Antimicrobials Flashcards
What are the different antimicrobial classifications?
- Antibacterial (antibiotics) agents
- Antifungal agents
- Antiviral agents
- Antiprotozoal agents
How do you classify antibacterial agents?
- Bactericidal (kill bateria) or bacteriostatic (slow growth or reproduction).
- Spectrum - broad v narrow
- Target site (mechanism of action)
- Chemical structure (antibacterial class)
What are the ideal features of an antimicrobial agent?
- Selectively toxic
- Few adverse effects
- Reach site of infection
- Oral / IV formulation - preferably have both forms
- Long half-life (infrequent dosing) - This increases compliance
- No interference with other drugs.
What are the classes of antibacterial and their mechanisms of action?
Cell Wall synthesis: Beta-lactams, Glycopeptides
Cell membrane function: Polymixins (e.g. colistin) - Last resort antibiotic as not very much resistance and kidney resistance.
Protein synthesis: Tetracyclines, Aminoglycosides, Macrolides.
Nucleic acid synthesis: Quinolone
How does penicillin work?
Penicillin and other β-lactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls.
How does vancomycin work?
It inhibits cell wall synthesis is gram positive bacteria.
What are the different types of bacterial resistance?
Intrinsic
- No target or access for the drug
- Usually permanent
Acquired
- Acquires New genetic material or mutates
- Usually permanent
Adaptive
- The organism responds to a stress (e.g. sub-inhibitory level of antibiotic)
- Usually reversible (if remove stimulus, revert back)
- This leads to failure at end of treatment.
What are some mechanisms of resistance?
Drug inactivating enzymes
- e.g. B-lactamase, aminoglycoside enzymes.
Altered target
- Target enzyme has lowered affinity for antibacterial e.g. resistance to meticillin, macrolides and trimethoprim.
Altered uptake
- Reduced permeability (e.g. B-lactams)
- Increase efflux (e.g. tetracyclines)
What is the genetic basis of antibiotic resistance?
Chromosomal gene mutation - kill off all bacteria with no mutation so all subsequent generations are resistant.
Horizontal gene transfer - Transfer via conjugation, bacteriophages or free bits of DNA.
How do we test for antimicrobial resistance in the lab?
Use disk sensitivity testing. Size of no growth zone shows resistance or sensitivity. The sizes of these zones are compared to a preset value.
Minimum inhibitory concentration - Set amount of bacteria and various concs of antibiotic. The MIC (min. Inhibitory conc) is the first concentration where bacterial growth does not occur.
Beta lactams
B-lactams have a four membered ring.
These antibiotics work by inhibiting the synthesis of the peptidoglycan layer of the cell wall.
They are expecially effective against Gram positive. Although some more broad spec ones work against Gram negative bacteria too
Resistance occurs when antibiotcis begin producing B-latamase, an enzyme that breaks down the B-lactam ring.
How do the Penicillin work?
Penicillin - Mainly active against streptococci (mostly Gram-positives).
Interferes with peptidoglycan synthesis which weakens cell wall of dividing bacteria.
How does amoxicillin work?
As well as being effective agaisnt streptococcci, it also has some activity against gram-negative
In general, Streptococcus, Bacillus subtilis, Enterococcus, Haemophilus, Helicobacter, and Moraxella are susceptible to amoxicillin.
Whereas Citrobacter, Klebsiella and Pseudomonas aeruginosa are resistant to it.
Some E. coli and most clinical strains of Staphylococcus aureus have developed resistance to amoxicillin to varying degrees.
What is Flucoxcillin active against?
Active against staphylococci and streptococci.
it is used to treat infections caused by susceptible Gram-positive bacteria. Unlike other penicillins, flucloxacillin has activity against beta-lactamase-producing organisms such as Staphylococcus aureus as it is beta-lactamase stable. However, it is ineffective against methicillin-resistant Staphylococcus aureus (MRSA).
B-lactamase inhibitor combinations?
Co-amoxiclav active against Streprococci, staphylococci, more Gram negatives and anaerobes.
Piperacillin / Tazobactam is effective against all of the above and even more Gram gegative bacteria incuding pseudomonas.
Cephalosporins?
First-generation are active predominantly against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (often with reduced activity against Gram-positive organisms).
Increased broad spectrum but no anaerobe activity
Broad but not as commmonly used now
Cetriaxone has good activty in the CSF
But, there is concern over its association with C. difficile
Carbapenems?
Carbapenems: Meropeoem (and imipenem)
First choice in sepsis
Very broad spectrum (inc anaerobes)
Active against most (but not all) Gram negatives
Generally safe in penecillin allergy
Glycopeptides?
Vancomycin
Active against gram positive and not gram neg as acts on cell wall
Some enterococcus resistance
Resistance in staphylococcus rare
Not absorbed (oral for C. Dif only)
Therapeutic drug monitoring is required (narrow herapeutic window)
Teicoplanin
Only once a day so given to outpatients
But, similar activity to vancomysin
Tetracyclines?
Tetracyclines and doxycycline
Similar spectrum, both oral only
Broad spec but specific in penicillin allergy, usually for Gam pos
Active in atypical pathogens in pneumonia
Active against chlamydia and some protozoa
Shouldnt be given to children under 12 as it will stain their teeth yellow
Aminoglycosides?
Most common agent is gentamicin
Profound activity against Gram negatives
Good activity in blood / urine
Potentially nephrotoxic / Ototoxic (toxic to ear)
Therapeutic drug monitoring required
Generally reserved for severe Gram negative sepsis
Macrolides?
E.g. erythromycin and clarithromycin
Well distributed inc. intracellular penetration
ALternative to penecillin for mild Gram positive infections
Also active agaisnt atypical respiratory pathogens
Quinolones?
Commonest example ciprofloxacin
Inhibit DNA gyrase (DNA synthesis)
Very active against Gram neg
Also active against atypical pathogens
Increasing resistance and risk of C. Difficile
Trimethoprim and sulphonamides?
Inhibitors of folic acid synthesis (not in first trimester of pregnancy)
Trimethoprim used alone in UK for UTI (2nd line as gets into urine well)
When combined with sulphamethoxalone
- Co-trimoxazole
- Used to treat PCP (Pneumocystis pneumonia)
- Has activity against MRSA
Antifungals - Azoles?
Active against yeasts +/- moulds
Inhibit cell-membrane synthesis
Fluconzole used to treat Candida
Itra / Vori / Posaconazole also acitve agaisnt Aspergillus
Antifungals - Poyenes?
Nystatin and Amphotericin
Inhibit cell membrane function
Nystatin for topical treatment of candida
Amphotericin for IV treatment of systemic fingal infections (e.g. aspergillus)
Antivirals - Aciclovir?
When phosphorylase inhibits viral DNA polymerase
Herpes simplex - genital herpes, encephalitis
Varicella zoster - chickenpox and shingles. Must be given within 48hrs
Oseltamivir?
‘Tamiflu’
Inhibit viral neuraminidase
Infuenza A and B
Metronidazole?
This is an antibacterial and antiprotozoal agent
Active against anaerobic bacteria
Also active against Protozoa:
- Amoebae (dysentery and systemic)
- Giardia (diarrhoea)
- Trichomonas (vaginitis)
