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Antimicrobial Use in Patients with Advanced Cancer Receiving Hospice Care
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Journal of Pain and Symptom Management
Vol. 25 No. 5 May 2003
Original Article
Antimicrobial Use in Patients with Advanced Cancer Receiving Hospice Care Patrick H. White, BS, Heather L. Kuhlenschmidt, BS, Benjamin G. Vancura, BA, and Rudolph M. Navari, MD, PhD Walther Cancer Research Center, University of Notre Dame, Notre Dame, Indiana, USA
Abstract Patients with advanced cancer receiving hospice and palliative care are highly susceptible to infections. The decision whether to treat an active or suspected infection in end-of-life care may be difficult. In order to develop guidelines for the use of antimicrobials (antibiotics and antifungals) in palliative care, we discussed antimicrobial options with 255 patients with advanced cancer at the time they entered a community-based hospice and palliative care program. We subsequently documented the use and effectiveness of the antimicrobials employed during the palliative care period. Most patients (79.2%) chose either no antimicrobials or symptomatic use only. Choices were influenced by age, the desire for symptom control, lifeprolongation issues, and the condition of the patient. After admission, 117 patients had a total of 129 infections, with the most common sites being urinary tract, respiratory tract, mouth/pharynx, and skin/subcutaneous tissues. The use of antimicrobials controlled symptoms in the majority of the urinary tract infections, but were less effective in controlling symptoms in the other sites of infection. Survival was not affected by the patients’ choice of whether to use antimicrobials, the prevalence of infections, or the actual use of antimicrobials. Symptom control may be the major indication for antimicrobial use for patients receiving hospice and palliative care. J Pain Symptom Manage 2003;25:438–443. © 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. Key Words Antimicrobials, advanced cancer, hospice, symptom control
Introduction There have been few reports on the use of antimicrobials in patients with advanced cancer who are receiving hospice or palliative care.1,2 Vitetta et al.1 performed a retrospective chart review on the prevalence of infections in
Address reprint requests to: Rudolph M. Navari, MD, PhD, Walther Cancer Research Center, 250 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA. Accepted for publication: July 22, 2002. © 2003 U.S. Cancer Pain Relief Committee Published by Elsevier. All rights reserved.
102 patients (92% terminal malignant illness) who died after admission to a tertiary care inpatient palliative care unit. Thirty-seven patients were diagnosed with 42 infections, with urinary tract, respiratory tract, blood, skin and subcutaneous tissues, and eyes as the most common sites of infection. E. Coli was the most common organism. Thirty-five of 37 patients were treated with antibiotics, with a symptom response in half of the patients treated; 2 of 37 patients were not treated with antibiotics due to survival limited to the day of admission. 0885-3924/03/$–see front matter doi:10.1016/S0885-3924(03)00040-X
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Antimicrobial Use in Hospice Patients with Advanced Cancer
Pereira et al.2 reported a retrospective chart review of the prevalence of infections in 100 consecutive admissions to a tertiary care palliative care unit. There were 74 infections in 55 patients, with urinary tract, respiratory tract, skin and subcutaneous tissue, blood, and mouth as the most common infection sites. E coli, S. aureus, and Enterococcus were the most common organisms. Twenty-one of the 74 infections were not treated. The reasons for not using antimicrobials were documented in 10 patients: very poor general condition in 5, not able to take oral antimicrobials and refusal of parenteral antimicrobials in 3, and family refusal in 2. The retrospective nature of the study did not allow for an adequate analysis of the symptom response to antibiotic therapy. The decision whether to treat an infection with antimicrobials in a patient with advanced cancer receiving palliative care may be difficult. Life-prolonging antimicrobials may or may not be appropriate in a palliative care setting. It is difficult in many situations to predict whether the use of antimicrobials will provide symptom relief, affect survival, or prolong the dying process. Although antimicrobials may be the most appropriate means of symptom control in the presence of certain infections, they may also be associated with symptom-producing interventions, such as laboratory testing, venous access, and direct antimicrobial toxicities. The patient’s overall condition and prognosis, the wishes of the patient and family, and the potential for symptom control all are important aspects of the decision to prescribe antimicrobials. The patient’s status in the palliative care setting and the goals of care may be the most important determinants of the use of antimicrobials. In order to develop guidelines for the use of antimicrobials in palliative care, we discussed antimicrobial options with patients having advanced cancer at the time they elected endof-life palliative care and subsequently documented the use and effects of antimicrobials in this patient population.
Methods Setting and Participants Patients were surveyed during a six-month period in 2001. Admissions to a communitybased outpatient hospice and palliative care
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program included 309 consecutive patients with advanced cancer, whose projected prognosis was less than six months. Patients were asked about their preference about future antimicrobial use. A discussion was performed with the admitting hospice nurse using a uniform script, which included the potential advantages and disadvantages of the use of antimicrobials in a palliative care setting. The antimicrobial use discussion complemented the standard discussion of the goals of the hospice and palliative care program, including the use of resuscitative measures. Fifty-four patients were excluded because they were taking antimicrobials at the time of admission, did not have decision-making capacity, or declined to participate in the discussion. Participating patients gave informed consent as approved by the University Committee on the Protection of Human Subjects, University of Notre Dame. The hospice and palliative care program was the predominant palliative care provider in a five-county area, which included a city of approximately 300,000. All patients had a caregiver and received their care at their place of residence. Hospice nurses visited the patients on a routine schedule and were available at any time for additional visits.
