Infections often impact care of hospice patients; however, limited guidance exists for end-of-life infection management. Regardless of patient prognosis, appropriate antibiotic use is necessary for maintaining quality of life. Antibiotics may be associated with serious adverse events, posing safety risks to patients that should be factored into the appropriateness determination. Fluoroquinolone antibiotics are prescribed frequently in hospice. There are 8 fluoroquinolone drug safety warnings regarding risk for serious adverse events communicated by the US Food and Drug Administration (FDA). A retrospective chart review at a national hospice pharmacy services provider identified decedents who used a fluoroquinolone during a 1-month period. Charts were evaluated for the presence of risk factors for serious adverse events, including advanced age (86.0%), orders for multiple QTc prolongation risk medications (51.5%), hypertension (64.1%), and concomitant corticosteroids (22.9%). Findings demonstrate notable risk with the use of at least 1 class of antibiotics in a hospice population.
STAMPS is a hospice decision support tool, developed to guide symptom-driven antibiotic use that incorporates safety assessment and individual goals of care into infection management planning. The tool can also serve as a framework for patient-centered communications about appropriate antibiotic use in hospice between providers, patients, and families.
BACKGROUND
The patient's decision to elect hospice care presents a unique opportunity for health care providers, patients, and caregivers to have an open dialogue on how to weave the hospice philosophy into the individual's plan of care. Among the important topics for discussion is the role of medications in symptom management at end of life. Health care specialists trained in end-of-life (EOL) care, the hospice interdisciplinary team, especially nurses and pharmacists, are well-suited to provide education to patients and caregivers about the therapeutic benefit versus risk of various medication classes, including antibiotics.
As goals shift from curative to quality of life and comfort, the role of antibiotics should be clearly defined and documented in each patient's plan of care. Incorporating discussions related to antibiotic use in EOL care during advance care planning, rather than at the time of suspected infection identification, is preferred.1 The potential for harm may be elevated in patients receiving empiric antibiotic therapy in the absence of routine laboratory monitoring, including renal and hepatic function. Factors such as prognosis, swallowing ability, perfusion to the site of infection, and route of administration should be integrated into care planning in advance of the need for antibiotic therapy and documented within the patient's medical record. With decline in health status, clinicians may prescribe antibiotics with the intent of palliating distressing or painful symptoms rather than for life-prolonging benefit or curative intent. This palliative approach must be clearly differentiated to both patient and caregiver to ensure realistic expectations are established. Literature suggests that upward of 38% of hospice patients receive interventions from which they are unlikely to experience benefit underscoring the importance of patient and caregiver education on the intent of antibiotic use and the extent of benefit or harm anticipated as a result of antibiotic use.2-4
In the setting of very limited prognosis, the importance of discussing deprescribing of nonessential medications with patients and caregivers cannot be overemphasized. In a 2016 retrospective study by Merel and colleagues,5 between 15% and 20% of patients continued to receive antimicrobial agents between 24 and 96 hours after EOL comfort care orders were introduced. Analysis of data from the 2007 National Home and Hospice Care Survey estimated that up to 27% of hospice patients received an antibiotic during the last 7 days of life, most without a documented infectious diagnosis.6 Additionally, nursing home residents receiving EOL care for advanced dementia are commonly prescribed antimicrobials during the last 2 weeks of life.1,7 Cheng and colleagues8 found that acute care interventions persisted for patients with hematologic-based cancers into their last week of life, with more than 90% of patients receiving antibiotics during this time. Global concerns related to the inappropriate overuse of antimicrobials and escalating rates of antibiotic resistance led to enhanced safeguards being implemented by the Centers for Medicare & Medicaid Services.9,10 Inappropriate antibiotic use elevates the potential for harm from adverse events and drug-drug interactions, increases antimicrobial resistance, and contributes to increased burden without benefit. Collectively, results from these studies demonstrate the continued need for clinical research, training, and hospice-based tools that provide guidance on assessing for appropriate use of antibiotics in end of life. Fluoroquinolones are one class of antibiotics that have the potential for an increase in harm due to associated risk of adverse events.
