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Cystic fibrosis and outpatient treatment with parenteral antibiotics in children
INTERN*~TIONILJOLRNALOF
Antimicrobial Agents International Journal of Antimicrobial Agents 5 (1995) 6345
Cystic fibrosis and outpatient treatment with parenteral antibiotics in children J. van der Laag *, L. van de Weg University Hospital_for Children and Youth, Wilhelmina Children’s Hospital, Postbox 18009, 3501 CA
Utrecht,
Netherlands
Received 8 September 1994; accepted 4 October 1994
Abstract Despite recent key insights into the pathogenesis of cystic fibrosis, the treatment of patients suffering from this disease remains largely symptomatic. Control of respiratory infections is a vital part of patient management, involving daily physiotherapy and administration of mucolytics, bronchodilators and oral or intravenous antibiotics as necessary. For those patients requiring frequent courses of intravenous antibiotics, home treatment appears preferable to repeated hospital admissions. A home care programme for cystic fibrosis has been running at the Wilhelmina Children’s Hospital in Utrecht since 1991, with the aid of two specialist nurses to provide support and instruction for children and their parents. While parents of younger children were often reluctant to accept the increased responsibility for their child’s care, children who had received a period of home treatment were enthusiastic about its use and eager for the programme to continue. However, anxiety of patients and parents and medical instability may be of such importance in certain circumstances that treatment is not always given at home, even after former successful periods of home care. Keywords:
Outpatient
parenteral antibiotic therapy (OPAT); Home care; Cystic fibrosis
1. Introduction Cystic fibrosis is one of the most frequent hereditary disorders among the Caucasian population. In The Netherlands 1 in 3600 newborns suffers from this autosomal recessive disease. From this prevalence the gene carrier rate can easily be calculated as 1 in 30 inhabitants. Many new insights into the pathogenesis of cystic fibrosis have been developeld in recent decades. Treatment has been adjusted accordingly and intensified, as a consequence of which the median survival rate in The Netherlands has improved from about 10 years in 1960, to 27 years in 1990 [l]. The discovery of the cystic fibrosis gene in 1989 has opened many paths to the basic mechanism of cystic fibrosis and posssible future treatments. Pathophysiology of cystic jibrosis In the epithelial lining cells of the lungs of a person with cystic fibrosis the chloride channels are blocked and
*Corresponding
author. Tel. (+31-30) 320911; Fax (+31-30) 334825.
0924-8579/95/$29.00 0 1995 Elsevier Science B.V. All rights reserved SSDI 0924-8579(94)00060-3
sodium reabsorption is increased. This means that the intraluminal airway is always more or less dehydrated. Secretions will be more viscous and obstruct the airways. A vicious circle is initiated of thickened secretions, bronchial obstruction and inflammation, colonization by pathogenic microorganisms which may easily lead to infections, damage of the bronchial wall and finally destruction of the lung tissue [2]. Staphylococcus aureus and Haemophilus inzuenzae predominantly live in the airways of younger patients; the prevalence of Pseudomonas aeruginosa increases with age.
2. Treatment of cystic fibrosis Basic treatment of cystic fibrosis is still symptomatic rather than directed at the disorder itself. As respiratory infections are the major causes of morbidity and mortality in people with cystic fibrosis, measures to treat or prevent these infections form an important part of cystic fibrosis treatment [3]. Almost all patients are taught to perform daily physiotherapy and to inhale mucolytics
J. van der Laag, L. van de Wegllnternational Journal of Antimicrobial Agents 5 (199.5) 6345
64
and bronchodilators if necessary. They are treated with oral or intravenous antibiotics whenever pulmonary exacerbations occur. In some cystic fibrosis centres patients get intravenous antibiotic courses against II aeruginosa (the predominant pathogen) every 3 months in order to keep tissue destruction by this microorganism at the lowest level possible [4]. Survival rates, however, between cystic fibrosis centres which treat their patients so intensively, compared to treatment of exacerbations only, do not seem to be different. Patients with cystic fibrosis who require intravenous antibiotic treatment have to be admitted to hospital. Courses are mostly given with a /3-lactam antibiotic in combination with an aminoglycoside because of their synergistic action against E! aeruginosu [5]. In hospital attention is also paid to the nutritional state, the way physiotherapy is performed and psychological issues. At the time of an exacerbation the appetite is poor and being stimulated to eat by nurses and fellow patients is much easier in these circumstances and more acceptable than support from the family. If hospitalization for intravenous antibiotic courses is necessary every 3 or 4 months however, the quality of life of the patient may decrease and school attendance will be poor. For these patients, home treatment with antibiotics seems a feasible option. The ultimate goal of home therapy is to offer cystic fibrosis patients treatment facilities at home to increase the general well-being of the patient as well as the parents despite the fact that hospital-based ways of treatment are used at home.
