Antibiotics Part 1 Flashcards
Explain what guided and empirical therapy is?
Guided - Narrow spectrum antibiotics used to target specific bacteria. Achieves clinical cure with as little impact on the colonisation and resistant as possible.
Empirical - Use of braod spectrum antibiotics. Must penetrate braodly throughout the body so will have impact on colonisation and resistance.
What are the different possible bacterial causes of an infection?
- Staphylococcus aureus (purple cocci in grape arrangement)
- Streptococci (Chains of cocci)
- Coliforms (gram negatives eg, e.coli. Can be found in andominal infections and UTIs)
- Difficult gram negatives (eg, Pseudomonas aeruginosa)
- Anarobics (Both gram +/- and seen in abscesses)
- Odd things (eg, legionella)
They are cheap, effective and safe!
Name the different antibiotics within the class of beta lactams
- Penicillins (amoxicillin, flucloxacillin)
- Cephalosporins (ceftriaxone)
- Carbapenems (Meropenem)
- Can be used with addition of beta-lactamase inhibitor
Explain the mechanism of action of beta lactams
All groups share the same structural features of beta-lactam motif analogue of branching structure of peptidoglycan. This can inhibit crosslinking of cell wall peptidoglycan causing lysis of bacteria. Hense they are bacteriacidal
What are the adverse effects of beta lactams?
- GI toxicity - Nausea and vomiting, diarrhoea, cholestasis (jaundice and abnormal LFTs)
- Hypersensitivity reactions - Type 1, type 4 (mild-severe dematological) and interstital nephritis).
- Infections - Candtitiasis (oral/vulvovaginal), Clostridium difficile, and resistance
- Miscellaneous (rare) - Seziures, haemolysis, Leukopaenia.
What are some examples of type 4 hypersensitivity reactions?
- Drug reaction with eosinophilia and systemic symptoms (DRESS)
- Stevens-Jonson syndrome - Flu-symptoms, followed by painful rash which can spread and blisters (mucosal sloughing)
Describe features of beta lactam type 1 hypersensitivity
- Urticaria and anyphlaxis
- Cross reaction between classes are variable, Some patients allrgic to penecilin may be able to safely use other beta lactams.
- Allergies are overreported as patients report GI upset and theraputic failure as allergies. Therefore must find out if patient has true allergy.
Describe features of amoxicillin
- Active principally against streptococci but also gram positives like haemophilus.
- Often prescribed for respiratory tract infections
- Resistance in E.coli and other coliforms so shouldn’t be used without sensitivity testing first.
Not active against S.aureus
Describe the mechanisms of resistance to beta lactams
- Alteration of target site which occurs through mutation/inherted mutation of pencillin binding proteins. This may result in loss of drug efficacy or decreased potency
- Production of inactivating enzymes called beta-lactamases. These lyse the beta lactam ring which inactivated the antibiotic.
- Influx/efflux mechanisms
Describe features of beta lactamases and methods to overcome them.
- Expressed in gram negative bacilli and S.aureus. Some are very easy to overcome eg S.aureus b-lactamase but others are much harder eg, metallo b-lactamases
- Can alter the beta-lactam to have different side chains making them resistant to beta-lactamases or can use beta-lactamases inhibitors
Describe features of Flucloxacillin
- Synthetic penicllin modified to overcome S.aureus beta lactamase
- Gold standard in treatment of soft tissue infection and MSSA
- Activity against streptococci (not as good as amoxicillin)
- Oral absorption not as good as amoxicillin
- Less well tolerated than amoxicilin due to GI upset and renal and liver dysfunction
No effect on MRSA, Coliforms, Difficult gram negatives and Anaerobes
Describe features of Co-amoxiclav
- Combination of Amoxicillin and the beta lactamase inhibitor clavulanic acid
- Broad spectrum antibiotic which is active against S.aureus, most coliforms and anaerobes
- BROADEST spectrum so use in mild infections empirically only. Causes ecological impact eg, thrush, c.diff.
- Cholestasis is common
Not effective in MRSA and difficult gram negatives
Describe features of Ceftriaxone
- Cephalosporin which is only avilable via IV
- Has a different affinity for PBPs so overcomes many beta lactamases
- Broader spectrum for gram negatives than co-amoxiclave
- Largely restricted to CNS infections
Not effective in MRSA, difficult gram negatices or anaerobes
Describe features of Tazocin
- Combination of Piperacillin and the beta lactamase inhibitor Tazobactam
- Only available IV
- Very broad spectrum active against Pseudomonas, MSSA, streptococci, colifroms and anaerobes.
- 1st line for management of neutropenic sepsis in severely immunocompromised patients
Describe features of Meropenem
- Part of the carbapenam class of ultra-broad spectrum antibiotics
- Only delivered IV
- Active against most causes of infections except MRSA and some extremely resistant gram negatices
- Ultra-broad spectrum means it has a substantial ecological impact
- Resustance is increasing - really not good
