Cystic Fibrosis Antibiotic Guidelines

Transcription

1 Cystic Fibrosis Antibiotic Guidelines Title of Guideline (must include the word Guideline (not protocol, policy, procedure etc) Contact Name and Job Title (author) Directorate & Speciality Date of submission December 016 Date when guideline reviewed December 01 Guideline Number Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis) Cystic Fibrosis Management Guidelines Section 5 - Antibiotic Guidelines Dr Jayesh Bhatt (supervising editor) Consultant in Paediatric Respiratory Directorate: Family Health Children Speciality: Respiratory Children and young people suspected of having cystic fibrosis and those with confirmed diagnosis Abstract Key Words Paediatrics. Children. Cystic Fibrosis Statement of the evidence base of the guideline has the guideline been peer reviewed by colleagues? 1a meta analysis of randomised controlled X trials a at least one well-designed controlled study without randomisation b at least one other type of well-designed quasi-experimental study well designed non-experimental descriptive studies (ie comparative / correlation and case studies) 4 expert committee reports or opinions and / or clinical experiences of respected authorities 5 recommended best practise based on the clinical experience of the guideline developer Consultation Process Staff at Nottingham Children s Hospital via the Guidelines process. Target audience Staff at the Nottingham Children s Hospital This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date. Dr Jayesh Bhatt Page 1 of 8 Issued: December 016

2 Document Control Document Amendment Record Version Issue Date Author V1 November 01 V September 015 Dr Jayesh Bhatt Professor Alan Smyth Dr Carol Bertenshaw V December 016 Dr Jayesh Bhatt (supervising editor) General Notes: Summary of changes for new version: Antibiotic guidelines and formulary updated in line with new evidence Dr Jayesh Bhatt Page of 8 Issued: December 016

3 NOTTINGHAM UNIVERSITY HOSPITALS NHS TRUST CHILDREN AND YOUNG PERSONS CYSTIC FIBROSIS UNIT CYSTIC FIBROSIS MANAGEMENT GUIDELINES Section 5 Obtaining respiratory specimens for microbiology & prescribing antibiotics (Revised by Alan Smyth & Anneka Sareen) Please see the UK CF Trust antibiotic guidelines for a more detailed discussion of the management issues discussed in this section. 1 Dr Jayesh Bhatt Page of 8 Issued: December 016

4 Section 5 - Antibiotic Guidelines 5.1 Collection of specimens for respiratory culture Cough swabs and sputum 5.1. Flexible bronchoscopy and bronchoalveolar lavage 5. Oral antibiotics 5..1 Staphylococcus aureus 5.. Haemophilus influenzae 5.. Mycoplasma or Chlamydia pneumoniae 5..4 Preventing chronic infection with Pseudomonas aeruginosa 5..5 Long term Azithromycin 5..6 Treatment of exacerbations in children with chronic P.aeruginosa infection 5. Inhaled antibiotics 5..1 Nebulised antibiotics 5..1 Nebulised Colistin 5.. Dry powder Colistin Colobreathe Turbospin 5.. Nebulised Tobramycin 5..4 Dry powder Tobramycin TOBI Podhaler 5.4 Intravenous antibiotic treatment Haemophilus influenza 5.4. Staphylococcus aureus 5.4. Multiply resistant Staphylococcus aureus (MRSA) Pseudomonas aeruginosa Burkholderia cepacia complex 5.5 Infection with non-tuberculous mycobacteria Mycobacterium abscessus 5.5. Mycobacterium avium complex 5.6 Fungal Secpticaemia 5.7 Allergic reactions 5.8 Heparin and sodium chloride flushes Section 5 Appendices Appendix 1 Paediatric guidelines for once daily tobramycin in cystic fibrosis Appendix CF Furmulary Appendix GP Antibiotic Guideline Dr Jayesh Bhatt Page 4 of 8 Issued: December 016

5 5.1 Collection of specimens for respiratory culture Cough swabs & sputum 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 the following Monday. The results are collated by the CF Clinical Nurse Specialist. 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 Section Appendix & ). 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 Flexible bronchoscopy and bronchoalveolar lavage Some children with CF, who have previously been free of cough, may develop a wet cough, which persists for many weeks, in the face of negative cultures and a poor response to oral antibiotics. Where this happens, it is important to consider differentials such as allergic bronchopulmonary aspergillosis (ABPA) (section 7.1) and cough related to bronchospasm. However no child with CF, who has previously been symptom free, should be allowed to develop a chronic wet, cough without full investigation which may include induced sputum or flexible bronchoscopy. When the induced sputum or bronchoalveolar lavage specimens are sent for culture, it is important to request culture for a full range of CF pathogens, including atypical mycobacteria. Indications for sputum induction or bronchoscopy: A wet cough has persisted for 6 weeks Two courses of oral antibiotics (each for weeks) have been given without improvement Respiratory cultures are negative Sputum induction: Sputum induction can be performed after a shorter period of cough, if there is clinical concern. If culture still negative proceed to flexible bronchoscopy and lavage. Dr Jayesh Bhatt Page 5 of 8 Issued: December 016

