Antibiotics Flashcards
Name two penicillin antibiotics? - actual penicillin e.g. not amoxicillin
- Benzylpenicillin (Penicillin G)
2. Phenoxymethylpenicillin (Penicillin V)
What is the mechanism of action of penicillins?
Penicillins inhibit the enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls, preventing them from maintaining an osmotic gradient. Uncontrolled entry of water into bacteria causes cell swelling, lysis and death.
What is the significance of the beta-lactam ring in penicillins?
Beta-lactam rings are responsible for antimicrobial activity. Side chains attached to the beta-lactam ring can be modified to make semi-synthetic penicillins. The nature of the side chain determines the antimicrobial spectrum and other properties of the drug.
How does bacterial resistance to beta-lactams occur?
Bacteria resist the actions of penicillins by making beta-lactamase, an enzyme which breaks the beta-lactam ring and prevents antimicrobial activity. Other mechanisms of resistance include limiting the intracellular concentration of penicillin (reduced bacterial permeability or increased extrusion) or changes in the target enzyme to prevent penicillin binding.
What percentage of people have a penicillin allergy?
1-10%
On first exposure, how does a penicillin allergy present?
Skin rash, 7-10 days after first exposure
What are the indications for use of penicillin V / penicillin G?
Streptococcal infections;
1. Tonsillitis
2. Pneumonia (in combination with a macrolide if severe)
3. Endocarditis
4. In combination with flucloxacillin for severe skin and soft tissue infections
Clostridium perfringens infections e.g. gas gangrene
Meningococcal infections:
1. Meningitis
2. Septicaemia
Which immunoglobulin is involved in the more common, less severe penicillin reaction, which can appear 1-2 days on repeat exposure?
IgG
In more severe penicillin allergies, which immunoglobulin is involved, and what kind of reaction is it? (this applies to all penicillins)
IgE-mediated anaphylactic reaction- this can be life threatening, occurring within minutes to hours, with hypotension, bronchial and laryngeal spasm/oedema and angioedema.
What can occur with high doses of penicillin or when severe renal impairment may delay excretion of penicillin?
Central nervous system toxicity (including convulsions and coma)
What is the obvious contraindication for use of penicillin?
Penicillin allergy
When should a reduced dose of penicillin be used? (this applies to all penicillins)
In someone with renal impairment
Penicillins reduce the excretion of which drug (often used to treat RA), increasing the risk of toxicity?
Methotrexate
Benzylpenicillin can only be administered via which routes?
IV or IM (as gastric acid prevents GI absorption)
Name the antipseudomonal penicillin?
Piperacillin with tazobactam = Tazocin
What are antipseudomonal penicillins reserved for (1) and in what conditions are they used? (3)
Antipseudomonal penicillins are reserved for severe infections, particularly where there is:
- a broad spectrum of potential pathogens (including Pseudomonas aeruginosa) OR
- antibiotic resistance is likely OR
- patients are immunocompromised
Which clinical infections are treated by piperacillin with tazobactam (Tazocin)? (4 - broad areas of infection)
- Lower respiratory tract infection
- Urinary tract infection
- Intra-abdominal sepsis
- Skin and soft tissue infection
How has the beta-lactam side chain been modified to form piperacillin?
The side chain of broad-spectrum penicillins has been converted to a form of urea. This longer side chain may improve affinity to penicillin binding proteins, increasing the spectrum of antimicrobial activity to include Pseudomonas aeruginosa.
Why is tazobactam combined with piperacillin?
Tazobactam is a beta-lactamase inhibitor, so confers antimicrobial activity against beta-lactamase-producing bacteria e.g. staph aureus, and gram-negative anaerobes.
What is the common possible side effect caused by Tazocin?
GI upset; nausea and diarrhoea are common
Less frequently, what side effects an occur from using Tazocin?
Antibiotic-associated colitis can occur (when broad-spectrum antibiotics kill normal GI flora, allowing overgrowth of toxin-producing C.diff).
What are the warnings (2)/contraindications (1) associated with using Tazocin?
- Use in caution with people at risk of C.diff infection
- Use in caution/reduced dose in patients with moderate/severe renal impairment
- Contraindicated in penicillin allergy
As with other penicillins, which drug do they reduce the renal excretion of?
Methotrexate
Antipseudomonal penicillins enhance the anticoagulant effect of which drug, and how?
Warfarin, by killing normal GI flora that synthesises vitamin K.
What is the only route of administration of piperacillin and tazobactam?
IV infusion
Name two commonly prescribed, broad spectrum penicillin based antibiotics?
- Amoxicillin
2. Co-amoxiclav
Name the 4 indications for use of amoxicillin or co-amoxiclav?
