• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Severity Assessment
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)
• Treatment Failure
• Referral Criteria

Criteria for use
Antibiotics are recommended for exacerbations with acute deterioration with worsening symptoms (cough, increased sputum production, increased sputum purulence, wheeze, breathlessness, haemoptysis) and/or systemic upset.

Investigations required

• SpO2, CXR, FBC, U&Es, LFTs, CRP, review previous sputum culture

Treatment
Non-Antimicrobial Management

• Effective clearance of respiratory secretions e.g. physiotherapy, postural drainage
• Nutritional support
• Identification and treatment of underlying cause
• Annual influenza vaccination
• Sodium Chloride 7% (Resp-Ease ®) nebulised solution 4ml twice daily

Antimicrobial treatment

Referral criteria for specialist input
Patients with bronchiectasis should be reviewed by a chest physician.

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Criteria for use of guidelines:

• Patients presenting with acute exacerbations in association with underlying bronchiectasis.

Evidence level: The recommendations in the guideline are supported by level [C] evidence

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Definition of an exacerbation requiring antibiotic therapy
Antibiotics are recommended for exacerbations with acute deterioration with worsening symptoms (cough, increased sputum production, increased sputum purulence, wheeze, breathlessness, haemoptysis) and/or systemic upset.

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Inpatient treatment recommended if:

1. unable to cope at home
2. Development of cyanosis or confusion
3. Breathlessness with a respiratory rate ≥ 25/minute
4. Circulatory failure
5. Respiratory failure
6. Temperature  ≥ 38^oC
7. Unable to take oral antibiotics
8. Intravenous therapy required in patients with clinical failure to appropriate oral antibiotics (if unsuitable for home IV service)

Prophylaxis – aerosolised antibiotics

Some patients with chronic Pseudomonas aeruginosa infection may benefit from long-term aerosolised antibiotic therapy. The first line option is Colomycin® (colistimethate sodium) nebuliser solution 2 million units twice daily. Tobramycin nebuliser solution 160mg twice daily is the second line alternative (in this situation the Tobramycin 80mg/2ml injection is administered via the nebulised route). The decision to use these should be taken clinically and depends on a number of factors (e.g. compliance, susceptibility, tolerability, etc.)

Tobramycin 300mg/5mL nebuliser solution is licensed only for patients with cystic fibrosis, but is approved for use in patients with non-Cystic Fibrosis Bronchiectasis under a shared care agreement with GPs as an Amber Drug Level 2 (for further information read this guideline). It can only be prescribed by the Leeds Teaching Hospitals Bronchiectasis Clinic after assessment of risks versus benefits and other clinical factors (e.g. renal function, serum levels).

Azithromycin as an anti-inflammatory is reserved for those with demonstrable chronic Pseudomonas aeruginosa infection e.g. growing mucoid strain. It can be used once non- tuberculosis mycobacterium infection is excluded.

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Specimens

• Sputum should be sent for culture prior to commencing antibiotic treatment.
• blood cultures should be taken from patients with single temperature > 38.5^oC or < 35^oC or persistent temperature >38^oC before antibiotic treatment

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• Effective clearance of respiratory secretions e.g. physiotherapy, postural drainage
• Nutritional support
• Identification and treatment of underlying cause
• Annual influenza vaccination
• Sodium Chloride 7% nebs Resp-Ease ® 4ml twice daily

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Whenever possible, therapy should be guided by sputum culture results

Prophylaxis – oral antibiotics

There is insufficient evidence to make any specific recommendations regarding the use of long term oral antibiotic prophylaxis (e.g. cyclical antibiotics)
Azithromycin as an anti-inflammatory is reserved for those with demonstrable chronic Pseudomonas aeruginosa infection e.g. growing mucoid strain. It can be use once non- tuberculosis mycobacterium infection is excluded.

Empirical therapy

NB. Intravenous therapy is required in patients who clinically fail to improve after appropriate oral antibiotics and/or exacerbation despite long-term aerosolised antibiotics

Low risk of P. aeruginosa (no previous positive sputum cultures, no recent hospitalisation)
Oral Amoxicillin 500mg 8-hourly (increase to 1g in severe infections)
Intravenous therapy required: IV Amoxicillin 1g 8-hourly

High risk of P. aeruginosa (previous positive sputum cultures, recent (last 3 months) hospitalization)

• Oral Ciprofloxacin 750mg 12-hourly
• Intravenous therapy required: IV Ceftazidime 2g 8-hourly*
  *Replace with IV Piperacillin/tazobactam 4.5g 6-hourly if age >65

Second line IV antibiotic (if Ceftazidime or Piperacillin/tazobactam  have failed and at the direction of a consultant respiratory physician):

• IV Meropenem 2g 8-hourly

In severe acute exacerbations of bronchiectasis, or where there is a poor clinical response or resistant strains:

• Consider the addition of a second agent to beta-lactam (e.g. IV Tobramycin 5mg/kg once daily or IV colistimethate sodium 1-2 million unit 8-hourly).

Antimicrobial allergy

• Penicillin allergy
  Replace oral Amoxicillin with oral Doxycycline 100mg 12-hourly (first line) or oral Levofloxacin 500mg 24-hourly (second line) (check susceptibilities)
  Replace iv Amoxicillin with iv Levofloxacin 500mg 12-hourly

If severe (i.e. anaphylaxis) penicillin and/or cephalosporin allergy, contact microbiology for advice.

¹ Prior to commencing Levofloxacin , the possibility of tuberculosis should be considered, and, if appropriate, sputum sent for AAFBs.