6 Also consider flexible bronchoscopy when a child is having a general anaesthetic for another reason e.g. insertion of portacath Consider combining flexible bronchoscopy with physiotherapist-directed bronchial lavage. A non bronchoscopic bronchial lavage can be requested from anaesthetic colleagues if bronchoscopy not possible. Procedure for induced sputum: This procedure is not suitable for pre-school children. Induced sputum should always be collected with the help of a physiotherapist or specialist nurse. Administer Salbutamol 4 x 100mcg via MDI & spacer Withdraw ml from a 4 ml vial of vial of hypertonic saline (Nebusal Forest) and dilute to 4ml with sterile water (% saline solution) Nebulise, using the patient s own nebuliser (or a Pari LC plus if unavailable) Ask the child to expectorate (with assistance from the physiotherapist or nurse) If insufficient sputum obtained: Repeat Salbultamol 4 x 100mcg Nebulise a 4ml vial of hypertonic saline without dilution Ask the child to expectorate again 5. Oral Antibiotics 5..1 Staphylococcus aureus (sensitive strains) Children under : This organism is common in young children and is often difficult to eradicate. Prophylactic antibiotics are therefore given continuously from birth until of age. CF START: The CF START trial is planned to begin recruitment in 016. This trial will randomise babies, diagnosed with CF by newborn screening, to prophylaxis or treatment as required. The parents of all babies cared for in Nottingham and shared care clinics should be offered the opportunity to participate in CF START. At months of age, S. aureus is present in the lower respiratory tract of up to one third of untreated infants with CF. If S. aureus is isolated while on prophylactic antibiotics then the child should be given the treatment dose of flucloxacillin for weeks (see below). If the repeat cough swab is clear then the child should restart the prophylactic dose. Prophylactic dose: Flucloxacillin Age Dose Frequency ORAL Up to 15mg Dr Jayesh Bhatt Page 6 of 8 Issued: December 016

7 Liquids are available as 15mg/5ml and 50mg/5ml. Some parents prefer to have the higher strength to reduce the volume administered please specify on the prescription if the 50mg/5ml strength is required. The Floxapen brand (Actavis UK Ltd, not available in the hospital) tastes different to the other brands and may be tolerated by young children who spit out other brands. To obtain this brand it will need to be specifically prescribed as Floxapen by the GP. Older children: a week course of treatment should be given whenever the organism is isolated. First Line: Flucloxacillin Age Dose Frequency Duration ORAL 1 month 18 5mg/kg 4 weeks Maximum single dose 1g. Total daily dose can be given in divided doses if necessary to improve adherence If S.aureus continues to be isolated when the patient has been prescribed a course of flucloxacillin first consider adherence to treatment. Then add a second antibiotic for 4 weeks (e.g. fusidic acid or rifampicin). If S.aureus continues to be isolated then discuss with consultant. Fusidic acid Age Dose Frequency (times daily) ORAL 1 month 1 year Suspension (fusidic acid) Tablets (sodium fusidate) Duration 15mg/kg - 4 weeks mg - 4 weeks mg - 4 weeks Over 1 & Adult 750mg (doubled for severe infections) 500mg (doubled for severe infections ) - 4 weeks Suspension contains fusidic acid (50mg in 5ml) and tablets contain sodium fusidate (50mg per tablet). 750mg fusidic acid is equivalent to 500mg sodium fusidate. Clarify which salt is required at the time of prescribing. Dr Jayesh Bhatt Page 7 of 8 Issued: December 016

8 Rifampicin Age Dose Frequency Duration (times daily) ORAL 1 month 1 year 5 10mg/kg weeks Haemophilus influenzae 10mg/kg (Maximum 450mg <50 kg & 600mg >50kg) weeks This is a frequent cause of exacerbations in school age children. 4 Most forms found in children with CF are non-encapsulated and so children are not protected by HiB immunisation. Recommended first line treatment is co-amoxiclav ( Augmentin ) (which will also treat concurrent infection with S. aureus). Second line is cefaclor (available on the NUH formulary for patients with CF) which 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. Coamoxiclav (Augmentin) Age Preparation Dose Frequency ORAL 1 month 1 year 15/1 in 5ml suspension /6 in 5ml suspension /6 in 5ml suspension Or 500/15 tablet /15 tablet Duration 0.5ml/kg weeks 5ml weeks 10ml weeks 1 tab weeks 1 tab weeks Cefaclor Age Dose Frequency Duration ORAL 0-1 year 15 mg weeks mg weeks over mg weeks Dr Jayesh Bhatt Page 8 of 8 Issued: December 016

9 5.. Mycoplasma or Chlamydia pneumoniae In children who are penicillin allergic, or where the chest X-ray and serology suggest these organisms use clarithromycin. Clarithromycin Weight / Dose Frequency Duration Age ORAL < 8kg 7.5mg/kg weeks 8 11kg 6.5mg weeks 1 19kg 15mg weeks 0 9kg 187.5mg weeks 0 40kg 50mg weeks mg weeks Doses can be doubled in severe infections. Maximum Adult dose 500mg bd 5..4 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. 5 Acquisition of P. aeruginosa can be prevented at least temporarily by treatment with ciprofloxacin orally and nebulised colistin. 6 A week course can achieve eradication in up to 80% of newly infected patients. 7 Nebulised colistin can provoke bronchospasm in some patients this usually occurs immediately after the drug has been given. 8 This should be mentioned to the patient/parent. Salbutamol may be given prior to nebulised colistin 9 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 0% of cases. 10 Nebulised antibiotics are not given on the ward. Therefore, nebulised colistin should be given at home, once the child has been discharged. TORPEDO-CF: Starting in 010 our CF clinic will participate in a large randomised controlled trial of intravenous antibiotics vs. oral ciprofloxacin (both with nebulised colistin) for eradication of P. aeruginosa in pseudomonas-naïve and pseudomonasfree patients. All patients previously negative, who have a new isolate of P. aeruginosa, should be considered for this trial. The trial is likely to be completed in 016. 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. 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. Dr Jayesh Bhatt Page 9 of 8 Issued: December 016

