No votes yet
Advanced Practice

Febrile Neutropenia: Decreasing Time to Antibiotic Administration in a Community Hospital Emergency Department

Susan D. Bruce
CJON 2021, 25(1), 23-26 DOI: 10.1188/21.CJON.23-26

Febrile neutropenia, a serious complication of cytotoxic chemotherapy, is an oncologic emergency associated with high rates of morbidity and mortality. Fever is often the only clinical sign of an underlying infection in neutropenic patients with cancer. Prompt treatment with empiric broad-spectrum antibiotics is crucial to ensuring best outcomes for patients; practice guidelines recommend antibiotic administration within one hour of fever onset. A quality improvement initiative to improve time to antibiotic administration among patients with febrile neutropenia presenting to a community hospital emergency department is described in this article.

AT A GLANCE

  • Neutropenia is a dose-limiting toxicity of chemotherapy administration that predisposes patients with cancer to serious infection.
  • Failure to meet the one-hour guideline to administration of antibiotics can lead to increased morbidity, mortality, and hospital length of stay.
  • Identification of key areas for improvement using evidence-based strategies can improve adherence to guideline-based practice in the treatment of febrile neutropenia.

Neutropenia is a dose-limiting toxicity of chemotherapy administration that predisposes patients diagnosed with cancer to serious infections. It is defined as an absolute neutrophil count (ANC) of less than 1 x 109/L or an ANC expected to fall below that level in combination with a fever (Flowers et al., 2013). Fever with neutropenia is a common complication of cytotoxic chemotherapy, occurring in 10%–15% of patients with solid tumors and more than 80% of patients with hematologic malignancies after receiving two or more neutropenia-inducing chemotherapy cycles (Freifeld et al., 2011; Klemencic & Perkins, 2019).

Neutropenic fever is defined as a single oral temperature of 38.3°C (101°F) or higher or a temperature of 38°C (100.4°F) or higher sustained for more than one hour (Taplitz et al., 2018). Fever is often the only clinical sign of an underlying infection in neutropenic patients with cancer (Rosa & Goldani, 2014). If febrile neutropenia is the result of infection, it is the most potentially lethal complication of chemotherapy administration (Bodey et al., 1966).

Febrile neutropenia is associated with high rates of morbidity and mortality (Keng et al., 2015) and is considered to be an oncologic emergency requiring prompt management to ensure the best outcomes for patients. Mortality rates range from 4% to 10%, depending on patient characteristics, type of malignancy, comorbidities, and infectious complications (Kuderer et al., 2006), and have been reported as high as 58% in patients with multiple comorbidities. A delay in time to antibiotic administration is associated with a decrease in survival and a reported increase in mortality of 7.6% for each hour of delay (Koenig et al., 2019); for example, a four-hour delay could result in a 30.4% higher risk of death.

Febrile Neutropenia Guidelines

Empiric broad-spectrum antibiotics are the standard of care for patients with febrile neutropenia. At the author’s institution, Duke Cancer Center Raleigh in North Carolina, empiric monotherapy with cefepime (fourth-generation cephalosporin) is used in the treatment of gram-negative organisms. According to American Society of Clinical Oncology clinical practice guidelines for the treatment of febrile neutropenia, antibiotics should be administered within one hour of emergency department presentation in patients with febrile neutropenia (Flowers et al., 2013). A one-hour time from triage to antibiotic administration for patients with febrile neutropenia is also recommended by the international guideline panel of the Surviving Sepsis Campaign (Flowers et al., 2013). The Society of Critical Care Medicine and European Society of Intensive Care Medicine’s (2019) Hour-1 bundle guides practice toward early assessment and actions within the first hour, including measuring lactate levels, obtaining blood cultures, and administering broad-spectrum antibiotics (Boucher & Carpenter, 2020).

Time to antibiotic administration begins at the initial patient triage and extends to barcode scanning of the antibiotic label. A time to antibiotic administration of longer than one hour has been associated with negative outcomes, including medical complications requiring a higher level of care (e.g., intensive care unit admission) and severe sepsis (e.g., septic shock, bacteremia, death) (Keng et al., 2015).

Meeting the international standard of time to antibiotic administration can be challenging in a busy community hospital emergency department. There are constant competing challenges in the emergency department that include overcrowding, high census, and high-acuity patients. In addition, there may be knowledge deficits among emergency department staff and providers regarding the emergent nature of febrile neutropenia in patients with cancer, recognition of this condition as an oncologic emergency, and application of evidence-based practice guidelines for this population (Goldsmith et al., 2018).