3. Home treatment programme for cystic fibrosis In 1991 a programme of home care was started in the Wilhelmina Children’s Hospital in Utrecht [6]. The programme was comparable to other schemes of home treatment, which have been used elsewhere, but was adjusted to local circumstances [7-lo]. Two cystic fibrosis nurses were appointed to inform and instruct patients and their families about all procedures concerning antibiotic treatment. The necessary inclusion criteria for training sessions are that the patient should: l have had at least one intravenous antibiotic course in hospital within the last year Table 1 Comparison
of hospital
and home treatment
Hospital Patient
in cystic fibrosis patients
Home Courses
Patient
Courses
1992 1993 1994
22 21 19
41 39 26
4 5 4
I 10 5
Total Home
39 7
106 46
1
22
not have any complication of the disease for which hospitalization is necessary l be compliant with all other kinds of treatment (physiotherapy, good nutrition, etc.) After a successful training a contract between the patient, parents and hospital was signed, in which the hospital agreed that home care was appropriate and guaranteed readmission in the case that home care failed or complications occurred. The paediatrician in charge of the patient remained responsible for the home treatment. The specialized cystic fibrosis nurse was authorised to give intravenous injections and was responsible for the instruction of patients and parents and control at home during the treatment period. l
4. Results During a 21/,-year period, 15 patients at this hospital have received 33 intravenous antibiotic courses at home for exacerbations of chronic respiratory infections due to l? aeruginosa, guided by the CF nurses. All have been treated with ceftazidime continuously at a dose of 106 150 mg/kg per day (maximum 6 g/day) in combination with tobramycin twice daily, the dose of which has been adjusted after measuring top and trough levels after a few days of hospitalization. These days are necessary for testing of allergic reactions to drugs, the organization of home care and final instructions to patients and parents. Insurance companies agreed to pay for leasing an electronic infusion pump and elastomeric balloon pumps. Local pharmacists were instructed to prepare the antibiotics and to organize regular home-delivery. The 15 home-treated patients included 7 children from the Wilhelmina Children’s Hospital (age range 7-17 years) and 8 patients from other hospitals (age range 7-32 years) for whom we started to organize home-care treatment. Since we do not have detailed follow-up data of these last patients, further data and decriptions are restricted to the 7 patients from the Wilhelmina Children’s Hospital. Between January 1992 and September 1994, 39 patients had to be admitted to our hospital a total of 106 times for an intravenous antibiotic course (Table 1). Seven of these 39 patients received 46 courses; 22 of these courses were subsequently continued at home. Total treatment days for the 7 patients are 18.3 f 3.2 (mean + s.d.) (range 15-26); hospital days 5.9 f 1.3 (range 4-9) and days of home treatment 12.4 ? 3.4 (range 8-20). The other 24 courses for the 7 children were given completely in hospital because of: l anxiety of patient and/or parents (11 cases), l complications of the disease which made home treatment not justified (10 cases), or l first antibiotic course in hospital (3 cases). Four instances of complications during the home treatment periods for which a 24 h on-call service existed,
J. van der Laag, L. van de Wegllnternational
were noted. These were: technical problems with the electronic pump, air bubbles im the cassettes of the pump due to the ceftazidime solution, and phlebitis for which a new venous access was needed (two cases). During the course, all patients were seen weekly at the outpatient department by their paediatrician. In all cases of home treatment patients improved their clinical condition, lung function and general well-being compared to former courses in hospital.
