Cystic Fibrosis, intravenous Antibiotics, n ad Home Therapy n Laura J. Hammond,
MSN, RN, Shirley Caldwell, EdD, Preston W. Campbell, MD
RNC,
FNP, and
The survival rate of patients with cystic fibrosis has improved considerably in the last 20 years. Although not all of the factors accounting for this change are understood, aggressive nutritional management and treatment of pulmonary exacerbations certainly play a role. Home intravenous (IV) antibiotic delivery for pulmonary exacerbation has proved to be as effective as hospital treatment and offers signiiant advantages to the patient and family. This article examines the microbiology of pulmonary infections in patients with cystic fibrosis, as well as antimicrobial therapy, methods of IV administration, home IV therapy, and the nurse practitioner’s role in this home program in the future. J PEDIATR HEALTH CARE (1991). 5, 24-30.
n
Wptimizing the management of patients with cystic fibrosis (CF) continues to he a challenge for the practitioner because the costs and benefits of each treatment modality must be weighed. These patients require hospitalizations for pulmonary infections caused by Pseudmonar m@ma (Gilbert, Robinson, & Littlewood, 1988). Generally, patients with CF begin to show improvement in lung function after 3 to 5 days of intravenous (IV) antibiotic treatment in the hospital, however, a total of 10 to 21 days of therapy usually are required (David, 1989). Patients with CF and their families become familiar with antimicrobial therapy as a result of the frequent hospitalizations, and some families exhibit a willingness to perform the treatment at home. Home IV antibiotic therapy was introduced recently as an alternative to hospitalization for aggressive treatment of pulmonary infections in patients wtih CF. Technological advances in venous access have been made during the last decade, making prolonged home IV antibiotics both safe and feasible. Thus, for patients
with CF, administering IV antibiotics at home has become a viable solution to prolonged hospiral stays with the inherent costs of these stays. Rucker and Harrison (1974) first described home IV therapy for patients with CF using a peripheral venous access called a “heparin-lock” system. Using this system, these researchers were successful in treating pulmonary infections at home. They also demonstrated that home therapy was convenient, with no significant complications and a high rate of patient acceptance. Other studies have compared hospital treatment with home therapy and have found similar clinical improvement (Donati, Guenette, & Auerbath, 1987; Gilbert et al., 1988). The rate of recurrent pulmonary infections was not significantly different between patients treated at home and those treated in the hospital (Donati et al., 1987). These encouraging results have led to greater use of home IV therapy. The nurse practitioner can play a vital role in ensuring the effective use of this important method of treatment.
T
he rate of recurrent pulmonary infections was not significantly different between patients treated at home and those treated in the hospital.
Laura I. Hammond is a recent graduate of the Master’s Program in Nursing at Vanderbilt University. Ms. Hammond is currently working in adolescent medicine at Vanderbilt University Hospital. Shirley Caldwell University.
is assistant
professor
in the School of Nursing,
Vanderbilt
Preston W. Campbell is assistant professor of pediatrics and Director of the Cystic Fibrosis Center in the Divisions of General Pediatrics and Pediatric Pulmonology, Vanderbilt University. Reprint Medical
requests: Laura 1. Hammond, MSN, Adolescent Medicine, 436 Center South, Vanderbilt University, Nashville, TN 37232-3571,
25/1/20996
24
n
MICROBIOLOGY
Although the lungs of 98% of patients with CF eventually undergo colonization with Pse aem@249s~ it typically is not the initial colonizing organism. Stqbybm aurew is usually the first organism JOURNAL
OF PEDIATRIC
HEALTH
CARE
Journal of Pediatric Health
Cystic Fibrosis
Care
to colonize the lung of the patient with CF (Hoiby, 1988). Haettwpbilw injuenzae and other gramnegative organisms occur less frequently. Antibiotics, including oral antibiotics, are effective in killing these organisms and even in eradicating colonization. The role of respiratory viruses in bacterial colonization or lung damage is not completely known. There seems to be an aflinity of P. aerugimsa for the lung with CF. The unique ability of P. a+?rz@wsa to colonize the lung with CF and to persist despite aggressive antimicrobial therapy is a significant factor in lung disease (Govan, Doherty, & Glass, 1987). The resulting chronic infection with its infkmmatory by-products leads to progressive lung damage (Ramphal & Vishwanath, 1987). Colonization with P. aerz&wsa is a harbinger of pulmonary decline, and the resulting pulmonary disease is the ultimate cause of death in 95% of patients with CF who live beyond 1 year of age.
C
olonization with P. aeruginosa is a harbinger of pulmonary decline, and the resulting pulmonary disease is the ultimate cause of death in 95% of patients with CF who live beyond 1 year of age.
Over the last thirty years, the incidence of infections caused by P. aertlginosa has increased while the incidence of infections caused by S. aurew, the main pathogen for many years, have decreased (Waite, 1988). In part, this may be the result of effective antistaphylococcal therapy that has become available (Michel, 1988). In contrast, the pathogen P. [email protected] will persist in the lung with CF once the lung has undergone colonization (Kulczycki, Wientzen, Heller, & Bellanti, 1988). P. cepaciais the most recent pathogen that has been isolated in the lungs of patients with CF. This organism is resistant to most antibiotics and is usually associated with rapid pulmonary deterioration (Waite, 1988). n
ANTIMICROBIAL
THERAPY
Because the lower respiratory tract in many patients with CF is chronically colonized with bacteria, the criteria for antibiotic therapy must be based on changes in the patient’s baseline respiratory status. Important changes include fever, increased cough with sputum production, decreased exercise tolerance, decreased appetite and weight, and deterioration on the lung examination, chest x-ray, or pulmonary function tests (Levy, 1988). Thus, evaluating the condition of the patient with CF for signs and
25
T
he goal of antimicrobial therapy is to eradicate or decrease the number of bacteria, enabling the patient with CF to return to baseline clinical status.
