Treatment of an Early / Mild Respiratory Exacerbation of Cystic Fibrosis

• Summary
• Aims
• Background
• Clinical Diagnosis
• Severity Assessment
• Investigation
• Antimicrobial treatment
• Appendix 1 Flow chart for CF doctors/CF Nurse Specialists
• Appendix 2

Summary

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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Aims

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

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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 Staphlyococcus 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,” guidelines 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 outwith the remit of this guideline to provide the management of these causes of cough. Symptoms suggestive of an alternative diagnosis include:

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Clinical Diagnosis

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

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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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Antimicrobial 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. The antibiotic will usually cover H. influenzae (e.g. amoxcillin). If the patient has had a resistant H.influenzae in the last year then co-amoxiclav, doxycycline or ciprofloxacin should be used depending on sensitivities and age. If the patient is known to be chronically infected with Pseudomonas aeruginosa, then oral ciprofloxacin will often be used. If S.aureus has been grown on a recent cough swab either flucloxacillin treatment dose for 2 weeks or 2 weeks of co-amoxiclav maybe appropriate. 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]. if there is any doubt please contact the CF doctor on call.

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/patientsPatients 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.

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APPENDIX 1 Flow chart for CF doctors/CF Nurse Specialists

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Appendix 2