Home intravenous antibiotic therapy: practical aspects ... - Europe PMC

JOURNAL OF THE ROYAL SOCIETY OF MEDICINE

Supplement No, 31

Volume 90

1997

Home intravenous antibiotic therapy: practical aspects in children Judith Leaver BSc(Hons) RSCN1 T J David PhD FRCP4

Franscine Radivan BSc (Hons) MRPharm2

J R Soc Med 1997;90(Suppl. 31):26-33

INTRODUCTION

Almost all cystic fibrosis (CF) centres give intravenous (i.v.) antibiotics either routinely or at the earliest sign of respiratory exacerbation. Enthusiasm for this more vigorous and aggressive approach, which possibly brings a better hope for survival1, has been, 'dampened by the enormous disruption to schooling, home life and thefamily brought about by spending 8 out of 52 weeks peryear in hospital'2. Much pressure for the same treatment to be given at home has come from parents and the patients themselves, who are eager to perform the task of drug administration which they perceive to be simple. Home treatment of CF with i.v. antibiotics is now widely established and its provision by CF centres is one ofthe recommendations made by the Clinical Standards Advisory Group3. CRITERIA FOR THE SELECTION OF PATIENTS

The following are suggested criteria: * The general practitioner must agree to home treatment. * The patient must be well enough for treatment at home. If the patient requires treatment that can only be given in hospital, then clearly hospitalization is essential. Home treatment can be used either for routine three monthly therapy, for treatment of recurrent exacerbations of chest infections, or for completion of therapy initiated in hospital. * The family should have successfully completed training for the administration of home i.v. antibiotics and be assessed as competent by the appropriate nursing team. * The family should definitely wish to undertake home i.v. antibiotic therapy. Not all families wish to participate, for a variety of reasons, and it would clearly be quite inappropriate to pressurize such families, for example, because of a shortage of hospital beds. 'Cystic Fibrosis Nurse Specialist,

Booth Hall Children's Hospital, Manchester,

2Dispensary Manager, Medical Directorate Pharmacist, Booth Hall Children's Hospital, Manchester; 'Senior Lecturer, Honorary Consultant Paediatrician, Department of Child Health, University of Manchester and Booth Hall Children's Hospital, Manchester; 4Professor of Child Health and Paediatrics, Honorary Consultant Paediatrician, Department of Child Health, University of Manchester and Booth Hall Children's Hospital, Charlestown Road, Blackley, Manchester

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M9 7AA, England Correspondence to: Professor T J David

Leena Patel MD MRCP3

SECTION OF PAEDIATRICS, 20 NOVEMBER 1996

* The patient should usually be old enough to cooperate with an i.v. infusion. Parents cannot be expected to safely administer i.v. antibiotics and at the same time restrain an infant who is thrashing around. * The family must understand the need to contact the CF team when problems arise with the i.v. line, and must be prepared to make journeys to hospital for this. Families in whom in the past there has been a marked reluctance to seek medical help when it is needed are unsuitable. * The family must understand the need for testing blood levels of certain antibiotics (e.g. aminoglycosides) and must be prepared to make journeys to the hospital for this (unless the CF centre or local community services have the facility for a nurse to visit the home to obtain the relevant samples). * The family should have a clean work surface at home where antibiotics can be reconstituted ready for administration. Patients who are supplied with reconstituted antibiotics will need a refrigerator. * The family should have a telephone at home, so that they can easily and quickly access advice or rapidly arrange transport to hospital in the event of a complication, e.g. haemorrhage from the insertion site. * The family should have a car or easy access to one to facilitate transport to hospital. * The family and patient should have been generally following recommendations about oral medications, physiotherapy, sputum samples and outpatient clinic attendance. Families who are unable to adhere to the basics of CF management are unsuitable for home i.v. antibiotic therapy. * Either the family or the CF team may withdraw from the home therapy programme and revert to inpatient treatment, permanently or temporarily, at any time. * Parents must be able to understand simple concepts such as drug dosages. There are a number of contraindications to home therapy, or areas where special care may be needed. * Severe hypersensitivity reactions (itchy erythematous skin rash which persists despite oral antihistamines, angioedema, laryngeal oedema, bronchospasm, hypotension) to i.v. antibiotics.


