Nottingham University Hospitals Children and Young Persons Cystic Fibrosis Unit Management Guidelines

Transcription

1 Nottingham University Hospitals Children and Young Persons Cystic Fibrosis Unit Management Guidelines 1

2 Section 1 - Diagnosis Index 1.1 Diagnosis 1.2 Neonatal screening 1.3 The Sweat Test 1.4 Meconium ileus 1.5 Failure to thrive 1.6 Chronic respiratory symptoms 1.7 Siblings 1.8 Antenatal diagnosis - genetic 1.9 Antenatal diagnosis - bowel abnormalities detected on ultrasound scan Section 2 - Outpatient Clinic 2.1 Outpatient clinic arrangements 2.2 Items performed at every clinic visit 2.3 Multidisciplinary meeting 2.4 Post clinic administration 2.5 Transfer to adult care 2.6 Holiday advice Section 3 - Annual Assessment 3.1 Annual assessment 3.2 Medical review 3.3 Documentation 3.4 Computer database 3.5 Multidisciplinary review Section 4 - Ward Management of CF Patients 4.1 Segregation Policy 4.2 Admission procedure 4.3 Ongoing care 4.4 Discharge summaries 4.5 Patient review Section 5 - Antibiotic Guidelines 5.1 Cough swab/sputum culture 5.2 Oral antibiotics 2

3 5.2.1 Staphylococcus aureus Haemophilus influenzae Mycoplasma or Chlamydia pneumoniae Preventing chronic infection with Pseudomonas aeruginosa Long term Azithromycin Treatment of exacerbations in children with chronic P.aeruginosa infection 5.3 Nebulised antibiotics Colistin Nebulised Tobramycin 5.4 Intravenous antibiotic treatment Haemophilus influenzae Staphylococcus aureus Multiply resistant Staphylococcus aureus (MRSA) Pseudomonas aeruginosa Burkholderia cepacia complex 5.5 Fungal septicaemia 5.6 Allergic reactions 5.7 Heparin and sodium chloride flushes Section 6 - Home "IV's" & Home Oxygen 6.1 Home intravenous (IV) antibiotic therapy 6.2 Indications for home IV treatment 6.3 Teaching sessions 6.4 Starting a course of home IV's 6.5 Prescribing instructions 6.6 Checklist for children going home on IV antibiotics 6.7 Antibiotic levels 6.8 Monitoring clinical response 6.9 Home oxygen Section 7 - Management of Other Respiratory Problems 7.1 Allergic bronchopulmonary aspergillosis 7.2 Haemoptysis 7.3 Pneumothorax 7.4 Referral for transplantation 7.5 Non-invasive ventilation (NIV) Section 8 - Management of Other CF Related Disease 8.1 Abdominal Pain - Distal intestinal obstruction syndrome (DIOS) 8.2 Cystic fibrosis related liver disease 8.3 Management of bleeding oesophageal varices 8.4 CF Bone disease Assessment of bone health Treatment recommendations 8.5 Joint pain and disease 8.6 Cystic fibrosis related diabetes (CFRD) Diagnosis of CFRD 3

4 8.6.2 Dietary management of Diabetes in Cystic Fibrosis Dietary management if patient is well and has good nutritional status Dietary management if patient is unwell and has poor clinical status Insulin Oral hypoglycaemic agents Section 9 - Dietetic & Nutritional Management 9.1 Nutritional management 9.2 Standards of dietetic care 9.3 Assessment of growth & nutritional status 9.4 Nutritional support Oral nutritional supplements Nasogastric and gastrostomy feeds 9.5 Pancreatic enzyme supplements 9.6 Vitamin supplements 9.7 Salt supplementation Section 10 - Guidelines for Obtaining Intravenous Access 10.1 Pic line/ Longline insertion 10.2 Indications for port-a-cath insertion 10.3 Preparation for port-a-cath insertion 10.4 Guidelines for needling a port-a-cath Introduction Equipment Process Outcomes 10.5 Flushing of longlines, cannulas and portacaths Section 11 - Physiotherapy 11.1 Introduction and principles 11.2 Airways Clearance Techniques (ACT) 11.3 Physiotherapy Services - Inpatients 11.4 Physiotherapy Services - CF Clinic 11.5 Physiotherapy Services - Community Section 12 - Guidelines for Bronchial Lavage 12.1 Aims and definition of bronchial lavage 12.2 Criteria for lavage 12.3 Contraindications/ Cautions 12.4 Pre-admission procedure 12.5 Pre-op procedure 12.6 Lavage technique 12.7 Post-op ward requirements 4

5 Section 13 - Dornase alfa & Hypertonic saline Dornase alfa 13.1 Introduction 13.2 Mode of action 13.3 Clinical efficacy 13.4 Dosage and administration 13.5 Indications 13.6 Initiating therapy 13.7 Adverse effects Hypertonic Saline 13.8 Introduction 13.9 Mode of action Clinical efficacy Dosage and administration Indications Initiating therapy Adverse effects Section 14 - Pain & Palliative Care in Cystic Fibrosis 14.1 Symptom control in the well child 14.2 Pain relief 14.3 Palliative care Anti-emetics Physiotherapy/ assisted ventilation Laxatives Other treatments Communication Section 15 - Psychosocial support 15.1 Role of the clinical psychologist 15.2 Role of the social worker and Sherwood Project 15.3 Services Available 15.4 Key times when support is offered Section 16 - Education 5