Procedures and Outcomes Patients were asked to elect one of three options: (1) Option A: full antimicrobial use for suspected or established infections as would be done in acute medical or surgical care, (2) Option B: antimicrobial use for symptomatic treatment only, or (3) Option C: no antimicrobial use. For the purpose of the study, antimicrobials were defined as antibiotics or antifungal agents. Antimicrobial use for symptomatic treatment only was defined as the institution of an antimicrobial to treat patients’ symptoms attributed to an active or suspected infection. If a patient was undecided about the use of antimicrobials at the time of the initial discussion, option A was employed in his/her care. Patients were invited to offer a rationale for their choice and were informed that they could alter their choice at any time. Patients in each group were subsequently followed for the duration of their participation in the hospice and palliative care program. When an infection was suspected clinically, symptoms (fever, dyspnea, dysuria, pain) were
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recorded, clinically indicated cultures were obtained, and antimicrobials were considered by the attending physician according to the option chosen by the patient. For the purpose of the study, an “infection” was defined as the presence of symptoms and physical signs that were interpreted by the attending physician to have been caused by a microbial agent and was documented as such in the patient’s chart. The antimicrobial used, the route and duration of use, and the presence of risk factors for infection, such as urinary catheters, central venous catheters, and/or the use of corticosteroids, were recorded. Patients were subsequently monitored to determine the prevalence of infections, the actual use of antimicrobials, the effects of antimicrobials on infection related symptoms, and the overall and infection related survival. Colonization was considered if there was an absence of inflammatory cells in the cultured specimen.
Statistics The Mann-Whitney and the Wilcoxon nonparametric tests were used to compare groups with and without an outcome of interest for ordinal and continuous data that were not normally distributed.
Vol. 25 No. 5 May 2003
Table 1 Patient Characteristics Number of Patients Age Range Mean Male: 50%; Female: 50% Spousal Status Married Divorced Single Widowed Caregiver Spouse Child Parent Other Diagnosis Colon Breast Lung Prostate Ovarian Lymphoma Leukemia Bladder Brain Treatment Chemotherapy Radiation Surgery Hormonal Experimental Payers Medicare Private Medicaid HMO Uninsured
255 47–89 years 63.1 years 69.4% 12.1% 9.0% 9.5% 58.1% 23.9% 6.3% 11.7% 21.9% 23.3% 25.9% 5.9% 4.5% 4.1% 5.7% 2.5% 1.6% 85.1% 71.9% 72.1% 21.0% 5.9% 49.6% 35.7% 17.5% 33.5% 2.9%
Results Patient Characteristics Table 1 lists the characteristics of the study patients at the time of admission to the hospice program. The majority of the patients had colon, breast, lung, or prostate cancer; had received extensive treatment in the form of chemotherapy, radiation, surgery, and/or hormonal therapy; and had various forms of health care insurance. Table 2 illustrates that over 80% of the patients had a Karnofsky performance of 60%, and many were receiving medication for pain, depression, and anxiety.
Patient Choices and Antimicrobial Use Table 3 shows the choices of the patients with regard to antimicrobial use and the actual use during their participation in the hospice program. Most of the patients (79.2%) chose either no antimicrobials or symptomatic use only. The actual antimicrobial use was significantly higher (P 0.01) in option A compared to Option B or Option C. Patients who chose
Option B or C were significantly older (P 0.01), and had significantly lower Karnofsky scores (P 0.01), compared to patients who chose Option A. The three groups did not differ according to gender, spousal status, caregivers, diagnosis, previous treatment, payers, or medication for pain, depression, or anxiety. The rationale offered by patients for their choices were as follows: For Option A, 43 of 53 patients (81%) requested measures for prolongation of life as well as symptom control. For Option B, 107 of 123 patients (87%) requested symptom control only. For Option C, 50 of 79 patients (63%) requested no interventions that might prolong life primarily due to their very poor condition, 10 patients (13%) were not able to take medications by mouth and refused parenteral antimicrobials, and 10 patients (13%) requested no further interventions. The remainder of the patients in each group offered no rationale.
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Antimicrobial Use in Hospice Patients with Advanced Cancer
nosed with an infection. Twenty-two patients had one or more positive cultures.