10 Step 1 Eradication Therapy: Step 1 Dose Frequency Oral Ciprofloxacin NEBULISED Colistin 1month 18 1 month 18 Duration 0mg/kg weeks (max 750mg) 1 mega unit weeks Also prescribe 1x5ml 0.9%sodium chloride/dose (use 4ml of this to reconstitute Colistin vial) Repeat cough swab/sputum: negative - stop treatment; positive - step. Step Eradication Therapy: Step Dose Frequency Duration ORAL 1 month 18 0mg/kg (max weeks Ciprofloxacin 750mg) NEBULISED 1 month 1 mega unit weeks Colistin 18 mega units 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.the highest eradication rate for P.aeruginosa is achieved with step. 11 Patients on step should be seen at the end of the clinic. Step Eradication Therapy: Step Dose Frequency ORAL Ciprofloxacin 1 month 18 0mg/kg (max 750mg) Duration months NEBULISED 1 month 1 mega unit months Colistin 18 mega units months Also prescribe 1x5ml 0.9% sodium chloride/dose (use 4ml of this to reconstitute Colistin vial) For some patients, nebulised tobramycin (00mg twice daily) for 8 days is an alternative eradication regimen, which has been shown to achieve good rates of eradication 1. Subsequent positive cultures for P. aeruginosa. If after step 1 repeat cough swabs are negative but the patient has subsequent positive cultures step should be prescribed. Dr Jayesh Bhatt Page 10 of 8 Issued: December 016

11 If the patient has a positive culture and has received step at any time previously then prescribe step. If a patient has previously received step then after a 6 month "clear" period re-isolates P. aeruginosa they can repeat step. The doctor who initiates eradication treatment must also arrange the repeat cough swab or sputum specimen. The result will be reviewed at the weekly microbiology meeting between the consultant and the CF Clinical Nurse Specialist. The community nurses are usually happy to arrange specimen collection. Patients may be classified into one of four groups, based on Pseudomonas status (UK CF Trust Registry Guidelines): 1. Never grown P. aeruginosa. Free of P. aeruginosa for at least 1 year. Intermittent grower of P. aeruginosa with < positive samples in the last year 4. Chronic P. aeruginosa infection with > positive samples in the last year. If a patient isolates P. aeruginosa within 6 months of completing step they will be in the intermittent or the chronic category of infection. This decision should be discussed sensitively with the parents (and child where appropriate). The child should commence maintenance nebulised antibiotics (see 5.) and be seen in the "pseudomonas clinic". Before a patient moves from category into category ensure that induced sputum or bronchial lavage specimens have been collected on at least one occasion over the previous 1 year and that they are negative for P. aeruginosa. Discuss with consultant Long term Azithromycin Clinical trials have shown long term azithromycin, may be of benefit to some patients, with established P. aeruginosa. 1;14 There is more recent evidence that azithromycin is helpful in the absence of P. aeruginosa 15. In patients not responding adequately to conventional treatment a 6 month trial should be considered. In children who produce sputum, ensure that the last annual assessment sputum specimen for non tuberculous mycobacteria was negative, before commencing long term azithromycin. Discontinue azithromycin for weeks before sending sputum for NTM testing. Azithromycin Age Dose Frequency Duration ORAL 6 18 and less than 40kg 50mg times a week e.g.mon,wed,fri 6 18 and more than 40kg 500mg times a week e.g.mon,wed,fri Initial 6 month period Initial 6 month period Dr Jayesh Bhatt Page 11 of 8 Issued: December 016

12 5..6 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..4) but courses are usually for weeks. More severe exacerbations need intravenous treatment (see below). 5. Inhaled antibiotics Inhaled antibiotics are used for chronic suppressive therapy against P. aeruginosa. Traditionally these have been given by nebuliser and newer devices have reduced the nebulisation time. Recently dry powder devices have become available. These may be more convenient for some patients (particularly adolescents). However, side effects include cough, sore throat, dysphonia, altered taste and bronchospasm. Both dry powder colistin 1 and tobramycin were reported to be non-inferior to nebulised tobramycin for the outcome of FEV1% Nebulised Colistin Maintenance Therapy: Colistin Age Dose Frequency NEBULISED 1 month mega units. Discuss with consultant Duration Lifelong mega unit Lifelong > 10 mega units Lifelong Also prescribe 1x5ml 0.9%sodium chloride/dose 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 (Respironics), 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. 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 1 mega unit 1 ml 1ml 0.5 mega units/ml mega unit 1 1ml 1ml 1 mega units/ml Dr Jayesh Bhatt Page 1 of 8 Issued: December 016

13 5.. Dry powder Colistin Colobreathe Turbospin Licensed in children 6 and over. Colobreathe 1, 66, 500 IU inhalation powder is approximately equivalent to 15mg of colistimethate sodium. The dose is one capsule twice daily. The patient is taught to perform inhalations per capsule, then inspect the capsule and ensure it is empty. Patients should rinse their mouth after use. 5.. Nebulised Tobramycin Consider prescribing tobramycin solution for inhalation (TSI), 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. The brand names are TOBI or Bramitob. This should be discussed with the consultant. Nebulised Tobramycin (TOBI/Bramitob) Age Dose Frequency Over 6 yrs 00 mg TSI is administered in cycles of 8 days followed by a 8 day break Dry powder Tobramycin TOBI Podhaler Licensed in children 6 and over. The dose for TOBI Podhaler is 4 x 8 mg capsules twice daily. As for the nebulised version, dry powder TOBI should be prescribed for 8 days on alternate months. The correct technique should be taught by the physiotherapist. The patient needs to perform a gentle slow inhalation followed by a breath hold and using cough suppression techniques to improve drug deposition. The patient is taught to perform inhalations per capsule, then inspect the capsule and ensure it is empty before proceeding to the next capsule. Patients should rinse their mouth after use. 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 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 ofintravenous Dr Jayesh Bhatt Page 1 of 8 Issued: December 016