6 Appendix 1 Management Plan Appendix 2 Outpatient Clinic Record Appendix 3 Clinic letter proforma Appendix 4 GP Antibiotic Guideline Appendix Index Appendix 5 Letter for GP & Family re sputum result and antibiotic required Appendix 6 Scoring Systems Northern CXR score Shwachman score Exercise tolerance Score Appendix 7 Annual Assessment Sheets Appendix 8 Gastrostomy Care Appendix 9 Guidelines for unblocking a Portacath Appendix 10 Paediatric guideline for once daily tobramycin in cystic fibrosis Appendix 11 Prescribing nebulisers on the ward Appendix 12 Evaluation form for patients on a trial of Dornase alfa Appendix 13 Transfer to Adult Care Documentation Appendix 14 CF Formulary Appendix 15 Giving 1 st dose of intravenous antibiotics at home 6

7 Section 1 - Diagnosis (Revised by Jayesh Bhatt) 7

8 1.1 Diagnosis The three main situations when CF diagnosis needs to be considered are 1. Clinical manifestations 2. Positive newborn screening test result 3. Family history In patients with the classical clinical picture, the diagnostic tests are mainly needed to CONFIRM the diagnosis. In other cases the diagnostic tests are necessary to SUPPORT OR EXCLUDE the diagnosis of CF or to POINT to an alternative diagnosis The European Diagnostic Working Group has proposed the following terminology for cystic fibrosis 1 Classical or Typical CF: if they have One or more Phenotypic characteristics (chronic sinopulmonary disease specific or characteristic GI or nutritional abnormalities, salt loss syndromes, and male genital abnormalities resulting in obstructive azospermia) AND A sweat chloride concentration of > 60 mmol/l The vast majority of CF patients fall in this category and usually one disease causing mutation can be identified on each CFTR gene. They can be pancreatic sufficient or insufficient. The disease can have a severe course with rapid progression or a milder course with very little deterioration over time. Non-classic or Atypical CF: have A CF phenotype in at least one organ system AND A normal (< 30 mmol/l) or borderline (30-60 mmol/l) sweat chloride level In these patients confirmation of diagnosis requires detection of one disease causing mutation on each CFTR gene or direct quantification by nasal potential difference measurement. These patients may have multiorgan or single organ involvement and most are pancreatic sufficient Apart form CFTR mutations, modifier genes, lifestyle, treatment, environment and age all play a role in determining the phenotype 1.2 Neonatal screening Currently 20% of newborn babies in England are screened for CF this includes babies that are born in the East Midlands and South Yorkshire / Northern Lincolnshire and parts of West Yorkshire. A national protocol for newborn CF screening has been developed by the UK Newborn Screening programme Centre on behalf of the National Screening Committee. 2 Children are screened for CF shortly after birth by means of a dried blood spot collected on the Guthrie Card on the 6 th day of life. False negatives, often due to rare genotypes, can occur. Screening began in 1989 and so anyone born before this date 8

9 has probably not been screened. Children born outside the Trent region may not have been screened. All infants with CF have some pancreatic damage at birth and this leads to a leakage of tryptic-like substances in to the blood detected by the immunoreactive trypsin (IRT) 3 blood test. If this is raised (i.e. > 99.5 th centile) genetic testing is done on the same blood spot. This initially looks for F508, which is the commonest CF gene mutation. 4 A firm diagnosis can be made in children who are homozygous for F508. If the sample is heterozygous for F508 then the blood will be screened for the next 20 most common CF gene mutations. Then GP and CF centre are contacted. Families should be offered an appointment with the CF consultant the following day. When the diagnosis is based on genotype, a written report stating the genotype must be available, before a diagnosis of CF is confirmed to the parents. This can be in the form of a fax from the molecular genetics department to the neonatal unit. When the diagnosis is suspected the neonatal screening service in Sheffield (telephone number below) should be contacted for the result of the day 6 IRT if this has already been sent. The consultant will discuss the diagnosis with the family, usually together with the CF social worker and the named nurse before they attend the CF Clinic. The GP should be sent a copy of the CF antibiotic guidelines. Consent for NCH database should also be obtained. If the diagnosis is confirmed, the physiotherapist and dietician will be involved and appropriate follow up arranged. A sweat test should always be performed at around 6 weeks of age (though this can often be done earlier if diagnosis has proven difficult). Contact telephone number: (ask for neonatal screening) 1.3 The Sweat Test Despite the availability of genotyping (and because of its limitations) the majority of children in whom CF needs to be excluded will undergo sweat testing. This group will include the following: Child with suggestive history / symptoms/ examination. Sibling of a known case (even if asymptomatic). This is still the gold standard method of diagnosis for cystic fibrosis. 5 If the genotype is shown to be homozygous F508, one confirmatory sweat test should still be carried out. In other situations, two positive sweat tests are required for a confirmed diagnosis. The tests are arranged with, at the Queens Medical Centre (ext ). For inpatients, the sweat test can be arranged with the Clinical Chemistry department, City Hospital (ext ). National guidelines recommend the following sweat chloride levels: <40mmol/L normal; >60mmol/L supports a diagnosis of CF; CF affected patients occur with similar frequency in the mmol/l range, as in the mmol/range 6 so a chloride cut off of 30 mmol/l has been suggested. Levels in between mmol/l are suggestive but not diagnostic. Sodium should not be interpreted without a chloride result. A sodium value below 60mmol/L is unlikely to be associated with cystic fibrosis. Sodium values above 90mmol/L support a diagnosis of cystic fibrosis. 7 A greater than 5-15 mmol/l discrepancy between sodium and chloride requires a repeat test. 9