- Pneumonia (which may be caused by gram positive e.g. strep pneumoniae, or gram negative e.g. haemophilus influenzae pathogens)
- UTI (most commonly caused by E.coli) (Trimethoprim and nitrofurantoin are alternatives).
- Hospital acquired infection/intra abdominal sepsis: co-amoxiclav (e.g. co-amoxiclav and clarithromycin)
- H.pylori associated peptic ulcers - combination therapy
For amoxicillin, what is added to the beta-lactam ring side chain?
An amino group is added to the side chain, this increases activity against aerobic Gram-negative bacteria, making this a broad spectrum antibiotic.
What is combined with amoxicillin to make co-amoxiclav?
Clavulanic acid
Why is clavulanic acid a useful addition to amoxicillin?
Clavulanic acid is a beta-lactamase inhibitor, therefore increasing the spectrum of antimicrobial activity further, to include beta-lactamase-producing bacteria (staph aureus and gram-negative anaerobes).
Which antibiotic does MRSA resist the action of?
Flucloxacillin
What are the indications for use of flucloxacillin, and which bacteria is it effective against? (3)
Staphylococcal infection:
- Skin and soft tissue infections e.g. cellulitis
- Osteomyelitis and septic arthritis
- Endocarditis
Which drug can flucloxacillin be used in combination with in severe skin and soft tissue infections?
Benzylpenicillin
What is added to the beta-lactam ring side chain in production of flucloxacillin?
An acyl side chain. It protects the beta-lactam ring from beta-lactamases.
How does methicillin-resistant staph. aureus resist the actions of flucloxacillin?
It reduces the penicillin binding affinity
Why is it important to check what symptoms a patient experienced when they say they are allergic to penicillin?
Patients may say they are allergic to penicillin when they may have experienced side effects including nausea and vomiting. This isn’t a true allergy, as opposed to symptoms including skin rash, bronchospasm or anaphylaxis.
Name two cephalosporins?
- Cefalexin
- Cefotaxime
- Cefadroxil
- Cefradine
Name two carbapenems?
- Meropenem
- Ertapenem
- Imipenem
What is the mechanism of action of cephalosporins and carbapenems?
Cephalosporins and carbapenems are derived from naturally occurring antimicrobials produced by fungi and bacteria. Like penicillins, their antimicrobial effect is due to their beta-lactam ring. During bacterial cell growth, cephalosporins and carbapenems inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls. This weakens cell walls –> cell swelling, lysis and death.
Are cephalosporins and carbapenems broad or narrow spectrum antibiotics?
Broad spectrum
What is the configuration of a cephalosporin in related to the beta-lactam ring?
Cephalosporins have a dihydrothiazine ring fused to the beta-lactam ring
What is the side chain attached to the beta-lactam ring in carbapenems?
Hydroxyethyl side chain
What are the indications for use of cephalosporins and carbapenems?
- Oral cephalosporins are second- and third- line treatment options for urinary and respiratory tract infections
- IV cephalosporins and carbapenems are reserved for the treatment of infections that are very severe or complicated, or caused by antibiotic resistance organisms. Due to their broad antimicrobial spectrum, they can be used for most indications.
What are the adverse effects associated with cephalosporin and carbapenem use? (4)
- GI upset
- Antibiotic associated colitis (C.diff)
- Hypersensitivity - as they share structural similarities to penicillins, reactivity can occur in penicillin-allergic patients
- Risk of CNS toxicity including seizures when carbapenems are prescribed at a high dose
What is the contraindication for use of carbapenems/cephalosporins?
Allergy to penicillin, cephalosporin or carbapenem, particularly if it was an anaphylactic reaction.
When should carbapenems be used with caution (related to the risk to CNS including seizures)?
In patients with epilepsy
When is a dose reduction required when using either carbapenems/cephalosporins?
In patients with renal impairment
Which drug do carbapenems reduce the efficacy of (related to the caution for use)?
Valproate
Trimethoprim is a first choice antibiotic for treatment of which infection?
Uncomplicated UTI
Trimethoprim can be combined with which drug to form co-trimoxazole?
Sulfamethoxazole
What is the indication for use of co-trimoxazole? (1)
Pneumocystis pneumonia: for treatment and prevention in people with immunosuppression e.g. due to HIV infection
What are the alternatives to trimethoprim for treating a UTI?
- Nitrofurantoin
2. Amoxicillin
What is the mechanism of action of trimethoprim?
Bacteria have to make their own folate for functions including DNA synthesis, trimethoprim inhibits bacterial folate synthesis, which in turn slows bacterial growth (bacteriostatic).
Is trimethoprim broad or narrow spectrum?
Broad spectrum against both Gram - positive and -negative bacteria, including enterobacteria e.g. E.coli.