14 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 Haemophilus influenzae Where recent isolates have shown only H. influenzae give intravenous cefuroxime as a single agent. Cefuroxime Dose Frequency Administration Duration (course) IV 50-60mg/kg or 4 Bolus over 5 mins or 0 min infusion weeks Maximum dose 1.5g For home treatment change to Ceftriaxone 50mg/kg (maximum 4g) once daily 5.4. 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..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 Administration Duration (course) IV 5mg/kg 4 Bolus over 5 mins or 0 min infusion weeks Dose can be doubled in severe infection (maximum single dose is 1g) Total daily dose may be given in divided doses Second Line: Teicoplainin IV Loading dose Continued dose Dose 10mg/kg (max 400mg) 10mg/kg (max 400mg) Frequency (for first doses) 1 Administratio n Bolus over 1 min or 0 min infusion Duration (course) weeks Vial sizes available are 00mg and 400mg. Dr Jayesh Bhatt Page 14 of 8 Issued: December 016

15 5.4. 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 times a day for 5 days. In addition the patient should wash with chlorhexidine 4% scrub (or octenisan if chlorhexidine contraindicated) for 5 days, during this time the hair should be washed twice. After days all swabs should be repeated. Discuss with consultant or the microbiologist if skin carriage is present. Eradication should be attempted for a new isolate of MRSA. If the patient is well enough to have oral antibiotics then the options are: First line: Oral cotrimoxazole and rifampicin (along with chlorhexidine mouthwash) for 14 days and repeat cultures. The dose of rifampicin is given in section 5..1). In a randomised controlled trial, this regimen achieved a significantly better eradication rate (81%) vs. the observation arm (%) at day 8. If still positive after 14 days, consider a further course of oral treatment or 14 days of intravenous teicoplanin. Cotrimoxazole Age Dose Frequency Duration ORAL 6 weeks 6 10 mg weeks months 6 months 40 mg weeks mg weeks mg weeks Minocycline is an alternative to co-trimoxazole but only for children >1. Minocycline Age Dose Frequency Duration ORAL mg weeks If IV treatment is to be given the choice of drug will obviously depend on the sensitivity pattern. Most MRSA isolated at NUH are sensitive to teicoplanin (see above for dose). For serious MRSA infections IV antibiotics should be combined with oral rifampicin. Linezolid 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 & LFT are monitored weekly and that the treatment is Dr Jayesh Bhatt Page 15 of 8 Issued: December 016

16 given for no more than days. (See current BNFC for further information). Discuss with consultant before commencing linezolid. Linezolid Age Dose Frequency Duration IV / PO Up to 1 10mg/kg days Over 1 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 times daily treatment. 18 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 (Section 5 Appendix 1). First Line: Ceftazidime Dose Frequency Administration Duration (course) IV 50 mg/kg Bolus over -5 mins or 0 min infusion weeks Maximum dose g tds Tobramycin Dose Doses / day Administration Duration (course) IV 10 mg/kg 1 0 min infusion weeks Round down dose to the nearest 10mg in children <0kg and to the nearest 0mg in children> 0kg. Maximum starting dose 660mg Tobramycin levels* Timing Normal range Peak (not routinely performed see prescribing guideline appendix) 0 minutes after the end of a 0 minute infusion 0-0 mg/l Trough pre-infusion <1 mg/l *All blood samples should be venous. A trough level and renal profile should be taken before the 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. Second Line: Colistin Dose Frequency Administration Duration (course) IV units/kg 0 min infusion weeks Maximum dose mega units ( million units) tds Combine with ceftazidime (above) or meropenem (below) according to sensitivities Meropenem (see section Burkholderia cepacia complex) is also a useful second line anti-pseudomonal antibiotic. Dr Jayesh Bhatt Page 16 of 8 Issued: December 016

17 Other options: Piperacillin Tazobactam Should only be initiated by a consultant due to risk of hypersensitivity reactions and blood dyscrasias. Piperacillin - Tazobactam ( Tazocin ) Age Dose Frequency Administration Duration 1 month mg/kg (max 4.5g).5 4.5g 6-8 hourly 0 min infusion weeks 6-8 hourly 0 min weeks infusion Adult 4.5g 6-8 hourly 0 min infusion weeks.5 g (piperacillin g and tazobactam 50 mg) 4.5 g (piperacillin 4 g and tazobactam 500 mg) vials. Hypersensitivity reactions, gastrointestinal reactions, blood dyscrasias. Fosfomycin Another option in patients with resistant organisms / drugs allergies. Fosfomycin should only be initiated by a consultant. Fosfomycin Dose Frequency Infusion Duration 1-1 (10-40kg) 100mg/kg 0mins > 1 5g (Total daily dose can be increased to 0g) - 0mins Fosfomycin dosage needs adjusting in patients with renal insufficiency seek advice from pharmacy. To prepare the infusion add 100ml water for injection to each 5g vial of fosfomycin and withdraw the appropriate volume Burkholderia cepacia complex: This organism is transmissible between patients and highly resistant to antibiotics. 19 Response to antibiotics is often poor but some isolates have in vitro sensitivity to Meropenem. 0 If a second line antibiotic is required discuss with consultant. First Line: Meropenem Dose Frequency Duration (infusion) Duration (course) IV 40mg/kg <1g dose: Bolus over 5 min > 1g dose: 15-0 min infusion weeks Maximum dose g tds. The use of a dose of g will require a prolonged infusion. Dr Jayesh Bhatt Page 17 of 8 Issued: December 016