Table 2 Patients Status Karnofsky Performance Scale
Percent
Infection Sites and Treatment Response
100% Normal; no complaints, no evidence of disease 90%: Able to carry on normal activity; minor symptoms 80%: Normal activity with effort; some symptoms 70%: Cares for self; unable to do active work 60%: Requires occasional assistance; can care for most needs 50%: Requires considerable assistance and frequent medical care 40%: Disabled; requires special care and assistance 30%: Severely disabled, hospitalization is indicated 20%: Hospitalization necessary; active supportive treatment Medications Pain Antidepressants Anti-anxiety
0 0 5 13 30 39 10 3 0 77.6 37.6 41.8
Thirty of the 53 patients who chose Option A received antimicrobials for diagnosed infections. Twenty of the thirty patients had one or more positive cultures. Forty-five of the 123 patients who chose Option B received antimicrobials for a diagnosed infection. Eleven additional patients who chose option B were judged to have an infection but did not receive antimicrobials due to the absence of symptoms. Thirty-nine patients in this group grew one or more organisms from the cultures taken. Two of the 79 patients who chose Option C received antimicrobials. Both of these patients had severely symptomatic thrush and antimicrobial treatment was strongly recommended despite their initial request for no antimicrobials. Thirty-one of the 79 patients were diag-
One-hundred seventeen of the 255 patients were diagnosed with a total of 129 infections. One-hundred eight patients were diagnosed with one infection, six patients were diagnosed with two separate infections, and three patients were diagnosed with three infections. Table 4 shows the sites of infection, the antimicrobials used, and the symptom response. The majority of the patients treated for urinary tract infections had improvement in their initial symptoms, but fewer than half the patients’ symptoms responded to antimicrobial used for infections of the respiratory tract, mouth/ pharynx, skin/subcutaneous tissues, or blood. Eighty-one patients had a total of 99 culturepositive infections, with 127 difference organisms involved (Table 5). The most frequent urinary tract organisms were E. coli, Enterococcus, and Klebsiella pneumoniae, with the majority being sensitive to trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, and amoxacillin. The most common respiratory tract pathogens were Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and these were most commonly sensitive to levofTable 4 Infection Sites, Antimicrobials Prescribed, and Symptom Response
Infection Site (na)
Antimicrobialb (nc)
Symptom Response (%)
Urinary Tract (54)
TMP/SMX (13) Ciprofloxacin (9) Amoxacillin (5) Norfloxacin (3) Levofloxacin (13) TMP/SMX (6) Azithromycin (3) Gatifloxacin (2) Clarithromycin (2) Fluconazole (6) Nystatin (3) Cephalexin (6) TMP/SMX (3) Cetriazone (2) Levofloxacin (1)
92 89 60 67 46 50 33 0 0 50 33 50 33 0 0
Respiratory Tract (45)
Table 3 Patient Choices and Antimicrobial Use Patient Choices and Antimicrobial Use Full Use (A) Symptomatic Use (B) No Antimicrobials (C) Actual Antimicrobial Use Option A Option B Option C
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n (%) 53 (20.8) 123 (48.2) 79 (31.0) n (%) 30 (56.6) 45 (36.6) 2 (2.5)
Mouth/Pharynx (13) Skin/Subcutaneous (12) Blood/Bacteremia (5) a Number
of infections. were given by mouth except for parenteral administration in the bacteremias. c Number of patients treated with this agent. TMP/SMX trimethoprim-sulfamethoxazole. bAntimicrobials
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Table 5 Overall Frequency of Organisms Organism Escherichia coli Staphylococcus aureus Enterococcus species Klebsiella pneumoniae Candida albicans Proteus mirabilis Pseudomonas aeruginosa Coagulase-negative staphylococci Hemophilus influenza Other
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Table 6 Patient Survival n (%) 29 (22.9) 19 (14.9) 14 (11.0) 10 (7.9) 9 (7.0) 8 (6.3) 8 (6.3) 7 (5.5) 5 (3.9) 18 (14.3)
loxacin and TMP/SMX. Oral thrush was clinically suspected in nine of the thirteen mouth/ pharynx infections and was treated with antifungal agents. Staphylococcus aureus was responsible for the skin and subcutaneous infections and was sensitive to cephalexin and TMP/ SMX. Vancomycin-resistant Enterococcus species was isolated from one patient. There were two isolates of methicillin-resistant Staphyloccus aureus in this patient population. Seventeen of the 117 infected patients (14.5%) had bladder catheters prior to, or at the time of infection, compared to 16 of the 138 noninfected patients (11.6%) (PNS). Forty-three of the 117 infected patients (36.7%) were receiving systemic corticosteroids at the time of infection, compared to 44 of the 138 noninfected patients (31.9%) (PNS). All of the nine patients treated for oral thrush were receiving systemic corticosteroids.
Patient Survival There was no significant difference in survival between the patients with a diagnosed infection (n117) and the group without an infection (n138). Patients’ overall survival and infection-related deaths were not significantly affected by the use of antimicrobials or the patients’ choices of antimicrobial use (Table 6). The thirteen infection-related deaths consisted of patients with infections of the respiratory tract (9), blood (3), and subcutaneous tissue (1).
