Treatment of an Early/Mild Respiratory Exacerbation of Cystic Fibrosis

Publication: 17/11/2017  --
Last review: 01/01/1900  
Next review: 17/11/2020  
Clinical Guideline
CURRENT 
ID: 5249 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Treatment of an Early / Mild Respiratory Exacerbation of  Cystic Fibrosis

Summary
Treatment of an Early/Mild Respiratory Exacerbation of Cystic Fibrosis

Key diagnostic criteria:
Any new cough/increase in sputum production in a person with cystic fibrosis

Investigations required
None if clinically well

Treatment
Each person with cystic fibrosis (CF) should have a predefined list of appropriate antibiotics recorded on their EMIS and GP medication list which can be prescribed (for two weeks) in the event of a new cough or increase in sputum production lasting more than 48 hours. Parents/adults with CF may have a two week supply of this specified antibiotic stored at home, to start if required as described in this guideline [C]. At the start of a respiratory exacerbation all people with cystic fibrosis should increase their daily physiotherapy.

If a new cough occurs parents/adults with CF should contact their CF service during working hours and speak with a CF doctor or CF nurse specialist. In the absence of severe features (see below),  the CF doctor/CF nurse specialist can follow this guideline

If out of hours, and the person with CF is not otherwise unwell (see severity assessment) parents/adults with CF may start the specified prescribed antibiotic as long as they contact the CF team the next working day. If in any doubt they should contact the CF team via the paediatric or adult CF ward for advice (as appropriate).

A flow chart is provided in Appendix 1.

For antibiotic dosages please see Appendix 2.

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Background

Evidence for the early treatment of mild respiratory exacerbations of cystic fibrosis is limited. We know that aggressive intravenous antibiotics, in combination with dietetics and physiotherapy, for exacerbations defined by strict criteria, results in improved outcomes (1). In the 1990s the Copenhagen group demonstrated improved clinical outcomes following the introduction of routine  2-3 monthly  IV antibiotics for patients with CF(7). Further studies support the beneficial effects of aggressive antibiotic therapy (1,2) . However may centres have changed to “as required” IV antibiotics due to long term sequelae such as increase prevalence of drug allergy, increase bacterial resistance and antibiotic induced complications (hearing loss, renal disease).

The evidence for the use of oral antibiotics in mild or early pulmonary exacerbations is limited. While oral antibiotics are effective in treating specific bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa), prescribing practice (type, duration, number of courses before starting IV antibiotics) varies significantly between hospital and countries. There are no European Cystic Fibrosis Society (ECFS) guidelines or consensus statements on the use of oral antibiotics for new cough or minor exacerbations. The Cystic Fibrosis Trust “Antibiotic treatment for cystic fibrosis” guideline contains advice on the use of oral antibiotics for mild respiratory exacerbations (2).

The CF Trust guidelines advise that the oral antibiotics prescribed at the start of mild respiratory exacerbations (not defined) should cover common respiratory bacteria pathogens such as Haemophilus influenzae or Streptococcus pneumoniae. If the patient has chronic P. aeruginosa infection ciprofloxacin may be prescribed to try and prevent a Pseudomonas-associated deterioration. It is important to recognise that patients chronically colonised with PA may developed acute infection due to other bacterial organisms and alternatives to ciprofloxacin may be beneficial. 

The additional oral antibiotic should be taken until the patient returns to his/her baseline. If the new symptoms (most important being a new cough) do not settle, the patient should have a clinical review to reassess the diagnosis (e.g. could this be reflux or another cause of cough,) or consider an alternative oral or IV antibiotic. Further sputum or cough swab cultures can be obtained at this time and a chest X-ray or induced sputum should be considered (2). It is always important to consider non-bacterial causes of a new cough (see below for some signs indicating alternative causes of cough).

Patients with CF often require higher doses for longer periods. A standard length would be considered to be 2 weeks (2). This is because of differences in antibiotic clearance and distribution, which may be further altered according to the severity of the respiratory infection (1, 2).