* Acute illness requiring management other than i.v. antibiotics and which can only be given in hospital (monitoring and observation, oxygen, intravenous fluids, surgery). * It may be difficult to provide home i.v. antibiotics when these are being delivered as a continuous infusion, because there are difficulties in providing suitable infusion devices for home use.

Once agreement has been reached that home i.v. antibiotic training is appropriate, training is supported by 'step by step' guidelines which clearly state the correct procedure for reconstituting and administering i.v. antibiotics. These guidelines also highlight potential hazards. The family is encouraged to ask questions and discuss what the transition to home i.v. therapy will mean to them. The training process involves progressing from the initial stage of observing the procedure, to being able to safely and competently complete the whole process at home without prompting. Training in hospital usually extends over two 14 day courses for three reasons. The first is to ensure that the patient does not react adversely to the antibiotics in use. The second is to allow sufficient time to train the parents. It may take several courses of inpatient treatment before the patient and staff are confident that training is complete. Finally, a gap between courses is essential to check that skills have been retained. Step by step guidelines are invaluable in the initial training period and act as an easy to follow guide to good practice. The most important section of the guidelines covers the preparation of the antibiotic and includes 16 pointers, from washing hands to expelling any remaining air bubbles from the antibiotic, prior to administration (see Table 1). It is important that these guidelines are followed by the ward-based nursing team during the training of families, to ensure continuity. It is also recommended that a copy of the guidelines is retained by the families on completion of the initial training period. The guidelines used at Booth Hall Children's Hospital clinic are broken down into the following aspects: * Why your child needs intravenous antibiotics? * How often will your child need treatment? * How will you be trained? * Preparing the antibiotic (see Table 1). * Preparing the heparin and saline (see Table 2). * Disposal of equipment (see Table 3). * Preparing the giving set (see Table 4) * Administering antibiotics through the giving set (see Table 5) 0 Problems with cannulae (see Table 6).

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Table 1 Preparing the antibiotic 1. 2. 3. 4.

5. 6.

TRAINING OF PARENTS

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7.

8. 9. 10. 11. 12.

13. 14. 15. 16.

Wash hands Check antibiotic bottle-correct antibiotic? dose? expiry date? Check water ampoule-secured? expiry date? Open the syringe and needle using a non-touch technique and connect them together Swab the top of the antibiotic bottle using an alcohol wipe. Allow to dry Adhere to your hospital's safety and sterile procedures, break top off water Remove needle cover and draw up correct amount of water, expelling any air bubbles Inject water into the antibiotic bottle Withdraw the needle and the syringe from the antibiotic bottle Shake well until all the powder is dissolved Reswab the bottle and allow it to dry Disconnect the needle from the syringe and pierce the bung on the top of the antibiotic bottle with the needle to expel the gas/ air. In the case of antibiotics which release gas (e.g. ceftazidine), wait until the fizzing stops Reconnect the syringe to the needle Draw up the appropriate amount of the antibiotic Withdraw the needle and replace the cover Expel any remaining air bubbles from the antibiotic

Table 2 Preparing the heparin and saline flushes 1. 2. 3. 4.

5.

Check the heparin and saline-correct strength? expiry date? Open the syringe and needle using a non-touch technique and connect them together Snap the top off the heparin ampoule, adhering to the hospital's safety procedures Check for fragments of glass in the ampoule Draw up the correct amount of heparin and replace the needle cover

6. 7.

Expel any air bubbles Repeat steps two to six for the saline

Table 3 Disposal of used equipment 1.

2.

3. 4

The used antibiotic bottle, heparin and sodium chloride ampoules, syringes, and needles should be placed in a sharps box/burns bin. When full please seal and return to the hospital or your health centre With used giving sets cut the spike off the top of the tubing and place in the sharps box/burns bin. Remaining tubing can be discarded with household refuse Other items can be thrown out with the household refuse Keep all equipment, used or unused, safely out of the reach of children

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Table 4 Preparing the giving set N.B. Change the infusion fluid and giving set every 24h 1. Wash your hands 2. Check the infusion fluid-is it clear? what is the expiry date? is it sealed? Remove the wrapper 3. Open the giving set wrapper; close the two clamps-one to the burette and one to the tube; open the air inlet 4. Remove the blue tag from the infusion fluid without touching the end 5. Remove the needle cover on the giving set and push the needle into the opening 6. Hang the infusion bag up, open the top clamp allowing the fluid into the chamber, then close the clamp 7. Squeeze the lower chamber until it is a third full 8. Open the bottom clamp, run the fluid through the tubing until all the air is expelled from the line. Close the clamp 9. Swab the drug additive inlet above the burette. Allow it to dry 10. Push the needle through the inlet, depress the plunger and withdraw the needle 11. Open the top clamp until the correc- 'mount of fluid is in the chamber 12. Shake the chamber to ensure that the antibiotic and fluid are evenly mixed

Table 5 Administering the antibiotic through

a

giving set.