symptoms of infection and isolating the pathogenic organisms is essential when determining the timing and choice of antimicrobial therapy. The goal of antimicrobial therapy is to eradicate or decrease the number of bacteria, enabling the patient with CF to return to baseline clinical status (Geddes, 1988). Other modalities such as nutritional supplementation, chest physiotherapy, and bronchial dilation are important, but the relative contribution of each is unknown. Improvement is assessed by changes in appetite, fever, cough, sputum production, respiratory rate, pulmonary examination findings, oxygen saturation, chest x-ray, and pulmonary function tests. Clinical improvement often is not seen for several days. Generally, those patients with CF who exhibit significant symptoms of pulmonary exacerbation require acute IV antibiotic therapy. Patients not colonized with Pseudomonas species may complete their antibiotic course orally if their clinical condition and sensitivity of the causative organism permit. For patients colonized with Pseudomonas species, combination therapy with an aminoglycoside, broadspectrum penicillin, or cephalosporin is given intravenously for 14 to 21 days (Kuzemko, 1988). The antibiotic choice depends on the sensitivity pattern exhibited by the infecting organism(s) to a panel of antibiotics. These agents must be given intravenously because they are not absorbed by the intestines (Horrevorts, Driessen, Michel, & Kerrebijin, 1988). P. aerz+$mJa routinely is resistant to older antimicrobial drugs such as ampicillin, penicillin, firstand second-generation cephalosporins, tetracycline, chloramphenicol, and cotrimoxizole (van Klingeren, 1988). P. amghwsa has shown degrees of susceptibility to some of the newer drugs introduced since 1967, including carbenicillin, ticarcillin, piperacillin, gentamycin, tobramycin, and ciprofloxacin (Prandota, 1988). Some of the new third-generation cephalosporins, such as ceftazidime, also have been clinically effective in treating Pseudomonas species infections (Perea, Clavijo, Nogales, & Luque, 1988). Studies have shown that a high percentage of patients whose lungs are colonized with Pseudomonas species have pulmonary function improvement when appropriate antibiotic therapy is initiated (Michel, 1988). Many antibiotic drugs have altered pharmacoki-
26
n
Hammond,
TABLE
Caldwell,
1 Antibiotics
Volume 5, Number 1 January-February 1991
& Campbell
used for exacerbations
of CF
essary treatment modality for patients with CF who are colonized with P. am++wsa. n
Compiled
from
Kuzemko
(1988);
Waite
(1988).
netics in patients with CF, necessitating higher than normal doses to achieve therapeutic effects against the organisms (Prandota, 1988). Recommended dosages will vary according to the individual patient. Commonly used intravenous antibiotic drugs administered for CF pulmonary infections are listed according to drug category in Table 1. This table provides the practitioner with a list of antimicrobial drugs that have been found to be safe and effective for home IV treatment of patients with CF. Plasma concentrations of aminoglycosides should be monitored closely because these drugs have a narrow therapeutic index. Monitoring for nephrotoxicity is essential because both the aminoglycosides and penicillins are excreted by the kidney (Prandota, 1988). Ciprofloxacin, a newer fluoroquinolone drug, is the first oral antibiotic with activity against P. ueru~ino~a lung infections. Its use is limited by concerns over cartilage damage in younger patients, and currently the drug is FDA approved for older patients only. The emergence of resistant strains with repeated dosages also may limit use of ciprofloxacin (Stutman, 1987). Therefore, despite this important development, IV antibiotic therapy remains a nec-
C iprofloxacin,
a newer fluoroquinoione drug, is the first oral antibiotic with activity against P. aeruginosd lung infections.
METHOD OF ADMINISTRATION
Various methods of administration of IV antibiotics have been attempted in patients with CF. Venous access may be problematic because of the numerous courses of antibiotics received. Multiple venipunctures are common when using a peripheral heparinlock system and also are painful and time consuming. Patients and practitioners have classified the heparinlock as the least desirable venous access system for home use (Stead, Davidson, Duncan, Hodson, & Batten, 1987). The percutaneous devices, (e.g., Hickman and Broviac catheters, Evermed, Inc., Kirkland, WA) have been used in some patients with CF. Problems with these catheters include daily dressing changes and increased risk of infections at the site (Stanislav et al., 1987). Two systems that are being used more frequently for patients with CF, both at home and in the hospital, are the percutaneous Silastic catheter (PSC) (Per-Q-Cath, Gesco International Corp., San Antonio, TX) and the totally implantable system (Port-A-Cath, Pharmacia, Inc., St. Paul, MN). (See accompanying article.) These catheters were reported to be less irritating to the veins and were effective for long-term hospital and home use (Cassey, Ford, O’Brien, & Martin, 1988; Dietrich & Lobas, 1988). The Per-Q-Cath has been examined in several studies with patients who have CF (Dietrich & Lobas, 1988; Williams, Smith, Woods, & Weller, 1988). Patients had less pain when antimicrobial treatment was administered using Per-Q-Caths than when treatment was given peripherally, thus decreasing anxiety and increasing patient comfort level (Dietrich & Lobas, 1988). The advantages of the Per-QCath are that it can be easily and safely placed in patients of almost any size by a trained health care provider. Dietrich and Lobas (1988) found that in 80% of the cases they studied, Per-Q-Cath was used as the single IV access for the entire hospital stay of the patient with CF. The Per-Q-Cath can be heparinlocked so that the patient is free to move about at home or in the hospital, and arm activity is not restricted when using this system. The mean life of the Per-Q-Cath was found to be 12.4 days (range 3 to 30 days)(Williams et al., 1988). Disadvantages of the Per-Q-Cath include a dressing change, daily heparin flushes, and possible complications. Two articles reviewed the use of the PerQ-Cath in patients with CF and found complications of sepsis (O%), thrombophlebitis (13%), occlusion
Journal of Pediatric Health Care
of the line (18%), and fluid leaking to the tissues (3%) (Dietrich & Lobas, 1988; Williams et al., 1988). Despite these infrequent problems, the PerQ-Cath has proved to be a reliable system. The Port-A-Cath is a more recently introduced venous access route for patients with CF (Cassey, et al., 1988). The Port-A-Cath is versatile and can be used for IV antibiotic and fluid administration for chemotherapy, delivery of blood products, and for blood sampling. Children receiving chemotherapy have used the Port-A-&h since 1982, and it has proved to be a dependable system with few complications (Lambert, Chadwick, McMahon, & Scarffe, 1988). The Port-A-Cath is the most feasible system for long-term antimicrobial therapy for patients with CF.
Cystic Fibrosis
m TABLE 2 General home IV therapy .‘I II
guidelines
27
for choosing
m
m l
l
m ,,, Compiled
from David
;.~,':: ,.
. (1989);
Gilbert,
Robinson,
_ ., 1,,:
& Littlewood
(1988).
T
he Port-A-Cath is the most feasible system for long-term antimicrobial therapy for patients with CF.
