C.Dif infections Flashcards
1
Q
Metronidazole
Common indications
A
- Antibiotic associated colitis- Caused by C.difficile, which is a gram +ve anaerobic bacteria
- Oral infections (Dental abscess) or aspiration pneumonia caused by gram -ve anaerobes from mouth
- Surgical and gynaecological infections cause by G-ve Anaerobes
- Protozoal infections including trichomonal vaginal infection and giardiasis
2
Q
Metronidazole
MOA
A
- Metronidazole enter bacterial cells by passive diffusion
- In Anaerobic bacteria, reduction of metronidazole generates a nitroso free radical
- This binds to DNA, reducing the synthesis and causing widespread damage, DNA degradation and cell death
- As aerobic bacteria are not able to reduce metronidazole in this manner metronidazole is for use in Anaerobic bacteria only
- Bacterial resistance is generally low but is increasing in prevalence
- Mechanisms: reduced uptake of drug and reduced free radical production
3
Q
Metronidazole
Adverse effects
A
- GIT irritation such as N&V
- Immediate and delayed hypersensitivity reactions
- When used for a prolonged course, metronidazole can cause neurological adverse effects including Peripheral and optic neuropathy, seizures and encephalopathy
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4
Q
Metronidazole
Warnings
A
- Metronidazole is metabolised by hepatic CYP enzymes so should be reduced in people with Severe liver disease
- Metronidazole inhibits acetaldehyde dehydrogenase, which is responsible for clearing the intermediate alcohol metabolite (Acetylaldehyde) from the body so NO Alcohol- cause N&V, flushing and headache
5
Q
Metronidazole
Important interaction
A
- Metronidazole has some inhibitory effects on CYP P450 enzymes - reducing the metabolism of Warfarin- increasing the risk of bleeding and Phenytoin- increasing the risk of toxicity= cerebral impairment)
- The reverse interaction can occur with CYP P450 inducers (Phenytoin, rifampicin) resulting in reduced plasma concentrations and impaired antimicrobial efficacy
- Also increases the risk of toxicity with Lithium
6
Q
Metronidazole
Communication and Monitoring
A
- Check history of allergies
- NO ALCOHOL- N&V, flushing or headache
- Check symptoms of infection make sure they improve
- If treatment for more than 10 days do full blood count and LFTs to monitor for adverse effects
7
Q
Metronidazole
Clinical tip
A
- Anaerobic bacteria are often resistant to penicillins due to production of B-lactamase
- However co-amoxiclac does have good efficacy against anaerobes- due to B-lactamase inhibition
- Where patients are taking co-amoxiclav anaerobic cover is often sufficient and there is no need to add metronidazole
- However check local antimicrobial guidelines
8
Q
Vancomycin
Common indication
A
- Treatment of G+ infections- endocarditis where infection is severe and or penicillins can not be used due to resistance
- Treatment of antibiotic-associated colitis caused by C.dif infection
9
Q
Vancomycin
MOA
A
- Vancomycin inhibits growth and cross-linking of peptidoglycan chains, inhibiting the synthesis of the cell wall of G+ bacteria
- It, therefore, has specific activity against G+ aerobic and anaerobic bacteria and is inactive against most G- bacteria
- Which have a different (lipopolysaccharide) cell wall structure
- Bacterial resistance to vancomycin is increasingly reported
- One mechanism is modification of cell wall structure to prevent vancomycin binding
10
Q
Vancomycin
Important adverse effects
A
- The most common adverse effect is pain and inflammation of the vein (thrombophlebitis) at the infusion site
- If vancomycin is infused rapidly, severe adverse reactions can occur
- Red-man syndrome- anaphylactoid reactions. This is characterised by generalised erythema and may be associated with hypotension and bronchospasm
- This reaction is not Ag-mediated (not true allergy)
- True allergic reactions may occur
- IV Vancomycin may cause Nephrotoxicity- renal failure
- Ototoxicity with tinnitus and hearing loss
- Blood disorder- neutropenia and thrombocytopenia
11
Q
Vancomycin
Warnings
A
- Vancomycin treatment requires careful monitoring of plasma drug concentrations and dose adjustment to avoid toxicity
- Particular caution including dose reduction should be taken when prescribing for people with renal impairment and the elderly (increased risk of hearing impairment
12
Q
Vancomycin
Important interaction
A
- Vancomycin increases the risk of ototoxicity and nephrotoxicity when prescribed with aminoglycosides and loop diuretics or ciclosporin
13
Q
Vancomycin
Administration
A
- Intravenous vancomycin must be given by slow infusion (not IV bolus or IM injection) to reduce the risk of anaphylactoid reactions and ‘red man syndrome’; 1 g of vancomycin must be diluted in at least 250 mL sodium chloride 0.9% or glucose 5% and infused over at least
60 minutes.
14
Q
Vancomycin
Communication
A
- Explain that the aim of treatment is to get rid of infection and improve symptoms
- For oral treatment, encourage the patient to complete the prescribed course
- Warn them to report any ringing in the ears or changes in hearing
- Check for allergic reaction
15
Q
Vancomycin
Monitoring
A
- Where IV therapy is used, pre-dose (trough) Plasma vancomycin concentrations should be measured during treatment
- Vancomycin dosage should be adjusted to keep plasma concentrations above 10mg/L to maintain therapeutic effect but below 15mg/L to minimise toxicity
- Check that Infection resolves
- Safety monitoring should include daily renal function, FBC monitoring during prolonged therapy