5. Social issues concerning home care in cystic fibrosis At the start of the home-care programme we expected many more patients would have taken the opportunity for home treatment. In practice, parents, especially of those in the younger age group (< 12 years), felt reluctant to accept such a great responsibility for their child’s treatment. Mothers were also anxious that the family and other siblings would suffer under the stress of home care. Hospital admissions were seen to give some kind of relief to the family unit. In the older age group (12-18 years) the youngsters themselves missed their daily contact with hospital staff anfd fellow patients on the ward. On the other hand they were glad to be able to attend their own school and to be at home without disruption of family life. After a successful home-treatment period, patients agreed eagerly to proposals for home care or even requested it on new admission for exacerbation of infections. In each case, however, indications for home care had to be considered carefully, since 10 cases showed so much anxiety after a former period of home treatment that a further course was given completely in hospital instead of at home.
6. Conclusion In a specialized disease like cystic fibrosis home treatment with antibiotics seems to be feasible only for a restricted number of patients. In the patient group we treated only four very young patients (aged 7, 8, 10 and 10 years old); the other 1I were all older than 12 years. This is in agreement with the experience of other centres.
Journal of Antimicrobial
Agents 5 (1995) 6345
65
The younger the children the more anxiety will be met. The home-treated children all needed frequent intravenous antibiotic treatment. Most of the other children received only one course in a year; four of them have been trained for home treatment and will probably have this next time. Complications of the disease and anxiety of patients and parents, even if they have had adequate training and instruction, are the most important reasons for not starting home treatment. Patients younger than 8 years are less suitable, as they do not need intravenous treatment very often and stress at home may be too great to have successful home treatment. During the information and instruction phase of home care much attention has to be paid, not only to the technical aspects of infusion pumps and drug delivery, but also to the social and psychological issues, to enable the full effect of antibiotic treatment at home to be felt. References
Ill Collee JM, Cobben JM, Bakker W, de Jongste JC, van der Laag J, ten Kate LP. Cystic Fibrosis in the Netherlands 1985-1990. Report, Dutch CF Registry, University of Groningen. 121Koch C, Hoiby N. Pathogenesis of cystic fibrosis. Lancet 1993;341:1065-1069. [31 Fiel SB. Clinical management of pulmonary disease in cystic fibrosis. Lancet 1993;341:1070-1074. 141Jensen T, Pedersen SS, Hoiby N, Koch C, Flensborg EW. Use of antibiotics in cystic fibrosis. The Danish approach. Antibiot Chemother 1989;42:237-246. PI Mouton JW, Kerrebijn KF. Antibacterial therapy in cystic fibrosis. Med Clin N Am 1990;74:837-850. bl Box JD. A family affair. Nurs Times 1993;89:38-39. 17 Strandvik B, Hjelte L, Malmborg AS, Widen B. Home intravenous antibiotic treatment of patients with cystic fibrosis. Acta Paediatr 1992;81:34&344. 181Gilbert J, Robinson T, Littlewood JM. Home intravenous antibiotic treatment in cystic fibrosis. Arch Dis Child 1988;63:512-517. [91 van Aalderen WMC, Mannes GP, van Bommel G, Voorthuis I, Bosma E, Heymans HSA. Continue intraveneuze thuisbehandeling met antibiotica van luchtweginfecties bij 11 patienten met cystische fibrose in Noord-Nederland. Ned Tijdschr Geneeskd 1993;137:2482-2486. DOI Bakker W, Vinks AATMM, Mouton JW, de Jonge P, Verzijl JG, Heijennan HGM. Continue intraveneuze thuisbehandeling van luchtweginfecties met Ceftazidime via een draagbare pomp bij patienten met cystische fibrose; een multicentrisch onderzoek. Ned Tijdschr Geneeskd 1993;137:24862491.