18 Infection with B. cepacia complex is usually accompanied by P.aeruginosa. Meropenem should be combined with a second antibiotic such as ceftazidime to which the patient s strain of P.aeruginosa is sensitive. Second Line: There are anecdotal reports of the use of cotrimoxazole and chloramphenicol against B. cepacia complex. Chloramphenicol Dose Frequency Duration (infusion) Child & Adult 1.5mg/kg 6 hourly 10% solution given by slow bolus or infusion Duration (course) weeks Avoid in infants. Maximum dose 1g 6 hourly. Blood disorders including aplastic anaemia. Monitor blood counts before and during treatment. Avoid, if possible, in renal or hepatic impairment. Also gastrointestinal disturbances, peripheral and optic neuritis. In view of possible toxicity stop or change this antibiotic as soon as clinically indicated. Co-trimoxazole INTRAVENOUS Dose Frequency Duration (infusion) Duration (course) 6 mths-6 40mg 1hourly 60 min weeks mg 1hourly 60 min weeks >1 960mg 1hourly 60 min weeks 480mg in 5ml; 960mg in 10ml. 40mg =.5ml in 6ml diluent. 480mg = 5ml in 15ml diluent. 960mg = 10ml in 50ml diluent 5.5 Infection with non-tuberculous mycobacteria A sample should be sent at each annual assessment requesting staining and culture for non-tuberculous mycobacteria (NTM). The organism can only be detected on a sputum sample and, if there is a strong clinical suspicion of NTM, induced sputum or bronchoscopy and lavage should be considered in patients who do not expectorate sputum (section 5.1.). Atypical mycobacteria are environmental organisms and careful evaluation is needed to distinguish asymptomic colonisation from infection 1. A high resolution CT scan should be assessed for specific abnormalities and positive sputum samples (or 1 lavage) are needed before starting treatment. New treatment guidelines for from the US CF Foundation and the European CF Society will be published in Thorax in 016. These guidelines will recommend that NTM antibiotic therapy should be prescribed for 1 months beyond culture conversion (defined as three consecutive negative cultures, with the time of conversion being the date of the first of the three negative cultures) as long as no positive cultures are obtained during this 1 months. Dr Jayesh Bhatt Page 18 of 8 Issued: December 016

19 5.5.1 Mycobacterium abscessus: This organism is more likely to be associated with clinical disease than other NTM. Initially at least weeks of intravenous treatment is given with intravenous antibiotics plus oral azithromycin (daily dose - see below). Suitable intravenous antibiotics include amikacin, imipenem, tigecycline and cefoxitin. Review amikacin at 10 days. Check renal function and audiogram and only continue if normal. Maximum cumulative dose 15g (15,000mg) per course. See also Amikacin Prescribing Guideline for Adult Patients (NUH guideline). Amikacin Dose Frequency Duration Duration (course) (infusion) 1 month 18 15mg/kg (max 1500mg) 1 0 min infusion weeks 100mg and 500mg in ml vials. Aim for trough level of <5 mg/l. Peak should be >50 mg/l at 1 hr. Levels should be taken pre and one hour post dose after 4 hours of treatment. If within range, pre dose levels should be taken twice weekly for duration of course. Amikacin is ototoxic, consider annual hearing test. Imipenem (with cilastatin) 1 month 18 Dose Frequency Administration 5mg/kg (max 1g) 4 0min infusion (doses over 500mg infuse over 40-60mins) For infusion dilute to 5mg/ml with sodium chloride 0.9% Duration (course) weeks Tigecycline Dose Frequency Administration Duration (course) (times daily) Over 1 1mg/kg (max 50mg) Infuse over 0mins weeks 50mg vials reconstituted to produce 10mg/ml. For infusion - dilute further with 100ml sodium chloride 0.9% or glucose 5% Cefoxitin Dose Frequency (times daily) months mg/kg (max total daily dose 1g) Administration 4 Infuse over - 5mins Duration (course) weeks One gram should be constituted with at least 10 ml, and grams with 10 or 0 ml, of Sterile Water for Injection. Initial treatment is followed by maintenance treatment with nebulised amikacin and oral azithromycin (section 5..5), in conjunction with - of the following additional oral antibiotics: minocycline (section 5.4.), linezolid (section 5.4.), and moxifloxacin Dr Jayesh Bhatt Page 19 of 8 Issued: December 016

20 . Amikacin Dose Frequency (nebulised) Child <1 50mg 1hourly Child >1 and Adult 500mg 1hourly 50mg/ml vial. Make up to 4ml with 0.9% sodium chloride. Give first dose in hospital, can cause bronchospasm, monitor lung function before and after. Moxifloxacin Age Dose Frequency ORAL >1 400 mg Once daily 5.5. Mycobacterium avium complex: The CFF and the ECFS guidelines will recommend that an initial course of intravenous amikacin should be considered for the treatment of M. avium complex pulmonary disease in the presence of one or more of the following: a. AFB smear positive respiratory tract samples b. Radiological evidence of lung cavitation or severe infection c. Systemic signs of illness This should be combined with a second intravenous antibiotic (discuss with consultant). The new treatment guidelines will recommend that clarithromycin-sensitive M. avium complex pulmonary disease should then be treated with a daily oral antibiotic regimen containing a macrolide - preferably azithromycin (section 5..5); rifampicin (section 5..1) and ethambutol. Ethambutol Age Dose Frequency ORAL 1 month 18 0mg/kg Once daily Children prescribed ethambutol should have regular visual acuity and colour vision testing. Symptoms may occur before measurable changes can be identified. Patients should be educated about the potential side effects of ethambutol and encouraged to self-report. 5.6 Fungal septicaemia Fungal septicaemia should be suspected in the following circumstances: Indwelling intravenous access device (e.g. port-a-cath ) And Patient receiving prolonged or repeated courses of intravenous antibiotics And Persistent spikes of fever Dr Jayesh Bhatt Page 0 of 8 Issued: December 016

