Glycopeptide antibacterials

Vancomycin

• Capsules 125mg, 250mg (£134.28 = 28 x 125mg)
• Powder for solution for infusion vial 500mg, 1g

Indications

• C. difficile infection

Notes

1. The intravenous route should not be used for C. difficile infections. Alternative oral formulations may be available, seek specialist advice
2. Therapeutic drug monitoring (serum-vancomycin measurement) is required for intravenous use

Fidaxomicin

Fidaxomicin

• Tablets 200mg (£1,350.00 = 20 tablets)
• Oral suspension sugar free 40mg/ml (£1,350.00 = 110ml bottle)

Indications and dose

• C. difficile infection
  • Tablets: Adults and children with body-weight ≥ 12.5kg: 200mg orally twice a day for 10 days
  • Oral suspension: Adults and children from birth to < 18 years of age (doses given twice a day for 10 days)
    • Body-weight under 4kg: 40mg (1ml reconstituted oral suspension)
    • Body-weight 4kg - < 7kg: 80mg (2ml reconstituted oral suspension)
    • Body-weight 7kg - < 9kg: 120mg (3ml reconstituted oral suspension)
    • Body-weight 9kg - < 12.5kg: 160mg (4ml reconstituted oral suspension)
    • Body-weight ≥ 12.5kg: 200mg (5ml reconstituted oral suspension)

Notes

1. The routine commissioning of fidaxomicin is accepted in Devon for the treatment of Clostridioides difficile infection (see Commissioning Policy for more details)
2. Reconstituted oral suspension may be administered via enteral feeding tube; for further information, including recommended tube size and flush volume of water are available refer to the SmPC.

Linezolid

Linezolid

• Tablets 600mg
• Oral suspension 100mg/5ml

Notes

1. The notes below are intended to highlight the key points to consider when prescribing linezolid; the prescriber is referred to the manufacturer's summary of product characteristics (SPC) for additional interaction and monitoring requirements associated with treatment.
2. The SPC states linezolid should only be initiated in a hospital environment and after consultation with a relevant specialist such as a microbiologist.
3. Linezolid should not be prescribed for longer than 14 days. At the time of writing (March 2018) the manufacturer's SPC states that the safety and effectiveness of linezolid when administered for periods longer than 28 days have not been established.
4. In exceptional circumstances patients may be initiated on longer courses under the direction of microbiology/infectious diseases.
5. Linezolid is not active against infections caused by Gram negative pathogens. Specific therapy against Gram negative organisms must be initiated concomitantly if a Gram negative pathogen is documented or suspected.
6. Following discussion with an infection specialist, linezolid should only be used for life-threatening or deep seated infections (including that due to MRSA) where alternate therapy, e.g. vancomycin, is unsuitable
7. Monitor full blood count (including platelet count) at baseline and a minimum of weekly during treatment.
   
8. BNF CHM advice
   • Optic neuropathy:
     Severe optic neuropathy may occur rarely, particularly if linezolid is used for longer than 28 days. The CHM recommends that:
     1. patients should be warned to report symptoms of visual impairment (including blurred vision, visual field defect, changes in visual acuity and colour vision) immediately;
     2. patients experiencing new visual symptoms (regardless of treatment duration) should be evaluated promptly, and referred to an ophthalmologist if necessary;
     3. visual function should be monitored regularly if treatment is required for longer than 28 days.
   • Blood disorders:
     Haematopoietic disorders (including thrombocytopenia, anaemia, leucopenia, and pancytopenia) have been reported in patients receiving linezolid. It is recommended that full blood counts are monitored weekly. Close monitoring is recommended in patients who:
     1. receive treatment for more than 10–14 days;
     2. have pre-existing myelosuppression;
     3. are receiving drugs that may have adverse effects on haemoglobin, blood counts, or platelet function;
     4. have severe renal impairment.
     If significant myelosuppression occurs, discuss urgently with an infection specialist for further advice.
9. Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAOI); however, at the doses used for antibacterial therapy, it does not exert an anti-depressive effect.
10. Spontaneous reports of serotonin syndrome associated with the co-administration of linezolid and serotonergic agents, including antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have been reported. Co-administration of linezolid and serotonergic agents is contraindicated except where administration of linezolid and concomitant serotonergic agents is essential. In those cases patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyperreflexia and incoordination.
11. Washout periods should be observed when switching between linezolid and SSRIs – a recommendation to separate administration linezolid from SSRIs by 7-14 days (in the case of fluoxetine, 5-6 weeks, owing to its extremely long half-life) is suggested. However, infection with a resistant organism is a serious illness, requiring prompt initiation of antibiotic therapy. For further advice discuss with an infection specialist