1. Remove the bandage at the cannula site 2. Check the site for redness, swelling, inflammation, pain, is the tape moist with fluid or blood? If any of these apply contact the hospital for advice 3. Remove the bung/i.v. end and connect to the end of the infusion tubing 4. Open the extension set clamp 5. Turn the lower clamp on the infusion set until a steady flow is achieved 6. Control the infusion rate by adjusting the clamp, to infuse the antibiotic over the recommended administration time (often 15 to 20 min) 7. When 1 0 mIs is left in the chamber, close the lower clamp, open the upper clamp and refill to the recommended volume (e.g. 20 ml). Close upper clamp reopen lower clamp 8. Continue the infusion until it is complete or there is very little left (as advised by the hospital); turn off the lower clamp 9. Clamp the extension tube on the cannula 10. Disconnect the giving set 11. Insert the heparin syringe into the extension tubing on the cannula 12. Put a clean i.v. bung on the giving set 13. Opening the extension set clamp, give heparin. (Stop if inflammation, swelling, tape moist, pain or feeling of resistance) 14. Close the clamp on the extension set, remove the syringe and insert a clean i.v. bung/end 15. Rebandage the cannula site

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* Administration of antibiotics through a long line (see Table 7). * Problems with long lines (see Table 8). * Totally implantable venous access devices (see Table 9). * Problems with totally implantable venous access devices (see Table 10). Standard practice involves keeping a record of the parents' progress. The benefits of such a record are that different members of the mutli-disciplinary team can see at a glance how training is progressing. These written records of competence are retained within the patient's medical notes. Once home i.v. antibiotic therapy is under way, a record card is issued, to be completed during each 14 day course of i.v. antibiotics. This provides information about the size of the antibiotic ampoule, the volume of water to be added to each ampoule, the volume of solution to be drawn up, the volume of solution to be given and details the guidelines to be followed during the administration of the antibiotic. It also contains a daily record of cough, sputum production, peak expiratory flow and details of any problems or comments. This ensures that the patient's condition is monitored throughout the two week course, to aid decisions about future treatment. Prior to the commencement of each course of i.v. antibiotics the patient's sputum cultures are checked to identify the most suitable antibiotic. A request is then sent to the general practitioner, who prescribes the i.v. antibiotic, any dilutants and the necessary flushing solutions (sodium chloride and heparinized saline). Either the hospital or the community services supply the syringes, needles, alcohol wipes, sharps bins and bandages. Patients attend the hospital for venous access to be established. The first dose of each course of i.v. antibiotics is always given in hospital to ensure the accuracy of the parents' technique and to ensure that the patient has not developed a hypersensitivity to the antibiotic. At the start of each course of i.v. antibiotics the patient is weighed and the dose calculated, then instructions for reconstituting and administering the antibiotics are written on the card. It is essential that the parents of all patients on home i.v. antibiotic therapy have 24 h open access to the hospital. Our practice is to continue to collect sputum samples that are sent into the hospital by post during home i.v. treatment in order to detect the emergence of resistance to the antibiotics. THE USE OF DISTRACTION THERAPY

Children of any age are anxious and fearful of injections. Play is an excellent stress reducing technique, and can be utilized during the preparation process. Allowing children to handle the equipment helps to familiarize them with frightening aspects of the procedure. Distraction is one of the many


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Table 6 Problems with cannulae

Infection

Bleeding

Tissued cannula

At the cannula site watch out for:

Due to disconnection of the cannula from the extension set or the giving set

Sometimes cannula may slip out During treatment care must be of the vein into the surrounding taken that air does not enter the vein. Air in the circulation could be tissue. If this happens, fluid