10 At the time of diagnosis stool should be sent for pancreatic elastase (which is a more sensitive indicator of pancreatic function than chymotrypsin and has replaced it as a test to indicate pancreatic insufficiency). 8 Normal values are > 200 mcg/g of faeces. Samples will be sent to Leeds, by arrangement with clinical chemistry at the City Hospital 1.4 Meconium ileus Meconium ileus is the presenting feature in about 15% of children with cystic fibrosis. The baby may present with the classical features of neonatal small bowel obstruction i.e. failure to pass meconium, bilious vomiting and abdominal distension. Important differential diagnoses include Hirschsprung s disease and midgut volvulus. The plain abdominal X-ray may show a distended small bowel and a granular appearance, due to bubbles of air within the meconium. Once perforation and meconium peritonitis have been excluded, a contrast enema can help confirm the diagnosis and will, in many cases, relieve the obstruction. Otherwise the baby will require surgery, which may involve an ileostomy. Meconium ileus in the absence of CF does occur but is uncommon. 9 Once the diagnosis of meconium ileus is strongly suspected, chest physiotherapy and an antistaphylococcal antibiotic should be started immediately (intravenously if the baby is not feeding). Flucloxacillin can be given orally (125mg bd) (see section 5.2.1) or intravenously (100 mg/kg/day in 4 divided doses) (see section 5.4.2). The physiotherapist should see the parents as soon as possible to demonstrate percussion and postural drainage to the parents. It is better to stop these interventions if the baby does not have CF than to allow lung damage to occur early in life. The consultant neonatologist should ensure the CF team are informed as soon as possible, once the diagnosis of CF is suspected. When infants are referred to the department of neonatal surgery with meconium ileus it is important to confirm the diagnosis of CF before the results of screening will be available. Up to 25 % of infants with meconium ileus do not have an IRT value above the cut off level 10 and a CFTR gene mutation analysis and/or a sweat test are required to confirm the diagnosis 1.5 Failure to thrive Pancreatic insufficiency is common in CF and occurs in over 90% of patients. 11 A sweat test forms part of the investigations for many children with failure to thrive. The reason for performing the test should always be clearly explained to the parent. Tests for malabsorption, such as microscopy for fat globules, and pancreatic elastase should also be performed. Rectal prolapse may be secondary to failure to thrive and may be the presenting feature of cystic fibrosis. 12 Once the diagnosis has been made, with good dietary management surgery can usually be avoided. 1.6 Chronic respiratory symptoms Severe recurrent wheeze in young children and a persistent productive cough in older children are indications to perform a sweat test. This is particularly important if the child is failing to thrive or has chronic atelectasis on the chest X-ray. Finger clubbing and 10

11 nasal polyps in an older child, isolation of S aureus or P aeruginosa from the respiratory tract are other important pointers. 1.7 Siblings Other children in the family should have a sweat test when the diagnosis of CF has been made in a sibling. Some parents may wish their children to have genetic testing for carrier status. Generally speaking this is not indicated until the child in question is old enough to make an informed decision. Siblings of the parents may wish to seek genetic counselling and testing. 1.8 Ante natal diagnosis genetic Parents of a child with CF are routinely offered genetic counselling after the birth of that child. The timing of this should be negotiated with them. When planning further children they may wish for counselling before and/or at the early stages of the next pregnancy. Referral to the clinical genetics department should be made if required. Some families choose to have ante-natal CVS testing in subsequent pregnancies, giving them the choice of termination of an affected fetus or being able to prepare themselves for the birth of a child with CF, should that be the case. 1.9 Ante natal diagnosis bowel abnormalities detected on ultra sound scan Second trimester detailed ultrasound scans are able to identify a range of structural anomalies. Occasionally, echogenic foci and/or dilated fetal bowel are found. There is a 4% risk of the fetus being affected with CF in the case of echogenic bowel and a 17-24% risk if both echogenic foci and dilated loops are found The risk of CF in an individual case is assessed jointly between the genetic/obstetric/neonatal and CF consultants, and takes into account factors such as family history, or parental carriage of the CF gene. The parents are counselled. Due to advances in ultrasonography, an increasing number of babies are being diagnosed antenatally. Please see Appendix 1 for the management plan for antenatal bowel abnormalities detected on Ultrasound scan. 1. De Boeck K, Wilschanski M, Castellani C, Taylor C, Cuppens H, Dodge J, et al. Cystic fibrosis: Terminology and diagnostic algorithms. Thorax 2006;61: Heeley AF,Bangert SK. The neonatal detection of cystic fibrosis by measurement of immunoreactive trypsin in blood. Ann Clin Biochem 1992;29: Anonymous. Worldwide survey of the delta F508 mutation--report from the cystic fibrosis genetic analysis consortium [letter]. Am J Hum genet 1990;47: Littlewood JM. The sweat test. Arch Dis Child 1986;61: Lebeccque P, Leal T, De Boeck K. Mutations of the cystic fibrosis gene and intermediate sweat chloride levels in children. Am J Respir Crit Care Med 2002;165: Report from a multidisciplinary working group. Guidelines for the performance of the sweat test for the investigation and diagnosis of CF in the UK Wallis C, Leung T, Cubitt D, Reynolds A. Stool elastase as a diagnostic test for pancreatic function in children. Lancet 1998;350: Fakhoury K, Durie PR, Levison H, Canny GJ. Meconium ileus in the absence of cystic fibrosis. Arch Dis Child 1992;67: Massie R, Olsen M, Glazner J, Robertson C, Francis I. Newborn screening for cystic fibrosis in Victoria: 10 years experience ( ). Med J Aust 2000;172:

12 11. Morgan W, Butler S, Johnson C. Epidemiologic study of cystic fibrosis. Pediatr Pulmonol 1999;28: Stern RC, Izant RJ, Jr., Boat TF, Wood RE, Matthews LW, Doershuk CF. Treatment and prognosis of rectal prolapse in cystic fibrosis. Gastroenterology 1982;82: Ghose I, Mason, G C, Martinez, D, Harrison K L et al. Hyperechogenic fetal bowel: a prospective analysis of 60 consecutive cases. BJOG 2000;107: Muller F, Dommergues M, Simon-Bouy B, Ferec C, Oury J-F, Aubry M-C et al. Cystic fibrosis screening: a fetus with hyperechogenic bowel may be the index case. J Med Genet 1998;35: Muller F, Simon-Bouy B, Girodon E, Monnier N, Malinge M C, Serre J L and the French Collaborative Group. Predicting the risk of cystic fibrosis with abnormal ultrasound signs of fetal bowel:results of a French Molecular Collaborative Study based on 641 prospective cases. Am J Genet 2002;110: Yaron Y, Hasson S, Geva E, Kuferminic K, Yavetz H, Evans M I. Evaluation of fetal echogenic bowel in the second trimester. Fetal Diagn Ther 1999;14:

