Evidence-based Guidelines for Empirical Therapy of Neutropenic Fever in Korea

Dong-Gun Lee; Sung-Han Kim; Soo Young Kim; Chung-Jong Kim; Chang-Ki Min; Wan Beom Park; Yeon-Joon Park; Young Goo Song; Joung-Soon Jang; Jun Ho Jang; Jong Youl Jin; Jung-Hyun Choi

doi:10.3947/ic.2011.43.4.285

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Lee, Kim, Kim, Kim, Min, Park, Park, Song, Jang, Jang, Jin, and Choi: Evidence-based Guidelines for Empirical Therapy of Neutropenic Fever in Korea

Special Article

Infection & Chemotherapy

Infection & Chemotherapy 2011; 43(4): 285-321.

Published online: 31 August 2011

DOI: https://doi.org/10.3947/ic.2011.43.4.285

Evidence-based Guidelines for Empirical Therapy of Neutropenic Fever in Korea

Dong-Gun Lee^1,²

, Sung-Han Kim³, Soo Young Kim⁴, Chung-Jong Kim¹, Chang-Ki Min², Wan Beom Park⁵, Yeon-Joon Park⁶, Young Goo Song⁷, Joung-Soon Jang⁸, Jun Ho Jang⁹, Jong Youl Jin², Jung-Hyun Choi²

¹National Evidence-based Healthcare Collaborating Agency, Seoul, Korea.

²Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

³Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

⁴Department of Family Medicine, Hallym University College of Medicine, Chuncheon, Korea.

⁵Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

⁶Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

⁷Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

⁸Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea.

⁹Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Correspondence to Dong-Gun Lee, M.D., Ph.D. Department of Internal Medicine, Seoul St. Mary's Hospital, #505, Banpo-dong, Seocho-gu, Seoul 137-701, Korea. Tel: +82-2-2258-6003, Fax: +82-2-535-2494, symonlee@catholic.ac.kr

Received 27 June 2011 Accepted 27 June 2011

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Neutrophils play an important role in immunological function. Neutropenic patients are vulnerable to infection, and except fever is present, inflammatory reactions are scarce in many cases. Additionally, because infections can worsen rapidly, early evaluation and treatments are especially important in febrile neutropenic patients. In cases in which febrile neutropenia is anticipated due to anticancer chemotherapy, antibiotic prophylaxis can be used, based on the risk of infection. Antifungal prophylaxis may also be considered if long-term neutropenia or mucosal damage is expected. When fever is observed in patients suspected to have neutropenia, an adequate physical examination and blood and sputum cultures should be performed. Initial antibiotics should be chosen by considering the risk of complications following the infection; if the risk is low, oral antibiotics can be used. For initial intravenous antibiotics, monotherapy with a broad-spectrum antibiotic or combination therapy with two antibiotics is recommended. At 3 5 days after beginning the initial antibiotic therapy, the condition of the patient is assessed again to determine whether the fever has subsided or symptoms have worsened. If the patient's condition has improved, intravenous antibiotics can be replaced with oral antibiotics; if the condition has deteriorated, a change of antibiotics or addition of antifungal agents should be considered. If the causative microorganism is identified, initial antimicrobial or antifungal agents should be changed accordingly. When the cause is not detected, the initial agents should continue to be used until the neutrophil count recovers.

Keywords: Practice guideline, Neutropenia, Fever, Korea

Figures and Tables

Figure 1

Algorithm for initial management of febrile neutropenic patients.

Figure 2

Algorithm for management of patients who become afebrile in the first 3-5 days of initial antibiotic therapy.

Figure 3

Algorithm for management of patients who still is despite of first 3-5 days of initial antibiotic therapy.

Table 1

Definition of Strength of Recommendation and Quality of Evidence

Adapted from the Canadian Task Force on the Periodic Health Examination[28].

Table 2

MASCC Risk Index Table

Points attributed to the variable "burden of illness" are not cumulative. The maximum theoretical score is therefore 26.

Table 3

Initial Risk Assessment for Febrile Neutropenic Patients

^aUncontrolled/progressive cancer is defined as any leukemic patients not in complete remission or non-leukemic patients with evidence of disease progression after more than 2 courses of chemotherapy.

Table 4

Overall Infection Risk in Cancer Patients by Type of Disease or Therapy

HSV, herpes simplex virus; HSCT, hematopoietic stem cell transplantation; CLL, chronic lymphocytic leukemia; 2-CdA, 2-Chlordexoyadenosine (also known as cladribine).

Table 5

Recommendation of Prophylactic Antimicrobial Agents

Table 6

Distribution of Bacterial Organisms in Patients with Neutropenic Fever in Korea

HSCT, hematopoietic stem cell transplantation; NA, not available; SMX/TMP, sulfamethoxazole/trimethoprim; MDI, microbiologically defined infection; CoNS, coagulase-negative Staphylococcus.

Table 7

Reasons for Persistent fever 3-5 Days after Initiating Antibiotic Therapy

Table 8

Recommendation of Antibacterial Agents in Neutropenic Fever

^aDose requires adjustment in patients with renal insufficiency. Dose in combined antibiotic therapy is same as that in single antibiotic therapy.

In the case of combination drug, the dose presented denotes total dose.

An antibacterial agent other than the listed antibiotics can be used if their efficacy is similar.

Table 9

Suggested Duration of Therapy for Documented Infection

HSV, herpes simplex virus; VZV, varicella-zoster virus.

Table 10

Suggested Indication of Catheter Removal

All of the recommendations are level A-II except for recommendation 7.

Table 11

Recommendation of Empirical Antifungal Agents in Neutropenic Fever

^aPanels do not recommend amphotericin B deoxycholate in the presence of risk factors for renal toxicity (B-I) (e.g. impaired renal function at baseline, nephrotoxic co-medication including cyclosporin or tacrolimus in allogeneic hematopoietic stem cell transplantation recipients, aminoglycosides antibiotics, old ages, history of previous toxicity).

Table 12

Survey Results

^aSome responders did not answer all items.

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ORCID iDs: Dong-Gun Lee
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