21 And Serial C reactive protein climbing over consecutive measurements in spite of intravenous antibiotics In these circumstances intravenous liposomal amphotericin may be indicated. Discuss with consultant and with microbiology. For further details see British National Formulary for Children. Discuss which brand and dose to use with microbiology as different brands have different dose recommendations. A test dose must be administered at the start of treatment (see BNFC for details). Consult with pharmacy about reconstitution and administration details. Amphotericin is incompatible with sodium chloride. A flush of glucose 5% in the line used must be administered before and after the amphotericin infusion. Successful treatment will involve line removal (discuss with consultant). Liposomal Dose Amphotericin (Ambisome brand) IV Test dose 100 micrograms/kg Maximum test dose 1mg Start - 1 mg/kg/day Increase by 1 mg/kg/day Maximum mg/kg/day Frequency (times daily) One dose only Duration (infusion) Duration (course) 15 min One dose only min weeks Always consult pharmacy. Subtract test dose from 1 st dose given on day Allergic Reactions Repeated courses of IV antibiotics are associated with the development of allergic reactions. This can severely limit antibiotic choice. The commonest reaction is a rash but life-threatening anaphylaxis can occur. Drug allergies should be clearly documented in the patient's notes and on all prescription charts. With some antibiotics it is possible to prescribe a desensitising regimen at the start of the antibiotic course, this should be done in liaison with the ward pharmacist. For patients having home IV's see protocol in section Heparin and Sodium Chloride Flushes All patients prescribed intravenous antibiotics must have sodium chloride 0.9% and heparin 10units/ml or 100units/ml prescribed (see table). The volume and frequency depends on the type of intravenous access. Dr Jayesh Bhatt Page 1 of 8 Issued: December 016

22 Sodium chloride 0.9% is given before & after each antibiotic administered (15 ml in total for antibiotics) Portacath Long Line Cannula 15ml TDS 15ml TDS 15ml TDS Heparin 100units/ml 4ml TDS 10units/ml ml 4hourly Not required Portacaths do not need flushing in between antibiotic doses to maintain patency. When the portacath is not being used for IV antibiotics it is needled and flushed with 10mls Sodium Chloride 0.9%, followed by 4mls 100units/ml of heparin every 4-6 weeks to maintain patency. However, if a child under the age of 5 has a portacath inserted an individual plan for the dose and strength of heparin needed to maintain the patency of the portacath must be discussed and agreed by the Respiratory Consultant Paediatricans and the CF Nursing Team. This must be noted in the medical notes. References (1) UK Cystic Fibrosis Trust Antibiotic Group. Antibiotic Treatment for Cystic Fibrosis (rd edition). London: UK Cystic Fibrosis Trust; 009 () Smyth A, Walters S. Prophylactic antibiotics for cystic fibrosis. Cochrane Database Syst Rev 00;Issue. Art. No.: CD DOI: / CD () Armstrong DS, Grimwood K, Carzino R, Carlin JB, Olinsky, A et al. Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis. BMJ 1995; 10: (4) Rayner RJ, Hiller EJ, Ispahani P, Baker M. Haemophilus infection in cystic fibrosis. Arch Dis Child 1997; 65: (5) Kerem E, Corey M, Gold R, Levison H. Pulmonary function and clinical course in patients with cystic fibrosis after pulmonary colonisation with Pseudomonas aeruginosa. J Pediatr 1990; 116: (6) Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 009;Issue 4. Art. No.: CD DOI:10.100/ CD pub. (7) Valerius N, Koch CHN. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 1991; 8: (8) Maddison J, Dodd M, Webb AK. Nebulised colistin causes chest tightness in adults with cystic fibrosis. Respir Med 1994; 88: Dr Jayesh Bhatt Page of 8 Issued: December 016

23 (9) Dodd ME, Abbott J, Maddison J, Moorcroft AJ, Webb AK. The effect of the tonicity of nebulised colistin on chest tightness and pulmonary function in adults with cystic fibrosis. Thorax 1997; 5: (10) Steinkamp G, Tummler B, Malottke R, von der Hardt H. Treatment of pseudomonas aeruginosa colonisation in cystic fibrosis. Arch Dis Child 1989; 64(7): (11) Frederiksen B, Koch C, Hoiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997; (5):0-5. (1) Ratjen F, Munck A, Kho P, Angyalosi G, for the ELITE study group. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax 009; 65: (1) Equi A, Balfour-Lynn IM, Bush A, Rosenthal M. Long term azithromycin in children with cystic fibrosis. Lancet 00; 60: (14) Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA et al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 00; 90(1): (15) Saiman L, Anstead M, Mayer-Hamblett N, Lands LC, Kloster M, Hocevar-Trnka J et al. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 010; 0(17): (16) Solis A, Brown D, Hughes J, Van Saene HK, Heaf DP. Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol. Pediatr Pulmonol 00; 6(): (17) Smyth A, Tan KHV, Hyman-Taylor P, Mulheran M, Lewis S, Stableforth D et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis - the TOPIC study: a randomised controlled trial. Lancet 005; 65(9459): (18) Govan JRW, Brown PH, Maddison J, Doherty CJ, Nelson JW, Dodd M et al. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis. Lancet 199; 4: (19) Pitt TL, Kaufmann ME, Patel PS, Benge LCA, Gaskin S, Livermore DM. Type characterisation and antibiotic susceptibility of Burkholderia (Pseudomonas) cepacia isolates from patients with cystic fibrosis in the United Kingdom and the Republic of Ireland. J Med Microbiol 1996; 44:0-10. (0) Schuster A, Haliburn C, Döring G, Goldman MH, Group ftfs. Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax 01; 68(4): Dr Jayesh Bhatt Page of 8 Issued: December 016