13 Section 2 - Outpatients Clinic (Revised by Jayesh Bhatt) 13

14 2.1 Outpatient Clinic Arrangements The CF clinic is held every Tuesday afternoon. Children with established Pseudomonas aeruginosa infection are seen in separate clinics from those without Pseudomonas. Pseudomonas and Non Pseudomonas clinics alternate every week. Parents may bring the child any week on request and this is preferable to being seen on the ward. If the child is to be seen in the wrong clinic, please arrange for non- Pseudomonas patients to be seen first on a Pseudomonas week and Pseudomonas patients to be seen last on a non-pseudomonas week. Children with Burkholderia cepacia complex infection should be seen at the end of a pseudomonas clinic where possible and should be seen in the interview room. The same applies to patients with MRSA who are also colonised with P.aeruginosa. Patients with MRSA who do not have P.aeruginosa may be seen in the interview room at the end of a non-pseudomonas clinic. All new isolates of Burkholderia cepacia complex are sent to Edinburgh (Tel /5) and Colindale (Tel ) for typing by the Department of Microbiology at the City Hospital. Children are usually seen every 2 months. Parents and child should see the physiotherapist and dietician at least twice a year in clinic. Compressors for nebulised drugs are lent from the clinic and should be serviced 6 monthly. Please update the lung function and microbiology spreadsheet at the front of the case notes at every encounter with the patient. 2.2 At every clinic visit: Use the clinic proforma to record the relevant details (see Appendix 2). The nursing staff will perform the lung function, oxygen saturation, record height and weight and obtain sputum (preferably) or cough swab for culture N.B. An increase in respiratory symptoms (increased cough, sputum production or chest congestion, change in sputum colour to green, diminished exercise tolerance or dyspnoea with exertion, increased school/work absenteeism), reduced appetite, fall of 10% or more in lung function or weight loss defines a respiratory exacerbation 1. Symptoms are more predictive than findings and on examination adventitial sounds may or may not be present. It is not necessary to perform a chest X-ray. Consider oral or intravenous antibiotics. Other: Advice e.g. flu immunisation (children over 6 months from September - November), salt replacement in hot weather (see section 9.7) Next clinic visit (give the parents a specific date do not overbook the clinics) 2.3 Multidisciplinary meeting: Occurs immediately after the CF clinic. All staff attending the clinic should take part in this meeting. Ensure any arranged admissions are notified to the ward. 14

15 2.4 Post Clinic Administration: Clinic letters to GPs (with copy to parents - see below) should be dictated and given to the consultant s secretary by the Monday following the Tuesday clinic. All cough swab / sputum results are reviewed and appropriate action taken by the Consultant on service for that week on the Monday following the Tuesday clinic. Trainees are encouraged to participate in this meeting. The parents and GP can be notified of any antibiotic treatment necessary using a standard letter. This is available from the CF secretary (appendix 5). It is faxed the same day. Record that the letters have been sent and what treatment has been given in the case notes. Telephone the GP and the parents if the result is urgent. In any case a standard clinic letter should still be written. A copy of the GP letter should be sent to the child's parents (and child if appropriate). 2.5 Transfer to Adult care Young persons should be transferred to adult care between the age of 16 and 18 years. The precise time of transfer will depend on factors such as the family s wishes, the young person s maturity and the stability of their condition. Imminent cases should be discussed in the joint meeting with the adult team twice a year. Procedure for transfer to adult care: Patients who might be ready for transfer should be discussed at the multidisciplinary meeting after the clinic. Preparation for transfer may take many months. Some issues should be raised with the young person well in advance of transfer e.g. fertility and contraception. Young people should be offered the chance to have part of a consultation without their parents to enable freer discussion of these issues. On their next visit to clinic, transfer is discussed with the family and, if appropriate, the forms for the patient and their parents (reproduced in appendix 13) are issued. A booklet, explaining the service offered in the adult clinic, should be issued at the same time. The doctor who sees the patient on that occasion writes a referral letter, and a copy is sent to the adult CF community nurses. An appointment date in the adult clinic is requested. The remaining documentation, shown in appendix 13, is distributed to the paediatric multidisciplinary team at the meeting following that clinic visit. These forms must be completed within 2 weeks. The paediatric secretary will collate the forms and pass them on to the adult team. The patient may be seen on one further occasion in the paediatric clinic but after that transfer should be complete. For shared care patients, the documentation shown in appendix 13 should be sent to the shared care consultant, for distribution to their multidisciplinary team. Again, a response is needed within 2 weeks. The forms are returned to the paediatric secretary who passes them on to the adult team with the referral letter (copy to the shared care consultant). 15

16 2.6 Holiday advice Reserve antibiotics these should be considered individually for each patient. Oxygen requirements Patients with an FEV1 <50% predicted should receive supplementary oxygen in flight at 2 L/min. 2 This must be arranged in advance with the airline, some of whom will make a charge. Portable nebulisers these are available from children s outpatients. Discuss if enteral feeds can be discontinued whilst on holiday. Suggest that portable wedges are available from the physiotherapists. Consider salt replacement for holidays in hot climates. Advise the use of sun block or advise to stay in the shade if patient is currently taking ciprofloxacin or will be using it as their reserve antibiotic. Provide a letter for the patient to take through customs (if he or she is going abroad) giving full details of the current medications. The medical staff may be required to write a letter for the insurance company with regard to the patient s fitness to travel. Do this as close as possible to the departure date. 1. Rosenfeld M, Emerson J, Williams-Warren J, Pepe M, Smith A, Bruce Montgomery A, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr 2001;139(3): Buchdahl RM, Francis J, Bennett S, Sheehan D, Bush A. Hypoxia during flight - an audit of the fitness to fly test in children with cystic fibrosis (CF). Arch Dis Child 2000; 82(suppl I):A43. 16