Fluoroquinolone Use and Safety Risks in Hospice Patients
In hospice, infections involving the urinary tract, respiratory tract, and skin are common indications for antibiotic therapy.11,12 For these and other infections, treatment guidelines detail fluoroquinolone antibiotics among agents that may be considered. In select indications, limited guidance also exists for empiric use of fluoroquinolones.13-15 Since their approval by the FDA in the 1980s, fluoroquinolones have been used frequently across inpatient, outpatient, and long-term care treatment settings to combat bacterial infections. In 2011, approximately 23.1 million patients were dispensed a prescription for an oral fluoroquinolone, and approximately 3.8 million patients were billed for an injectable fluoroquinolone product in the hospital setting.16 The prevalence of fluoroquinolone use in hospice is not clearly defined. In a study of advanced dementia patients in a nursing home, 95% of proxies for patients receiving antibiotics stated a primary goal of comfort, whereas 39.8% of suspected infections were treated with a fluoroquinolone. Furthermore, fluoroquinolones and third- and fourth-generation cephalosporins were most commonly associated with subsequent colonization of multidrug-resistant organisms for these patients.17
Bacterial resistance and antibiotic-associated adverse effects, along with growing evidence for toxicity, elevate the concerns related to widespread fluoroquinolone prescribing. Since 2004, the FDA has released 8 drug safety communications regarding the risk for serious adverse events associated with various fluoroquinolones.16,18-22 All members of a patient's health care team share responsibility for safe medication use. Effective communication between disciplines, especially pharmacists, nurses, and prescribers, is key.23,24 Pharmacists can advise prescribers and nurses about potential toxicities related to the use of fluoroquinolones to appropriately assess use and monitor for adverse effects. A summary of safety warnings is presented in Table 1. In an effort to minimize toxicity risks for all patients, the FDA issued a Boxed Warning for appropriate use of fluoroquinolones: avoid use to treat acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections, when other treatment options are available.21 Additionally, a recent retrospective review revealed an association between central nervous system stimulant use (methylphenidate, mixed amphetamine salts) with cardiac symptoms such as tachycardia, palpitations, and syncope when used concomitantly with fluoroquinolones.25 Although less common than other antidepressants, methylphenidate can be used to treat depression and fatigue in advanced illness.26 With this in mind, fluoroquinolone utilization was reviewed using the pharmacy claims database of a national pharmacy benefits services provider to evaluate safety risks that may be commonly present in hospice patients.
This retrospective chart review studied decedents with pharmacy claims for fluoroquinolones during January 2019. Demographics and claims data were collected with respect to the FDA safety communication alerts including primary hospice diagnosis, presence of cardiac disease or hypertension medications, concomitant corticosteroid or QTc-prolonging medication use, sex, and fluoroquinolone claims within 14 days of death. Nearly 15% (n = 10 719) of decedents had at least 1 antibiotic claim during the review period (average age, 80.1 years). Fluoroquinolones comprised 24.4% of claims (n = 4651), the largest percentage of all antibiotic claims. Fluoroquinolones prescriptions were predominantly ciprofloxacin (51.4%) and levofloxacin (48.6%). More than 24% of patients filled the fluoroquinolone within 14 days of date of death. The top 5 hospice diagnoses in the study population were cardiac (21.4%), dementia (21.3%), pulmonary (18.3%), cancer (15.6%), and stroke (8.7%). Known QTc prolongation risk factors identified in the study population included female patients (60.2%), age older than 65 years (86.0%), and use of multiple QTc risk medications (51.5%). Additional FDA fluoroquinolone risk factors present were hypertension (64.1%) and concomitant corticosteroid use (22.9%).
Because of the complex care needs in EOL patient populations, the toxicities and safety warnings associated with fluoroquinolones should carry significant weight. Notably, renal function, drug-drug interactions, and chronic comorbid conditions must be thoroughly evaluated when selecting antibiotics, as well as dosing and determining treatment duration. In hospice care, where comfort is prioritized, the burdens associated with medication-related adverse events must be weighed against potential benefit. Fluoroquinolones are associated with peripheral neuropathy, tendinitis, and central nervous system adverse events risking a substantial impact on patient quality of life. Further, fluoroquinolones may disrupt glycemic regulation and increase the risk for hypoglycemia in all patients, whereas those with comorbid cardiovascular disease have an increased risk of an aortic tear or rupture secondary to fluoroquinolone exposure. For hospice patients considering antibiotic therapy, the potential risks of fluoroquinolone use must be considered in the context of other available palliative modalities such as comfort-based nonpharmacologic and nonantibiotic symptom management strategies.
Hospice Antibiotic Decision Support Tool: STAMPS
There is limited guidance for infection management and antibiotic use in EOL care. A proposed algorithm for antimicrobial use in end of life emphasizes the importance of establishing symptom relief benefit primarily over the survival benefit, as care shifts to palliation of disease.2 In contrast, others suggest antimicrobial avoidance should be considered when full comfort or hospice care is established (ie, no prolongation of life).27,28 However, literature describes the potential for hospice patients to achieve symptom relief from antibiotics particularly in the setting of urinary tract infections, less so for respiratory tract and bloodstream infections.11 Burden versus benefit will vary by patient and can be affected by changes in condition, locations of care, caregiver support, infection type or severity, and available antibiotic options. Navigating the decision to pursue versus avoid antibiotics can be difficult for clinicians, and involving patients and caregivers may add additional layers of complexity.
