RESEARCH/PRACTICE REPORTS
AEROSOLIZED PENTAMIDINE AND PNEUMOCYSTIS CARINII PNEUMONIA: PATIENT COMPLIANCE AND OUTCOMES Darrel C. Bjornson, Charles N. Oster, Linda M. Cortese, and Bruce A. Nelson
The study objectives were to compare compliance betweenevery-two-week and every-four-week aerosolized pentamidine regimens, and to determine if patientswho were more compliantwith the use of aerosolizedpentamidine were at decreased risk for developing Pneumocystis carinii pneumonia(PCP). DESIGN: Nonrandornized observational study of patientsreceiving aerosolized pentamidine for PCP prophylaxis using the hospital pharmacycomputersystem to documentaerosolized pentamidine use and compliance, and the PatientAdministration Division's computerto documentcases of PCP. SETIlNG: Tertiarycare, US Army medicalcenter. PATIENTS: All patientswho were prescribedaerosolized pentamidine (60 mg every two weeks,300 mg every four weeks,or both) over a 3.5-yearperiod. MAIN OUTCOME MEASURES: Mean percentcompliancewas determinedand comparedbetweenevery-two-week and every-fourweek regimens. The relationship betweencomplianceand cases of PCP was determined using nonparametric statistics. RESULTS: Patients(n=I46) who were prescribedaerosolized pentamidine 60 mg every two weeks were more compliant (p=O.OO6) than those prescribed 300 mg every four weeks. In addition, those patientswho initially receivedthe 6O-mg regimen and were switchedto the 3QO-mg regimen were more compliant when takingthe 6O-mg dose (p=O.027). There was no association betweencompliance with either regimen and cases of PCp. Compliancegenerallywas poor with both regimens. CONCLUSIONS: Patientson every-two-week regimensof aerosolized pentamidine were more compliantthan those on every-four-week regimens. However,regardless of compliance, some patientsfailed aerosolized pentamidineover the 3.5-yearperiod.Other agents that lend themselves to compliancemay be more appropriate for PCP prophylaxis than aerosolized pentamidine. OBJECfIVE:
Ann Pharmacother 1992;26:1066-70. TIIE ADVANCES TIIAT HAVE BEEN MADE in the understanding
of the etiology of many diseases as well as the develop-
DARREL C. BJORNSON, Ph.D .. at the time of writing. was a Clinical Research Pharmacist. Walter Reed Army Medical Center (WRAMC). Washington. DC; he is now an Associate Professor. College of Pharmacy and Health Sciences. Drake University. Des Moines. IA 5031 I; CHARLES N. OSTER, M.D .• COL. MC. is the Chief. Infectious Disease Service. WRAMC; LINDA M. CORTESE, M.S.•is a Clinical Research Pharmacist. Henry M. Jackson Foundation for the Advancement of Military Medicine. Rockville. MD; and BRUCE A. NELSON, M.S.• COL. MS. is the Chief. Pharmacy Service. WRAMC. Reprints: Darrel C. Bjornson. Ph.D. The views and assertions contained herein are those of the authors and do not purport to represent the position of the Department of Defense or the US Anny.