Antimicrobial Agents International Journal of Antimicrobial Agents 5 (1995) 6345
Cystic fibrosis and outpatient treatment with parenteral antibiotics in children J. van der Laag *, L. van de Weg University Hospital_for Children and Youth, Wilhelmina Children’s Hospital, Postbox 18009, 3501 CA
Utrecht,
Netherlands
Received 8 September 1994; accepted 4 October 1994
Abstract Despite recent key insights into the pathogenesis of cystic fibrosis, the treatment of patients suffering from this disease remains largely symptomatic. Control of respiratory infections is a vital part of patient management, involving daily physiotherapy and administration of mucolytics, bronchodilators and oral or intravenous antibiotics as necessary. For those patients requiring frequent courses of intravenous antibiotics, home treatment appears preferable to repeated hospital admissions. A home care programme for cystic fibrosis has been running at the Wilhelmina Children’s Hospital in Utrecht since 1991, with the aid of two specialist nurses to provide support and instruction for children and their parents. While parents of younger children were often reluctant to accept the increased responsibility for their child’s care, children who had received a period of home treatment were enthusiastic about its use and eager for the programme to continue. However, anxiety of patients and parents and medical instability may be of such importance in certain circumstances that treatment is not always given at home, even after former successful periods of home care. Keywords:
Outpatient
parenteral antibiotic therapy (OPAT); Home care; Cystic fibrosis
1. Introduction Cystic fibrosis is one of the most frequent hereditary disorders among the Caucasian population. In The Netherlands 1 in 3600 newborns suffers from this autosomal recessive disease. From this prevalence the gene carrier rate can easily be calculated as 1 in 30 inhabitants. Many new insights into the pathogenesis of cystic fibrosis have been developeld in recent decades. Treatment has been adjusted accordingly and intensified, as a consequence of which the median survival rate in The Netherlands has improved from about 10 years in 1960, to 27 years in 1990 [l]. The discovery of the cystic fibrosis gene in 1989 has opened many paths to the basic mechanism of cystic fibrosis and posssible future treatments. Pathophysiology of cystic jibrosis In the epithelial lining cells of the lungs of a person with cystic fibrosis the chloride channels are blocked and
*Corresponding
author. Tel. (+31-30) 320911; Fax (+31-30) 334825.
0924-8579/95/$29.00 0 1995 Elsevier Science B.V. All rights reserved SSDI 0924-8579(94)00060-3
sodium reabsorption is increased. This means that the intraluminal airway is always more or less dehydrated. Secretions will be more viscous and obstruct the airways. A vicious circle is initiated of thickened secretions, bronchial obstruction and inflammation, colonization by pathogenic microorganisms which may easily lead to infections, damage of the bronchial wall and finally destruction of the lung tissue [2]. Staphylococcus aureus and Haemophilus inzuenzae predominantly live in the airways of younger patients; the prevalence of Pseudomonas aeruginosa increases with age.
2. Treatment of cystic fibrosis Basic treatment of cystic fibrosis is still symptomatic rather than directed at the disorder itself. As respiratory infections are the major causes of morbidity and mortality in people with cystic fibrosis, measures to treat or prevent these infections form an important part of cystic fibrosis treatment [3]. Almost all patients are taught to perform daily physiotherapy and to inhale mucolytics
J. van der Laag, L. van de Wegllnternational Journal of Antimicrobial Agents 5 (199.5) 6345
64
and bronchodilators if necessary. They are treated with oral or intravenous antibiotics whenever pulmonary exacerbations occur. In some cystic fibrosis centres patients get intravenous antibiotic courses against II aeruginosa (the predominant pathogen) every 3 months in order to keep tissue destruction by this microorganism at the lowest level possible [4]. Survival rates, however, between cystic fibrosis centres which treat their patients so intensively, compared to treatment of exacerbations only, do not seem to be different. Patients with cystic fibrosis who require intravenous antibiotic treatment have to be admitted to hospital. Courses are mostly given with a /3-lactam antibiotic in combination with an aminoglycoside because of their synergistic action against E! aeruginosu [5]. In hospital attention is also paid to the nutritional state, the way physiotherapy is performed and psychological issues. At the time of an exacerbation the appetite is poor and being stimulated to eat by nurses and fellow patients is much easier in these circumstances and more acceptable than support from the family. If hospitalization for intravenous antibiotic courses is necessary every 3 or 4 months however, the quality of life of the patient may decrease and school attendance will be poor. For these patients, home treatment with antibiotics seems a feasible option. The ultimate goal of home therapy is to offer cystic fibrosis patients treatment facilities at home to increase the general well-being of the patient as well as the parents despite the fact that hospital-based ways of treatment are used at home.
