Role of Pharmacist

Question 1

Read bit in lecture on guidelines

Answer 1

Read bit in lecture on guidelines

Question 2

Clostridium difficile characteristics Prevalence

Answer 2

Gram +ve spore formning rods Present in the gut of up to 3% of healthy adults Inhibited by normal gut flora

Question 3

C. diff cycle

Answer 3

Question 4

Risk factors C. diff infection

Answer 4

Elderly Recent antibiotic use, (1/12) (NG-tubes, PPIs)

Question 5

Symptoms of C. diff infection

Answer 5

Diarrhoea (BSC 6-7) Often with mucus Offensive smell

Question 6

Secondary symptoms of C.diff

Answer 6

raised CRP/WCC

Pyrexia

Toxic confusional state in elderly

Question 7

C. diff disease outcomes

Answer 7

• Mild disease; self-limiting.
• Severe disease; Pseudomembraneous Colitis. Damaged mucosa Pseudomembranes
• Clinical signs (PMC): - Abdominal distension, High WCC, usually diarrhoea

Question 8

C. diff management

Answer 8

• Stool sample for toxin.
• Patient isolation, strict enteric precautions, perfect hand hygiene (soap and water).
• Stool chart and daily monitoring of stools
• Stop offending antibiotics.
• Review drugs that may cause diarrhoea (PPIs, Laxatives etc.)

Question 9

Current standard C. diff treatment

Answer 9

PO Vancomycin

• Main C.diff treatment - Oral not IV 125-250mg four times a day Better efficacy in severely ill
• Higher dose 250-500mg with adjunct IV metronidazole (?ileus) if complicated – fulminant disease.

PO Fidaxomicin

Lower relapse rate vs Vanc. (12-15% vs 25-27%)

• Consider for: - Severe disease in patients with concurrent abx. and co-morbidities - Recurrence if C.diff within ~30 days £1350/course

Question 10

Emerging C. diff therapies

Answer 10

• Rifaximin IV
• Immunoglobulins, Bezlotoxumab
• Faecal Microbiota Transplants

Question 11

uses of FMT

Answer 11

Appears to be highly effective for the treatment of CDI: 90% resolution across 33 case series

Indication:

• Recurrent CDI
• Refractory CDI
• Acute Severe CDI: not initial therapy

Question 12

Antibiots associated with C.diff

Answer 12

• 10-40% of patients exposed to antibiotics.
• Most/all antibiotics can cause Antibiotic associated diarrhoea (AAD) and C.diff. 25% of AAD.
• High-Risk – mostly “broad- spectrum” -
• Clindamycin
• Cephalosporins
• penicillins (e.g. co-amoxiclav piperacillin/tazobactam) -
• Quinolones (e.g. ciprofloxacin)
• Carbapenems
• Erythromycin also causes diarrhoea by stimulating motility.

Question 13

Examples of lower risk (narrow spectrum) antibiotics

Answer 13

• Tetracyclines (e.g. doxycycline)
• Metronidazole
• Glycopeptides (e.g. vancomycin) – limited GI exposure
• Aminoglycosides (e.g. gentamicin) – limited GI exposure
• Flucloxacillin, penicillin V, benzylpenicillin Trimethoprim

Question 14

When to use Therapeutic drug monitoring?

Answer 14

Drug with narrow therapeutic index E.G Aminoglycosides (Gentamicin)

Question 15

When to use aminoglycosides and considerations

Answer 15

• Effective against most Gram –ve bacteria (inc Pseudomonas sp.) and Staph. aureus (inc. MRSA).
• Sufficient peak for efficacy. Low trough before re-dosing to reduce Nephrotoxicity/ toxicity.

Question 16

Adult gentamicin dosing

Answer 16

• Once daily gentamicin = 4-7mg/kg/day
• Multiple daily dosing = 3-5mg/kg in divided doses
• Dose altered in renal impairment.

Question 17

Monitoring gentamicin

Answer 17

Multiple daily dosing = Peaks and Trough taken around 3rd or 4th dose

Once daily gentamicin = Trough levels only, prior to second dose.

Target range: - Once daily gentamicin:

• Trough = <1mg/L,
• Peak = not measured

Multiple daily dosing:

• Trough = <2mg/L
• Peak = Usually 5-10mg/L

Pseudomonas sp. 7-10mg/L . For synergy in streptococcal or enterococcal infections (e.g. endocarditis) 3-5mg/L

Question 18

Considerations for gentamicin

Answer 18

Gentamicin major cause of preventable drug related toxicity (nephro- and ototoxicity).

• Risk increased by other nephrotoxic drugs (e.g. NSAIDs, Vancomycin)
• Monitor renal function Routinely: Twice weekly levels
• Decline in renal function/urine output. - Once daily - immediate trough level and await result before re-dosing.
• Multiple daily dosing – levels around next dose.