Antimicrobials Flashcards
BACTERIAL CELL WALL and MEMBRANE
areaffected by what type of antibiotics?
Beta lactam antibiotics -> · Penicillins · Cephalosporins · Carbapenems · Monobactams · Glycopeptides · Polymxins
NUCLEIC ACID SYNTHESIS is interuppted by what antibiotics
Folate anatgonists DNA gyrase · Quinolones RNA polymerase · Rifmycins (Rifampicin)
PROTEIN SYNTHESIS
50S subunits affected by?
· Macrolides · Lincomycins (Clindamycin) · Oxozolidinones (Linezolid) · Chroamphenicol (Chlorampehnicol)
Protein synthesis affecting 30S subunits are
· Tetracyclines · Aminoglycosides
What is the difference between bacteriostatic and bactericidal?
BACTERIOSTATIC antibiotics inhibit the growth and replication of bacteria (non-lethal) Eg. inhibitors of folate synthesis, quinolones
BACTERICIDAL antibiotics kill bacteria (lethal), but note that at low concentration these antibiotics may only be bacteriostatic Eg. penicillin, aminoglycosides
What is the core structure of penicillin?
What is the use of the side chain?
B-lactam
Side chain - absorption
What are 5 classes of penicillin?
5 classes of penicillin:
- Natural penicillins
- Penicillinase-resistant penicillins(staph infection)
- Aminopenicillins(gram positive and gram neg - ecoli,hinfluenza)
- Carboxypenicillins(pesudomonal-> pseudomonas, enteroccocus, Klebsiella)
- Acyl ureidopenicillins(pseudomonas aeroginosa)
Penicillins
Are they broad or narrow spec?
Absorption level is good or bad?
Is it safe in pregnancy?
Narrow spectrum
Excellent absorption
Safe in pregnancy
- Penicillin V
- Amoxicillin
- Flucloxacillin
- Benzylpenicillin
Cephalosporins
Are they broad or narrow spec?
Absorption level is good or bad?
Is it safe in pregnancy?
Broad spectrum
Safe in pregnancy
• Cefuroxime • Ceftaxime • Ceftazidime
Carbapenams
Are they broad or narrow spec?
Can they be taken orally or IV?
Is it safe in pregnancy?
Broad spectrum
IV only Safe in pregnancy
• Meropenem • Ertapenem • Imipenem
Monobactams
What is the one licenced monobactam called?
Only one licensed monobactam (Aztreonam)
mainly for severe aerobic gram-negative bacillary infections (including meningitis) in patients who have a serious beta-lactam allergy
•Glycopeptides
Narrow or broad spec?
When is it IV and when is it oral?
is it safe in pregnancy
Examples of it.
Narrow spectrum
IV only – except CDiff (need oral)
Safe in pregnancy
• Vancomycin • Teicoplanin • (Dalbavancin)
Polymyxins (colistin) side effect and what bacteria is it used in
nephrotoxic
pseudomonas
What is the MOA of sufonamide and trimethoprim?
Broad spectrum
Often used in combination for SYNERGISTIC effects (Sulfamethoxazole plus trimethoprim, TMP/SMX)
Bacteriostatic
Not safe in pregnancy
DNA gyrase • Quinolones
Broad or narrow spectrum Excellent bioavailability • Ciprofloxacin • Levofloxacin • Ofloxacin • Gatafloxacin
Can cause problems with pregnancy
RNA polymerase = Rifamycins (Rifampicin)
What is it a potent inducer of ?
Is it safe in pregnancy?
can it be used alone?
What is it used for?
Semisynthetic derivative of rifamycin B produced by Streptomyces mediterranei
Potent liver inducer and significant interactions
Safe in pregnancy
Never used alone due to low genetic barrier (RpoB gene)
Used in few conditions • Tuberculosis • Prosthetic joint infections
Macrolides
Broad or narrow?
Bacteriostatic or cidal
Examples?
Broad spectrum
Bacteriostatic
• Erythromycin • Azithromycin • Clarithromycin
Lincosamide (Clindamycin)
What type of bacteria does it kill?
What is it’s bioavailbility like
Gram positive and anaerobic infections
Excellent bioavailability
Bacteriostatic or bactericidal depending on dose and organism
Oxazolidinones (Linezolid)
What type of bacteria does it kill
What is it’s bioavailability like
Is it bacteriostatic or cidal
Gram positive infections
Excellent bioavailability
Bacteriostatic
• Chloramphenicol (Chloramphenicol)
Broad or narrow?
Usual mode of delivery?
Does it penetrate CNS
is it bacteriostatic or bacteriocidal?
Broad spectrum
Topical treatment
CNS penetration
Bacteriostatic
Tetracyclines
Broad or narrow spec
Bacteriostatic or cidal
Safe in pregnancy?
Examples
Side effect?
Broad spectrum
Bacteriostatic
Not safe in pregnancy, breastfeeding and children
- Doxycycline
- Tetracycline
- Minocycline
Side effect: stained teeth. Angioedema; diarrhoea; headache; Henoch-Schönlein purpura; hypersensitivity; nausea; pericarditis; photosensitivity reaction; skin reactions; systemic lupus erythematosus exacerbated; vomiting
Aminoglycosides(gentamycin)
broad or narrow
Narrow spectrum
gram negative infections (and second-line TB Rx)
IV (or Neb tobramycin)
• Gentamycin • Amikacin • Tobramycin • Streptomycin
Define the following causes of in vitro antibiotic effectiveness
Minimum inhibitory concentration (MIC)
MINIMUM BACTERICIDAL CONCENTRATION (MBC)
Detection of resistance mutation is done by?