* the child complaining of

passing through the cannula will fatal. Watch out for:

pain at the site

* air bubbles in the giving set (if the giving set and infusion fluid are properly set up there should be no bubbles). Do not * pain at or near the cannula let the lower chamber or the site, swelling or redness of the burette become empty whilst skin just above where the giving the infusion (air could cannula enters the skin enter the tubing and pass into * the infusion running less freely the circulation) or very slowly

go into the tissue of the arm causing pain and swelling Watch for:

* redness or inflammation, possibly spreading up the arm from the cannula site * the child being generally unwell, temperature, loss of appetite

Action Contact the hospital and remove the cannula

Air in the tube

Action Action Action * If you see bubbles in the giving * The infusion set has become * Do not give the antibiotic or set or extension tubing, stop stop the infusion if in disconnected. Clamp the the infusion immediately by progress. Phone the hospital cannula extension set and the closing the extension set for further advice giving set. Flush the cannula clamp. Disconnect the giving extension with 2 ml heparin. set and put an i.v. bung/end Put a clean i.v. bung/end on into the extension set. Check the cannula extension set there is enough fluid in the * The extension set has fallen burette and lower chamber, out of the cannula. Raise the open the lower clamp and run arm above the point where the fluid through until all the air cannula is inserted. Put i.v bubbles have gone. bung/end onto the end of the Reconnect and continue. If cannula. Flush through a new you think any air has entered extension set with heparin. the vein, bring your child Flush 2 ml heparin through the immediately to hospital cannula. Apply i.v. bung/end * If the cannula has fallen out completely. Raise the arm and press the cannula site until the bleeding stops

behavioural therapies used to help children cope with pain. It aims to help children cope with pain and anxiety, to help them understand the pain and to help take their mind off the procedure. The advantages of distraction therapy are, it helps children to relax, it reduces the intensity and the unpleasantness of procedures, allows children a degree of control and it involves them positively in the procedure. Distraction therapy provides fun, and an understanding of the child's emotions and feelings. It allows children and their parents to fully understand their treatment. The following are simple forms of distraction therapy: breathing gamesblowing bubbles, party blowers, etc.; books-sound books, pop-up books, etc.; relaxation techniques-imaginary journeys; and music- personal stereos and tapes, tranquil tapes. It is important that distraction therapy is appropriate for the age of the child and takes into account the child's stage of development and previous experiences.

TYPES OF VENOUS ACCESS DEVICES

Cannulae

Cannulae can be used, but suffer from several drawbacks. There is the likelihood that repeated cannulation will be necessary during each course of i.v. antibiotics, which means repeated trips to hospital and additional trauma. In addition, the administration of i.v. antibiotics via a peripheral vein tends to be more painful than via a long line. Finally, cannulae are more likely to disrupt everyday activities as they are more easily dislodged, and a poorly sited cannula may also impede joint movement. Long lines

fine bore flexible tubes whose tips do not extend beyond the axillary vein. This method of i.v. access is now the most commonly used in CF centres. The Long lines

are

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Table 7 Administering antibiotics through a long line N.B. Never use less than a 5 ml syringe with a long line 1. Wash your hands (and wear gloves if advised by your hospital) 2. Remove the bandage; check site for redness, swelling or leakage from connection 3. Remove the needle from syringe containing the saline 4. Remove the i.v. bung/end (or clean the injectable bung if used with an alcohol wipe and inset the needle into the bung) 5. Connect the syringe to the end of the longline 6 Open the clamp, maintaining positive pressure on the syringe plunger 7. Keeping finger/thumb on the end of the syringe, administer the saline, noting any increase in resistance. If unable to flush do not force 8. Close the clamp, remove the syringe from the end of the line, or from the needle if using an injectable bung 9 Remove the needle from the antibiotic syringe and connect the syringe to the end of the longline or the needle in the bung, taking care not to introduce any air 10. Open the clamp. Administer the antibiotic maintaining positive pressure on the syringe plunger. 11. Close clamp, remove syringe 12. Remove needle from the heparin syringe and connect to the end of the longline or the needle in the bung 13. Open clamp, administer the heparin (often 3 ml) 14. Close the clamp and seal by removing the needle from the bung 15. Rebandage the long line Footnote: If more than one antibiotic is needed flush the long line with saline between antibiotics

advantages of this form of venous access are, that if cared for as recommended, the line should last for 14 days. Additionally, there is little pain associated with the administration of i.v. antibiotics and normal activity should