STAMPS is a hospice decision support tool that provides clinicians with a structured process for the evaluation of treatment burden versus benefit, providing a guide to symptom-driven antibiotic use (Table 2). When clinicians, patients with limited prognosis, and their caregivers are faced with an infection, it helps answer the question: "What symptom management strategy should be used to provide comfort to the patient: antibiotic or nonantibiotic?" The STAMPS decision support tool can facilitate conversations about infection management with patients, families, or other clinicians participating in the patient's care, helping them make informed decisions that align with documented goals of care. Finally, when an antibiotic is warranted, based on the individual assessment, STAMPS promotes antimicrobial stewardship by directing prescribers to ensure selection of the correct drug, dosage, route, and duration of therapy. Figure 1 illustrates a treatment approach applying the STAMPS framework to redefine appropriate antibiotic use in end of life.
STAMPS is well-suited for inclusion in the transition-of-care process. For the hospice patient currently completing a course of antibiotics, STAMPS provides the framework for streamlining therapy and minimizing risks associated with antibiotics while improving patient-centered care during transitions of care. In these settings, when antibiotics are not discontinued, STAMPS may prompt more timely conversion to an oral regimen or ensure duration of antibiotic therapy is no longer than necessary. Use of the STAMPS tool creates an opportunity to ascertain hospital-based prescriber expectations for the antibiotic course (ie, survival benefit, intended duration, preventive vs curative goals), ultimately assisting hospice clinicians with decision making when those expectations do not align with patient goals of care. Incorporation of the STAMPS clinical decision support tool, during the transition from hospital discharge to hospice admission, can foster a patient-centered team approach to antibiotic decision making while unifying clinical information shared by hospital and hospice providers to patients and their families.
A recent survey of hospital antibiotic stewardship programs (ASPs) gives insight into educational opportunities to promote symptom-driven antibiotic use for EOL patients.29 Less than two-thirds of ASPs reported monitoring antimicrobial use in patients during EOL care and noted that most recommendations involved intravenous antimicrobials, suggesting less support for evaluating oral therapy. Guidance for antimicrobial use in EOL patients was facilitated by only 36% of the ASPs, with 8% reporting formal antibiotic stewardship guidance for comfort care patients. Institutionally, 14% noted availability of EOL guidelines addressing antimicrobial use. Palliative care practitioners were employed by 92% of the hospitals that responded, and only 8% of ASPs reported known antibiotic stewardship education for their palliative care practitioner. Notably, they also identify the need for formal guidelines to assist providers with antibiotic decision making for palliative care and hospice transitions of care.29 The importance of addressing this need is supported by evidence of increased hospital lengths of stay associated with antibiotic use for advanced cancer patients who transition to comfort care.30 The STAMPS tool can serve as a general framework for education and guidelines. Figure 2 provides a case example using the STAMPS tool for hospice patient communication and decision making.
STAMPS places emphasis on interdisciplinary clinicians identifying and communicating the risks, expectations, and appropriateness of therapy in conversations with patients, caregivers, and fellow health care colleagues.
CONCLUSION
Studies have shown that hospice patients are commonly treated with antibiotics.11 Bacterial resistance and antibiotic-associated adverse effects are a growing concern for patient safety. Despite warnings of serious and potentially irreversible adverse events, fluoroquinolone antibiotics were shown to be the most commonly prescribed antibiotic at a large hospice pharmacy services provider. To this point, limited guidance exists for infection management and antibiotic use in EOL care. STAMPS is a hospice decision support tool that provides clinicians with a standardized approach to evaluating treatment burden versus benefit, guiding symptom-driven antibiotic use. The STAMPS decision support tool can facilitate conversations between providers, or with patients and families, about infection management, supporting informed decision making that aligns with documented goals of care. Ultimately, STAMPS promotes antimicrobial stewardship by helping further define appropriate antibiotic use in hospice, shaped by symptom management indications, prognosis, and overall quality-of-life goals. Applying a standardized approach to evaluating burden and benefit of antibiotics may lower the occurrence of common and serious antibiotic-associated adverse events in the hospice population and reduce risk of bacterial resistance associated with antibiotic misuse. Future research is needed to determine the feasibility of incorporating STAMPS into the antibiotic-prescribing process for transition of care to hospice.
References