Discussion A large majority of patients with advanced cancer who entered a community outpatient hospice program chose either not to use anitmicrobials or limit their use to symptomatic in-
Antimicrobial Option Option A Option B Option C
Survival (median days)
Infection Related Deaths (n)
26.3 30.1 29.7
3 6 4
fections. Patients’ choices were based primarily on symptom control, the condition of the patient, and whether to employ life-prolonging interventions. The choice of the restricted use of antimicrobials was more common among patients who were older and had lower performance levels. The choices were made after a full disclosure and discussion of the potential advantages and disadvantages of the use of antimicrobials and were independent of the type of malignancy, gender, caregiver or spousal status, previous treatment, health care payer, or medications for pain, depression, or anxiety. Two retrospective chart reviews3,4 reported that incurably ill dying hospitalized patients commonly received systemic antibiotics in their last days or weeks of life, often empirically. In these reviews, antimicrobial use was common in patients with “do not resuscitate” or “comfort measures only” orders. The current study suggests that if these patients were given a choice of antimicrobial use, many may have restricted antimicrobial use. The types of infections, the antimicrobials employed, and the organisms found in this patient population were similar to that seen in two previous studies,1,2 despite the differences in location and setting (outpatient residential versus inpatient institutions). Forty-six percent of the patients experienced at least one infection in this study, which compares to 36.3% and 55% in the two previous studies.1,2 Urinary tract infections, infections of the respiratory tract, and infections of the skin/subcutaneous tissue made up the majority of infections, with E. coli, Staphylococcus aureus, and Enterococcus the main isolated organisms in the present and the past studies. The similarity of the infections may suggest that patients with advanced cancer may have common patterns of infection during their final phase of care. The use of urinary catheters or the use of corticosteroids did not increase the incidence
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Antimicrobial Use in Hospice Patients with Advanced Cancer
of overall infections in this group of patients. There were more oral thrush infections in this study compared to the rate reported in the literature, and these infections certainly could be attributed to the use of corticosteroids. Although the use of antimicrobials improved symptoms in a large majority of patients with urinary tract infections, symptom control was less successful with antimicrobial use in infections of the respiratory tract, mouth/ pharynx, skin/subcutaneous tissue, or blood. Since the majority of the organisms cultured were sensitive to the antimicrobials used, the lack of symptom response in some patients may have been due to co-morbid conditions, such as an immunocompromised state, malnutrition, the failure of host barriers, decreased level of consciousness or immobility, or the presence of a neoplasm in the symptomatic organ. This pattern of symptom response was also seen in the study of Vitetta et al.,1 who reported a similar symptom response of 40-50% in terminally ill hospice patients Symptom response to antimicrobials may vary widely among patients with advanced lifethreatening diseases. Fabiszewski et al.5 reported that treatment of fever with antibiotics did not alter the outcome of fever in institutionalized advanced Alzheimer patients, while some authors have reported improved pain control with the use of antimicrobials in a small number of patients with acute systemic or local infections.6–8 Patient survival in this study was not affected by the presence of infection or the use of antimicrobials. In the study by Vitetta et al.,1 patients with documented infections had a longer median survival. The proposed explanation for the increased survival was that the probability of infection increases with the duration of survival rather than an increased survival due to the use of antimicrobials. The effect of the use of antimicrobials on survival would be very important information to patients entering hospice care. This information might strongly influence their choice of antimicrobial use.
Conclusions The major conclusions of this study are that patients with advanced cancer entering hospice care chose limited use of antimicrobials, mainly for symptomatic care. The choices were affected
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by their age, current condition, and concerns about life-prolonging interventions. The use of antimicrobials controlled symptoms from urinary tract infections, but were less effective in controlling symptoms in infections of the respiratory tract, mouth/pharynx, skin/subcutaneous tissue, or blood. Although a formal quality of life measure was not used in this study, patients were clinically improved when their symptoms responded to the use of antimicrobials. Overall survival and infection related deaths were not altered by the use of antimicrobials. This information should aid patients and clinicians in decisions concerning the use of antimicrobials for infections in patients with advanced cancer receiving hospice care. Additional studies will be needed to generate clinical guidelines for the use of antimicrobials in this patient population.
Acknowledgments This work was supported by the Walther Cancer Institute and The Reich Family Endowment for Excellence on Care of the Whole Patient.
References 1. Vitetta L, Kenner D, Sali A. Bacterial infections in terminally ill hospice patients. J Pain Symptom Manage 2000; 20:326–334. 2. Pereira J, Watanabe S, Wolch G. A retrospective review of the frequency of infections and patterns of antibiotic utilization on a palliative care unit. J Pain Symptom Manage 1998; 16:374–381. 3. Ahronheim JC, Morrison RS, Baskin SA, et al. Treatment of the dying in the acute care hospital. Arch Intern Med. 1996; 156: 2094–2100. 4. Goodlin SJ, Winzeberg GS, Teno JM, et al. Death in the hospital. Arch Intern Med1998; 158: 1570–1572. 5. Fabiszewski KJ, Volicer B, Volicer L. Effect of antibiotic treatment on outcome of fevers in institutionalized Alzheimer patients. JAMA 1990; 263: 3168–3172. 6. Bruera E. Intractable pain in patients with advanced head and neck tumors: a possible role of local infection. Cancer Treat Rep 1986;70:691–692. 7. Green K, Webster H, Watanabe S, Fainsinger R. Case report: management of nosocomial respiratory tract infections in terminally ill cancer patients. J Palliative Care 1994;10:31–34. 8. MacKey J, Birchall I, MacDonald N. Occult infection as a cause of hip pain in a patient with metastatic breast cancer. J Pain Symptom Manage 1995: 10:569–572.