Other causes of symptoms in a well child with CF that may mimic an acute respiratory exacerbation, that should be considered contemporaneously, would include reflux, habit cough, or asthma. It is outside the remit of this guideline to provide the management of these causes of cough. Symptoms suggestive of an alternative diagnosis include:

Symptom

Potential alternative diagnosis

Cough with change on posture(8)

Gastro-oesphageal reflux (GOR)

Cough with speaking/throat clearing(8)

GOR

Heartburn(8)

GOR

Associated with certain foods/meal times(8)

GOR/aspiration

Wheeze(8)

Asthma/GOR/Viral infection

Not present when asleep(8)

Habit cough/GOR

Dry cough, present after an acute infection

Habit cough

Long standing cough (more than 2 weeks)

GOR, habit cough, aspiration, asthma

Frontal headache (9)

Sinus problem

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Clinical Diagnosis

These guidelines can be followed if any of the following in box 1 are present:

Box 1

  • Increased cough (i.e. more frequent than baseline for that person) for more than 48 hours.
  • Increased sputum production or chest congestion for more than 48 hours
  • Change in sputum appearance
  • Increased respiratory rate or dyspnoea at rest
  • Increased nasal congestion or drainage
  • Decreased exercise tolerance or increased dyspnoea with exertion
  • Fever (present in a minority of patients)
  • Increased fatigue
  • Decreased appetite
  • Absenteeism from school or work

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Severity Assessment

If the child/person with CF is well other than the symptoms above, and consideration is given to alternative non-infectious causes, then antibiotics could be appropriately commenced at home as per this guidance. If any of the following features are present, then urgent medical review either at the CF Centre, or in primary or secondary care is recommended:

  • Chest pain
  • Rigors (any uncontrolled shaking with temperatures)
  • Lethargy/reduced consciousness
  • Increased shortness of breath with moderate exercise
  • Inability to tolerate oral fluids
  • Duskiness/blueness of tongue or lips
  • Ongoing symptoms despite two weeks current use of oral antibiotic
  • Child under 1 year who is not feeding well.

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Investigation

Where possible, it would be useful for cough swabs and/or sputum samples, and nasopharyngeal aspirates (NPA) if viral aetiology is suspected, to be obtained before starting antibiotics.

Management of patients with CF includes routine cultures of respiratory secretions to identify infecting organisms and guide antibiotic selection. Because patients with CF frequently carry the same bacteria for prolonged periods of time, past culture results can be used to guide antibiotic choices when a patient’s condition warrants intensifying treatment. The current recommendation is to perform cultures as a minimum every three months so that relatively current information is available to guide treatment when a pulmonary exacerbation occurs (2). In Leeds, surveillance screening through cough swabs or sputum occurs at least every 8 weeks.

Where no culture result is available, antibiotic choice must be made empirically. S. aureus is the earliest isolate from the lungs, usually followed by non-typeable Haemophilus influenzae (not covered by vaccines) and Pseudomonas. S. pneumoniae is occasionally isolated but is relatively rare.

Cough swabs taken at home by parents/carers are not as useful as hospital obtained cough swabs. Self-obtained sputum samples may be more helpful.

If there is no positive microbiology on surveillance screening in a patient with persistent cough, performing induced sputum should be discussed with the CF team prior to starting IV antibiotics.

Bronchoscopy may be useful in children who cannot provide induced sputum, where there is no known microbiological cause for respiratory deterioration. Where appropriate it may be possible to combine this with other procedures that may aid the care of the patient or help diagnosis e.g. CT scan/pH study.

A negative sputum culture does not exclude bacterial infection.

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Treatment

For a mild respiratory exacerbation, in an otherwise well person with CF, with none of the severity features listed above, a pre-determined specific oral antibiotic that is on the EMIS/GP medication list should be commenced, for a total of two weeks. It is usual practice to allow a new cough 48 hours to settle before starting the antibiotic. This will usually cover both H. influenzae and S. aureus (e.g. co-amoxiclav). If the patient is known to be chronically infected with Pseudomonas aeruginosa, then oral ciprofloxacin will often be used. Parents/adults with CF may have a two week supply of this specified antibiotic stored at home, to start if required as described in this guideline [C].

