Beta-lactams (Antibiotics Part 1) Flashcards
What are the components of the wall in a gram positive bacteria?
Cell membrane
Peptidoglycan cell wall
What is the structure of the wall of gram negative bacteria?
Cell membrane
Peptidoglycan cell wall
Outer membrane
Periplasm
Name four areas of a bacterium that an antibiotic may target.
Cell wall peptidoglycan
Metabolism within the bacterium
DNA
Ribosomes
Describe bactericidal antibiotic action.
Achieve sterilisation of the infected site by directly killing bacteria.
- lysis of bacteria can lead to release of toxins and inflammatory material
Describe bacteriostatic antibiotic action.
Suppresses growth but does not directly sterilise the infected site
- requires additional factors to clear bacteria-immune mediated killing
What is an antibiotic spectrum.
Spectrum refers to the range of bacterial species effectively treated by the antibiotic
- can vary widely even within the same antibiotic class
- be aware of difference between lack of activity and resistance
Name a broad spectrum antibiotic.
Meropenem - active against almost all gram positive and gram negative species
- resistance is rare except for MRSA
Name a narrow spectrum antibiotic.
Benzyl-penicillin - highly active against streptococci
- most other disease causing bacteria are resistant
Describe broad spectrum antibiotics.
Antibiotics that are active against a wide range of bacteria
- treat most causes of infection, but also have a substantial effect on colonising bacteria
Describe narrow spectrum antibiotics.
Antibiotics that are active against a limited range of bacteria
- have a much more limited effect on colonising bacteria
When a narrow spectrum antibiotics useful, and when are broad spectrum antibiotics.
Narrow - useful when you know the cause of the infection
Broad - when someone is very acutely ill, and you don’t know which bacteria is causing it
Name 2 anaerobes that may infect a patient.
Bacteroides
Clostridium
Name 4 gram positive bacterial groups.
Clostridium
Steptococcus
Enterococcus
Staphylococcus
Name 6 gram negative bacterial groups.
Bacteroides Pseudomonas Haemophilus Neisseria Other coliforms E.Coli
Describe guided therapy use in regards to antibiotic treatment.
Depends on identifying cause of infection and selecting an agent based on sensitivity testing
Gold standard - but means you have to wait 48hrs for the lab results, which isn’t always possible in very ill patients
Describe empirical therapy in regards to antibiotic treatment.
Best (educated) guess therapy based on clinical acumen
Used when therapy cannot wait for culture
Describe prophylactic therapy in regards to antibiotic treatment.
Preventing infection before it begins, e.g. in immunocompromised patients.
Antibiotic associated harm. Overgrowth of yeast and bowel flora leads to…..?
Yeast - thrush
Bowel flora - diarrhoea
How does antibiotic use lead to development of C.diff colitis.
Antibiotics unbalance the natural flora and resistant organisms already in the local environment colonise
Compare the impacts of narrow and broad spectrum antibiotics on colonisation.
Narrow - achieve clinical cure with as little impact on colonisation and resistance as possible
- penetration can be limited to site of infection
Broad - accept that impact on colonisation and resistance may be greater
- penetration broadly throughout the body (don’t know where the infection is)
What is the largest class of antibiotics?
Beta-lactams
Name the four sub-classes of antibiotics within beta-lactams?
Penicillins
Cephalosporins
Carbapenems
Monobactams
List some of the most important beta-lactam antibiotics.
Penicillins - Benzylpenicillin - Flucoloacillin - Amoxicillin Cephalosporins - Ceftriaxone Carbapenems - Meropenem Monobactams - Aztereonam
What are the components of Augmentin and Tazocin?
They are both combination beta-lactams.
Augmentin - amoxicillin/clavulanic acid
Tazocin - piperacillin/tazobactam
Describe the mechanism of action of beta-lactams.
Beta-lactam motif analogue of branching structure of peptidoglycan. This inhibits cross-linking of cell wall peptidoglycan, and lysis of bacteria
Bacteriostatic
What do beta-lactamases target?
The ring of the beta-lactam antibiotics
Which bacteria most commonly secrete beta-lactamases?
Gram negatives and S.aureus.
How are beta-lactams usually administered?
IV (poorly absorbed by GI tract and normally excreted unchanged into urine and bile)
Some are given orally (causes vomiting)
Which beta-lactams can be given orally?
amoxicillin and flucloxacillin
What are the possible adverse effects of giving beta-lactams?