The major advantage of the Port-A-Cath is that the entire system is internal and there is no risk for infection until the system is accessed from the outside, thus providing a route of transmission from skin to port (Lambert et al., 1988). The feature is unique to the Port-A-Cath. Access to the Port-A-Cath can be obtained using a 20 or 22 gauge huber needle for approximately 2000 punctures. The system only requires maintenance of heparin saline flushes every 4 to 6 weeks. Weekly dressing changes are necessary only when the system is accessed for IV administration. Patients are able to swim and bathe without worries of a dressing. There is minimal interference with chest physiotherapy and there are no restrictions on patient activities when the system is not in use (Stead et al., 1987). Disadvantages of the Port-A-Cath include pain with the needle stick to access the system, but most patients develop a tolerance to this temporary discomfort. The initial cost of implantation of the PortA-Cath is high, but the relative maintenance cost is low (Cassey et al., 1988). Complications that have been reported with the Port-A-Cath include catheter occlusion (4%), infection (3%), and catheter tip migration (2%) (Lambert et al., 1988). Patients also complain of a “salty or bad” taste in their mouth as the catheter is flushed with saline. This can be alleviated by sucking on hard candy or chewing gum. Overall, the advantages of the Port-A-Cath systemthat it is easy to care for, is generally inconspicuous, and has a low rate of infection-seem to outweigh
the disadvantages. These advantages suggest that the quality of life for patients with CF can be improved through home IV antibiotic therapy using either the Port-A-Cath or Per-Q-Cath. n
HOME THERAPY
Families and patients must adjust to a new lifestyle and adapt to the life-long home therapy needs of a child with CF. In time some families become very skilled at performing chest physiotherapy and aerosol treatments. Also, because many of these patients now live into their 20s and 3Os, they often become experts in caring for themselves (Levison, Garner, MacMillian, & Cowen, 1987). It is very feasible for both parents and patients to be taught how to administer home intravenous antibiotics. However, the patients’ response to the antibiotics and possible side effects must be assessed first in the hospital before the patient is discharged home. The advantages of treating patients with CF using a home IV antibiotic program include: decreasing the number of days the patient spends in the hospital, returning the patient to the home environment more quickly, increasing the number of available hospital days for insurance, and decreasing the cost of treatment (Kane, Jennison, Wood, Black, & Herbst, 1988). Several studies have focused on the significant cost savings to families of patients with CF when IV antibiotics are administered at home (Bosso, Huckendubler-Stephenson, & Herbst, 1985; Kane et al., 1988). These studies agreed that the home administration of antibiotics should be easy, cost effective, and safe. Kane et al. ( 1988) found in their study that savings
28
n
Hammond,
TABLE
Caldwell,
3 Practitioner’s
Volume 5, Number 1 January-February 1991
& Campbell
checklist
for teaching
/ ^‘,,; ti~ms
home IV therapy
I.
-step care for venous access system and a&&tic
up to $286 to $445 per day could be realized if combination antibiotic therapy was initiated at home, depending on the home care agency. Blue Cross/Blue Shield and other commercial providers will pay between 80% to 100% of the cost of home IV antimicrobial therapy, which leaves a possible copayment from families, depending on their insurance (Kane et al., 1988). Practitioners must be aware of the potential costs to the families and of methods to conserve and control health care resources. The effectiveness of long-term home IV antibiotic therapy has been demonstrated with other chronic diseases, and patient acceptance, safety, cost effec-
tiveness, and therapeutic efficiency were seen (Stiver et al., 1978). Because of this, the number of home antibiotic programs is growing as this alternative treatment becomes more popular (Boss0 et al., 1985). Although certain antimicrobials may be administered as an IV push, most patients with CF will be instructed on the use of an infusion pump by the home care agency. Several infusion pumps, including the Provider 5000 (Pancretec Inc., San Diego, CA) and the Intermate (Caremark, Inc., Lincolnshire, IL) can deliver continuous or intermittent IV fluids and antibiotics over a 24-hour period. Other necessary
Journal of Pediatric Health
home care supplies include syringes and connectable tubing for the pump, tape, alcohol and betadine swabs, gauze dressings, needles, and heparin. Thus, the costs, the ability to provide medical care at home, and the availability of a home IV program all are essential factors to examine when considering transferring a patient with CF to home IV antibiotics.
For home
IV therapy to be successful, patients with CF and their parents must learn to adniinister the antibiotic accurately and how to recognize and manage complications.
n
Cystic
Care
ROLE OF THE NURSE PRACTITIONER
For home IV therapy to be successful, patients with CF and their parents must learn to adminster the antibiotic accurately and how to recognize and manage complications. The patient with CF and the patient’s family may be overwhelmed when the task of administering IV antimicrobials is added to their home routine because it requires skills, knowledge, and time. This task may not be realistic for every family, and the practitioner must be aware of this possibility. However, teaching families to administer home IV antibiotics may decrease the disruption of family routines overall and may allow the patient with CF to return to school or employment earlier. The nurse practitioner is able to coordinate the teaching efforts of the CF team members as they instruct the patient and family about home IV antibiotic therapy. The combined efforts of the physician, nurse practitioner, pharmacist, social worker, patient, family, and home care agency are necessary for an easy and feasible transfer of care from the hospital setting to the home environment. Once the patient with CF is classified by the physician as an appropriate candidate for home IV therapy (Table 2), teaching by the CF team begins. Determining both the appropriate time during the hospital stay for teaching and the willingness of the patient and family to learn is essential. The practitioner’s checklist found in Table 3 identifies the teaching instructions for home IV antibiotic therapy that must be completed while the patient is in the hospital. Following instruction in the hospital, the nurse should observe the patient and family performing their new skills using the proper procedure. The nurse practitioner’s role is to instruct the patient and family about care and maintenance of the venous accesssystem, the mechanics of administering the IV antibiotic, and troubleshooting complications. As-
Fibrosis
29
sisting the family and patient with CF in writing down their daily home routine and scheduled IV antibiotics will provide guidance and may identify potential problems that can be discussed. Potential complications that may occur at home when administering the IV antibiotics or with the venous access system should be addressed by the nurse practitioner. Any signs of clotting, IV infiltration, or infection at the venous access site must be reported to the nurse practitioner immediately. Prevention of these problems is addressed by the nurse practitioner when demonstrating proper dressing changes and heparin flushes for each system. The nurse practitioner also instructs the family to observe for changes in their child’s symptoms, such as increased cough, fever, or sputum, while receiving home IV antimicrobials. In this case, the physician may need to reassessthe child’s physical status or the IV therapy. The social worker is responsible for contacting the home care agency. The agency orders the medical equipment and supplies and provides home nursing visits, which are covered by the family’s insurance or by other financial sources. The home care agency usually provides the infusion pump and the prescribed IV antibiotic(s) to be administered. Having the home equipment and supplies in the hospital when teaching the patient and family will provide continuity of skill to the home setting. The home care agency arranges nursing visits to assemble the home IV equipment and IV antimicrobial drugs and to provide support and further teaching for both the patient with CF and the family when the patient is discharged home.
A team
effort will enhance the family’s understanding and new skills when teaching home IV antibiotic delivery.