3. Home treatment programme for cystic fibrosis In 1991 a programme of home care was started in the Wilhelmina Children’s Hospital in Utrecht [6]. The programme was comparable to other schemes of home treatment, which have been used elsewhere, but was adjusted to local circumstances [7-lo]. Two cystic fibrosis nurses were appointed to inform and instruct patients and their families about all procedures concerning antibiotic treatment. The necessary inclusion criteria for training sessions are that the patient should: l have had at least one intravenous antibiotic course in hospital within the last year Table 1 Comparison
of hospital
and home treatment
Hospital Patient
in cystic fibrosis patients
Home Courses
Patient
Courses
1992 1993 1994
22 21 19
41 39 26
4 5 4
I 10 5
Total Home
39 7
106 46
1
22
not have any complication of the disease for which hospitalization is necessary l be compliant with all other kinds of treatment (physiotherapy, good nutrition, etc.) After a successful training a contract between the patient, parents and hospital was signed, in which the hospital agreed that home care was appropriate and guaranteed readmission in the case that home care failed or complications occurred. The paediatrician in charge of the patient remained responsible for the home treatment. The specialized cystic fibrosis nurse was authorised to give intravenous injections and was responsible for the instruction of patients and parents and control at home during the treatment period. l
4. Results During a 21/,-year period, 15 patients at this hospital have received 33 intravenous antibiotic courses at home for exacerbations of chronic respiratory infections due to l? aeruginosa, guided by the CF nurses. All have been treated with ceftazidime continuously at a dose of 106 150 mg/kg per day (maximum 6 g/day) in combination with tobramycin twice daily, the dose of which has been adjusted after measuring top and trough levels after a few days of hospitalization. These days are necessary for testing of allergic reactions to drugs, the organization of home care and final instructions to patients and parents. Insurance companies agreed to pay for leasing an electronic infusion pump and elastomeric balloon pumps. Local pharmacists were instructed to prepare the antibiotics and to organize regular home-delivery. The 15 home-treated patients included 7 children from the Wilhelmina Children’s Hospital (age range 7-17 years) and 8 patients from other hospitals (age range 7-32 years) for whom we started to organize home-care treatment. Since we do not have detailed follow-up data of these last patients, further data and decriptions are restricted to the 7 patients from the Wilhelmina Children’s Hospital. Between January 1992 and September 1994, 39 patients had to be admitted to our hospital a total of 106 times for an intravenous antibiotic course (Table 1). Seven of these 39 patients received 46 courses; 22 of these courses were subsequently continued at home. Total treatment days for the 7 patients are 18.3 f 3.2 (mean + s.d.) (range 15-26); hospital days 5.9 f 1.3 (range 4-9) and days of home treatment 12.4 ? 3.4 (range 8-20). The other 24 courses for the 7 children were given completely in hospital because of: l anxiety of patient and/or parents (11 cases), l complications of the disease which made home treatment not justified (10 cases), or l first antibiotic course in hospital (3 cases). Four instances of complications during the home treatment periods for which a 24 h on-call service existed,
J. van der Laag, L. van de Wegllnternational
were noted. These were: technical problems with the electronic pump, air bubbles im the cassettes of the pump due to the ceftazidime solution, and phlebitis for which a new venous access was needed (two cases). During the course, all patients were seen weekly at the outpatient department by their paediatrician. In all cases of home treatment patients improved their clinical condition, lung function and general well-being compared to former courses in hospital.