24 (1) Konstan MW, Flume PA, Kappler M, Chiron R, Higgins M, Brockhaus F, Zhang J, Angyalosi G, He E, Geller DE. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros 011; 10(1): () Goss CH, Thompson V, Popowitch E, Howe DL, Baines A, Mayer-Hamblett N, Jill V, Muhlebach MS, Team S-tS. Efficacy of a protocol for eradication of newly acquired MRSA: Results of the STAR-too trial. J Cyst Fibros 015; 14(S1). Dr Jayesh Bhatt Page 4 of 8 Issued: December 016

25 Section 5 Appendix 1 Paediatric guidelines for once daily tobramycin in cystic fibrosis There is now robust evidence that aminoglycoside antibiotics, such as tobramycin, should be given once daily, as this is less nephrotoxic 1;. The following guideline is for use with children with cystic fibrosis. Dosage 10 mg/kg given as a 0 minute infusion made up to 0mls with 0.9% saline. Maximum dose 660mg. Round down dose to nearest 10 mg for younger children or 0mg for children > 0kg. Current timing for Tobramycin levels and renal function Renal function should be performed before the 1 st dose of tobramycin and again before the 8 th dose. If the patient has renal impairment, inform the consultant or pharmacist about the dosing. Trough tobramycin levels are measured before the nd and 8 th doses of tobramycin. All bloods should be venous. Target levels Trough level < 1mg/L If the initial renal function is normal, do not wait for the trough level to come back before giving the next dose of tobramycin. Patients receiving intravenous tobramycin at home may need to come to the ward for the blood tests. This should be discussed with the Community CF nurses and a plan made prior to the patient s discharge. Suitability of patients Some patients who are already on an extended regimen for tobramycin (e.g. twice daily), are not suitable for once daily tobramycin. Patients who have impaired renal function or hearing may not be suitable for tobramycin on any regimen and these cases should be discussed individually with the consultant in charge. Interpreting tobramycin levels A raised trough level is an indication for stopping tobramycin. Then check renal function and send a further (random) tobramycin level. Raised trough levels should occur very infrequently. If the renal function is normal and the repeat level very low, the raised trough may be an error. If the repeat level is still raised, continue to monitor until it is <1mg/L. References (1) Smyth A, Tan KH, Hyman-Taylor P, Mulheran M, Lewis S, Stableforth D et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis--the TOPIC study: a randomised controlled trial. Lancet 005; 65(9459): Dr Jayesh Bhatt Page 5 of 8 Issued: December 016

26 () Smyth A, Bhatt J. Once daily versus multiple daily dosing with intravenous aminoglycosides for cystic fibrosis. The Cochrane Database of Syst Rev 000; Issue 4. Art. No.: CD DOI: / CD00009.pub. (updated 009). () Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group,Pharmaceutical Press, and RCPCH Publications [Accessed on 7th April 015] Dr Jayesh Bhatt Page 6 of 8 Issued: December 016

27 CF Formulary (Reviewed by Libby Upton 016) Section 5 Appendix DRUG (+ forms available) ROUTE AGE/WEIGHT DOSE FREQUENCY (Times daily) Abidec PO 1month-1 year 1-18 Alendronic PO acid Alendronate (5mg, 10mg & 70mg tablets) -see section 8.4 Amikacin IV 1 month- 18 Amikacin Nebulised <1 >1 Amphotericin IV (liposomal) Ambisome (important see section 5.6) Azithromycin 00mg/5ml 50mg tabs 500mg tabs Cefaclor 15mg/5ml 50mg/5ml 50mg caps 500mg caps Cefoxitin PO PO Test dose Start Maximum dose Above 6 & 5 < 40kg > 40kg 50mg 500mg 0-1 year 1-7 > 7 IV >1month Cefuroxime IV 1 month 18 Ceftazidime IV 1 month 18 Ciprofloxacin PO 1month 18 (treatment of exacerbation) 50mg/5ml 50mg tabs 500mg tabs Ciprofloxacin (eradication therapy see section 5..4) PO 1month 18 Clarithromycin IV 1 month Clarithromycin 15mg/5ml 50mg/5ml 50mg tabs 500mg tabs PO < 8kg 8-11 kgs 1-19 kgs 0-9 kgs 0-40 kgs ml ml Adult dose 10mg daily or 70mg weekly MAX DOSE DURATION 1 1.ml continuous mg continuous 15mg/kg 1 1.5g per day 50mg 15g per 500mg course 100mcg/kg 1 dose max test mg/kg/day 1 dose 1mg 5mg/kg/day 1 max dose 5mg/kg/day 15mg 50mg 500mg times a week e.g.mon,wed,fri weeks 1 dose weeks Initial 6 month period weeks 0-40mg/kg 4 1g per day weeks 50-60mg/kg or g weeks 50mg/kg g weeks 0mg/kg 750mg weeks 0mg/kg 750mg Steps 1 & for weeks Step for months 7.5mg/kg 500mg weeks 500mg 7.5mg/kg 6.5mg 15mg 187.5mg 50mg mg 500mg weeks Dr Jayesh Bhatt Page 7 of 8 Issued: December 016