A team effort will enhance the family’s understanding and new skills when teaching home IV antibiotic delivery. The primary health care provider decides on the IV antibiotic, schedules routine visits to monitor blood levels, determines frequency of follow-up clinic visits, and provides support to the families. The home care pharmacist provides guidelines for the rate of administration, amount of dilution, and adverse reactions of the antibiotic. Most antibiotics can be administered over 30 to 60 minutes by an infusion pump. The nurse practitioner reviews with the family information concerning the prescribed home IV antibiotic, the proper infusion rate
30
Hammond,
Caldwell,
& Campbell
using an infusion pump, and monitoring for possible side efkcts of the antimicrobial drug. The nurse practitioner plays a vital role when the patient with CF and the family begin home IV antibiotic therapy. A thorough examination is necessary before discharging the patient home. An adequate venous accesssystem should be in place and the family should demonstrate the correct knowledge, willingness, and skills to administer the Iv antibiotic through this system. Arrangements also should be made for home care supplies and nursing visits. Any possible barriers to participation in home IV therapy must be addressed and approached by the nurse practitioner to aid in the success of this therapy. Nurse practitioners have a responsibility to confi+ont these issues and to become acquainted with home IV antibiotic programs for patients with CF so that they are prepared for this future link. The potential contribution of a home IV antibiotic program that enhances the quality of life for patients with CF deserves further research by nurse practitioners in the future. n REFERENCES Basso, J. A., Huckendubler-Stephenson, S. E., & Herbst, J. J. (1985). Feasibility and cost savings of intravenous administration of aminoglycosides in outpatients with cystic fibrosis. Dtxg Intelligent and Clinical Pbamusy, 19, 52-54. Cassey, J., Ford, W. D. A., O’Brien, L., & Martin, A. J. (1988). Totally implantable system for venous accessin children with cystic fibrosis. Clinical Ped&riq 27, 91-94. David T. J. (1989). Intravenous antibiotics at home in children with cystic fibrosis. Jorrmal of the Rcyzl SocietyofMedkine, 82, 130-131. Dietrich, K. A., & Lobas, J. G. (1988). Use of a single Silastic intravenous catheter for cystic fiborsis pulmonary exacerbation. Pediati Puhwrwlo~, 4, 181-184. Donati, M. H., Guenette, G., &Auerbach, H. (1987). Prospective controlled study of home and hospital therapy of cystic fibrosis pulmonary disease. The Journ& of Pedktria, 111, 28-33. Geddes, D. M. (1988). Antimicrobial therapy against Stql$coccusaurem, PseuAmnonar aem@wsa and Pserrdmnonm czpachz. chest, 94, (2), 14Os-143s. Gilbert, J., Robinson, T., & Littlewood, J. M. (1988). Home intravenous antibiotic treatment in cystic fibrosis. Archives of Disease in CbW, 63, 5 12-517. Govan, J. R. W., Doherty, C., & Glass, S. (G87). Rational parameters for antibiotic therapy in patients with cystic fibrosis. Injktims, 4, 300-306. Hoiby, N. (1988). Hamwpbihu inpucnZue, Stlripl?vloMEnrraurew, Pseudomonas cepac& and Pseudummas aeru&xa in patients with cystic fibrosis. Chest, 94, 97s-101s.
Volume 5, Number 1 January-February 1991
Horrevom, A. M., Driessen, 0. M. J., Michel, M. F., & Kerrebijin, K. F. (1988). l?harma&k&cs of antimicrobial drugs in cystic fibrosis: AminogIycoside antibiotics. Cb&, 94, (2),102s-125s. Kane, R. E., J cnnison, K., Wood, C., Black, P. G., & He&t, J. J. (1988). Cost savings and economic considerations using home intravenous antibiotic therapy for cystic fibrosis patients. Pedbmk Ptdmom&y, 4, 84-89. Kulczycki, L. L., Wientzen, R. L., Heller, T., & Gellanti, J. A. (1988). Factors influencing pseudomonas colonization in cystic fibrosis. Amud of’Al&gy, 60,423-428. Kuzemko, J. A. (1988). Home treatment of pulmonary infections in cystic fibrosis. Chest, 94,162~165s. Lambert, M. A, Chadwick, G. A., McMahon, A., & Scar& J. H. (1988). Experience with the Port-a-Cath. Hcnu&gy Oneokyy, 6, 57-63. Levison, H., Garner, D., Ma&ii&an, H., & Cowen, L. (1987). Living with cystic fibrosis: Patient, My and physician realities. comprchnrril Tbm, 13,(10), 38-45. Levy, J. (1988). Antibiotic therapy in cystic fibrosis. Cb&, 94, 15os-153s. Michel, B. C. (1988). Antibacterial therapy in cystic fibrosis. Chest, 94, 129s-139s. Peres, E. J., Clavijo, E., Nogales, M. C., & Luque, I. G. (1988). Interaction of aminoglycosides and cephalosporins against Pwdommus aem&wsa comelation between interaction index and killing curve. Journal ofAntiab&d Cbemotberq, 22, 175-183. Prandota, J. (1988). Clinical pharmacology of antibiotics and other drugs in cystic fibrosis. m, 35, 542-578. Ramphal, R., & Vishwanath, S. (1987). Why is pseudomonas the colonizer and why does it persist? In/icrimr, 15, 281-286. Rucker, R. W., & Harrison, G. M. (1974). Outpatient intravenous medications in the management of cystic fibiosis. Pea%atria, 54, 358-360. Stanislav, G. V., Fitzgibbons, R. J., Bailey, R. T., Mail&d, J. A., Johnson, P. S., & Feole, J. B. (1987). Reliability of implantable central venous accessdevices in patients with cancer. Archives of Surgny, 122, 1280-1283. Stead, R. J., Davidson, T. I., Duncan, F. R., Hodson, M. E., & Batten, J. C. (1987). Use of a totally implantable system for venous accessin cystic fibrosis. Tbm, 42, 149-150. Stiver, H. G., Telford, G. O., Massey, J. M., Cote, D. D., van Middlesworth, E. J., Trosky, S. K., McKay, N. L., &Mossey, W. L. (1978). Intravenous antibiotic therapy at home. Ann& of Internal Medicine, 89, 690-693. Stutman, H. R. (1987). Summary of a workshop on Ciprofloxacin’ use in patients with cystic fibrosis. Pediatric Infieasc Journal, 6, 932-935. van Klingerin, B. (1988). Antibiotic resistance in Pmabmm~ arrUgnasa, Hem@ih injuenzae and Stllphylococn*r aurcus. chest, 94, 103s-106s. Waite, W. W. (1988). Pharmacologic management of cystic fibrosis. The Jownal of Pr& Nursing, 38,(3), 19-27. Williams, J., Smith, H. L., Woods, C. G., &Weller, P. H. (1988). Silastic catheters for antibiotics in cystic fibrosis. AY&+ of Dkeam in Childboo~ 63, 658-659.
