This meeting has been initiated and funded by Astellas Pharma Ltd.
Fidaxomicin: CDDFT Case
Studies
Dr Deepa Nayar
County Durham and
Darlington Foundation Trust
FIS 2013, Birmingham
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
County Durham and Darlington NHS
Foundation Trust (CDDFT)
One of the largest hospital and community healthcare
providers in the NHS
Serves a population of ~600,000
2 Acute sites
6 Community Hospitals
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
CDDFT Contractual and upper
threshold 2012/2013
Target Actual Acute 47 60 Community Services 4 6 Total:
51 66
CDDFT Contractual and upper
threshold 2013/2014 Ambition Acute 40 Community Services 4 Total:
44
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Are we doing everything we can?
Trust HCAI reduction group weekly meetings
Antimicrobial Stewardship
Infection Control
Role of fidaxomicin? All C. difficile positive cases reviewed
Every case discussed between Microbiologist, infection
control, Antibiotic Pharmacists and Clinical team for use
of fidaxomicin
Reviewed at weekly C. diff MDTs along with a
Gastroenterologist until discharge
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Fidaxomicin
Between Nov 12 and Sep 13, there were 111 patients
with confirmed C. difficile infection across the health
economy (74 Community/37 Trust apportioned)
17 cases treated with fidaxomicin
0
1
2
3
4
5
6
7
8
9
10
Pre 48hr Post 48hr
Nu
mb
er
of
Pat
ien
ts
Pre 48hr vs Post 48hr
Female
Male
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Age range
0
2
4
6
8
10
12
14
<60 60-69 70-79 >80
Nu
mb
er
of
Pat
ien
ts
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Indication for fidaxomicin and
C. difficile severity
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Case Study 1
Date of preparation: November 2013 DIF13049UKh
Patient profile and examination
Profile
88 year old, Male
57 kg
Presenting complaint
Shortness of breath, difficulty in swallowing
Past medical history
COPD
Chronic dysphagia
Delirium
Poor nutritional intake
Date of preparation: November 2013 DIF13049UKh
Case history
Community acquired pneumonia (CAP), treated with
Amoxicillin and Clarithromycin for 7 days
Patient then suffered a new cerebro-vascular event
and poor swallow on background of chronic
dysphagia
Need for peg feeding was identified, but family and
patient refused in view of “Quality of life” feeding
Date of preparation: November 2013 DIF13049UKh
Ongoing management
Hospital stay prolonged by cerebro-vascular event
Poor oral intake on background of chronic dysphagia
and poor swallow led to recurrent aspirations
Another chest infection, treated with IV Tazocin for 7
days
Patient suffered loose stools and found to be positive
for C. difficile
Date of preparation: November 2013 DIF13049UKh
C. difficile management
Clinical team referred to Microbiology for treatment of
C. difficile, first episode
Due to poor swallow, treated with IV Metronidazole
and PO Vancomycin for 14 days
As high risk of recurrent aspiration and chest
infections, PO Vancomycin was continued for 4 more
weeks as a tapered, pulsed regime
Patient discharged
Date of preparation: November 2013 DIF13049UKh
Readmission
Aspiration pneumonia treated with IV Tazocin for
7 days
After 3 days of IV Tazocin, new onset diarrhoea
and was found to be C. difficile positive again
Diagnosis: Recurrence of C. difficile infection
MDT decision to treat the recurrent episode of C.
difficile with fidaxomicin as:
Concomitant antibiotics
Associated comorbidities
Risk of recurrent aspiration and pneumonia
Date of preparation: November 2013 DIF13049UKh
Follow-up
Patient responded very well to fidaxomicin when
he suffered 1st recurrence of C. difficile infection
Patient has been followed up and evaluated
since Dec ’12 and has had 3 further episodes of
chest infections secondary to aspiration
He has had 2 further courses of antibiotics for
chest infections and 1 hospital admission in the
last 7 months
Despite these courses, no further recurrence of
his diarrhoea
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Case Study 2
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Patient profile and examination
Profile
43 year old, Female
65 kg
Presenting complaint
Diarrhoea, Fever, Spontaneous Bacterial Peritonitis
(SBP), Sepsis
Past medical history
Alcoholic Liver Disease, Child C Cirrhosis
Recurrent SBP leading to recurrent antibiotics
Pancytopenia
Recent CDI in past 28 days
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Case history
Diagnosed with E. coli septicaemia and SBP on
current admission
Treated with IV Tazocin for 7 days
Diarrhoea on admission, suspected C. difficile on
background of recent C. difficile (within last 28 days)
C. difficile management
MDT decision to treat the recurrent episode of C.
difficile with fidaxomicin as:
Concomitant antibiotics
Associated comorbidities - Pancytopenia, Child C Cirrhosis
Risk of recurrent SBP and need for antibiotics
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Follow-up
Patient responded very well to fidaxomicin,
discharged home diarrhoea free
Patient has been followed up and evaluated
since April 13 and has had 1 further admission
with SBP
No further diarrhoea reported, no further stool
samples received
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
28 day follow up post fidaxomicin
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Follow up End Sep ’13
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
What’s next?