1066 •
The Annals ofPharmacotherapy •
ment of new therapeutic agents have provided cures, symptomatic control, or prevention of many diseases. However, concurrent with the increasing sophistication in the diagnosis and treatment of disorders has been the recognition that drugs are not being used in a manner that provides optimal benefit and safety. In many cases, failure to achieve desired outcomes has been attributable to patient noncompliance. Noncompliance with drug therapy has been reported to range from 25 to 75 percent' and has been directly associated with poor treatment outcomes in patients with primary hypercholesterolemia,' diabetes,' epilepsy,' infectious diseases," hypertension,' and organ transplants.' There are several factors that influence patient compliance. First, patient compliance is substantially influenced by the perceived threat posed by the disease. Patients who have chronic illnesses with few or no symptoms are more likely to be noncompliant. Patients' acceptance of a sick role and their perception that compliant behavior will reduce the threat posed by the illness increase their motivation to comply with therapy. Secondly, their perception of the drug regimen's complexity, difficulty, duration, safety, and cost influences compliance. Conditions such as multiple drug therapy, frequent medication administration, and long duration of therapy make the treatment regimen substantially more complex and often interfere with the patient's lifestyle and daily routine," Looking at the influence of frequency of administration of a single drug on compliance over a one-month period, one study showed that in a fourtimes-daily regimen, 70 percent of the subjects failed to take 25-50 percent of the prescribed dose. Compliance improved as the dosage interval was lengthened: three times daily, 40 percent compliant; twice daily, 70 percent compliant; and once daily, 93 percent compliant. Therefore, patients are more likely to be compliant as their dosage regimen requires less frequent administration.' Finally, the interaction patients have with their healthcare professionals is a major determinant of their understanding of and attitude toward their illness and therapeutic regimen. Patients who believe they have some control over decisions that are made, who are well informed, and who feel that their caregivers are concerned, tend to be more compliant," Pneumocystis carinii pneumonia (PCP) is the most common life-threatening opportunistic infection in patients with late-stage Hl'V infection, occurring in 80 percent of patients sometime during the course of their disease. to The
1992 September,Volume 26
mortality rate is 20-60 percent depending on the severity of the immune deficiency and the number and severity of previous episodes. Prevention of pcp is important because each episode causes some degree of irreversible lung damage and is associated with a higher mortality rate. A variety of prophylactic regimens have been employed to prevent infection. These include oral systemic regimens such as trimethoprim/sulfamethoxazole (TMP/SMX), dapsone, and sulfadoxine/pyrimethamine, as well as localized prophylaxis using aerosolized pentamidine. Based on previous literature on compliance, patients who are prescribed prophylactic drug therapy for pcp appear likely to be noncompliant. Patients typically are asymptomatic and the treatment regimens for sulfadoxine/pyrimethamine or aerosolized pentamidine require long hiatuses. In addition, aerosolized pentamidine prophylaxis requires that patients make a trip to an infectious disease clinic, which may be inconvenient, to receive treatment. In early 1988, we initiated PCP prophylaxis at our institution for patients who were at risk for developing PCP (CD4 cell count
AEROSOLIZED PENTAMIDINE AND PNEUMOCYSTIS CARINII PNEUMONIA: PATIENT COMPLIANCE AND OUTCOMES Darrel C. Bjornson, Charles N. Oster, Linda M. Cortese, and Bruce A. Nelson
The study objectives were to compare compliance betweenevery-two-week and every-four-week aerosolized pentamidine regimens, and to determine if patientswho were more compliantwith the use of aerosolizedpentamidine were at decreased risk for developing Pneumocystis carinii pneumonia(PCP). DESIGN: Nonrandornized observational study of patientsreceiving aerosolized pentamidine for PCP prophylaxis using the hospital pharmacycomputersystem to documentaerosolized pentamidine use and compliance, and the PatientAdministration Division's computerto documentcases of PCP. SETIlNG: Tertiarycare, US Army medicalcenter. PATIENTS: All patientswho were prescribedaerosolized pentamidine (60 mg every two weeks,300 mg every four weeks,or both) over a 3.5-yearperiod. MAIN OUTCOME MEASURES: Mean percentcompliancewas determinedand comparedbetweenevery-two-week and every-fourweek regimens. The relationship betweencomplianceand cases of PCP was determined using nonparametric statistics. RESULTS: Patients(n=I46) who were prescribedaerosolized pentamidine 60 mg every two weeks were more compliant (p=O.OO6) than those prescribed 300 mg every four weeks. In addition, those patientswho initially receivedthe 6O-mg regimen and were switchedto the 3QO-mg regimen were more compliant when takingthe 6O-mg dose (p=O.027). There was no association betweencompliance with either regimen and cases of PCp. Compliancegenerallywas poor with both regimens. CONCLUSIONS: Patientson every-two-week regimensof aerosolized pentamidine were more compliantthan those on every-four-week regimens. However,regardless of compliance, some patientsfailed aerosolized pentamidineover the 3.5-yearperiod.Other agents that lend themselves to compliancemay be more appropriate for PCP prophylaxis than aerosolized pentamidine. OBJECfIVE:
Ann Pharmacother 1992;26:1066-70. TIIE ADVANCES TIIAT HAVE BEEN MADE in the understanding
of the etiology of many diseases as well as the develop-
DARREL C. BJORNSON, Ph.D .. at the time of writing. was a Clinical Research Pharmacist. Walter Reed Army Medical Center (WRAMC). Washington. DC; he is now an Associate Professor. College of Pharmacy and Health Sciences. Drake University. Des Moines. IA 5031 I; CHARLES N. OSTER, M.D .• COL. MC. is the Chief. Infectious Disease Service. WRAMC; LINDA M. CORTESE, M.S.•is a Clinical Research Pharmacist. Henry M. Jackson Foundation for the Advancement of Military Medicine. Rockville. MD; and BRUCE A. NELSON, M.S.• COL. MS. is the Chief. Pharmacy Service. WRAMC. Reprints: Darrel C. Bjornson. Ph.D. The views and assertions contained herein are those of the authors and do not purport to represent the position of the Department of Defense or the US Anny.