5. Social issues concerning home care in cystic fibrosis At the start of the home-care programme we expected many more patients would have taken the opportunity for home treatment. In practice, parents, especially of those in the younger age group (< 12 years), felt reluctant to accept such a great responsibility for their child’s treatment. Mothers were also anxious that the family and other siblings would suffer under the stress of home care. Hospital admissions were seen to give some kind of relief to the family unit. In the older age group (12-18 years) the youngsters themselves missed their daily contact with hospital staff anfd fellow patients on the ward. On the other hand they were glad to be able to attend their own school and to be at home without disruption of family life. After a successful home-treatment period, patients agreed eagerly to proposals for home care or even requested it on new admission for exacerbation of infections. In each case, however, indications for home care had to be considered carefully, since 10 cases showed so much anxiety after a former period of home treatment that a further course was given completely in hospital instead of at home.
6. Conclusion In a specialized disease like cystic fibrosis home treatment with antibiotics seems to be feasible only for a restricted number of patients. In the patient group we treated only four very young patients (aged 7, 8, 10 and 10 years old); the other 1I were all older than 12 years. This is in agreement with the experience of other centres.
Journal of Antimicrobial
Agents 5 (1995) 6345
65
The younger the children the more anxiety will be met. The home-treated children all needed frequent intravenous antibiotic treatment. Most of the other children received only one course in a year; four of them have been trained for home treatment and will probably have this next time. Complications of the disease and anxiety of patients and parents, even if they have had adequate training and instruction, are the most important reasons for not starting home treatment. Patients younger than 8 years are less suitable, as they do not need intravenous treatment very often and stress at home may be too great to have successful home treatment. During the information and instruction phase of home care much attention has to be paid, not only to the technical aspects of infusion pumps and drug delivery, but also to the social and psychological issues, to enable the full effect of antibiotic treatment at home to be felt. References
Ill Collee JM, Cobben JM, Bakker W, de Jongste JC, van der Laag J, ten Kate LP. Cystic Fibrosis in the Netherlands 1985-1990. Report, Dutch CF Registry, University of Groningen. 121Koch C, Hoiby N. Pathogenesis of cystic fibrosis. Lancet 1993;341:1065-1069. [31 Fiel SB. Clinical management of pulmonary disease in cystic fibrosis. Lancet 1993;341:1070-1074. 141Jensen T, Pedersen SS, Hoiby N, Koch C, Flensborg EW. Use of antibiotics in cystic fibrosis. The Danish approach. Antibiot Chemother 1989;42:237-246. PI Mouton JW, Kerrebijn KF. Antibacterial therapy in cystic fibrosis. Med Clin N Am 1990;74:837-850. bl Box JD. A family affair. Nurs Times 1993;89:38-39. 17 Strandvik B, Hjelte L, Malmborg AS, Widen B. Home intravenous antibiotic treatment of patients with cystic fibrosis. Acta Paediatr 1992;81:34&344. 181Gilbert J, Robinson T, Littlewood JM. Home intravenous antibiotic treatment in cystic fibrosis. Arch Dis Child 1988;63:512-517. [91 van Aalderen WMC, Mannes GP, van Bommel G, Voorthuis I, Bosma E, Heymans HSA. Continue intraveneuze thuisbehandeling met antibiotica van luchtweginfecties bij 11 patienten met cystische fibrose in Noord-Nederland. Ned Tijdschr Geneeskd 1993;137:2482-2486. DOI Bakker W, Vinks AATMM, Mouton JW, de Jonge P, Verzijl JG, Heijennan HGM. Continue intraveneuze thuisbehandeling van luchtweginfecties met Ceftazidime via een draagbare pomp bij patienten met cystische fibrose; een multicentrisch onderzoek. Ned Tijdschr Geneeskd 1993;137:24862491.