Journal of Pain and Symptom Management
Vol. 25 No. 5 May 2003
Original Article
Antimicrobial Use in Patients with Advanced Cancer Receiving Hospice Care Patrick H. White, BS, Heather L. Kuhlenschmidt, BS, Benjamin G. Vancura, BA, and Rudolph M. Navari, MD, PhD Walther Cancer Research Center, University of Notre Dame, Notre Dame, Indiana, USA
Abstract Patients with advanced cancer receiving hospice and palliative care are highly susceptible to infections. The decision whether to treat an active or suspected infection in end-of-life care may be difficult. In order to develop guidelines for the use of antimicrobials (antibiotics and antifungals) in palliative care, we discussed antimicrobial options with 255 patients with advanced cancer at the time they entered a community-based hospice and palliative care program. We subsequently documented the use and effectiveness of the antimicrobials employed during the palliative care period. Most patients (79.2%) chose either no antimicrobials or symptomatic use only. Choices were influenced by age, the desire for symptom control, lifeprolongation issues, and the condition of the patient. After admission, 117 patients had a total of 129 infections, with the most common sites being urinary tract, respiratory tract, mouth/pharynx, and skin/subcutaneous tissues. The use of antimicrobials controlled symptoms in the majority of the urinary tract infections, but were less effective in controlling symptoms in the other sites of infection. Survival was not affected by the patients’ choice of whether to use antimicrobials, the prevalence of infections, or the actual use of antimicrobials. Symptom control may be the major indication for antimicrobial use for patients receiving hospice and palliative care. J Pain Symptom Manage 2003;25:438–443. © 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. Key Words Antimicrobials, advanced cancer, hospice, symptom control
Introduction There have been few reports on the use of antimicrobials in patients with advanced cancer who are receiving hospice or palliative care.1,2 Vitetta et al.1 performed a retrospective chart review on the prevalence of infections in
Address reprint requests to: Rudolph M. Navari, MD, PhD, Walther Cancer Research Center, 250 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA. Accepted for publication: July 22, 2002. © 2003 U.S. Cancer Pain Relief Committee Published by Elsevier. All rights reserved.
102 patients (92% terminal malignant illness) who died after admission to a tertiary care inpatient palliative care unit. Thirty-seven patients were diagnosed with 42 infections, with urinary tract, respiratory tract, blood, skin and subcutaneous tissues, and eyes as the most common sites of infection. E. Coli was the most common organism. Thirty-five of 37 patients were treated with antibiotics, with a symptom response in half of the patients treated; 2 of 37 patients were not treated with antibiotics due to survival limited to the day of admission. 0885-3924/03/$–see front matter doi:10.1016/S0885-3924(03)00040-X
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Antimicrobial Use in Hospice Patients with Advanced Cancer
Pereira et al.2 reported a retrospective chart review of the prevalence of infections in 100 consecutive admissions to a tertiary care palliative care unit. There were 74 infections in 55 patients, with urinary tract, respiratory tract, skin and subcutaneous tissue, blood, and mouth as the most common infection sites. E coli, S. aureus, and Enterococcus were the most common organisms. Twenty-one of the 74 infections were not treated. The reasons for not using antimicrobials were documented in 10 patients: very poor general condition in 5, not able to take oral antimicrobials and refusal of parenteral antimicrobials in 3, and family refusal in 2. The retrospective nature of the study did not allow for an adequate analysis of the symptom response to antibiotic therapy. The decision whether to treat an infection with antimicrobials in a patient with advanced cancer receiving palliative care may be difficult. Life-prolonging antimicrobials may or may not be appropriate in a palliative care setting. It is difficult in many situations to predict whether the use of antimicrobials will provide symptom relief, affect survival, or prolong the dying process. Although antimicrobials may be the most appropriate means of symptom control in the presence of certain infections, they may also be associated with symptom-producing interventions, such as laboratory testing, venous access, and direct antimicrobial toxicities. The patient’s overall condition and prognosis, the wishes of the patient and family, and the potential for symptom control all are important aspects of the decision to prescribe antimicrobials. The patient’s status in the palliative care setting and the goals of care may be the most important determinants of the use of antimicrobials. In order to develop guidelines for the use of antimicrobials in palliative care, we discussed antimicrobial options with patients having advanced cancer at the time they elected endof-life palliative care and subsequently documented the use and effects of antimicrobials in this patient population.