MSN, RN, Shirley Caldwell, EdD, Preston W. Campbell, MD
RNC,
FNP, and
The survival rate of patients with cystic fibrosis has improved considerably in the last 20 years. Although not all of the factors accounting for this change are understood, aggressive nutritional management and treatment of pulmonary exacerbations certainly play a role. Home intravenous (IV) antibiotic delivery for pulmonary exacerbation has proved to be as effective as hospital treatment and offers signiiant advantages to the patient and family. This article examines the microbiology of pulmonary infections in patients with cystic fibrosis, as well as antimicrobial therapy, methods of IV administration, home IV therapy, and the nurse practitioner’s role in this home program in the future. J PEDIATR HEALTH CARE (1991). 5, 24-30.
n
Wptimizing the management of patients with cystic fibrosis (CF) continues to he a challenge for the practitioner because the costs and benefits of each treatment modality must be weighed. These patients require hospitalizations for pulmonary infections caused by Pseudmonar m@ma (Gilbert, Robinson, & Littlewood, 1988). Generally, patients with CF begin to show improvement in lung function after 3 to 5 days of intravenous (IV) antibiotic treatment in the hospital, however, a total of 10 to 21 days of therapy usually are required (David, 1989). Patients with CF and their families become familiar with antimicrobial therapy as a result of the frequent hospitalizations, and some families exhibit a willingness to perform the treatment at home. Home IV antibiotic therapy was introduced recently as an alternative to hospitalization for aggressive treatment of pulmonary infections in patients wtih CF. Technological advances in venous access have been made during the last decade, making prolonged home IV antibiotics both safe and feasible. Thus, for patients
with CF, administering IV antibiotics at home has become a viable solution to prolonged hospiral stays with the inherent costs of these stays. Rucker and Harrison (1974) first described home IV therapy for patients with CF using a peripheral venous access called a “heparin-lock” system. Using this system, these researchers were successful in treating pulmonary infections at home. They also demonstrated that home therapy was convenient, with no significant complications and a high rate of patient acceptance. Other studies have compared hospital treatment with home therapy and have found similar clinical improvement (Donati, Guenette, & Auerbath, 1987; Gilbert et al., 1988). The rate of recurrent pulmonary infections was not significantly different between patients treated at home and those treated in the hospital (Donati et al., 1987). These encouraging results have led to greater use of home IV therapy. The nurse practitioner can play a vital role in ensuring the effective use of this important method of treatment.
T
he rate of recurrent pulmonary infections was not significantly different between patients treated at home and those treated in the hospital.
Laura I. Hammond is a recent graduate of the Master’s Program in Nursing at Vanderbilt University. Ms. Hammond is currently working in adolescent medicine at Vanderbilt University Hospital. Shirley Caldwell University.
is assistant
professor
in the School of Nursing,
Vanderbilt
Preston W. Campbell is assistant professor of pediatrics and Director of the Cystic Fibrosis Center in the Divisions of General Pediatrics and Pediatric Pulmonology, Vanderbilt University. Reprint Medical
requests: Laura 1. Hammond, MSN, Adolescent Medicine, 436 Center South, Vanderbilt University, Nashville, TN 37232-3571,
25/1/20996
24
n
MICROBIOLOGY
Although the lungs of 98% of patients with CF eventually undergo colonization with Pse aem@249s~ it typically is not the initial colonizing organism. Stqbybm aurew is usually the first organism JOURNAL
OF PEDIATRIC
HEALTH
CARE
Journal of Pediatric Health
Cystic Fibrosis
Care
to colonize the lung of the patient with CF (Hoiby, 1988). Haettwpbilw injuenzae and other gramnegative organisms occur less frequently. Antibiotics, including oral antibiotics, are effective in killing these organisms and even in eradicating colonization. The role of respiratory viruses in bacterial colonization or lung damage is not completely known. There seems to be an aflinity of P. aerugimsa for the lung with CF. The unique ability of P. a+?rz@wsa to colonize the lung with CF and to persist despite aggressive antimicrobial therapy is a significant factor in lung disease (Govan, Doherty, & Glass, 1987). The resulting chronic infection with its infkmmatory by-products leads to progressive lung damage (Ramphal & Vishwanath, 1987). Colonization with P. aerz&wsa is a harbinger of pulmonary decline, and the resulting pulmonary disease is the ultimate cause of death in 95% of patients with CF who live beyond 1 year of age.
C
olonization with P. aeruginosa is a harbinger of pulmonary decline, and the resulting pulmonary disease is the ultimate cause of death in 95% of patients with CF who live beyond 1 year of age.
Over the last thirty years, the incidence of infections caused by P. aertlginosa has increased while the incidence of infections caused by S. aurew, the main pathogen for many years, have decreased (Waite, 1988). In part, this may be the result of effective antistaphylococcal therapy that has become available (Michel, 1988). In contrast, the pathogen P. [email protected] will persist in the lung with CF once the lung has undergone colonization (Kulczycki, Wientzen, Heller, & Bellanti, 1988). P. cepaciais the most recent pathogen that has been isolated in the lungs of patients with CF. This organism is resistant to most antibiotics and is usually associated with rapid pulmonary deterioration (Waite, 1988). n
ANTIMICROBIAL
THERAPY
Because the lower respiratory tract in many patients with CF is chronically colonized with bacteria, the criteria for antibiotic therapy must be based on changes in the patient’s baseline respiratory status. Important changes include fever, increased cough with sputum production, decreased exercise tolerance, decreased appetite and weight, and deterioration on the lung examination, chest x-ray, or pulmonary function tests (Levy, 1988). Thus, evaluating the condition of the patient with CF for signs and
25
T
he goal of antimicrobial therapy is to eradicate or decrease the number of bacteria, enabling the patient with CF to return to baseline clinical status.