To analyse cost benefit of using fidaxomicin
To analyse impact on LOS and bed days
To analyse TTROD
To develop local guidelines/protocol identifying
patients with risk factors for recurrence/relapse
EARLY
To continue use of fidaxomicin in selected
patients and with MDT consensus
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Summary
Small numbers
Fidaxomicin well tolerated – no patients needed
to stop course
Good clinical response – initial data encouraging
3 relapses/recurrences so far – 1 confirmed
microbiologically, 2 clinical
Early recognition of risk factors for
relapse/recurrence would help teams find a place
for fidaxomicin
Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd. Date of preparation: November 2013 DIF13049UKh
This meeting has been initiated and funded by Astellas Pharma Ltd.
Acknowledgements
Stuart Brown, Antibiotic Pharmacist
Dr D Allison, Dr C Aldridge, Dr L Lim, Dr J Sloss
(Microbiologists)
Dr A Dhar and Dr D Kejariwal (Gastroenterologists)
Tricia Gordon, Lead ICN
Mike Wright, DIPC
Prof Chris Gray, Medical Director
Sue Jacques, CEO, CDDFT
Date of preparation: November 2013 DIF13049UKh
Date of preparation: November 2013 DIF13049UKi
Questions?
Date of preparation: November 2013 DIF13049UKi
Thank you
Please complete your evaluation forms and hand
them in on your way out
Date of preparation: November 2013 DIF13049UKi
Prescribing Information
DificlirTM ▼(fidaxomicin) Prescribing Information
Presentation: Dificlir™ tablets contain 200 mg fidaxomicin.
Indication: The treatment of Clostridium difficile infections
(CDI) also known as C. difficile-associated diarrhoea (CDAD)
in adults. Consideration should be given to official guidelines
on the appropriate use of antibacterial agents. Posology and
method of administration: Adults and elderly (≥ 65 years of
age): The recommended dose is one 200 mg tablet to be
administered twice daily (once every 12 hours) for 10 days
and can be taken with or without food. Paediatrics: The safety
and efficacy of fidaxomicin in children aged below 18 years
has not yet been established. Renal impairment: No dose
adjustment is considered necessary. Use with caution in
patients with severe renal impairment. Hepatic impairment: No
dose adjustment is considered necessary. Use with caution in
patients with moderate to severe hepatic impairment.
Contraindications: Hypersensitivity to the active substance
or to any of the excipients. Warnings and Precautions:
Hypersensitivity reactions including severe angioedema have
been reported. If a severe allergic reaction occurs during
treatment with Dificlir, the medicinal product should be
discontinued and appropriate measures taken. Due to limited
clinical data, fidaxomicin should be used with caution in
patients with severe renal impairment or moderate to severe
hepatic impairment. Fidaxomicin should also be used with
caution in patients with pseudomembranous colitis, fulminant
or life threatening CDI. No data is available in patients with
concomitant inflammatory bowel disease, caution should be
used in these patients due to a risk of enhanced absorption
and a potential risk for systemic adverse reactions. Co-
administration of potent P-glycoprotein inhibitors such as
cyclosporine, ketoconazole, erythromycin, clarithromycin,
verapamil, dronedarone and amiodarone is not
recommended. Drug interactions: Fidaxomicin is a
substrate of P-gp and may be a mild to moderate inhibitor of
intestinal P-gp. Co-administration of potent inhibitors of P-gp,
such as cyclosporine, ketoconazole, erythromycin,
clarithromycin, verapamil, dronedarone and amiodarone are
not recommended. Fidaxomicin had a small but not clinically
relevant effect on digoxin exposure. However, a larger effect
on P-gp substrates with lower bioavailability, more sensitive to
intestinal P-gp inhibition, such as dabigatran etexilat, cannot
be excluded. Undesirable effects: Common (≥ 1/100 to <
1/10): vomiting, nausea, constipation. Uncommon (≥ 1/1,000
to < 1/100): rash, pruritus, decreased appetite, dizziness,
headache, dysgeusia, abdominal distension, flatulence, dry
mouth, increased alanine aminotransferase. Consult SmPC
for complete information on side effects. Packs and Cost:
200 mg tablet x 20 £1,350.00. Legal Classification: POM.
Marketing authorisation number: EU/1/11/733/001-004
Date of Preparation of PI: June 2013. Further information
available from: Astellas Pharma Ltd, 2000 Hillswood Drive,
Chertsey. KT16 0RS. For Medical Information phone: 0800
783 5018
Adverse events should be reported. Reporting forms and
information can be found at www.mhra.gov.uk/yellowcard.
Adverse events should also be reported to Astellas Pharma
Ltd. Please contact 0800 783 5018