17 Section 3 - Annual Assessment (Revised by Jayesh Bhatt) 17

18 3.1 Annual assessment This is undertaken around the child s birthday to assess progress and identify areas where treatment can be improved. An individual treatment plan should be formulated after the annual review. It should be postponed if the child is unwell. It is usually organised at an out-patient visit, but can be done at the end of a hospital admission. A separate annual assessment out patient clinic is held on most Wednesdays of the year. This is planned a year in advance and parents are sent out appointment letters nearer the time with a list of topics that they may want to discuss at the annual assessment. All medical staff perform annual assessments, but in the case of shared care patients, it is usual for the child to be seen by the consultant or associate specialist. The child should also be seen by the dietician, physiotherapist and social worker. At the clinic attendance prior to the annual assessment an x-ray request card should be given to the family so that the chest x-ray can be carried out on their arrival. The "annual assessment blood tests" are often performed at this attendance so the results are available when the annual assessment is performed. For children aged 12 years or over an oral glucose tolerance test should be performed annually. This should be arranged as a day case admission to D33, prior to the annual assessment clinic visit. (See section 8.5) 3.2 Medical review Use the annual assessment proforma sheet to perform the review. See appendix Documentation (see Appendix 7) When completing the report, please fill in the annual assessment summary sheets and also ensure the general summary sheet is up to date. The report is dictated as shown on the annual assessment sample letter. (Appendix 7) If the specialist registrar sees the patient they should complete the report, this should then be checked and signed by both the SpR and Consultant. Copies of the annual assessment are sent to the parent (and the child if a teenager), the GP and the shared care consultant (where appropriate). Appropriate professionals involved in the patient s care may also be sent a copy. Parents and patients will vary in the amount of detail they will find useful. Always offer to elaborate on any questions in the next clinic. 3.4 Computer database All annual assessment details are entered on the Nottingham City Hospital CF computer database, and the UK CF registry (Port CF) by the data entry clerk. 3.5 Multidisciplinary review At the time of the annual assessment, a review of care should be carried out by the dietician, physiotherapist and social worker. 18

19 Section 4 - Ward Management of CF Patients (Revised by Amanda Ward & Michael Yanney) 19

20 4.1 Segregation policy We operate a segregation policy on the ward to reduce risk of cross infection between CF patients (and between CF patients and those with bronchiectasis). There is no risk to patients without CF or bronchiectasis. Patients with Burkholderia cepacia complex or resistant strains of Pseudomonas aeruginosa should be admitted in the negative pressure cubicle on wrad D33 or on a cubicle on othe paediatric wards at QMC> Pseudomonas aeruginosa All patients colonised with P.aeruginosa should be admitted to a cubicle on D33 and should not mix on the ward (e.g. in the classroom) with non- Pseudomonas CF patients. Resistant strains of Pseudomonas aeruginosa Where patients carry resistant strains of Pseudomonas, their inpatient accommodation should be arranged by the CF consultant in charge. MRSA All patients who carry MRSA should be confined to a cubicle on D33 for the duration of their admission. A patient may be considered to be free of MRSA after 6 months of negative sputum results (minimum 3 negative sputum results) and negative nasal swab. Burkholderia cepacia complex Where patients carry Burkholderia cepacia complex, their inpatient accommodation should be arranged by the CF consultant in charge. A patient may be considered to be free of B. cepacia complex when they have had negative sputum cultures for 1 year (minimum 6 negative sputum results). All new isolates of Burkholderia cepacia complex will be sent (by the Department of Microbiology at the City Hospital) to the reference laboratories (Colindale Tel , Edinburgh tel /5) for typing. 4.2 Admission procedure The most common indication for admission is for intravenous antibiotics to treat a pulmonary exacerbation. Other indications include DIOS. The following general guidelines apply: Nursing responsibilities: Weigh and measure all children on admission Measure lung function (> 5 years) and SaO 2 (all patients) Collect a sputum sample / cough swab 20

21 Needle the port-a-cath if present, at the same time blood is taken for renal profile, FBC, magnesium and CRP (medical staff may request additional blood tests). Complete patient contract for adolescent patients and for younger ones if appropriate. Medical responsibilities: Perform full history and examination Record the weight and lung function at admission in the case notes using preprepared stamp. Plot weight and height on the growth chart Obtain IV access if required and take blood for renal profile, FBC, magnesium and CRP. If no port-a-cath in situ then a long line is preferable to a cannula (section 10). Prescribe IV antibiotics (in discussion with the doctor who planned the admission) and oral nystatin to patients with a port-a-cath for two weeks whilst on antibodies and one week after.(see section 5.4) Prescribe home IVs if indicated. See section 6 Inform the physio, CF nurse and dietician of the admission (see section 11). 4.3 Ongoing care Nursing responsibilities: Record weight and lung function on Monday, Wednesday and Friday to coordinate for Tuesday, Thursday, Friday ward rounds days and on discharge. Send a sputum sample / cough swab on day 6 of admission in conjunction with the physio. Liase with the dietician where appropriate. Administer IV antibiotics as prescribed. A nurse may administer the first dose of an antibiotic. Arrange home IV s if appropriate in conjunction with doctor. Oxygen should be administered to keep SaO 2 > 90%. Medical responsibilities: Ward rounds: Patients are seen and examined daily by the ward doctor. Consultant ward rounds are held on Tuesday am and Friday pm or Tuesday am and Thursday am depending on the Consultant on service. Ward meeting: There is a multidisciplinary meeting held on Tuesday at 12.00pm during the Summer months and pm during the Winter months in the seminar room to discuss the progress of the inpatients. The JHO /SHO should prepare acetates detailing patients lung function and weight. Case notes: Record the weight and lung function in the case notes using pre-prepared stamp. 21