Methods Setting and Participants Patients were surveyed during a six-month period in 2001. Admissions to a communitybased outpatient hospice and palliative care
439
program included 309 consecutive patients with advanced cancer, whose projected prognosis was less than six months. Patients were asked about their preference about future antimicrobial use. A discussion was performed with the admitting hospice nurse using a uniform script, which included the potential advantages and disadvantages of the use of antimicrobials in a palliative care setting. The antimicrobial use discussion complemented the standard discussion of the goals of the hospice and palliative care program, including the use of resuscitative measures. Fifty-four patients were excluded because they were taking antimicrobials at the time of admission, did not have decision-making capacity, or declined to participate in the discussion. Participating patients gave informed consent as approved by the University Committee on the Protection of Human Subjects, University of Notre Dame. The hospice and palliative care program was the predominant palliative care provider in a five-county area, which included a city of approximately 300,000. All patients had a caregiver and received their care at their place of residence. Hospice nurses visited the patients on a routine schedule and were available at any time for additional visits.
Procedures and Outcomes Patients were asked to elect one of three options: (1) Option A: full antimicrobial use for suspected or established infections as would be done in acute medical or surgical care, (2) Option B: antimicrobial use for symptomatic treatment only, or (3) Option C: no antimicrobial use. For the purpose of the study, antimicrobials were defined as antibiotics or antifungal agents. Antimicrobial use for symptomatic treatment only was defined as the institution of an antimicrobial to treat patients’ symptoms attributed to an active or suspected infection. If a patient was undecided about the use of antimicrobials at the time of the initial discussion, option A was employed in his/her care. Patients were invited to offer a rationale for their choice and were informed that they could alter their choice at any time. Patients in each group were subsequently followed for the duration of their participation in the hospice and palliative care program. When an infection was suspected clinically, symptoms (fever, dyspnea, dysuria, pain) were
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recorded, clinically indicated cultures were obtained, and antimicrobials were considered by the attending physician according to the option chosen by the patient. For the purpose of the study, an “infection” was defined as the presence of symptoms and physical signs that were interpreted by the attending physician to have been caused by a microbial agent and was documented as such in the patient’s chart. The antimicrobial used, the route and duration of use, and the presence of risk factors for infection, such as urinary catheters, central venous catheters, and/or the use of corticosteroids, were recorded. Patients were subsequently monitored to determine the prevalence of infections, the actual use of antimicrobials, the effects of antimicrobials on infection related symptoms, and the overall and infection related survival. Colonization was considered if there was an absence of inflammatory cells in the cultured specimen.
Statistics The Mann-Whitney and the Wilcoxon nonparametric tests were used to compare groups with and without an outcome of interest for ordinal and continuous data that were not normally distributed.
Vol. 25 No. 5 May 2003
Table 1 Patient Characteristics Number of Patients Age Range Mean Male: 50%; Female: 50% Spousal Status Married Divorced Single Widowed Caregiver Spouse Child Parent Other Diagnosis Colon Breast Lung Prostate Ovarian Lymphoma Leukemia Bladder Brain Treatment Chemotherapy Radiation Surgery Hormonal Experimental Payers Medicare Private Medicaid HMO Uninsured
255 47–89 years 63.1 years 69.4% 12.1% 9.0% 9.5% 58.1% 23.9% 6.3% 11.7% 21.9% 23.3% 25.9% 5.9% 4.5% 4.1% 5.7% 2.5% 1.6% 85.1% 71.9% 72.1% 21.0% 5.9% 49.6% 35.7% 17.5% 33.5% 2.9%
Results Patient Characteristics Table 1 lists the characteristics of the study patients at the time of admission to the hospice program. The majority of the patients had colon, breast, lung, or prostate cancer; had received extensive treatment in the form of chemotherapy, radiation, surgery, and/or hormonal therapy; and had various forms of health care insurance. Table 2 illustrates that over 80% of the patients had a Karnofsky performance of 60%, and many were receiving medication for pain, depression, and anxiety.
Patient Choices and Antimicrobial Use Table 3 shows the choices of the patients with regard to antimicrobial use and the actual use during their participation in the hospice program. Most of the patients (79.2%) chose either no antimicrobials or symptomatic use only. The actual antimicrobial use was significantly higher (P 0.01) in option A compared to Option B or Option C. Patients who chose
Option B or C were significantly older (P 0.01), and had significantly lower Karnofsky scores (P 0.01), compared to patients who chose Option A. The three groups did not differ according to gender, spousal status, caregivers, diagnosis, previous treatment, payers, or medication for pain, depression, or anxiety. The rationale offered by patients for their choices were as follows: For Option A, 43 of 53 patients (81%) requested measures for prolongation of life as well as symptom control. For Option B, 107 of 123 patients (87%) requested symptom control only. For Option C, 50 of 79 patients (63%) requested no interventions that might prolong life primarily due to their very poor condition, 10 patients (13%) were not able to take medications by mouth and refused parenteral antimicrobials, and 10 patients (13%) requested no further interventions. The remainder of the patients in each group offered no rationale.