- GI toxicity
- Hypersensitivity
- Infection
- Rare
GI toxicity - nausea, vomiting, diarrhoea and cholestasis.
Hypersensitivity - type 1, type 4, interstitial nephritis
Infection - candidiasis, C.diff and resistant bacteria
Rare - seizure, haemolysis and leukopenia
What are the complications of type 1 hypersensitivity reactions?
Urticarial rash - itchy and rasied
Anaphylaxis
Why must you be careful when a patient claims to be allergic to an antibiotic?
They usually mean there are GI symptoms or there is a therapeutic failure, rather than a hypersensitivity reaction
Can a patient with an allergy to a penicillin be given other antibiotics?
They will usually be allergic to other penicillins.
But cross-reactivity with other antibiotic classes are much lower (e.g. other beta-lactams)
What is the first choice antibiotic for serious streptococcal infections?
Benzylpenicillin
- IV route
- narrow spectrum (not good at treating anything other than streptococcus)
Describe how amoxicillin is a semi-synthetic penicillin.
As resistance towards it increased, scientists modified a small area on one of the side chains.
- amino penicillin
Is amoxicillin broad or narrow spectrum?
Broad
- good action against most gram positives (except staphylococcus)
- good action against haemophilus and neisseria (gram negative)
For what conditions is amoxicillin normally given?
Chest infections
- COPD flare up
- pneumonia
Which penicillin was developed to be resistance against beta-lactamase produced by staphylococcus?
Flucloxacillin
What is Flucloxacillin active against?
Staphylococcus aureus (not MRSA)
Steptococci
No gram negative action
Name the two beta-lactamase inhibitors
Clavulanic acid
Tazobactum
What is the purpose of co-administering beta-lactamases with penicillin?
Greatly broadens the spectrum of penicillins that work against gram negatives and S.auerus.
Which penicillins are clavulanic acid and tazobactum co-administered with? (respectively)
Clavulanic acid and amoxicillin = co-amoxiclav
Tazobactum and piperacillin = tazocin
Which bacteria are co-amoxiclav active against?
Gram positives (not MRSA) Gram neagtives (not Pseudomonas)
Which bacteria are tazocin active against?
Gram positives (not MRSA) Gram negatives
What is the go to antibiotic for very ill patients?
Tazocin
Which drug is more susceptible to beta-lactamases, cephalosporins or penicillins?
Cephalosporins
- and they have good activity against gram positives and gram negatives
Multiple generations of cephalosporins have been adapted as people have adapted over time. What happens to the spectrum with each generation?
Gram negative spectrum increases, with some loss of gram positive activity.
Latest generation is MRSA active
Name a cephalosporin
Ceftriaxone
What is Ceftriaxone active against?
Gram positive (not MRSA or enterococcus) Gram negative (not pseudomonas)
Are cabapenems active against beta-lactamases?
Yes, but there are new beta-lactamases emerging which can lyse carbapenems
Do carbapenems have a good spectrum of treatment?
Excellent spectrum against gram positives and negatives - ultra broad spectrum antibiotics
Describe which bacteria Meropenem is active against?
EVERYTHING
- except MRSA
Why isn’t Merpenem used more often?
It’s very effective, so we don’t want bacteria to develop resistance too quickly
What is the only member of Monobactam class?
Aztreonam - being used more as doctors avoud using Merpenem
What bacteria are Aztreonam active against?
Good activity against gram negative bacteria, and no effect at all against gram positive
What class does Vancomycin belong to?
Glycopeptide class
What is the mechanism of action of Vancomycin?
Inhibits cell wall formation in gram positives only (can’t fit though the thicker wall in gram negatives)
Why does Vancomycin work on MRSA?
Not dependent of penicillin binding proteins - so it’s effective against resistant organisms
How is Vancomycin administered?
Not absorbed from GI tract - must be given IV
If C.diff present in the gut needs treatment - should be given orally (doesn’t need to pass the gut wall to encounter the bacteria)
What are the possible effects of Vancomycin toxicity?
Nephrotoxicity - more likely with higher doses
Red-man syndrome if injected too rapidly
- anaphlactoid reaction (rare)
Ototoxicity
What is the main clinical issue with Vancomycin?
Underdosing - people are worried about toxicity
Which antibiotic mentioned somewhere in these flashcards requires therapeutic drug monitoring?
Vancomycin
- narrow therapeutic range
- concentration is higher in severe illness
For what conditions is Flucloxacillin normally given?
Soft tissue injury
- Wound infection
- Cellulitis