During working hours parents/adults with CF should contact their CF service and speak with a CF doctor or CF nurse specialist. If no severity features are present, then the CF doctor/CF nurse specialist can recommend that this guideline is followed and the specific prescribed antibiotic for this indication can be used.

If out of hours, and the person with CF is not otherwise unwell (see severity assessment) parents/adults with CF may start the specified prescribed antibiotic as long as they contact the CF team the next working day. If in any doubt, they should contact the CF team via the paediatric or adult CF ward for advice (as appropriate).

It is becoming increasingly recognised that coughs should be treated early to prevent later bronchiectasis, but also that many coughs are viral. If the cough clears within a few days of commencing antibiotics, and there is no recent positive microbiology, then the course may be truncated to five to seven days at the clinician’s discretion. Not all patients with viral infections may need oral antibiotics. Many symptoms will resolve without complications.
 
For Dosages please see Appendix 2.

Assessment of Response [C]
Monitor response in terms of reduction in cough/sputum production, and improvement in lung function.

Counselling of parents/patients

Patients and parents should be counselled that all antibiotic treatment courses have potential risks as well as benefits, and all courses of additional antibiotics for new cough should be discussed with the CF team as above. Parents and patients should be advised of the severe features listed above so that they can seek urgent medical review should these develop. They should be advised to seek advice if the cough persists beyond two weeks. Patients or parents should be advised to report any suspected side effects of treatment promptly. All patients should be advised to increase physiotherapy.

Parent of a child or Adult with CF rings the CF Unit describing a new cough, increase in cough frequency or change in amount/type of sputum or other symptoms described in box 1

Appendix 1

Appendix 2

Drug doses

Appendix 2

Antibiotic

Organism

Paediatric Dose
Age 1 month-16 years

Adult dose

Route

Comments

AMOXICILLIN

 Streptococcus pneumoniae

Under 1 year:
125mg three times a day increased to 30mg/kg three times a day if necessary

1-4 years:
250mg three times a day increased to 30mg/kg three times a day if necessary

5-11years:
500mg three times a day increased to 30mg/kg (maximum 1gram) three times a day if necessary

Child >12 years:
500mg three times a day increased to 1gram three times a day if necessary

500mg-1gram three times a day.

oral

Amoxicillin capsules: 250mg, 500mg
Suspension: 125mg in 5mL,
250mg in 5mL

 

Rashes and loose stools may occur.
20% H. influenzae are resistant to amoxicillin

CEFACLOR

Haemophilus Influenzae

Broad spectrum activity against Gram positive organisms

Child 1 month–1 year
125mg three times daily

Child 1–4 years
250mg three times daily

Child 5–11 years
500 mg three times daily

Child 12–18 years
500mg three times daily

500mg three time a day

oral

To be used when initial therapies have failed, only under the advice of the consultant. Not recommended as a first line agent
Suspension: 125mg/5ml, 250mg/5ml
Capsules: 250mg,500mg
Cefaclor is associated with protracted skin reactions, especially in children.

CIPROFLOXACIN

Pseudomonas aeruginosa

20mg/kg (max: 750mg) twice daily.

750mg twice daily

oral

Ciprofloxacin Suspension: 250mg/5ml
Tablets: 100mg, 250mg, 500mg,750mg

Beware drug interactions including ciclosporin, NSAIDS and theophylline. Calcium, magnesium and iron, taken at the same time of day, reduce absorption of ciprofloxacin. Milk will reduce absorption and patients should be advised not to take dairy products two hours before or after ciprofloxacin
Photosensitivity is common. In summer sunblock should be applied.
C/I in patients with joint disease.  .
Ciprofloxacin

