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)
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