Quality Improvement Team

Using the time to antibiotic administration guidelines, the current author, a clinical nurse specialist (CNS) at Duke Raleigh Hospital, reviewed facility metrics to evaluate guideline concordance in June 2019, finding evidence of patients with febrile neutropenia receiving antibiotics as many as eight hours after emergency department presentation. The CNS brought together an interprofessional team of emergency department and oncology nursing leadership, as well as the emergency department medical director, to review the facility metrics. A quality improvement project was launched to improve time to antibiotic administration and guideline concordance.

Development of standard work processes was identified as necessary to improve the amount of timely and appropriate care provided while decreasing delays in time to antibiotic administration. Initial work included identification of barriers to meeting the one-hour time to antibiotic administration guideline. Key areas of improvement and evidence-based strategies were identified (see Table 1). As monthly meetings were established with emergency department and oncology nursing leadership, the CNS performed case reviews of all emergency department admissions of patients with febrile neutropenia. The case reviews facilitated a root cause analysis of delays in time to antibiotic administration. Identified issues were included for discussion during monthly meetings, and strategies were developed. The emergency department medical director followed up on all physician issues, particularly those cases in which antibiotics other than the standardized protocol were prescribed. A learning need was identified on the part of the emergency department staff who did not have a clear understanding of febrile neutropenia, the urgent need for management in patients with cancer with febrile neutropenia, or awareness of relevant guidelines. This lack of understanding highlights the need for staff education to ensure guideline implementation in practice.

Staff Education

The CNS developed an educational presentation that was offered during emergency department staff meetings during a four-month period. The presentation defined the terms “neutropenia” and “nadir,” explained how to calculate the absolute neutrophil count, and identified risk factors for neutropenia (including treatment-related and other factors, such as comorbidities, history of multiple chemotherapy treatments, and previous episodes of febrile neutropenia). The standardized febrile neutropenia workup was outlined, the appropriate standard of care for antibiotic coverage was discussed, the fever alert wallet card (see Figure 1) was shared, and a case study was used to unite all education topics. Emergency department staff received monthly reports on adherence to time to antibiotic administration guidelines.

Febrile Neutropenia Care in the Emergency Department

The CNS had previously developed a fever alert wallet card that was distributed to all clinic or infusion patients receiving chemotherapy, as well as to those hospitalized with febrile neutropenia. As a part of this project, patients were instructed to present the fever alert wallet card at the time of emergency department registration to assist with expeditious transfer to the triage nurse. Febrile neutropenia is not recognized on the national Emergency Severity Index, an emergency department system used to assist with triage; patients are stratified into five groups ranging from 1 (most urgent) to 5 (least urgent). The team decided to designate febrile neutropenia as a level 1 or 2 issue, allowing these patients to be fast-tracked to triage.

Emergency department physicians used the chief complaint of oncology and fever for those suspected to have febrile neutropenia. The triage nurse was responsible for documenting patients’ temperature and receipt of chemotherapy in the previous 7–14 days. After triage and physician assessment, a standardized electronic health record order was used to reduce practice variation. A standardized broad-spectrum antibiotic was chosen (IV cefepime) and was stocked in the emergency department medication cabinet. When possible, patients with febrile neutropenia were placed in an emergency department examination room rather than returned to the emergency department waiting room.

Implementation and Outcomes

During the first two months of education and evidence-based strategies, the CNS provided feedback to emergency department staff and the leadership team regarding adherence to the standard emergency department workflow for febrile neutropenia and opportunities for improvement. During these first two months while education was ongoing, there was no improvement from a baseline adherence of 0%. However, afterward, adherence improved to 66% (see Figure 2). Implementation of a standardized work process guided by evidence-based strategies decreased time to antibiotic administration.

By the third month of implementation, staff adoption of time to antibiotic administration guidelines was observed. Adherence improved to 66%. Despite some monthly variation, an overall improvement trend can be observed since implementation. In January 2020, adherence dropped to 0%, which was a result of either the administration of a nonstandard antibiotic or delayed administration. Discussions were held during team meetings regarding continued cases of nonadherence, with the hope of reaching the goal of 100%; improvement was noted thereafter. The impact of the COVID-19 pandemic was observed in this project. Beginning in February 2020, the emergency department shifted its focus to emergency management of an infectious disease pandemic. In August 2020, the CNS restarted monthly meetings and provided education sessions to review content.

Conclusion

Extended time to antibiotic administration in patients with febrile neutropenia may result in sepsis and increased morbidity and mortality. Hospital length of stay may also be prolonged; for every one-hour delay in time to antibiotic administration, adult patients with cancer experience an eight-hour increase in length of stay (Perron et al., 2014). Timely treatment of febrile neutropenia minimizes patient complications and promotes improved patient outcomes.

