Antimicrobials and Antimicrobial Stewardship Flashcards
What does antimicrobials cover as a term?
Antibacterial, antifungal, antiviral and antiprotozoal agents.
How are antibacterials classified?
Bacteriocidal (kill)/bacteriostatic (inhibitory) Spectrum as to whether they are broad or narrow Target site (i.e. mechanism of action) Chemical structure
What are the ideal features of an antimicrobial agent?
- Selectively toxic
- Few adverse effects
- Reach site of infection
- Oral/IV formulation
- Long half-life so the dose is infrequent
- No interference with other drugs
What 4 ways does antibacterials work?
- Inhibiting cell wall synthesis such as beta-lactams and glycopeptides
- Inhibiting protein synthesis such as tetracyclines, aminoglycosides and macrolides
- Inhibiting cell membrane function such as polymixins (colisitin)
- Inhibiting nucleic acid synthesis such as quinolones (trimethoprim and rifampicin also work this way)
How do penicillin work?
Penicillin binding protein’s function is to cross link structures in the cell wall of bacteria. Penicillin binds to this protein and prevents it from doing this job.
How does vancomycin work?
Vancomycin also interferes in the cell wall but by sitting on the cross linking chains and prevents penicillin binding protein from binding and carrying out its function.
How does fluroquinolones work?
Fluoroquinolones bind to 2 nuclear enzymes, inhibiting DNA replication in bacteria.
How can pathogens become resistant to antimcrobials?
- Drug inactivating enzymes such as B-lactamases, aminoglycoside enzymes
- Altered targets i.e. the target enzyme or structure has a lowered affinity for the antibacterial e.g. resistance to methicillin, macrolides and trimethoprim
- Altered uptake – reduced permeability such as B-lactams or increased efflux such as with the tetracyclins
How does resistance come about/transferred?
When using antibacterial you may select especially for the resistant bacteria by killing off all the bacteria but those who are resistant taking away their competition and allowing them to flourish.
Chromosomal gene mutation
Horizontal gene transfer
Vertical gene transfer
How does horizontal gene transfer occur?
Horizontal gene transfer involves transferring DNA, the gene can be within the chromosome, plasmids or transposon (free floating). This can take place via conjugation (sexual process), transduction (bacteriophages transfer DNA) or transformation (through the cell wall).
How does a resistance characteristic become stable within the population?
Plasmids can be integrated into the chromosomes of the bacteria. This makes the resistance stable within the bacteria population.
What is the minimum inhibitory concentration of an anitbiotic?
The minimum inhibitory concentration of an antibiotic is the lowest concentration of antibiotic (in mg/L) that has an inhibitory effect on the bacteria. This must be done with two sets of controls one without any bacteria in and one with just bacteria and no antibiotic.
Name some Beat-Lactams
Penicillin’s, B-lactamase inhibitors, cephalosporins and carbapenems.
Discuss penicillins
Penicillins
Penicillin itself is mainly active against gram positive bacteria such as streptococci, Amoxicillin is similarly mainly gram positive but also has some activity against gram negative bacteria. Flucloxacillin is active against staphylococci ad streptococci.
Discuss B-lactamase inhibitors
B-lactamase inhibitor combinations is when you combine an antibiotic with an inhibitor of the resistance mechanism present in bacteria (B-lactam antibiotics are a broad classification of antibiotics that all have a B-lactam ring and include penicillin derivatives) examples of these are Co-amoxiclav and Piperacillin/Tazobactam which are effect against gram positive and negative as well as anaerobes.
Discuss Cephalosporins
Many different types that all are broad spectrum against gram positive and negative bacteria but not anaerobes. Cetriaxone has a good activity in the cerebral spinal fluid so very useful in treatment of meningitis. However, there is limited use at the moment due to worries about its selection for Clostridium Difficile.
Discuss Carbapenems
Very broad spectrum antibiotic including anaerobes and active against the majority of gram negative bacteria. Generally safe in penicillin allergies other than anaphylaxis. Example is Meropenem.
Discuss glycopeptides?
Vancomycin is active against more gram positive but not gram negative, rare resistance in staph bacteria but some present in enterococci. Must have therapeutic drug monitoring (TDM) as the therapeutic window is very small. Teicoplanin has a similar activity to vancomycin and is easier to administer.
Discuss tetracyclines
Tetracycline and doxycycline similarly broad spectrum but oral use only. Usually used in people with a penicillin allergy usually for Gram positive bacteria Useful for atypical pathogen in pneumonia and also against chlamydia and some protozoa – should not be given to children because they stain teeth and bones.
Discuss Aminoglycosides
Mostly gram negative agents most common example is Gentamicin and reserved for gram negative sepsis. Good activity in the blood and urine but has a low therapeutic window so must have TDM especially in consideration with nephrons and the ear.
Discuss Macrolides
Such as erythromycin and clarithromycin oral administered and has a good distribution including intracellular penetration. Used in general practice as an alternative for penicillin for mild gram positive infections. Again active against atypical respiratory pathogens.
Discuss Quinolones
Such as ciprofloxacin, inhibits DNA gyrase, very active against gram negative and also atypical pathogens however there is now an increasing resistance and risk of C.difficile.
What are sulphonamides and trimethoprim?
Trimethoprim and sulphonamides which inhibit folic acid synthesis. Trimethoprim used in the UK against UTI and when combined with sulphamenthoxazole it is called Co-trimoxazole and is used to treat PCP (pneumocystis pneumonia) and has activity against MRSA.
What is metronidazole?
Metronidazole is an antibacterial and antiprotozoal agent specific for anaerobes and certain protozoas (amoebae – dysentery, giardia - diarrhoea and trichomonas - vaginitis).