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Antimicrobial Use in Hospice Patients with Advanced Cancer
nosed with an infection. Twenty-two patients had one or more positive cultures.
Table 2 Patients Status Karnofsky Performance Scale
Percent
Infection Sites and Treatment Response
100% Normal; no complaints, no evidence of disease 90%: Able to carry on normal activity; minor symptoms 80%: Normal activity with effort; some symptoms 70%: Cares for self; unable to do active work 60%: Requires occasional assistance; can care for most needs 50%: Requires considerable assistance and frequent medical care 40%: Disabled; requires special care and assistance 30%: Severely disabled, hospitalization is indicated 20%: Hospitalization necessary; active supportive treatment Medications Pain Antidepressants Anti-anxiety
0 0 5 13 30 39 10 3 0 77.6 37.6 41.8
Thirty of the 53 patients who chose Option A received antimicrobials for diagnosed infections. Twenty of the thirty patients had one or more positive cultures. Forty-five of the 123 patients who chose Option B received antimicrobials for a diagnosed infection. Eleven additional patients who chose option B were judged to have an infection but did not receive antimicrobials due to the absence of symptoms. Thirty-nine patients in this group grew one or more organisms from the cultures taken. Two of the 79 patients who chose Option C received antimicrobials. Both of these patients had severely symptomatic thrush and antimicrobial treatment was strongly recommended despite their initial request for no antimicrobials. Thirty-one of the 79 patients were diag-
One-hundred seventeen of the 255 patients were diagnosed with a total of 129 infections. One-hundred eight patients were diagnosed with one infection, six patients were diagnosed with two separate infections, and three patients were diagnosed with three infections. Table 4 shows the sites of infection, the antimicrobials used, and the symptom response. The majority of the patients treated for urinary tract infections had improvement in their initial symptoms, but fewer than half the patients’ symptoms responded to antimicrobial used for infections of the respiratory tract, mouth/ pharynx, skin/subcutaneous tissues, or blood. Eighty-one patients had a total of 99 culturepositive infections, with 127 difference organisms involved (Table 5). The most frequent urinary tract organisms were E. coli, Enterococcus, and Klebsiella pneumoniae, with the majority being sensitive to trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, and amoxacillin. The most common respiratory tract pathogens were Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and these were most commonly sensitive to levofTable 4 Infection Sites, Antimicrobials Prescribed, and Symptom Response
Infection Site (na)
Antimicrobialb (nc)
Symptom Response (%)
Urinary Tract (54)
TMP/SMX (13) Ciprofloxacin (9) Amoxacillin (5) Norfloxacin (3) Levofloxacin (13) TMP/SMX (6) Azithromycin (3) Gatifloxacin (2) Clarithromycin (2) Fluconazole (6) Nystatin (3) Cephalexin (6) TMP/SMX (3) Cetriazone (2) Levofloxacin (1)
92 89 60 67 46 50 33 0 0 50 33 50 33 0 0
Respiratory Tract (45)
Table 3 Patient Choices and Antimicrobial Use Patient Choices and Antimicrobial Use Full Use (A) Symptomatic Use (B) No Antimicrobials (C) Actual Antimicrobial Use Option A Option B Option C
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n (%) 53 (20.8) 123 (48.2) 79 (31.0) n (%) 30 (56.6) 45 (36.6) 2 (2.5)
Mouth/Pharynx (13) Skin/Subcutaneous (12) Blood/Bacteremia (5) a Number
of infections. were given by mouth except for parenteral administration in the bacteremias. c Number of patients treated with this agent. TMP/SMX trimethoprim-sulfamethoxazole. bAntimicrobials
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White et al.
Table 5 Overall Frequency of Organisms Organism Escherichia coli Staphylococcus aureus Enterococcus species Klebsiella pneumoniae Candida albicans Proteus mirabilis Pseudomonas aeruginosa Coagulase-negative staphylococci Hemophilus influenza Other
Vol. 25 No. 5 May 2003
Table 6 Patient Survival n (%) 29 (22.9) 19 (14.9) 14 (11.0) 10 (7.9) 9 (7.0) 8 (6.3) 8 (6.3) 7 (5.5) 5 (3.9) 18 (14.3)
loxacin and TMP/SMX. Oral thrush was clinically suspected in nine of the thirteen mouth/ pharynx infections and was treated with antifungal agents. Staphylococcus aureus was responsible for the skin and subcutaneous infections and was sensitive to cephalexin and TMP/ SMX. Vancomycin-resistant Enterococcus species was isolated from one patient. There were two isolates of methicillin-resistant Staphyloccus aureus in this patient population. Seventeen of the 117 infected patients (14.5%) had bladder catheters prior to, or at the time of infection, compared to 16 of the 138 noninfected patients (11.6%) (PNS). Forty-three of the 117 infected patients (36.7%) were receiving systemic corticosteroids at the time of infection, compared to 44 of the 138 noninfected patients (31.9%) (PNS). All of the nine patients treated for oral thrush were receiving systemic corticosteroids.