symptoms of infection and isolating the pathogenic organisms is essential when determining the timing and choice of antimicrobial therapy. The goal of antimicrobial therapy is to eradicate or decrease the number of bacteria, enabling the patient with CF to return to baseline clinical status (Geddes, 1988). Other modalities such as nutritional supplementation, chest physiotherapy, and bronchial dilation are important, but the relative contribution of each is unknown. Improvement is assessed by changes in appetite, fever, cough, sputum production, respiratory rate, pulmonary examination findings, oxygen saturation, chest x-ray, and pulmonary function tests. Clinical improvement often is not seen for several days. Generally, those patients with CF who exhibit significant symptoms of pulmonary exacerbation require acute IV antibiotic therapy. Patients not colonized with Pseudomonas species may complete their antibiotic course orally if their clinical condition and sensitivity of the causative organism permit. For patients colonized with Pseudomonas species, combination therapy with an aminoglycoside, broadspectrum penicillin, or cephalosporin is given intravenously for 14 to 21 days (Kuzemko, 1988). The antibiotic choice depends on the sensitivity pattern exhibited by the infecting organism(s) to a panel of antibiotics. These agents must be given intravenously because they are not absorbed by the intestines (Horrevorts, Driessen, Michel, & Kerrebijin, 1988). P. aerz+$mJa routinely is resistant to older antimicrobial drugs such as ampicillin, penicillin, firstand second-generation cephalosporins, tetracycline, chloramphenicol, and cotrimoxizole (van Klingeren, 1988). P. amghwsa has shown degrees of susceptibility to some of the newer drugs introduced since 1967, including carbenicillin, ticarcillin, piperacillin, gentamycin, tobramycin, and ciprofloxacin (Prandota, 1988). Some of the new third-generation cephalosporins, such as ceftazidime, also have been clinically effective in treating Pseudomonas species infections (Perea, Clavijo, Nogales, & Luque, 1988). Studies have shown that a high percentage of patients whose lungs are colonized with Pseudomonas species have pulmonary function improvement when appropriate antibiotic therapy is initiated (Michel, 1988). Many antibiotic drugs have altered pharmacoki-
26
n
Hammond,
TABLE
Caldwell,
1 Antibiotics
Volume 5, Number 1 January-February 1991
& Campbell
used for exacerbations
of CF
essary treatment modality for patients with CF who are colonized with P. am++wsa. n
Compiled
from
Kuzemko
(1988);
Waite
(1988).
netics in patients with CF, necessitating higher than normal doses to achieve therapeutic effects against the organisms (Prandota, 1988). Recommended dosages will vary according to the individual patient. Commonly used intravenous antibiotic drugs administered for CF pulmonary infections are listed according to drug category in Table 1. This table provides the practitioner with a list of antimicrobial drugs that have been found to be safe and effective for home IV treatment of patients with CF. Plasma concentrations of aminoglycosides should be monitored closely because these drugs have a narrow therapeutic index. Monitoring for nephrotoxicity is essential because both the aminoglycosides and penicillins are excreted by the kidney (Prandota, 1988). Ciprofloxacin, a newer fluoroquinolone drug, is the first oral antibiotic with activity against P. ueru~ino~a lung infections. Its use is limited by concerns over cartilage damage in younger patients, and currently the drug is FDA approved for older patients only. The emergence of resistant strains with repeated dosages also may limit use of ciprofloxacin (Stutman, 1987). Therefore, despite this important development, IV antibiotic therapy remains a nec-
C iprofloxacin,
a newer fluoroquinoione drug, is the first oral antibiotic with activity against P. aeruginosd lung infections.
METHOD OF ADMINISTRATION
Various methods of administration of IV antibiotics have been attempted in patients with CF. Venous access may be problematic because of the numerous courses of antibiotics received. Multiple venipunctures are common when using a peripheral heparinlock system and also are painful and time consuming. Patients and practitioners have classified the heparinlock as the least desirable venous access system for home use (Stead, Davidson, Duncan, Hodson, & Batten, 1987). The percutaneous devices, (e.g., Hickman and Broviac catheters, Evermed, Inc., Kirkland, WA) have been used in some patients with CF. Problems with these catheters include daily dressing changes and increased risk of infections at the site (Stanislav et al., 1987). Two systems that are being used more frequently for patients with CF, both at home and in the hospital, are the percutaneous Silastic catheter (PSC) (Per-Q-Cath, Gesco International Corp., San Antonio, TX) and the totally implantable system (Port-A-Cath, Pharmacia, Inc., St. Paul, MN). (See accompanying article.) These catheters were reported to be less irritating to the veins and were effective for long-term hospital and home use (Cassey, Ford, O’Brien, & Martin, 1988; Dietrich & Lobas, 1988). The Per-Q-Cath has been examined in several studies with patients who have CF (Dietrich & Lobas, 1988; Williams, Smith, Woods, & Weller, 1988). Patients had less pain when antimicrobial treatment was administered using Per-Q-Caths than when treatment was given peripherally, thus decreasing anxiety and increasing patient comfort level (Dietrich & Lobas, 1988). The advantages of the Per-QCath are that it can be easily and safely placed in patients of almost any size by a trained health care provider. Dietrich and Lobas (1988) found that in 80% of the cases they studied, Per-Q-Cath was used as the single IV access for the entire hospital stay of the patient with CF. The Per-Q-Cath can be heparinlocked so that the patient is free to move about at home or in the hospital, and arm activity is not restricted when using this system. The mean life of the Per-Q-Cath was found to be 12.4 days (range 3 to 30 days)(Williams et al., 1988). Disadvantages of the Per-Q-Cath include a dressing change, daily heparin flushes, and possible complications. Two articles reviewed the use of the PerQ-Cath in patients with CF and found complications of sepsis (O%), thrombophlebitis (13%), occlusion
Journal of Pediatric Health Care
of the line (18%), and fluid leaking to the tissues (3%) (Dietrich & Lobas, 1988; Williams et al., 1988). Despite these infrequent problems, the PerQ-Cath has proved to be a reliable system. The Port-A-Cath is a more recently introduced venous access route for patients with CF (Cassey, et al., 1988). The Port-A-Cath is versatile and can be used for IV antibiotic and fluid administration for chemotherapy, delivery of blood products, and for blood sampling. Children receiving chemotherapy have used the Port-A-&h since 1982, and it has proved to be a dependable system with few complications (Lambert, Chadwick, McMahon, & Scarffe, 1988). The Port-A-Cath is the most feasible system for long-term antimicrobial therapy for patients with CF.
Cystic Fibrosis
m TABLE 2 General home IV therapy .‘I II
guidelines
27
for choosing
m
m l
l
m ,,, Compiled
from David
;.~,':: ,.
. (1989);
Gilbert,
Robinson,
_ ., 1,,:
& Littlewood
(1988).
T
he Port-A-Cath is the most feasible system for long-term antimicrobial therapy for patients with CF.