1066 •
The Annals ofPharmacotherapy •
ment of new therapeutic agents have provided cures, symptomatic control, or prevention of many diseases. However, concurrent with the increasing sophistication in the diagnosis and treatment of disorders has been the recognition that drugs are not being used in a manner that provides optimal benefit and safety. In many cases, failure to achieve desired outcomes has been attributable to patient noncompliance. Noncompliance with drug therapy has been reported to range from 25 to 75 percent' and has been directly associated with poor treatment outcomes in patients with primary hypercholesterolemia,' diabetes,' epilepsy,' infectious diseases," hypertension,' and organ transplants.' There are several factors that influence patient compliance. First, patient compliance is substantially influenced by the perceived threat posed by the disease. Patients who have chronic illnesses with few or no symptoms are more likely to be noncompliant. Patients' acceptance of a sick role and their perception that compliant behavior will reduce the threat posed by the illness increase their motivation to comply with therapy. Secondly, their perception of the drug regimen's complexity, difficulty, duration, safety, and cost influences compliance. Conditions such as multiple drug therapy, frequent medication administration, and long duration of therapy make the treatment regimen substantially more complex and often interfere with the patient's lifestyle and daily routine," Looking at the influence of frequency of administration of a single drug on compliance over a one-month period, one study showed that in a fourtimes-daily regimen, 70 percent of the subjects failed to take 25-50 percent of the prescribed dose. Compliance improved as the dosage interval was lengthened: three times daily, 40 percent compliant; twice daily, 70 percent compliant; and once daily, 93 percent compliant. Therefore, patients are more likely to be compliant as their dosage regimen requires less frequent administration.' Finally, the interaction patients have with their healthcare professionals is a major determinant of their understanding of and attitude toward their illness and therapeutic regimen. Patients who believe they have some control over decisions that are made, who are well informed, and who feel that their caregivers are concerned, tend to be more compliant," Pneumocystis carinii pneumonia (PCP) is the most common life-threatening opportunistic infection in patients with late-stage Hl'V infection, occurring in 80 percent of patients sometime during the course of their disease. to The
1992 September,Volume 26
mortality rate is 20-60 percent depending on the severity of the immune deficiency and the number and severity of previous episodes. Prevention of pcp is important because each episode causes some degree of irreversible lung damage and is associated with a higher mortality rate. A variety of prophylactic regimens have been employed to prevent infection. These include oral systemic regimens such as trimethoprim/sulfamethoxazole (TMP/SMX), dapsone, and sulfadoxine/pyrimethamine, as well as localized prophylaxis using aerosolized pentamidine. Based on previous literature on compliance, patients who are prescribed prophylactic drug therapy for pcp appear likely to be noncompliant. Patients typically are asymptomatic and the treatment regimens for sulfadoxine/pyrimethamine or aerosolized pentamidine require long hiatuses. In addition, aerosolized pentamidine prophylaxis requires that patients make a trip to an infectious disease clinic, which may be inconvenient, to receive treatment. In early 1988, we initiated PCP prophylaxis at our institution for patients who were at risk for developing PCP (CD4 cell count