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be possible. The disadvantages of this form of venous access are that doctors and nurses need to be taught how to insert the line using an aseptic technique, and how to use the long line. Additionally, the line may fail if not carefully handled. Finally, there is the potential for the line to migrate, if it becomes dislodged and travels to a central vein or the heart4. Totally implantable venous access devices Totally implantable venous access devices are mainly used by patients in whom ordinary peripheral venous access has become difficult or impossible. The device is made up of two components, a thin flexible catheter attached to a chamber with a self sealing injection port (Figures 1, 2). The whole unit is implanted surgically under the skin, usually in a convenient but inconspicuous location on the chest or arm. There is no permanent opening on the skin

surface. For those who need them, implanted devices allow easy and long lasting venous access. There are however numerous associated disadvantages, a general anaesthetic may be required for the initial insertion of the port. Additionally, there is a risk of infection and the possibility that the device becomes blocked. Health professionals, whether they are doctors or nurses, require specialist training to flush, access or troubleshoot these ports. The device requires flushing every four weeks in order to maintain its patency. DRUG INFUSION DEVICES In order to make home intravenous antibiotic therapy easier a number of systems using premixed drugs have been

developed. These devices comprise a closed system which is supplied ready filled with each individual dose of the patient's prescription. There are a number of such devices

Table 8 Problems with long lines Infection

* At the site of the long line * observe for redness at the site * pain on giving antibiotics * swelling of the arm

Action Do not give any further treatment through the line. Phone the hospital

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Leakage

Blockage

Line blown

From the line, occasionally the line will rupture * observe for wetness under the dressing

Unable to flush saline through the line

Action Return to the hospital

Action Do not force as this may cause the long line to rupture, check that the clamp is undone, and that there are no kinks in the tubing. Try again with heparin. Phone the hospital for further advice

The line has ruptured and is leaking * Never use less than a 5 ml syringe on the longline as this causes undue pressure and may blow the line Action Phone the hospital for advice


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Table 9 Administering antibiotics via a totally implantable venous access device (TIVAD) N.B. Never use less than a IOml syringe with a TIVAD 1 Wash your hands with soap 2 Prepare the * prescribed drugs in 10 ml or 20 ml syringes * sodium chloride 5 to 10 ml, a flushes before and after each drug (draw each flush up in a separate syringe) * prepare hepflush 5 ml (heparin 100 units/ml) 3 4

5

6

7

8 9

Wash your hands Hold the extension set above the clamp and clean down towards the bung/tap using an alcowipe, cleaning around the bung also. This end is now clean and should not be touched (i.e. a non-touch procedure) Attach a sodium chloride flush (to check patency) by inserting the needle into the bung. Open the clamp, maintain positive pressure and slowly administer. Close clamp without releasing positive pressure Attach syringe containing the antibiotic to the needle in the bung and follow the above procedure for administering the flush Attach the sodium chloride syringe following the above procedure Attach the hepflush syringe following the above procedure Remove the needle from the bung

Figure 1 The components of a totally implantable venous access device

Self-sealing

Skin line

Table 10 Problems with totally implantable venous access devices (TIVADs)

Blockage Any problems giving antibiotics, contact the hospital or cystic fibrosis nurse specialist immediately. Infection Any temperature, redness, swelling around the TIVAD, contact the hospital or cystic fibrosis nurse specialist immediately

on the market, in each a reservoir is filled with the antibiotic, creating a positive pressure or vacuum which delivers the medication through the system to the patient at a controlled rate once connected to an intravenous line. Examples of this type of infusion device include the 'Home pump' (Fresenius, Figure 3), the 'Intermate' (Baxter Homecare Ltd) and the 'Sidekick' (I-Flow, Figure 4). The reconstituted antibiotics are delivered preloaded in the infusion device to the patient's home where they are stored in a refrigerator until needed. The advantages of this type of system are a reduction in time to prepare the antibiotics for administration, making the system more convenient for both the patient and the carer. The main disadvantage of these systems is their enormous cost. Additionally, not all antibiotics are suitable for use in these devices because of instability of the

antibiotic solution.