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Meticillin-susceptible Staphylococcus aureus
IV Flucloxacillin 1g 6-hourly. Switch to PO Flucloxacillin 1g 6-hourly when clinically appropriate

Meticillin-resistant Staphylococcus aureus
If oral therapy is appropriate: oral Doxycycline 100mg 12-hourly.
If IV therapy required: IV Teicoplanin 6mg/kg (see dosing guideline) or Oral Linezolid (see dosing guideline). Contact Microbiology for further advice if required.

Haemophilus influenzae
Oral: Amoxicillin 500mg 8-hourly or Doxycycline 100mg 12-hourly or Clarithromycin 500mg 12-hourly (check susceptibilities)
High-dose Amoxicillin 3g 12-hourly (use 500mg capsules) may be needed in patients with severe bronchiectasis chronically colonised with Haemophilus influenzae

Intravenous: Amoxicillin 1g 8-hourly or Co-Amoxiclav (Amoxicillin-Clavulanate) 1.2g 8-hourly or Clarithromycin 500mg 12-hourly (check susceptibilities)*

Pseudomonas aeruginosa
Oral: Ciprofloxacin 750mg 12-hourly
Intravenous: Ceftazidime 2g 8-hourly*†

*Replace with IV Piperacillin/tazobactam † 4.5g 6-hourly if age >65

Second line IV antibiotic (if Ceftazidime or Piperacillin/tazobactam failed and at the direction of a consultant respiratory physician):

• IV Meropenem 2g 8-hourly

In severe acute exacerbations of bronchiectasis, or where there is a poor clinical response or resistant strains:

• Consider the addition of a second agent to beta-lactam (e.g. IV Tobramycin 5mg/kg once daily or IV colomycin 1-2 million unit 8-hourly).

†Please Discuss with Microbiology if resistance and/or allergy prevents the use of the listed options

Information on Tobramycin Dosing and Administration

• Dose: Intravenous Tobramycin 5mg/kg once daily.
  • Dilute to 50-100mL (5% glucose or 0.9% sodium chloride) and infuse over 20-60 minutes and flush with Sodium Chloride 0.9%.
• Dosing should be based on ideal body weight (IBW) not actual body weight (ABW) unless the ABW is less than the IBW (i.e. they are underweight)
• Doses should be rounded to the closest number divisible by 40 for ease of administration of the drug
• Reduce dose in renal impairment (see section below for dosing in renal impairment)
  • Creatinine Clearance (CrCl) not eGFR should be used to calculate the patient’s renal function

Dose adjustment in renal impairment

• Renal function and electrolytes should be monitored daily
• When renal function is unstable, serum levels should be performed daily and the dose adjusted as necessary based on the patients creatinine clearance
• If renal function deteriorates whilst the patient is receiving Tobramycin the trough level should be checked and the renal function monitored daily. A dose reduction may be required.

Monitoring of Tobramycin

• Trough levels should be taken immediately prior to the next dose of Tobramycin . Do not take the blood sample from the IV line used for Tobramycin administration
  • Document on the microbiology request form the EXACT time and date the infusion was set up (see prescription chart) and the EXACT time and date the sample was taken in addition to the patient details
• The first trough level should be taken prior to the 2nd dose and then at 3 day intervals during therapy
• The Target trough level should be <1mg/mL
• Obtain advice from microbiology if the trough level is ≥1mg/mL

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Continue therapy for 14 days. Intravenous therapy should be switch to oral therapy as soon as clinically indicated. If treating P. aeruginosa, intravenous antibiotics should be extended to 14 days.

Prophylaxis

Aerosolised antibiotics
Some patients with chronic P. aeruginosa infection may benefit from long-term aerosolised antibiotic therapy. The first line option is Colomycin® (colistimethate sodium) nebuliser solution 2 million units twice daily. Tobramycin nebuliser solution 160mg twice daily is the second line alternative (in this situation the Tobramycin 80mg/2ml injection is administered via the nebulised route). The decision to use these should be taken clinically and depends on a number of factors (e.g. compliance, susceptibility, tolerability, etc.)

Tobramycin 300mg/5mL nebuliser solution is licensed only for patients with cystic fibrosis, but is approved for use in patients with non-Cystic Fibrosis Bronchiectasis under a shared care agreement with GPs as an Amber Drug Level 2 (for further information read this guideline).It can only be prescribed by the Leeds Teaching Hospitals Bronchiectasis Clinic after assessment of risks versus benefits and other clinical factors (e.g. renal function, serum levels).

Oral antibiotics
There is insufficient evidence to make any specific recommendations regarding the use of long term oral antibiotic prophylaxis (e.g. cyclical antibiotics)

Azithromycin as an anti-inflammatory is reserved for those with demonstrable chronic Pseudomonas aeruginosa infection e.g. growing mucoid strain. It can be use once non- tuberculosis mycobacterium infection is excluded.

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The following criteria may be considered when deciding to switch from intravenous to oral therapy:

• Resolution of fever.
• Pulse rate <100 beats/min
• Resolution of tachypnoea
• Clinically hydrated and taking oral fluids
• Resolution of hypotension
• Absence of hypoxia
• Improving white cell count
• Non-bacteraemic infection
• No concerns over gastrointestinal absorption

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Consider the following explanations:

• Incorrect diagnosis
• Resistant organism (including Mycobacterium tuberculosis)
• Antibiotic hypersensitivity reaction
• Complication e.g. empyema, abscess
• Immunosuppression (known or unexpected)

Please note that these are guidelines. On some occasions you may be advised to manage patients differently, depending on clinical circumstances, microbiology results, etc.

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