Polymixins

Colistimethate sodium

• Powder for solution for injection vial 1million unit, 2million unit (£18.00 = 10 x 1million unit vials; £32.40 = 10 x 2million unit vials) (non-CF bronchiectasis only)
• Colobreathe 1,662,500unit dry powder for inhalation (Cystic Fibrosis (CF) treatment only)
• Promixin 1 million unit powder for nebuliser solution (CF treatment only)

Dose

• Consult product literature and seek specialist advice for dosing information

Notes

1. CF patients: Inhaled treatment is funded by NHS England. Colistimethate sodium should be initiated, monitored and ongoing prescriptions issued by secondary care only, with supply via Homecare provider (including diluent). CF Teams will organise provision of nebuliser and plastic consumables such as nebuliser delivery pot, tubing, mouthpiece and venting system (some of which are drug-specific).
2. National commissioning criteria for inhaled treatments for CF can be found in the NHS England commissioning policy, available here
3. Non-CF bronchiectasis patients: Colistimethate sodium powder for solution for injection is included for nebulised use in this patient group (unlicensed). Respiratory specialist to initiate treatment, including first prescription and training of use of nebuliser. Response to treatment should be reassessed and monitored by specialist at regular intervals, and where appropriate repeat prescribing of colistimethate sodium (plus diluent) may be performed in primary care on specialist advice. Specialists will organise provision of nebuliser and plastic consumables such as nebuliser delivery pot, tubing, mouthpiece and venting system.
4. The dose and treatment plan for each patient will be decided by the respiratory specialist team and will be communicated in the clinical letter to the GP.
5. First dose to be under medical supervision by member of the respiratory team according to Trust Policy.
6. Following test dose, specialists will advise GP and patient of choice of diluent (e.g. water for injection, 0.9% sodium chloride, salbutamol) and volume (usually 2-4ml), depending on patient tolerability.
7. If other treatments are being inhaled, they should be taken in the order recommended by the respiratory specialist.
8. NICE TA276: Colistimethate sodium and tobramycin dry powders for inhalation for treating pseudomonas lung infection in cystic fibrosis (March 2013):
   1. Colistimethate sodium DPI (Colobreathe) is recommended as an option for treating chronic pulmonary infection caused by Pseudomonas aeruginosa in people with CF only if the criteria within the NICE TA are met

Rifaximin

Rifaximin

• Tablets 550mg (£259.23 = 56 tablets)

Indications

• Rifaximin is recommended in accordance with NICE TA337 and within its marketing authorisation, as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in people aged 18 years or older.

Dose

• 550 mg twice a day.
• The clinical benefit of rifaximin was established from a controlled study in which subjects were treated for 6 months. Treatment beyond 6 months should take into consideration the individual balance between benefits and risks, including those associated with the progression of hepatic dysfunction.
• Rifaximin may be co-prescribed alongside lactulose if lactulose monotherapy has been unsuccessful.

Notes

1. Treatment with rifaximin should be initiated by a Gastroenterology Consultant. Once the patient is stabilised on treatment repeat prescriptions may be issued by primary care, however the ongoing management of the patient's liver disease will continue to be the responsibility of secondary care.
2. Rifaximin is a non-absorbed antibacterial agent and there are no specific monitoring requirements associated with treatment.
3. Secondary care will monitor the ongoing need for continuation of rifaximin in individual patients.
4. Rifaximin is hygroscopic and requires protection from light. At the time of writing (October 2016) the inclusion of rifaximin in a medicines compliance aid is not recommended by the manufacturer; if considered on an individual patient basis that this is required, the UKMI Medicine Compliance Aid Stability Database states that the maximum supply of rifaximin for inclusion in a compliance aid should be 7 days.