Essential to the progress and success of this performance improvement initiative was the collaboration between the oncology and emergency departments. The CNS was able to recognize a population-specific and high-priority problem and organize an interprofessional team that could bring about practice change and create efficient, sustainable workflows. The emergency department medical director and staff were receptive to examination of their current processes and identification of areas for improvement. Throughout this process, emergency department staff gained a better understanding of the urgent nature of febrile neutropenia management to provide the best care possible to patients with febrile neutropenia.

Patient education by the clinic or infusion nurse using the fever alert wallet card was identified as a key initiative. Having this card empowered patients and their family to reinforce an expectation to be triaged promptly, as well as provided an agreed-upon communication tool to emergency department staff. The evidence-based strategies implemented in the current article are not complicated or specific to any particular institution. Therefore, this project would be easy to replicate in any setting, community based or academic.

About the Author(s)

Susan D. Bruce, MSN, RN, OCN®, AOCNS®, is a clinical nurse specialist at Duke Cancer Center Raleigh in North Carolina. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. Bruce can be reached at susan.bruce@duke.edu, with copy to CJONEditor@ons.org.

 

References 

Bodey, G.P., Buckley, M., Sathe, Y.S., & Freireich, E.J. (1966). Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Annals of Internal Medicine, 64(2), 328–340. https://doi.org/10.7326/0003-4819-64-2-328

Boucher, J.E., & Carpenter, D. (2020). Sepsis: Symptoms, assessment, diagnosis, and the Hour-1 bundle in patients with cancer. Clinical Journal of Oncology Nursing, 24(1), 99–102. https://doi.org/10.1188/20.CJON.99-102

Flowers, C.R., Seidenfeld, J., Bow, E.J., Karten, C., Gleason, C., Hawley, D.K., . . . Ramsey, S.D. (2013). Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline. Journal of Clinical Oncology, 31(6), 794–810. https://doi.org/10.1200/jco.2012.45.8661

Freifeld, A.G., Bow, E.J., Sepkowitz, K.A., Boeckh, M.J., Ito, J.I., Mullen, C.A., . . . Wingard, J.R. (2011). Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clinical Infections Diseases, 52(4), e56–e93. https://doi.org/10.1093/cid/cir073

Goldsmith, C., Kalis, J., & Jeffers, K.D. (2018). Assessment of initial febrile neutropenia management in hospitalized cancer patients at a community cancer center. Journal of the Advanced Practitioner in Oncology, 9(6), 659–664. https://doi.org/106004/jadpro.2018.9.6.8

Keng, M.K., Thallner, E.A., Elson, P., Ajon, C., Sekeres, J., Wenzell, C.M., . . . Sekeres, M.A. (2015). Reducing time to antibiotic administration for febrile neutropenia in the emergency department. Journal of Oncology Practice, 11(6), 450–455. https://doi.org/10.1200/JOP.2014.002733

Klemencic, S., & Perkins, J. (2019). Diagnosis and management of oncologic emergencies. Western Journal of Emergency Medicine, 20(2), 316–322. https://doi.org/10.5811/westjem.2018.12.37335

Koenig, C., Morgan, J., Ammann, R.A., Sung, L., & Phillips, B. (2019). Protocol for a systematic review of time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN) and interventions aiming to reduce TTA. Systematic Reviews, 8, 82. https://doi.org/10.1186/s13643-019-1006-8

Kuderer, N.M., Dale, D.C., Crawford, J., Cosler, L.E., & Lyman, G.H. (2006). Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer, 106(10), 2258–2266. https://doi.org/10.1002/cncr.21847

Perron, T., Emara, M., & Ahmed, S. (2014). Time to antibiotics and outcomes in cancer patients with febrile neutropenia. BMC Health Services Research, 14, 162. https://doi.org/10.1186/1472-6963-14-162

Rosa, R.G., & Goldani, L.Z. (2014). Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrobial Agents and Chemotherapy, 58(7), 3799–3803. https://doi.org/10.1128/AAC.02561-14

Society of Critical Care Medicine & European Society of Intensive Care Medicine. (2019). Surviving Sepsis Campaign: Hour-1 bundle: Initial resuscitation for sepsis and septic shock. https://bit.ly/38uu2Fw

Taplitz, R.A., Kennedy, E.B., Bow, E.J., Crews, J., Gleason, C., Hawley, D.K., . . . Flowers, C.R. (2018). Outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America clinical practice guideline update. Journal of Clinical Oncology, 36(14), 1443–1453. https://doi.org/10.1200/JCO.2017.77.6211