22 Investigations: A patient receiving once daily tobramycin should have a trough Tobramycin level and renal profile taken before the 2 nd dose. If the levels are satisfactory and the renal function is normal, a trough level and renal profile should be performed before the 8 th dose (Section 5.4.4). Further levels are required if dose adjustments are made. Blood results should be seen and acted upon. E.g. if creatinine is raised the tobramycin dose may require reduction. For children on home IVS it is the Doctors responsibility to contact the family if changes are required. Sputum results sent on D1and D6 should be seen by the SHO and discussed with the consultant if changes in antibiotic sensitivity have occurred or a new organism is found. 4.4 Discharge summaries These should be completed at discharge using pre-prepared proforma and given to the consultant s secretary for typing. 4.5 Patient Review If parents would like their child to be reviewed earlier than their routine appointment, then the majority should be seen in the next CF clinic. If the problem is more urgent, a ward review can be arranged either at the next consultant ward round or by the registrar at another time. 22

23 Section 5 - Antibiotic Guidelines (Revised by Alan Smyth and Sue Clarke) 23

24 5.1 Cough Swab/Sputum culture Each time children attend CF clinic, a cough swab or sputum sample is sent for culture and so a culture result will usually be available from within the last 8 weeks. Empirical prescriptions should be guided by the last positive culture result. When a positive result is received, antibiotic treatment should always be given, even when the child is asymptomatic. (The only exception to this rule are organisms designated as coliforms often found in young children.) Culture results from the Tuesday CF clinic are usually available on Monday. The results are sent to the CF secretary. Individual results should be checked by the consultant on service. When a child has a positive culture and antibiotics are prescribed it is important that arrangements are made for the cough swab/sputum sample to be repeated (at the end of the antibiotic course). Prescriptions are usually arranged on a standard letter, which is sent to the child's GP and parents (see appendix 5). A microbiology form should be sent to the family with this letter. Cough swabs/sputum samples can be performed in children's OPD at a time to suit the family. If this is inconvenient the family should contact one of the CF nurses. Alternative arrangements can then be made. Each time a child is seen for ward review it is essential to send a cough swab or sputum and to measure lung function in children over 5 years. 5.2 Oral Antibiotics Staphylococcus aureus Children under 3 years: This organism is common in young children and is often difficult to eradicate. Prophylactic antibiotics are therefore given continuously from birth until 3 years of age. 1 At 3 months of age, S. aureus is present in the lower respiratory tract of up to one third of untreated infants with CF. 2 If S. aureus is isolated while on prophylactic antibiotics then the child should be given the treatment dose of flucloxacillin for 2 weeks (see below). If the repeat cough swab is clear then the child should restart the prophylactic dose. Prophylactic dose: Flucloxacillin Age Dose Frequency (times daily) ORAL Up to 3 years 125mg 2 Liquids are available as 125mg/5ml and 250mg/5ml. Some patients prefer to have the higher strength to reduce the volume needed to be taken please specify on the prescription if the 250mg/5ml strength is required. The Floxapen brand (not available in the hospital) tastes different to the other brands and may be tolerated by patients who spit out other brands. For a patient to obtain this brand it will need to be specifically prescribed as Floxapen by the GP. Older children: a 2 week course of treatment should be given whenever the organism is isolated. 24

25 First Line: Flucloxacillin Age Dose Frequency Duration (times daily) ORAL 1 month 18 years mg/kg 4 2 weeks Maximum single dose 1g. Total daily dose can be given in 3 divided doses if necessary If S.aureus continues to be isolated when the patient has been prescribed a course of flucloxacillin first consider adherence to treatment. Then consider prescribing a second line antibiotic for a 2 week period (e.g. clarithromycin or cephradine). If S.aureus continues to be isolated then discuss with consultant. Second Line: Clarithromycin Weight / Age Dose Frequency Duration (times daily) ORAL < 8kg 7.5mg/kg 2 2 weeks 8 11kg 62.5mg 2 2 weeks 12 19kg 125mg 2 2 weeks 20 29kg 187.5mg 2 2 weeks 30 40kg 250mg 2 2 weeks years 250mg 2 2 weeks Doses can be doubled in severe infections. Maximum Adult dose 500mg bd Haemophilus influenzae This is a frequent cause of exacerbations in school age children. 3 Most forms found in children with CF are non-encapsulated and so children are not protected by HiB immunisation. Use cefaclor or, if concurrent infection with S. aureus is likely or proven, co-amoxiclav ( Augmentin ). Cefaclor is also suitable for infections with Moraxella catarrhalis. Antibiotics are often given to children with CF at the time of a cold. A cough swab or sputum sample should be taken and antibiotics prescribed to cover H.influenzae. The antibiotic prescribed can be reviewed in light of the culture result. Cefaclor Age Dose Frequency Duration (times daily) ORAL 0-1 year 125 mg 3 2 weeks 1-7 years 250 mg 3 2 weeks over 7 years 500 mg 3 2 weeks 25

