Fidaxomicin: CDDFT Case Studies Dr Deepa Nayar County ... · (fidaxomicin) Prescribing Information Presentation: Dificlir™ tablets contain 200 mg fidaxomicin. Indication: The treatment

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


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



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



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



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



Age range

0

2

4

6

8

10

12

14

<60 60-69 70-79 >80

Nu

mb

er

of

Pat

ien

ts



Indication for fidaxomicin and

C. difficile severity



Case Study 1


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


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


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


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


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


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



Case Study 2



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



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



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



28 day follow up post fidaxomicin



Follow up End Sep ’13



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



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


This meeting has been initiated and funded by Astellas Pharma Ltd. Date of preparation: November 2013 DIF13049UKh


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 DIF13049UKi

Questions?


Thank you

Please complete your evaluation forms and hand

them in on your way out


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

http://www.mhra.gov.uk/yellowcard

Documents

Fidaxomicin: CDDFT Case Studies Dr Deepa Nayar County ... · (fidaxomicin) Prescribing Information Presentation: Dificlir™ tablets contain 200 mg fidaxomicin. Indication: The treatment