Patient Survival There was no significant difference in survival between the patients with a diagnosed infection (n117) and the group without an infection (n138). Patients’ overall survival and infection-related deaths were not significantly affected by the use of antimicrobials or the patients’ choices of antimicrobial use (Table 6). The thirteen infection-related deaths consisted of patients with infections of the respiratory tract (9), blood (3), and subcutaneous tissue (1).
Discussion A large majority of patients with advanced cancer who entered a community outpatient hospice program chose either not to use anitmicrobials or limit their use to symptomatic in-
Antimicrobial Option Option A Option B Option C
Survival (median days)
Infection Related Deaths (n)
26.3 30.1 29.7
3 6 4
fections. Patients’ choices were based primarily on symptom control, the condition of the patient, and whether to employ life-prolonging interventions. The choice of the restricted use of antimicrobials was more common among patients who were older and had lower performance levels. The choices were made after a full disclosure and discussion of the potential advantages and disadvantages of the use of antimicrobials and were independent of the type of malignancy, gender, caregiver or spousal status, previous treatment, health care payer, or medications for pain, depression, or anxiety. Two retrospective chart reviews3,4 reported that incurably ill dying hospitalized patients commonly received systemic antibiotics in their last days or weeks of life, often empirically. In these reviews, antimicrobial use was common in patients with “do not resuscitate” or “comfort measures only” orders. The current study suggests that if these patients were given a choice of antimicrobial use, many may have restricted antimicrobial use. The types of infections, the antimicrobials employed, and the organisms found in this patient population were similar to that seen in two previous studies,1,2 despite the differences in location and setting (outpatient residential versus inpatient institutions). Forty-six percent of the patients experienced at least one infection in this study, which compares to 36.3% and 55% in the two previous studies.1,2 Urinary tract infections, infections of the respiratory tract, and infections of the skin/subcutaneous tissue made up the majority of infections, with E. coli, Staphylococcus aureus, and Enterococcus the main isolated organisms in the present and the past studies. The similarity of the infections may suggest that patients with advanced cancer may have common patterns of infection during their final phase of care. The use of urinary catheters or the use of corticosteroids did not increase the incidence
Vol. 25 No. 5 May 2003
Antimicrobial Use in Hospice Patients with Advanced Cancer
of overall infections in this group of patients. There were more oral thrush infections in this study compared to the rate reported in the literature, and these infections certainly could be attributed to the use of corticosteroids. Although the use of antimicrobials improved symptoms in a large majority of patients with urinary tract infections, symptom control was less successful with antimicrobial use in infections of the respiratory tract, mouth/ pharynx, skin/subcutaneous tissue, or blood. Since the majority of the organisms cultured were sensitive to the antimicrobials used, the lack of symptom response in some patients may have been due to co-morbid conditions, such as an immunocompromised state, malnutrition, the failure of host barriers, decreased level of consciousness or immobility, or the presence of a neoplasm in the symptomatic organ. This pattern of symptom response was also seen in the study of Vitetta et al.,1 who reported a similar symptom response of 40-50% in terminally ill hospice patients Symptom response to antimicrobials may vary widely among patients with advanced lifethreatening diseases. Fabiszewski et al.5 reported that treatment of fever with antibiotics did not alter the outcome of fever in institutionalized advanced Alzheimer patients, while some authors have reported improved pain control with the use of antimicrobials in a small number of patients with acute systemic or local infections.6–8 Patient survival in this study was not affected by the presence of infection or the use of antimicrobials. In the study by Vitetta et al.,1 patients with documented infections had a longer median survival. The proposed explanation for the increased survival was that the probability of infection increases with the duration of survival rather than an increased survival due to the use of antimicrobials. The effect of the use of antimicrobials on survival would be very important information to patients entering hospice care. This information might strongly influence their choice of antimicrobial use.
Conclusions The major conclusions of this study are that patients with advanced cancer entering hospice care chose limited use of antimicrobials, mainly for symptomatic care. The choices were affected
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by their age, current condition, and concerns about life-prolonging interventions. The use of antimicrobials controlled symptoms from urinary tract infections, but were less effective in controlling symptoms in infections of the respiratory tract, mouth/pharynx, skin/subcutaneous tissue, or blood. Although a formal quality of life measure was not used in this study, patients were clinically improved when their symptoms responded to the use of antimicrobials. Overall survival and infection related deaths were not altered by the use of antimicrobials. This information should aid patients and clinicians in decisions concerning the use of antimicrobials for infections in patients with advanced cancer receiving hospice care. Additional studies will be needed to generate clinical guidelines for the use of antimicrobials in this patient population.
Acknowledgments This work was supported by the Walther Cancer Institute and The Reich Family Endowment for Excellence on Care of the Whole Patient.
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