26 Coamoxiclav Age Preparation Dose Frequency Duration (Augmentin) (times daily) ORAL 1 month 125/31 susp 0.5ml/kg 3 2 weeks 1 year 1-6 years 125/31 susp 10ml 3 2 weeks /62 10ml 3 2 weeks years or 250/125 tab 2 tabs 3 2 weeks years 250/125 tab 2 tabs 3 2 weeks When a prescription for two tablets of Augmentin is prescribed, pharmacy will actually issue 1 tablet of 250/125 Augmentin and 1 capsule of 250mg amoxicillin for each dose. Augmentin is also available as a dispersible tablet in 250/125 strength Mycoplasma or Chlamydia pneumoniae In children who are penicillin allergic, or where the chest X-ray and serology suggest these organisms use clarithromycin (see dose above) Preventing chronic infection with Pseudomonas aeruginosa Most patients with CF will eventually develop chronic infection with P.aeruginosa. This is associated with more frequent exacerbations, productive cough and a drop in lung function. 4 Acquisition of P.aeruginosa can be prevented at least temporarily by treatment with ciprofloxacin orally and nebulised colistin. A 3 week course can achieve eradication in up to 80% of newly infected patients. 5 When P.aeruginosa is isolated this should be clearly documented in the hospital notes with details of the eradication therapy prescribed. When the prescription is written the "step" being prescribed should be stated. Nebulised colistin can provoke bronchospasm in some patients this usually occurs immediately after the drug has been given. 6 This should be mentioned to the patient/parent. Salbutamol may be given prior to nebulised colistin 7 this may also aid drug delivery. The schedule is as follows for asymptomatic children. For children with increased cough or reduced lung function consider intravenous treatment. Nebulised colistin should still be given as intravenous antibiotics alone are successful in eradicating P.aeruginosa in only 20% of cases. 8 Nebulised antibiotics are not given on the ward. Therefore, nebulised colistin should be given at home, once the child has been discharged. Discuss new infections of P.aeruginosa with the consultant. The family may wish to meet the consultant to discuss the isolation of P.aeruginosa. If the child has problems taking the prescribed medication this should be discussed with the consultant. 26

27 Step 1 Eradication Therapy: Step 1 Dose Frequency Duration (times daily) Oral 1 month 5 15mg/kg 2 3 weeks Ciprofloxacin years 5 18 years 20mg/kg 2 3 weeks (maximum 750mg) NEBULISED Colistin 1 MU 2 3 weeks Also prescribe 1x5ml 0.9%sodium chloride/dose (use 4ml of this to reconstitute Colistin vial) If the repeat cough swab/sputum is negative, stop treatment. If it is positive, proceed to step 2. Step 2 Eradication Therapy: Step 2 Dose Frequency Duration (times daily) ORAL 1 month 5 15mg/kg 2 3 weeks Ciprofloxacin years 5 18 years 20mg/kg 2 3 weeks (maximum 750mg) NEBULISED 1 month 2 1 MU 3 3 weeks Colistin years 2 18 years 2 MU 3 3 weeks Also prescribe 1x5ml 0.9% sodium chloride/dose (use 4ml of this to reconstitute Colistin vial) If repeat cough swab/sputum is negative, stop treatment. If it is positive then proceed to step 3.The highest eradication rate for P.aeruginosa is achieved with step 3. 9 When a patient on step 3 is seen in clinic they should be seen in a separate room ideally at the end of the clinic. Step 3 Eradication Therapy: Step 3 Dose Frequency (times daily) Duration ORAL Ciprofloxacin 1 month 5 years 15mg/kg 2 3 months 5 18 years 20mg/kg 2 3 NEBULISED Colistin (maximum 750mg) months 1 MU 3 3 months 1 month 2 years 2 18 years 2 MU 3 3 months Also prescribe 1x5ml 0.9% sodium chloride/dose (use 4ml of this to reconstitute Colistin vial) 27

28 Subsequent positive cultures for P.aeruginosa. If after step 1 repeat cough swabs are negative but the patient has subsequent positive cultures step 2 should be prescribed. If the patient has a positive culture and has received step 2 at any time previously then prescribe step 3. If a patient has previously received step 3 then after a 6 month "clear" period reisolates P.aeruginosa they can repeat step 3. The doctor who initiates eradication treatment must also arrange the repeat cough swab or sputum specimen and must see and act on the result. The community nurses are usually happy to arrange specimen collection. Chronic infection is defined as the culture of P.aeruginosa on 2 or more occasions extending over a 6 month period. 10 If a patient isolates P.aeruginosa within 6 months of completing step 3 they should be considered as chronically infected. This decision should be discussed sensitively with the parents (and child where appropriate). The child should commence maintenance nebulised antibiotics (see 5.3) and be seen in the "pseudomonas clinic" Long term Azithromycin Recent studies suggest long term azithromycin, may be of benefit to some patients, with established P.aeruginosa. 11;12 In patients not responding adequately to conventional treatment a 6 month trial should be considered. Azithromycin Age Dose Frequency Duration ORAL Above 6years and less than 40kg 250mg 3 times a week e.g.mon,wed,fri > 40kg 500mg 3 times a week e.g.mon,wed,fri Initial 6 month period Initial 6 month period Treatment of exacerbations in children with chronic P.aeruginosa infection Colds and mild exacerbations can be treated with oral ciprofloxacin. The dose is the same as for eradication therapy (see section 5.2.4) but courses are usually for 2 weeks. More severe exacerbations need intravenous treatment (see below). 5.3 Nebulised antibiotics Colistin Maintenance Therapy: Colistin Age Dose Frequency Duration (times daily) NEBULISED Up to 1year 0.5 MU 2 Lifelong 1-10 years 1 MU 2 Lifelong > 10 years 2 MU 2 Lifelong Also prescribe 1x5ml 0.9%sodium chloride/dose 28

