifampin?
Against mycobacteria in the treatment of tuberculosis and leprosy
What is the method of action of the quinolones and fluoroquinolones?
Nucleic acid synthesis inhibitors - inhibits an enzyme needed for the replication of DNA
DNA gyrase
The first quinolone group of antimicrobials is
Nalidixic acid
Nalidixic acid has a limited use, explain.
Only application is for urinary tract infections
Why were the quinolones of use?
Allowed the development of the synthetic quinolones known as the fluoroquinolones
When were the fluoroquinolones developed from the quinolones?
In the 1980’s
Fluoroquinolones have a ______ spectrum of activity compared to quinolones
Broader
Name two of the earliest generation fluoroquinolones
Norfloxacin and ciproflaxacin
Name two of the newer groups of fluoroquinolones
Gemifloxacin and moxifloxacin
What is a major issue with fluoroquinolones?
Resistance can develop rapidly, even during the course of a treatment
Give an example of a group of antimicrobials which kill by the competitive inhibition of essential metabolites
Sulfonamides
Why is folic acid important in microbes?
Folic acid is an important co enzyme needed for the synthesis of proteins, DNA and RNA
How do sulfonamides act?
They are structurally similar to the folic acid precursor called para-aminobenzoic acid (PABA)
Competitively bind with the enzyme meant for PABA
Block folic acid production
Give an example of drug-synergism
TMP-SMZ = trimethoprim and sulfamethoxazole
What is drug synergism ?
Drug synergy occurs when drugs can interact in ways that enhance or magnify one or more effects
The TMP-SMZ combination has what advantage?
Broader spectrum of activity and reduces the emergence of resistant strains
How do most antifungal drugs work?
By targeting the sterols in the plasma membrane
In fungal membranes, the principle sterol is?
Ergosterol
In human membranes, the principle sterol is?
Cholestrol
How does inhibition of ergosterol biosynthesis of fungal cells cause death?
The membranes become excessively permeable
Name the most commonly used member of the antifungal polyene group.
Amphotericin B
What is amphotericin B used for?
Fungal diseases - histoplasmosis, coccididomycosis and blastomycosis
Azoles are widely used anti____ drugs
antifungal
What were the first azoles?
The imidazoles
Give two examples of the imidazoles
Clotrimazole and miconazole
Azoles can be used without prescription for
topical application such as athlete’s foot
What is an advantage of triazole as an antifungal?
It is less toxic, and more water soluble
The low toxicity and water solubility of triazole means that it is
more effective against systemic infections
What are systemic infections?
Infections that affect the entire body
Give two examples of triazoles
Fluconazole and itraconazole
The allylamines work by…
Inhibiting the biosynthesis of ergosterols
Give two examples of allylamines
Terbinafine and naftifine
Other than the plasma membrane of fungal cells, what is another primary target for antifungal agents?
The beta-glucan of the cell wall
What type of antifungals inhibit the biosynthesis of glucans?
The echinocandins
The echinocandins inhibit the biosynthesis of glucans, what does this result in?
An incomplete cell wall which then results in cell lysis
Other than targeting the fungal cell membrane or the fungal cell wall, what else can be target by antifungals?
Inhibition of nucleic acids
Give an example of an antifungal which interferes with the biosynthesis of RNA and therefore disrupts protein synthesis
Flucytosine