CLARITHROMYCIN

Staphylococcus aureus
Atypicals e.g. mycoplasma

<8kg:
7.5mg /kg twice daily

8-11kg:
62.5mg twice daily

12-19kg:
125mg twice daily

20-29kg:
187.5mg twice daily

30-40kg:
250mg twice daily

12-18years:
500mg twice daily

500mg bd

oral

Clarithromycin tablets 250mg, 500mg
Suspension 125mg in 5mL, 250mg in 5mL

Active against most S. aureus. Can cause tooth and tongue discolouration.
There are many drug interactions with clarithromycin but interactions with drugs more commonly used in patients with cystic fibrosis include all azole antifungals, ciclosporin, ivacaftor, tacrolimus, theophylline and warfarin. See SPC for full details.
Caution in use with other drugs that may increase QT interval.
Clarithromycin

CO-AMOXICLAV

Haemophilus influenzae
Staphylococcus aureus
Moraxella
Streptococci

1month-11months:
0.5mL/kg of 125/31 suspension three times a day

1-5 years:
5mL of 250/62 suspension three times a day

6-12 years:
10mL of 250/62 suspension or one 500/125 tablet three times a day

12-18years:
one 500/125 tablet three times a day

 

500mg/125mg-One tablet three times a day

oral

Co-amoxiclav suspension:125/31 in 5mL
250/62 in 5mL
Tablets: 250/125mg tablets
500/125mg tablets
NB: If higher doses are required add in extra amoxicillin instead of increasing co-amoxiclav dose.
In order to avoid excessive doses of clavulanic acid, children less than 40kg should not be prescribed the product with a ratio of 2:1 (i.e. the 250mg/125mg tablet). The 625mg tablets are not suitable for halving.

FLUCLOXACILLIN

Staphylococcus aureus

1month-18years;
25mg/kg four times a day.

Maximum dose: 1gram four times a day

 

1gram four times a day

oral

Flucloxacillin suspension:
125mg in 5mL,250mg in 5mL Capsules:250mg, 500mg

Give 1 hour BEFORE meals or on an empty stomach. Liquid tastes unpleasant – different brands may be tolerated better than others.

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Provenance

Record: 5249
Objective:

Aims

  • To improve the diagnosis and management of early respiratory exacerbations in people with cystic fibrosis

Objectives

  • To commence appropriate treatment of lung infection
  • To prevent permanent lung scarring (bronchiectasis)
  • To prevent a decline in lung function
  • To prevent unnecessary inpatient admission for exacerbation of CF
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
Clinical condition: New cough
Target patient group: Adults and children with cystic fibrosis (CF)
Target professional group(s):
Adapted from:

Evidence base

References

  1. http://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-lung-disease accessed June 2015
  2. CF Trust. Antibiotic Treatment for cystic fibrosis. Third edition. May 2009
  3. Regelmann WE; Schechter MS; Wagener JS. Pulmonary exacerbations in cystic fibrosis: young children with characteristic signs and symptoms. Pediatric Pulmonology, July 2013, vol./is. 48/7(649-57),
  4. Blackburn R, Henderson L,Lillie M. Empirical treatment of influenza-associated pneumonia in primary care: a descriptive study of the antimicrobial susceptibility of lower respiratory tract bacteria (England, Wales and Northern Ireland, January 2007 to March 2010) Thorax Online First, published on February 25, 2011 as 10.1136/thx.2010.134643
  5. Verhoefa J, Gillissen A. Resistant Haemophilus influenzae in community-acquired respiratory tract infections: a role for cefixime.International Journal of Antimicrobial Agents. Volume 21, Issue 6, June 2003, Pages 501–509
  6. Mortenson J. Himes S Comparative In Vitro Activity of Cefixime against Haemophilus influenzae Isolates, Including Ampicillin-Resistant, Non-3-Lactamase-Producing Isolates, from Pediatric Patients Antimicrobial agents and chemotherapy, July 1990, p. 1456-1458
  7. Frederiksen B1, Lanng S, Koch C, Høiby N. Improved survival in the Danish center-treated cystic fibrosis patients: results of aggressive treatment. Pediatr  Pulmonol 1996;21:153–8.
  8. Everett C. Clinical history in gastroesophageal cough Respiratory Medicine Volume 101, Issue 2, February 2007, Pages 345–348
  9. Smith J. Cough frequency and patterns of cough in cystic fibrosis JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 46 Volume 99 2006

 Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

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