29 Colistin comes as a powder for injection, reconstituted in 4 ml of 0.9% sodium chloride. Staff in children s outpatients will supply the appropriate nebuliser. A different brand of colistin, Promixin, is supplied with an Adaptive Aerosol Delivery system (AAD) this dispenses the drug in a shorter time (around 4 mins). If the patient finds the administration time of the standard nebuliser problematic then promixin may improve compliance. This drug is more expensive and before a prescription is issued it should be discussed with the child's GP. The nominal dose of promixin is the same but the dose released from the nebuliser is less, as the nebuliser is more efficient. The dose and fill volume for the ineb device are summarised in the table. Nominal dose of colistin Number of 1MU vials Vol. diluent Fill volume Concentration 1MU 1 2ml 1ml 0.5 MU/ml 2MU 1 1ml 1ml 1 MU/ml Nebulised Tobramycin Consider prescribing the preservative free preparation of tobramycin (TOBI) as an alternative maintenance therapy to colistin if colistin is poorly tolerated, if there is additional chronic infection with S.aureus or if clinical progress is unsatisfactory. This should be discussed with the consultant. Nebulised Tobramycin (TOBI) Age Dose Frequency (times daily) Over 6 yrs 300 mg 2 TOBI is administered in cycles of 28 days followed by a 28 day break. 5.4 Intravenous antibiotic treatment The antibiotic used is determined by the most recent organism isolated. A cough swab/sputum should always be sent before starting intravenous antibiotics and the antibiotics used may need to be changed, depending on the result. Blood should be sent for electrolytes (including magnesium) and creatinine when the long line is inserted or the port-a-cath accessed. Lung function should be recorded in the notes and the discharge summary at the beginning and the end of each course of intravenous antibiotics. Courses of intravenous treatment should be for at least 2 weeks. Where P aeruginosa has been isolated (even on one occasion) anti-pseudomonal antibiotics should be given. A dose should be prescribed which can be conveniently administered e.g. consider vial size. The dose prescribed should be within 5% of the dose calculated on the patient's weight. Patients with an indwelling intravenous device such as a port-a-cath should receive oral nystatin (5ml qds) to slosh and swallow throughout every course of intravenous antibiotics and for 1 week after the course is completed. This will suppress oral and gut carriage of candida and may prevent a port-a-cath becoming infected with candida. 29

30 5.4.1 Haemophilus influenzae Where recent isolates have shown only H. influenzae give intravenous cefuroxime as a single agent. Cefuroxime Dose Frequency Duration Duration (course) (times daily) (infusion) IV 50-60mg/kg 3 or 4 Bolus or 30 min infusion 2 weeks Maximum dose 1.5g For home treatment change to Ceftriaxone 50mg/kg (maximum 4g) once daily Staphylococcus aureus: If a patient has previously isolated P.aeruginosa, give IV anti-pseudomonal antibiotics (see below) and oral flucloxacillin (see treatment dose in section 5.2.1). Intravenous flucloxacillin may also be used for S. aureus. If a patient has isolated MRSA in the past then prescribe teicoplanin. First Line: Flucloxacillin Dose Frequency (times daily) Duration IV 25mg/kg 4 2 weeks Dose can be doubled in severe infection Maximum standard single dose 1g. Total daily dose may be given in 3 divided doses Second Line: Teicoplanin Dose Frequency (times daily) Duration IV Loading dose 10 mg/kg 2 X 3 doses Continue on 10 mg/kg 1 2 weeks Maximum dose 400mg Vial sizes available are 200mg and 400mg Multiply resistant Staphylococcus aureus (MRSA) Eradication is difficult (sometimes impossible) and intravenous treatment may be required. Discuss the treatment plan with the consultant. Take the following samples before starting treatment: cough swab/sputum sample, anterior nares swab and perineal swab. Add mupiricin cream if nasal carriage is present, apply 3 times a day for 5 days. In addition the patient should wash with aquasept for 5 days, during this time the hair should be washed twice. After 2 days all swabs should be repeated. Discuss with consultant or the microbiologist if skin carriage is present. If IV treatment is to be given the choice of drug will obviously depend on the sensitivity pattern. Most MRSA isolated at NCH are sensitive to teicoplanin (see above for dose). For serious MRSA infections IV antibiotics should be combined with oral rifampicin. 30

31 Rifampicin Age Dose Frequency Duration (times daily) ORAL 1 month 1 year 5 10mg/kg 2 2 weeks 1 18 years 10mg/kg (Maximum 600mg) 2 2 weeks Linezolid is a new antibiotic, which may be given by the oral route in patients with severe exacerbations due to MRSA. (Oral Linezolid has a high bioavailability and so it is rarely necessary to give it IV). Linezolid should not be prescribed if there is hepatic or renal impairment. Haematopoietic disorders have been reported in patients receiving Linezolid. It is recommended that FBC is monitored weekly and that the treatment is given for no more than days. (See current BNFC for further information). Discuss with consultant before commencing linezolid. Linezolid Age Dose Frequency Duration (times daily) IV / PO Up to 12years 10mg/kg days Over 12 years 600mg days Maximum dose 600 mg bd Pseudomonas aeruginosa: Antibiotics are always used in combination. Once daily tobramycin has been shown to be just as effective and less nephrotoxic, than conventional 3 times daily treatment. 13 If the patient has had once daily tobramycin in the last 6 months, use the dose which achieved satisfactory levels last time. See tobramycin prescribing guidelines (appendix 10) First Line: Ceftazidime Dose Frequency Duration Duration (course) (times daily) (infusion) IV 50 mg/kg 3 30 min 2 weeks Maximum dose 3 g tds Tobramycin Dose Doses / day Duration Duration (course) (infusion) IV 10 mg/kg 1 30 minutes 2 weeks Round down dose to the nearest 10mg in children< 20kg and to the nearest 20mg in children> 20kg Maximum starting dose 660mg Tobramycin levels* Timing Normal range Peak (not routinely 30 minutes after the end mg/l performed see prescribing guideline appendix) of a 30 minute infusion Trough pre-infusion <1 mg/l 31