Figure 2 Accessing a totally implantable venous access device

POTENTIAL PROBLEMS Updating parents' technique As with any skill there is always the potential for developing bad habits. This is one of the reasons why parents are asked to reconstitute and administer the first dose of each new course of i.v. antibiotics at the hospital, to observe their technique. Once families undertake home i.v. antibiotic therapy a good deal of support is required, to ensure that correct procedures are being followed. Adverse drug reactions Hypersensitivity to i.v. antibiotics is a potential risk5. Once patients are safely established on regular i.v. antibiotics, hypersensitivity may develop in between courses, and is manifested as a reaction, possibly a dangerous reaction to the first dose of the next course of treatment. This is the main reason why the first dose of each course of i.v. antibiotics is given in hospital, under medical supervision. The development of drug hypersensitivity during treatment

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________Fill port cap Medication

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remains a theoretical possibility and parents need to be trained to recognze and report symptoms that would indicate an allergic reaction and to seek appropriate help.

fill port

Things can and do go wrong

The following are a few examples of things that can go wrong.

r nd cap Figure 3 The Homepumlp

C

'

I. Failure to complete therapy. Patients who receive their i.v. antibiotic treatment at home may fail to complete a full course of intravenous antibiotics should l C> lamp their venous access fail. Unlike hospital based patients < /Tubing who would be reviewed by a doctor prior to discontinuing i.v. antibiotic treatment, home based patients may be disadvantaged, as decisions are invariably made over the telephone, often at night or during the particleweekend by doctors who may not know the patient.

~~~Airand particle eliminating fllter* Air and

(Fresenius Health Care Group)

II. Poor technique. During a home visit to the family of a five year old who was receiving i.v. antibiotics via a totally implantable venous access device, it was observed that the mother was pulling the needle caps off the syringes of reconstituted antibiotics with her teeth. Discussions revealed that the child's mother was totally unaware of her actions, which had become subconscious. Another example of poor technique was detected on a home visit when a family was making up 24 h worth of i.v. antibiotics at the same time, and storing the drug uncovered in a domestic refrigerator. This family was unaware that this was unsafe. They had noted that when in hospital 24 h worth of i.v. antibiotics were delivered at the same time and stored in a refrigerator. What they had failed to recognize was that the antibiotics were reconstituted in an aseptic suite, that they were delivered in sealed packets and that they were stored in a specially controlled refrigerator specifically designed for drug storage. III. Reluctance to follow advice. A child receiving an aminoglycoside was found to have toxic serum levels, and the family were instructed to reduce the dose. They dechned to do so, because they believed that a higher dosage was needed. THE ROLE OF THE CYSTIC FIBROSIS NURSE SPECIALIST One of the main tasks of the cystic fibrosis nurse specialist is to provide training and supervision of families who are to take on the responsibility of home i.v. antibiotic therapy. Once parental training has been completed, there is a need

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Finure 4 The Sidekick (I.I-Flow)

(Central Laboratories Ltd)

for monitoring progress and compliance, as well as providing support to the patients and their families.


Another task is to feed information back to the CF team at the hospital. Home visits by cystic fibrosis nurse specialists often permit a better assessment of problems than that which could be achieved in the outpatient department. Monitoring and follow-up of families on home i.v. antibiotics may involve home visits, phone calls or clinic visits. There are no rules concerning the times of antibiotic doses but, as in hospital most families choose to give the antibiotic doses at 08:00h, 16:00h and 24:00h in order that disruptions to the school day are kept to a minimum. CONCLUSION

Whilst recognizing the valuable contribution that the provision of a home i.v. antibiotic programme can make to the quality of patients lives, it should not be forgotten that for some, home treatment is not always practicable or indeed possible. The provision of a home i.v. antibiotic

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programme should not therefore be at the expense of inpatient services, nor should home care provision be based purely on its merits as a means of saving costs. In order to fulfil patient needs and maintain standards home care needs to be fully resourced. REFERENCES I Szaff M, Hoiby N, Flensborg EW. Frequent antibiotic therapy improves survival of cystic fibrosis with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand 1983;72:651-7 2 David TJ. Intravenous antibiotics at home in children with cystic fibrosis. J R Soc Med 1989;82:130-1 3 Clinical Standards Advisory Group. Cysticfibrosis, access to and availability of specialist services. London: HMSO, 1993 4 Doughty IM, David TJ. Migration of fire bore silastic catheter to the pulmonary artery. Arch Dis Child 1994;70:451 5 Battersby NC, Patel L, David TJ. Increasing dose regimen in children with reactions to ceftazidime. Clin Exp Allergy 1995;25:1211-17

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