The major advantage of the Port-A-Cath is that the entire system is internal and there is no risk for infection until the system is accessed from the outside, thus providing a route of transmission from skin to port (Lambert et al., 1988). The feature is unique to the Port-A-Cath. Access to the Port-A-Cath can be obtained using a 20 or 22 gauge huber needle for approximately 2000 punctures. The system only requires maintenance of heparin saline flushes every 4 to 6 weeks. Weekly dressing changes are necessary only when the system is accessed for IV administration. Patients are able to swim and bathe without worries of a dressing. There is minimal interference with chest physiotherapy and there are no restrictions on patient activities when the system is not in use (Stead et al., 1987). Disadvantages of the Port-A-Cath include pain with the needle stick to access the system, but most patients develop a tolerance to this temporary discomfort. The initial cost of implantation of the PortA-Cath is high, but the relative maintenance cost is low (Cassey et al., 1988). Complications that have been reported with the Port-A-Cath include catheter occlusion (4%), infection (3%), and catheter tip migration (2%) (Lambert et al., 1988). Patients also complain of a “salty or bad” taste in their mouth as the catheter is flushed with saline. This can be alleviated by sucking on hard candy or chewing gum. Overall, the advantages of the Port-A-Cath systemthat it is easy to care for, is generally inconspicuous, and has a low rate of infection-seem to outweigh
the disadvantages. These advantages suggest that the quality of life for patients with CF can be improved through home IV antibiotic therapy using either the Port-A-Cath or Per-Q-Cath. n
HOME THERAPY
Families and patients must adjust to a new lifestyle and adapt to the life-long home therapy needs of a child with CF. In time some families become very skilled at performing chest physiotherapy and aerosol treatments. Also, because many of these patients now live into their 20s and 3Os, they often become experts in caring for themselves (Levison, Garner, MacMillian, & Cowen, 1987). It is very feasible for both parents and patients to be taught how to administer home intravenous antibiotics. However, the patients’ response to the antibiotics and possible side effects must be assessed first in the hospital before the patient is discharged home. The advantages of treating patients with CF using a home IV antibiotic program include: decreasing the number of days the patient spends in the hospital, returning the patient to the home environment more quickly, increasing the number of available hospital days for insurance, and decreasing the cost of treatment (Kane, Jennison, Wood, Black, & Herbst, 1988). Several studies have focused on the significant cost savings to families of patients with CF when IV antibiotics are administered at home (Bosso, Huckendubler-Stephenson, & Herbst, 1985; Kane et al., 1988). These studies agreed that the home administration of antibiotics should be easy, cost effective, and safe. Kane et al. ( 1988) found in their study that savings
28
n
Hammond,
TABLE
Caldwell,
3 Practitioner’s
Volume 5, Number 1 January-February 1991
& Campbell
checklist
for teaching
/ ^‘,,; ti~ms
home IV therapy
I.
-step care for venous access system and a&&tic
up to $286 to $445 per day could be realized if combination antibiotic therapy was initiated at home, depending on the home care agency. Blue Cross/Blue Shield and other commercial providers will pay between 80% to 100% of the cost of home IV antimicrobial therapy, which leaves a possible copayment from families, depending on their insurance (Kane et al., 1988). Practitioners must be aware of the potential costs to the families and of methods to conserve and control health care resources. The effectiveness of long-term home IV antibiotic therapy has been demonstrated with other chronic diseases, and patient acceptance, safety, cost effec-
tiveness, and therapeutic efficiency were seen (Stiver et al., 1978). Because of this, the number of home antibiotic programs is growing as this alternative treatment becomes more popular (Boss0 et al., 1985). Although certain antimicrobials may be administered as an IV push, most patients with CF will be instructed on the use of an infusion pump by the home care agency. Several infusion pumps, including the Provider 5000 (Pancretec Inc., San Diego, CA) and the Intermate (Caremark, Inc., Lincolnshire, IL) can deliver continuous or intermittent IV fluids and antibiotics over a 24-hour period. Other necessary
Journal of Pediatric Health
home care supplies include syringes and connectable tubing for the pump, tape, alcohol and betadine swabs, gauze dressings, needles, and heparin. Thus, the costs, the ability to provide medical care at home, and the availability of a home IV program all are essential factors to examine when considering transferring a patient with CF to home IV antibiotics.
For home
IV therapy to be successful, patients with CF and their parents must learn to adniinister the antibiotic accurately and how to recognize and manage complications.
n
Cystic
Care
ROLE OF THE NURSE PRACTITIONER
For home IV therapy to be successful, patients with CF and their parents must learn to adminster the antibiotic accurately and how to recognize and manage complications. The patient with CF and the patient’s family may be overwhelmed when the task of administering IV antimicrobials is added to their home routine because it requires skills, knowledge, and time. This task may not be realistic for every family, and the practitioner must be aware of this possibility. However, teaching families to administer home IV antibiotics may decrease the disruption of family routines overall and may allow the patient with CF to return to school or employment earlier. The nurse practitioner is able to coordinate the teaching efforts of the CF team members as they instruct the patient and family about home IV antibiotic therapy. The combined efforts of the physician, nurse practitioner, pharmacist, social worker, patient, family, and home care agency are necessary for an easy and feasible transfer of care from the hospital setting to the home environment. Once the patient with CF is classified by the physician as an appropriate candidate for home IV therapy (Table 2), teaching by the CF team begins. Determining both the appropriate time during the hospital stay for teaching and the willingness of the patient and family to learn is essential. The practitioner’s checklist found in Table 3 identifies the teaching instructions for home IV antibiotic therapy that must be completed while the patient is in the hospital. Following instruction in the hospital, the nurse should observe the patient and family performing their new skills using the proper procedure. The nurse practitioner’s role is to instruct the patient and family about care and maintenance of the venous accesssystem, the mechanics of administering the IV antibiotic, and troubleshooting complications. As-
Fibrosis
29
sisting the family and patient with CF in writing down their daily home routine and scheduled IV antibiotics will provide guidance and may identify potential problems that can be discussed. Potential complications that may occur at home when administering the IV antibiotics or with the venous access system should be addressed by the nurse practitioner. Any signs of clotting, IV infiltration, or infection at the venous access site must be reported to the nurse practitioner immediately. Prevention of these problems is addressed by the nurse practitioner when demonstrating proper dressing changes and heparin flushes for each system. The nurse practitioner also instructs the family to observe for changes in their child’s symptoms, such as increased cough, fever, or sputum, while receiving home IV antimicrobials. In this case, the physician may need to reassessthe child’s physical status or the IV therapy. The social worker is responsible for contacting the home care agency. The agency orders the medical equipment and supplies and provides home nursing visits, which are covered by the family’s insurance or by other financial sources. The home care agency usually provides the infusion pump and the prescribed IV antibiotic(s) to be administered. Having the home equipment and supplies in the hospital when teaching the patient and family will provide continuity of skill to the home setting. The home care agency arranges nursing visits to assemble the home IV equipment and IV antimicrobial drugs and to provide support and further teaching for both the patient with CF and the family when the patient is discharged home.
A team
effort will enhance the family’s understanding and new skills when teaching home IV antibiotic delivery.