MINIMUM INHIBITORY CONCENTRATION (MIC) is the minimum in vitro concentration which an antibiotic can inhibit growth
MINIMUM BACTERICIDAL CONCENTRATION (MBC) is the minimum in vitro concentration which an antibiotic can kill bacteria
The detection of RESISTANCE MUTATIONS by PCR
In vivo antibiotic effectiveness depend on?
Pharmacokinetics
Pharmacodynamics
Drug interactions
Foreign material
Source control
Host immune responses
Define bioavailability and which antibiotics are excellent?
BIOAVAILABILITY of oral agents is the proportion of drug absorbed into systemic circulation
Excellent (>90%): • Amoxicillin • Linezolid • Clindamycin • Levofloxacin • Ciprofloxacin • Rifampicin • Metronidazole
VOLUME OF DISTRIBTUTION
relates the [drug]blood relative to the dose given
- Small volume of distribution (plasma bound)
- Large volume of distribution (fat soluble)
Which drugs is a CYP3A4 inducer?
Which antibiotic is a CYP3A4 inhibitor?
- CYP3A4 inducers (Rifampicin)
- CYP3A4 inhibitors (Ketoconazole, Clarithromycin)
HALF-LIFE
How is ceftriaxone excreted
How is azithromycin excreted?
of the drug is the time
taken for [drug]blood to reduce by 50% from Cmax
- Renal excretion
- Non-renal excretion
- Biliary (Ceftriaxone)
- Gut (Azithromycin)
Give examples of concentration dependent killing(cmax/mic ratio), Time dependent killing (AUC/MIC ratio), Exposure dependent killing (AUC 24/ratio)
CONCENTRATION dependent killing (Cmax/MIC ratio) means drug PK needs to reach high drug concentration above the MIC
TIME dependent killing (AUC/MIC ratio) means drug PK needs to spend time above the MIC
EXPOSURE dependent killing (AUC24/ratio)
POST-ANTIBIOTIC EFFECT (PAE)
is the time when bacterial growth is still inhibited when [drug]
18yo normally healthy female in A&E admitted with
• Fever, dysuria, polyuria, flank pain and hypotension
Rx Co-amoxiclav and stat dose Gentamycin(Gentamycin so works quickly and then the comoxiclav works slower but longer)
Antimicrobial resistance (AMR)
is the ability of a microbe to resist the effects of medication that once could successfully treat the microbe
Main mechanisms of AMR
What are the 3 big resistant pathogens?
- Production of enzymes
- Changes to target sites or metabolic pathways
- Efflux pumps
Methicillin-resistant Staphylococcus aureus (MRSA)
Vancomycin-resistant Enterococci (VRE)
Extended-spectrum β– lactamase producing Enterobacteriaceae (ESBL)
How do you combact mutation of enzymes - b lactam specifically
β-lactamase enzyme and hydrolysis of the β-lactam molecule
Use of decoy substrates • Amoxicillin/clavulanic acid • Piperacillin/tazobactam • Ceftazidime/avibactam Carbapenamase enzymes
Changes to target sites or metabolic pathways
b-lactams
Macrolides and lincosomides
Quinolones
Carpapenams
Folate antagonist
Mutations in PBPs that stop binding (β-lactams)
Methylation of rRNA (macrolides and lincosomides)
Mutations in the gene for DNAgyrase (quinolones)
Mutations in porin channels (carbapenems)
Use of exogenous thymidine or thymidine for DNA synthesis (folate antagonists)
What have bacteria developed against tetracylins:
Active pumping out of antibiotics from the bacterial cell via porins (tetracyclines)
Main mechanisms of AMR
Natural resistance
Point mutations (SNPs)
Transformation (uptake of DNA from other cells)
Transduction (infection from bacteriophage)
Conjugation (exchange of genetic material)
- Plasmids (extrachromosomal)
- Transposons (chromosomal)
Antimicrobials in special populations
- Antibiotic allergy
- Extremes of age – infants and the elderly
- Impaired drug absorption or excretion
- Obesity
- Pregnancy and breastfeeding women
Antibiotic allergy types
Most adverse drug reactions are not immune mediated
Immune mediated reactions:
• Type 1 (immediate, IgE mediated) resulting in urticaria, angioedema or anaphylaxis (medical emergency)
• Type 2 (cytotoxic) resulting in drug induced haemolysis (uncommon) • Type 3 (immune complexes) resulting in serum sickness like reactions (fever, rash, arthralgia) after several days)
• Type 4 (delayed hypersensitivity) resulting in multiorgan involvement after several weeks (DRESS, SJS/TEN and potentially life threatening)
What are the reactions that occured after they had their antibiotics?
DRESS syndrome is a delayed type IVb hypersensitivity reaction thought to be mediated by antiviral T cells. 2. It is a severe, idiosyncratic multisystem reaction to a drug, characterised by fever, skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement.
Most common reported allergy (10-15%) Most are not allergic – check the history
Allergic: more common to have delayed reactions
Allergic: immediate hypersensitivity reactions decrease over time (50% at 5yrs) but avoided in all
Allergic: cross reactivity with cephalosporins
What antibiotics are safe to give
What antibiotics re not and what can you get?
SAFE • Penicillins • Cephalosporins • Clindamycin • Glycopeptides • Metronidazole
NOT SAFE
- Carbapenems (manufacturer warning)
- Macrolides (manufacturer warning)
- Quinolones (animal skeletal development)
- Folate antagonists (neural tube defects)
- Tetracyclines (skeletal development)
- Aminoglycosides (gentamycin) (auditory/vestibular nerve damage)
