Session 4- antimicrobials Flashcards
What is a protozoa?
Single celled eukaryote
Types of antimicrobial
Antibacterials
Antifungals
Antiprotozoals
Antivirals
How can you classify antibacterials?
By their
- mechanism of action
- spectrum (broad/narrow)
- chemical structure
- kill/ inhibit growth and replication (bacteriostatic vs bactericidal)
3 ways of measuring antibiotic activity
Explain each
- Disc sensitivity
- MIC, broth microdilution
- MIC, E test (slow)
Disc loaded with antibiotic is placed in on an inoculated agar plate and the zone of inhibition/ clearance measured. (Larger diameter= more antibiotic inhibition).
Minimum inhibitory concentration. Concentration of antibiotic is doubled each time until no bacterial growth occurs.
E- test; strip contains an antibiotic gradient and is placed on an inoculated agar. Circumference of zone of clearance begins from the MIC
Which 3 types of antibiotic inhibit protein synthesis?
Give an example of each
- Tetracyclines (doxycycline)
- Aminoglycosides (Gentamicin)
- Macrolides (erythromycin)
Tetracyclines: Mechanism Use Adverse effects Example
Inhibit protein synthesis
Used as an alternative to penicillin in gram positive infection
Causes staining to developing teeth so no children < 12 or pregnant women
E.g. Doxycycline
Gentamicin: Type of antibiotic Mechanism Use Adverse effects
Aminoglycoside
Inhibits protein synthesis
Endocarditis
Severe gram negative sepsis
Can be nephrotoxic and ototoxic
Erthromycin:
Type of antibiotic
Mechanism
Use
Macrolide
Inhibits protein synthesis
Alternative to penicillin against gram positive infection
Two types of antibiotic which inhibit cell wall synthesis?
Examples
- Beta lactams;
Penicillins (flucloxacillin)
Cephalosporins (ceftriaxone)
Carbapenems - Glycopeptides (vancomycin)
Antibiotics used for meningitis and why?
Empirical ceftriaxone
Penicillin G/ Ampicillin
Bc both pass inflamed BBB and have action in CSF
What does flucloxacillin treat?
Cellulitis- caused by Staphylococcus Aureus/ Streptococcus Pyogenes
Penicillin is mainly active against ___?
Gram positives-
Staphylococcus
Streptococcus (especially)
Carbapenems:
Type of antibiotic
Mechanism
Use
Example
- Beta lactams (others are penicillins and cephalosporins)
- Inhibits cell wall synthesis
- Reserve for gram negative infections (+ penicillin allergy)
- imipenem
Vancomycin:
Type of antibiotic
Mechanism
Use
Features
- Glycopeptide
- Inhibits protein synthesis (along with tetracyclines and macrolides)
- MRSA & serious C .difficile (oral). Gram positives.
- Poor oral absorption so use IV or IM usually. Narrow therapeutic index so needs TDM, therapeutic drug monitoring.
Is clostridium difficile gram positive or negative?
Gram positive and spore-forming
Antibiotics which inhibit nucleic acid synthesis? (3)
How do they do this?
- Quinolones (Ciprofloxacin)
Inhibit DNA gyrase (relaxes the supercoil in transcription) - Rifampicin
Inhibits bacterial RNA polymerase - Trimethoprim (UTI) + Sulphonamides
Inhibit folate synthesis
Quinolones:
Mechanism
Use
Adverse effects
Example
- Inhibit nucleic acid synthesis (through inhibition of DNA gyrase)
- Against gram negatives
- Aortic dissection, tendinitis and rupture, plus CNS effects
- ciprofloxacin
What do Azoles and Polyenes do?
Examples
Antifungals (fungistatic)
Azoles inhibit cell membrane synthesis
Polyenes inhibit CM function
- Azoles fluconazole (candida) itraconazole (aspergillus) - Polyenes nyastatin (topical for candida) Amphoteracin (IV systemic fungal infection- aspergillus)
Antifungals for aspergillus?
Itraconazole (azole)
I.V. Amphoteracin if systemic (type of polyene)
Acyclovir:
What is it?
Mechanism
Uses
Anti viral agent
Prevents DNA synthesis (inhibition of DNA polymerase when phosphorylated)
Varicella zoster virus- Chicken pox, shingles,
Herpes simplex virus- genital herpes, encephalitis
What is encephalitis?
Which infection causes it?
Inflammation of the brain caused by Herpes Simplex virus
What does Varicella Zoster virus cause?
Medication?
Chicken pox and shingles
Acyclovir
What does Herpes Simplex virus cause?
Genital warts and encephalitis
Tamiflu;
What is it?
Mechanism
Uses
Also know as oseltamivir, it’s an antiviral agent
Inhibits viral neuraminidase in flu so the newly formed virions cannot be released into the blood stream (viral replication stops)
Influenza A and B
What does neuraminidase enzyme do?
Cleaves the sialic acid residues to break the glycosidic linkage between the new virion and host cell enabling release into the blood stream (to further infect cells)
What’s special about metronidazole?
It’s antibacterial (anerobic bacteria) AND antiprotozoal (eukaryotic)
Amoebae
Giardia
Trichomonas
are all types of what?
What can you treat them with?
Protozoa
G and T are parasites
Metronidazole
Amoebae
Giardia
Trichomonas
What do they cause?
Dysentery (inflammation of intestines causing bloody diarrhoea)
Diarrhoea
Vaginitis / trichomoniasis (STI)
Use of trimethoprim
UTI
How do sulfonamides work?
How does trimethoprim work?
Sulfonamides inhibit de novo synthesis of folate in bacteria
Trimethoprim inhibits conversion of dihydrofolate (DHF) to tetrahydrofolate (THF) in bacterial but not human cells.
Why do we need folate?
To synthesise DNA nucleotides we (and bacteria) require enzymes which use co-factors deriving from folate.
Specifically the derivative THF, tetrahydrofolate, is critical to enzyme activity
List some mechanisms of bacterial antibiotic resistance
Reduced uptake
Mutation of target site
Down regulating expression of target site
Increased efflux
Enzymes which inactive the drug. E.g. beta lactamases inhibit beta lacta drugs
Types of bacterial resistance? (3)
Innate
Acquired- gain new DNA, usually permanent
Adaptive- response to a stress like sub-inhibitory level of antibiotic; can be reversible
Protective mechanisms against infections in the lungs? (Innate immunity)
Mucociliary clearance
Coughing
IgA (immunogolbulin of mucous membranes)
Alveolar macrophages
Antimicrobial proteins;
- lysozyme (breaks bacterial cell walls)
- lactoferrin (bacteriocidal; associated with mucus)
Dyspnea?
Shortness of breath
What is co-amoxiclav?
When is it used?
Combination drug which includes a beta lactam drug (amoxicillin) and a beta lactamase inhibitor
- In community acquired pneumonia when the bacteria is resistant to amoxicillin (produce beta lactamases). E.g. Haemophilus Influenzae.
- Or in severe pneumonia caused by Streptococcus Pneumoniae.
