T3-L1: Antibacterial and Antifungal Agents Flashcards
What is the role of antimicrobials?
The role of antimicrobials is to increase the chance that a person with an infection will make a clinical recovery. It inhibits critical processes in bacterial/fungal cells - antimicrobials targets. It is not an exact science, they may or may not recover.
What are the different categories of antimicrobials?
They may inhibit Enzymes, molecules or physical structures such as those in:
- Cell Wall
- Cell membrane
- Protein synthesis
- DNA synthesis
- RNA synthesis
Define antibiotic.
Chemical products of microbes that inhibit or kill other organisms.
What is the difference between an bacteriostatic and a bacteriocidal agent?
Bacteriostatic or fungostatic) - inhibit the growth. they do not bring about killing; most do this by protein synthesis inhibitors. The minimum concentration it is able to do this is known as the minimum inhibitory concentration.
Bactericidal (or fungicidal) agents cause cell death. This is mainly bye cell wall active agents.
The distinction is rather imprecise, some are bacteriostatic at some concentrations and bactericidal at other concentrations. The minimum concentration it is able to do this is known as the minimum bactericidal concentration.
Define synergy.
The effect observed with a combination is greater than the sum of the effects observed with the two drugs independently.
Define antagonism.
Activity of two antimicrobials given together is less than the activity of either if given separately.
What is antibiotic spectrum?
This is the range of bacteria or fungi that are sensitive to a particular antibacterial/antifungal agent.
Broad spectrum kills most types of bacteria/fungi encountered.
Narrow spectrum kills only a narrow range of organisms.
The narrowest-spectrum antibiotic that is appropriate should be used at all times. This is done to minimise the change to the patients normal flora.
What are the cell wall inhibitors antibacterial agents?
The cell wall is made of peptidoglcyan. This is a polymer made of glucose-derivatives. It forms a rigid network around the bacterial cell. Oligopeptide crosslinks are formed by transpeptidases known as “penicillin binding proteins” (PBPs). In being bound to penicillin, penicillin inhibits them.
The cell wall synthesis inhibitors are called the Beta-Lactams. They work by inhibiting PBPs.
Examples include:
- Penicillin such as benzylpenicillin, amoxicillin and fluxoacillin (narrow spectrum)
- Cephalosporins such as cefuroxime and ceftazidime (broad spectrum and cover gram negative better)
- Carbapenems such as meropenen and imipenen - extremely broad spectrum
- Monobactams - aztreonam - gram negative activity only. Since it has a different structure, it does not affect people with beta lactic allergy.
The other group is glycopeptides. Examples include Vanocymcin and Teicoplanin. These inhibit binding to transpeptidases and therefore peptidoglycan cross-linking. Only affect gram positive activity.
What type of antibacterial agents is gentamicin? Give other antibacterial agents of that type?
Bacterial protein synthesis inhibitors:
- Aminoglycosides (e.g. gentamicin, amikacin)
- Macrolides (e.g. erythromycin, clarithromycin) and lincosamides (e.g. clindamycin)
- Tetracycline and doxycycline
- Linezoid (gram positive infections)
- Mupirocin - topical agents for staphylococcal/streptococcal infections
- Fusidic acid
What is the action of trimethoprim and sulphonamides?
DNA synthesis inhibitors. These both inhibit folate synthesis. Trimethoprim is used commonly in UTIs and co-trimoxazole is an antibacterials antifungal and antiparasitic agent.
What is the action of fluoroquinolones?
DNA synthesis inhibitors - inhibit DNA gyrase and topoisomerase IV. These are involved in remodelling of DNA in replication. Examples include ciprofloxacin and levofloxacin.
What is the main RNA synthesis inhibitor used in antibacterial treatment?
Rifampicin
It is an RNA polymerase inhibitor and so prevents synthesis of mRNA.
This is cornerstone of anti-tuberculous chemotherapy. It is also used alongside staphylococcus infections alongside other agents. It is always used in combination with other agents - this is as it is easy to develop mutations in RNA polymerase and become resistant.
What is the action in Colistin/Polyxin E and Daptomycin?
Cell membrane agents (antibacterial).
What is special about pneumocystis jiroveci?
It is susceptible to the antibacterial agent - co-trimoxazole (trimethoprim-sulfamethoxazole).
How do anti fungal cell wall inhibitors work?
The cell wall is made of beta-1,3-glucan. The main group of antifungal cell group are Echinocandins (antifungal). These inhibit beta-1,3-glucan synthase. Examples
○ Anidulafungin
○ Caspofungin
○ Micafungin
The are remarkably free of adverse affects, possibly due to the target which is unique to fungi.