A team effort will enhance the family’s understanding and new skills when teaching home IV antibiotic delivery. The primary health care provider decides on the IV antibiotic, schedules routine visits to monitor blood levels, determines frequency of follow-up clinic visits, and provides support to the families. The home care pharmacist provides guidelines for the rate of administration, amount of dilution, and adverse reactions of the antibiotic. Most antibiotics can be administered over 30 to 60 minutes by an infusion pump. The nurse practitioner reviews with the family information concerning the prescribed home IV antibiotic, the proper infusion rate
30
Hammond,
Caldwell,
& Campbell
using an infusion pump, and monitoring for possible side efkcts of the antimicrobial drug. The nurse practitioner plays a vital role when the patient with CF and the family begin home IV antibiotic therapy. A thorough examination is necessary before discharging the patient home. An adequate venous accesssystem should be in place and the family should demonstrate the correct knowledge, willingness, and skills to administer the Iv antibiotic through this system. Arrangements also should be made for home care supplies and nursing visits. Any possible barriers to participation in home IV therapy must be addressed and approached by the nurse practitioner to aid in the success of this therapy. Nurse practitioners have a responsibility to confi+ont these issues and to become acquainted with home IV antibiotic programs for patients with CF so that they are prepared for this future link. The potential contribution of a home IV antibiotic program that enhances the quality of life for patients with CF deserves further research by nurse practitioners in the future. n REFERENCES Basso, J. A., Huckendubler-Stephenson, S. E., & Herbst, J. J. (1985). Feasibility and cost savings of intravenous administration of aminoglycosides in outpatients with cystic fibrosis. Dtxg Intelligent and Clinical Pbamusy, 19, 52-54. Cassey, J., Ford, W. D. A., O’Brien, L., & Martin, A. J. (1988). Totally implantable system for venous accessin children with cystic fibrosis. Clinical Ped&riq 27, 91-94. David T. J. (1989). Intravenous antibiotics at home in children with cystic fibrosis. Jorrmal of the Rcyzl SocietyofMedkine, 82, 130-131. Dietrich, K. A., & Lobas, J. G. (1988). Use of a single Silastic intravenous catheter for cystic fiborsis pulmonary exacerbation. Pediati Puhwrwlo~, 4, 181-184. Donati, M. H., Guenette, G., &Auerbach, H. (1987). Prospective controlled study of home and hospital therapy of cystic fibrosis pulmonary disease. The Journ& of Pedktria, 111, 28-33. Geddes, D. M. (1988). Antimicrobial therapy against Stql$coccusaurem, PseuAmnonar aem@wsa and Pserrdmnonm czpachz. chest, 94, (2), 14Os-143s. Gilbert, J., Robinson, T., & Littlewood, J. M. (1988). Home intravenous antibiotic treatment in cystic fibrosis. Archives of Disease in CbW, 63, 5 12-517. Govan, J. R. W., Doherty, C., & Glass, S. (G87). Rational parameters for antibiotic therapy in patients with cystic fibrosis. Injktims, 4, 300-306. Hoiby, N. (1988). Hamwpbihu inpucnZue, Stlripl?vloMEnrraurew, Pseudomonas cepac& and Pseudummas aeru&xa in patients with cystic fibrosis. Chest, 94, 97s-101s.
Volume 5, Number 1 January-February 1991
Horrevom, A. M., Driessen, 0. M. J., Michel, M. F., & Kerrebijin, K. F. (1988). l?harma&k&cs of antimicrobial drugs in cystic fibrosis: AminogIycoside antibiotics. Cb&, 94, (2),102s-125s. Kane, R. E., J cnnison, K., Wood, C., Black, P. G., & He&t, J. J. (1988). Cost savings and economic considerations using home intravenous antibiotic therapy for cystic fibrosis patients. Pedbmk Ptdmom&y, 4, 84-89. Kulczycki, L. L., Wientzen, R. L., Heller, T., & Gellanti, J. A. (1988). Factors influencing pseudomonas colonization in cystic fibrosis. Amud of’Al&gy, 60,423-428. Kuzemko, J. A. (1988). Home treatment of pulmonary infections in cystic fibrosis. Chest, 94,162~165s. Lambert, M. A, Chadwick, G. A., McMahon, A., & Scar& J. H. (1988). Experience with the Port-a-Cath. Hcnu&gy Oneokyy, 6, 57-63. Levison, H., Garner, D., Ma&ii&an, H., & Cowen, L. (1987). Living with cystic fibrosis: Patient, My and physician realities. comprchnrril Tbm, 13,(10), 38-45. Levy, J. (1988). Antibiotic therapy in cystic fibrosis. Cb&, 94, 15os-153s. Michel, B. C. (1988). Antibacterial therapy in cystic fibrosis. Chest, 94, 129s-139s. Peres, E. J., Clavijo, E., Nogales, M. C., & Luque, I. G. (1988). Interaction of aminoglycosides and cephalosporins against Pwdommus aem&wsa comelation between interaction index and killing curve. Journal ofAntiab&d Cbemotberq, 22, 175-183. Prandota, J. (1988). Clinical pharmacology of antibiotics and other drugs in cystic fibrosis. m, 35, 542-578. Ramphal, R., & Vishwanath, S. (1987). Why is pseudomonas the colonizer and why does it persist? In/icrimr, 15, 281-286. Rucker, R. W., & Harrison, G. M. (1974). Outpatient intravenous medications in the management of cystic fibiosis. Pea%atria, 54, 358-360. Stanislav, G. V., Fitzgibbons, R. J., Bailey, R. T., Mail&d, J. A., Johnson, P. S., & Feole, J. B. (1987). Reliability of implantable central venous accessdevices in patients with cancer. Archives of Surgny, 122, 1280-1283. Stead, R. J., Davidson, T. I., Duncan, F. R., Hodson, M. E., & Batten, J. C. (1987). Use of a totally implantable system for venous accessin cystic fibrosis. Tbm, 42, 149-150. Stiver, H. G., Telford, G. O., Massey, J. M., Cote, D. D., van Middlesworth, E. J., Trosky, S. K., McKay, N. L., &Mossey, W. L. (1978). Intravenous antibiotic therapy at home. Ann& of Internal Medicine, 89, 690-693. Stutman, H. R. (1987). Summary of a workshop on Ciprofloxacin’ use in patients with cystic fibrosis. Pediatric Infieasc Journal, 6, 932-935. van Klingerin, B. (1988). Antibiotic resistance in Pmabmm~ arrUgnasa, Hem@ih injuenzae and Stllphylococn*r aurcus. chest, 94, 103s-106s. Waite, W. W. (1988). Pharmacologic management of cystic fibrosis. The Jownal of Pr& Nursing, 38,(3), 19-27. Williams, J., Smith, H. L., Woods, C. G., &Weller, P. H. (1988). Silastic catheters for antibiotics in cystic fibrosis. AY&+ of Dkeam in Childboo~ 63, 658-659.