28 DRUG ROUTE AGE/WEIGHT DOSE FREQUENCY MAX DURATION (Times daily) DOSE Clofazimine PO 7.5mg/kg 1 50mg Discuss with microbiology Co-amoxiclav PO 1 month 1year 15/1 0.5ml/ kg 500/15 weeks 15/1 liquid 50/6 liquid 50/15 tablet 500/15 tablet /1 susp 10ml 50/6 susp 10ml Or 500/15 tablets 1 tab 500/15 tablets 1 tab Colistin IV <60kg units/kg weeks Colistin (maintenance) Colistin (eradication therapy see section 5..4) >60kg Nebulised 1 month 18 Nebulised Step 1 Step 1 month yrs 18 mega units mega units 1 mega units 1 mega unit 1 mega unit mega units megaunits continuous weeks weeks Colistin (Colobreathe ) Inhaled Step 1 month yrs mega unit mega units 1.66 million units (1 capsule) months Creon (see section 9.4) Cyclizine IV 1 month- 6 yrs Diclofenac 5mg E/C tabs 50mg E/C tabs 50mg dispersible tabs 1.5mg 8up 5mg 8up PO/ Rectal 0.5-1mg/kg 5mg 50mg 5mg 5mg 50mg > 6 months 0.-1mg/kg Max daily dose 150mg 50mg supp Dornase alfa Nebulised mg 1 (in evening) Continuous Flucloxacillin (prophylactic dose) 15mg/5ml 50mg/5ml 50mg caps 500mg caps PO Birth 15mg Prophylactic Birth Flucloxacillin PO 1 month 18 yrs 5mg/kg 4 1g weeks Dr Jayesh Bhatt Page 8 of 8 Issued: December 016

29 DRUG ROUTE AGE/WEIGHT DOSE FREQUENCY (Times daily) MAX DOSE DURATION Flucloxacillin IV 1 month 18 yrs 5mg/kg (Dose can be doubled to 50 mg/kg in severe infection) 4 g weeks Fosfomycin IV 1 month -1 year (body weight up to 10kg) 1 11 (10-40kg) 100mg/kg 100mg/kg 4 (Total daily dose can be increased to 4g) Sodium Fusidate (Fusidic acid) (see section 5..1) 50mg/5ml 50mg tabs 1 18 (>40kg) PO 1 month- 1 year >1 Gastrograffin PO 1month 6-8g 15mg/kg 50mg 500mg 750mg (Approx. equivalent to 500mg sodium fusidate tablets) 15-0ml in 45-90ml water/juice - Single dose -4 weeks -4 weeks -4 weeks -4 weeks 15-5kg 50ml in 150ml water/juice Single dose Healthy Start Children s Vitamin Drops Heparin flushes Over 5kg PO 1 month 5 100ml in 00ml water/juice 5 drops IV See sections 5.8 or 10. Imipenem IV 1 month 18 Insulin (see section 8.6) Itraconazole PO < 1 50mg/5ml > 1 100mg caps Lactulose PO 1 month 1 yr Linezolid 100mg/5ml 600mg tabs Meropenem IV/PO 1 month < 1 > 1 IV <1g 5 mins >1g 15-0 mins infusion 1 month-1 or < 50kg Single dose 0-40mg/kg 4 1g -5mg/kg 00mg.5ml.5-10ml 5 0ml 10mg/kg 600mg 40mg/kg months 600mg days g weeks 1-18 and > 50kg g g Dr Jayesh Bhatt Page 9 of 8 Issued: December 016

30 DRUG ROUTE AGE/WEIGHT DOSE FREQUENCY MAX DURATION (Times daily) DOSE Methyl prednisolone IV Child 1 month 18 10mg/kg 1 1g days every month for 6 month Midazolam Sedation for procedure (see section 10.1) Morphine (see section 14) Morphine (see section 14) Movicol Paediatric Plain sachets Moxifloxacin (400mg tablets or 100mg/5ml suspension made in Pharmacy) Octreotide (see section 8.) Contact pharmacy for advice on dilution Omeprazole 10mg, 0mg & 40mg caps or 10mg, 0mg MUPS dispersible tablets PO PO 1month mcg/kg 1 dose 0mg 00-00mcg/kg 5-10mg IV infusion Loading dose mcg/kg then 10-0mcg/kg/hr PO <6 >6 1 sachet sachets sachets 4 sachets PO 10mg/kg 1 400mg IV PO 1month - Weight 10-0kg 1mcg/kg/hr (higher doses may be required initially) 700mcg/kg increase to mg/kg if necessary 10mg increase to 0mg if necessary Continuous infusion mcg/hour 0mg 0mg Piperacillin- Tazobactam (Tazocin) Posaconazole liquid 00mg/5ml Note: tablets and liquid are not interchangeabl e Posaconacole 100mg tablets Weight > 0kg IV 1 month PO < 1 > 1 0mg increase to 40mg if necessary 90mg/kg 4.5g 4mg/kg 00mg 1 or 4 or Note- doses may need to be adjusted according to levels PO >1 00mg for 1 day then 1 times a day thereafter 40mg 4.5g weeks 00mg 00mg weeks Dr Jayesh Bhatt Page 0 of 8 Issued: December 016