S4) Antimicrobials and Resistance ❌❌❌❌❌ Flashcards
Identify 4 different ways in which antibacterial agents can be classified
- Bactericidal / bacteriostatic (kill/disable)
- Broad / narrow (spectrum)
- Mechanism of action (target site)
- Antibacterial class (chemical structure)
What are the 6 ideal features for antimicrobial agents?
- Selectively toxic
- Few adverse effects
- Reach site of infection
- Oral/IV formulation
- Long half-life (infrequent dosing)
- No interference with other drugs
Identify the different classes of antimicrobials based on their different mechanisms of action
Identify and describe the different types of resistance
- Intrinsic: no target or access for the drug (usually permanent)
- Acquired: acquires new genetic material or mutates (usually permanent)
- Adaptive: organism responds to a stress (usually reversible)
Identify the different mechanisms of resistance and provide examples
- Drug-inactivating enzymes e.g. b-lactamases, aminoglycoside enzymes
- Altered target (lowered affinity for antibacterial) e.g. resistance to macrolides & trimethoprim
- Altered uptake
I. ↓permeability e.g. b-lactams
II. ↑efflux e.g. tetracyclines
Identify the four Beta-lactam subgroups
- Penicllins
- Cephalosporins
- Carbapenems
- Monobactams
Provide some examples of penicillins in the Beta-lactam sub-group and describe their use
- Penicillin – active against strep
- Amoxicillin – active against staph & strep (+ ↑Gneg)
- Flucloxacillin – active against staph & strep
- Β-lactamase inhibitor combinations e.g. co-amoxiclav – acitive against staph & strep and anaerobes (↑Gneg)
Describe the use of cephalosporins in the Beta-lactam sub-group and provide some examples
- ↑Gneg and ↓Gpos activity
- ↑broad-spectrum (no anaerobes)
- E.g. ceftriaxone has good activity in the CSF IV but associated with C. difficile*
Describe the use of carbapenems in the Beta-lactam subgroup and provide some examples
- Broad spectrum (+ anaerobes)
- Active against most Gnegs
- Safe in penicillin allergy
- E.g. meropenem and imipenem*
Provide two examples of glycopeptides
- Vancomycin
- Teicoplanin
Describe the use of vancomycin in the Glycopeptide subgroup
- Active against most Gpos
- Rare resistance in staphs
- Oral for C. difficile only (otherwise IV)
- stops cell wall linkage
Describe the use of teicoplanin in the Glycopeptide subgroup
- Similar activity to vancomycin
- Easier to administer
Provide two examples of tetracyclines
- Tetracycline
- Doxycycline
Describe the use of doxycyline & tetracycline in the tetracyline subgroup
- Oral administration
- Broad-spectrum
- Gpos (use in pencillin allergy)
- Active in atypical pathogens in pneumonia & against chlamydia
- Shouldn’t be given to children < 12 years
Provide an example of an aminoglycoside
Gentamicin
Describe the use of gentamicin in the aminoglycoside subgroup
- Activity against Gnegs
- Good activity in the blood/urine
- Generally reserved for severe Gram neg sepsis
Provide two examples of macrolides
- Erythromycin
- Clarithromycin
Describe the use of erythromycin and clarithromycin in the macrolide subgroup
- Used for mild Gpos infections (alternative to penicillin)
- Active against atypical respiratory pathogens
Provide an example of a quinolone
Ciprofloxacin
Describe the use of quinolones
- Inhibit DNA gyrase
- Very active against Gnegs
- Active against atypical pathogens
- Increasing resistance
- Risk of C. difficile
Describe the use of trimethoprim
- Inhibits folic acid synthesis
- Used alone in the UK for UTI
Identify two subgroups of antifungal agents
- Azoles
- Polyenes
Describe the use of azoles and provide some examples
Inhibit cell membrane synthesis:
- Flucanazole used to treat candida
- Posaconazole also active against aspergillus
Describe the use of polyenes and provide some examples
Inhibit cell membrane function:
- Nystatin for topical treatment of candida
- Amphotericin for IV treatment of systemic fungal infections
Provide some examples of antiviral agents
- Aciclovir
- Oseltamivir
- Specialist agents for HIV, HBV, HCV, CMV
Describe the use of aciclovir
- Inhibits viral DNA polymerase (when phosphorylated)
- Used to treat HSV and varicella zoster virus
Describe the use of oseltamivir
- Inhibits viral neuraminidase
- Used to treat influenza A & B
Describe the use of metronidazole (antibacterial and antiprotozoal agent)
- Active against anaerobic bacteria
- Also active against protozoa e.g. amoebae, giardia (diarrhoea), trichomonas (vaginitis)
What are the consequences of antibacterial resistance?
- Treatment failure
- Prophylaxis failure
- Economic costs
Identify and describe the different definitions of antimicrobial resistance
- MDR (multi-drug resistant): non-susceptibility to at least one agent in three or more antimicrobial categories
- XDR (extensively drug resistant): non-susceptibility to at least one agent in all but two or fewer antimicrobial categories
- PDR (pan-drug resistant): non-susceptibility to all agents in all antimicrobial categories
how to choose an antibiotic
- is it active against target organism
- does it reach site of infection (can it pass the blood brain barrier)
- is it available in the right formulation (IV/oral) - eg if they have had bowel surgery then it cant absorb
- whats the half life
- does it interact with other drugs
- is there toxicity issues
- does it require therapeutic drug monitoring
measuring antibiotic activity
disc testing - put different antibiotics and then see the spread of bacteria
quick and inexpensive
MIC - but different concentrations of antibiotics and see what conc the bacteria stops growing. sterile control ( only antibiotic and one with only bacteria to see if its growing) MIC is the conc at which it stops growing
MIC - E test - strip with different concs of antibiotcs and then place it with bacteria and see dostance it grows
intrinsic antibiotic resistance
bacterial species naturally resistant to a certain antibiotic family withiut the need for further mutations of genes
permenant
acquired antibiotic resistance
when a particular organism obtains the ability to resist the activity of a particular antimicrobial agent to which it was previously susceptible
the change is due to gene mutation or gene transfer via plasmid
mechanisms
enzyme modification // destruction of antibiotics
enzyme alteration of antibiotic
adaptive antibiotic resistance
responds from stress
gram negative bacterial replication
punjugation
single strand of plasmid from donor bacteria transfers to new bacteria via the pillus
both manufacture a second strand = 2 complete plasmids
DANGEROUS as they dont have to be the same species
