Febrile neutropenia studies in Brazil: treatment and cost management based on analyses of cases

SCIENTIFIC COMMENTS

Febrile neutropenia studies in Brazil - treatment and cost management based on analyses of cases

Marcelo Bellesso

Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo - USP, São Paulo, Brazil Instituto HEMOMED, São Paulo, Brazil

^{Corresponding author}

The management of neutropenia is a challenge in the clinical practice. It is known since the 1960s that risk of infection is associated with the intensity and duration of neutropenia⁽¹⁾.

Neutropenic patients with an infection usually present incomplete signs and symptoms considering the severity of the condition. Thus, rubor, erythema and pustules may not be seenin neutropenia associated with a cutaneous infection, just as pulmonary infections may fail to present classical signs and symptoms such as cough, dyspnea and characteristic physical examination findings⁽²⁾. Sometimes the only sign found is fever. Studies published in the 1970shave taught us that the quick administration of broad-spectrum antimicrobial agents dramatically reduces mortality from 50-90% to 10-40% within the first 72 hours of treatment^(3-5).

It is also known that the microbial isolation rate is low, and that there is a predominance of gram-negative bacilli. The use of antibiotics for gram-positive cocci should be adopted in cases of clear-cut risk situations such as mucositis, evident infection of a central venous catheter, hemodynamic instability and cutaneous infections⁽⁶⁾. As of the 1980s, several studies on febrile neutropenia were performed in an attempt to differentiate risk groups for severe complications and death. The studies started with Talcott et al., who showed that patients with neutropenia undergoing chemotherapy and fever at home, without comorbidities and with the oncological disease under control, presented a low risk^(7,8). In 2000, a study that standardized the risk evaluation of patients with febrile neutropenia undergoing chemotherapy was published. The index of the Multinational Association for Supportive Care of Cancer (MASCC) standardized the risk evaluation in febrile neutropenia based on clinical parameters; this evaluation that took into account the intensity of symptoms, hypotension, presence of previous fungal infection, dehydration, age and home fever was widely tested and recognized as one of the best methods to screen patients with febrile neutropenia⁽⁹⁾. In Brazil, there are few studies that applied the MASCC index^(10,11), but the mortality rate among high- and low-risk febrile neutropenia groups is notorious (Table 1).

Differentiating the risk groups is important because it can lower the costs of the treatment of febrile neutropenia. Pharmacoeconomic studies have estimated that the cost of each febrile neutropenia event varies between US$ 2000 and US$ 11000. According to Canadian and British studies, 25.8% of this cost is related to antibiotics and 16.4% to complementary tests. It is further estimated that about US$ 5000 can be saved per febrile neutropenia episode when the patient can be discharged early and followed up as an outpatient. The use of orally instead of intravenously administered antibiotics reduces the cost by about 80%⁽¹⁵⁾.

The article published in this journal, "Neutropenic patients and their infectious complications at a University Hospital"⁽¹⁶⁾, reports on a cross-sectional study of the universe of neutropenicinpatients with infections in a general hospital. This matter needs to be further studied, andBrazilian multicentric prospective studies need to be performed given the importance of studies like this in reconfirming the relevance of the MASCC index in respect to mortality. The profile of the microbial agents isolated and their sensitivity profile help our understanding of febrile neutropenia cases and improves treatment provided to patients and a better management of the costs.

References

1. Bodey GP, Buckey M, Sathe YS, Freireich EJ. Quantitative relationship between circulating leukocytes and infections in patients with acute leukemia. Ann Intern Med. 1966;64(2):328-40.

2. Sickles EA, Greene WH, Wiernik PH. Clinical presentation of infection in granulocytopenic patients. Arch Intern Med. 1975;135(5):715-9.

3. Schimpff S, Saterlee W, Young VM, Serpick A. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971;284(19):1061-5.

4. Bryant RE, Hood AF, Hood CE, Koening MG. Factors affecting mortality of gram-negative rod bacteremia. Arch Intern Med. 1971;127(1):120-8.

5. Love LJ, Schimpff SC, Schiffer CA, Wiernik PH. Improve prognosis for granulocytopenic patients with gram-negative bacteremia. Am J Med. 1980;68(5):643-8.

6. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer 2010 update by the infectious diseasessociety of america. Clin Infect Dis. 2011;52(4):e56-93.

7. Talcott JA, Finderg R, Mayer R, Goldman L. The medical course of cancer patients with fever and neutropenia. Arch Intern Med. 1988;148(12):2561-8.

8. Talcott JA, Siegel RD, Finberg R, Goldman L. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of prediction rule. J Clin Oncol. 1992;10(2):316-22.

9. Klatersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, et al. The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifyinglow-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18(16):3038-51.

10. Bellesso M, Costa SF, Pracchia LF, Santos Dias LC, Chamone D, Dorlhiac-Llacer PE. Outpatient treatment with intravenous antimicrobial therapy and oral levofloxacin in patients with febrile neutropenia and hematological malignancies. Ann Hematol. 2011;90(4):455-62.

11. Viana LS, Serufo JC, Rocha MO, Costa RN, Duarte RC. Performance of a modified MASCC index score for identifying low-risk febrile neutropenic cancer patients. Support Care Cancer. 2008;16(7):841-6.

12. Cherif H, Johansson E, Björkholm M, Kalin M. The feasibility of early hospital discharge with oral antimicrobial therapy in low risk patients with febrile neutropenia following chemotherapy for hematologic malignancies. Haematologica. 2006;91(2):215-22. Comment in: Haematologica. 2006;91(2):150a.

13. Girmenia C, Russo E, Carmosino I, Breccia M, Dragnoni F, Latagliata R, et al. Early hospital discharge with oral antimicrobial therapy in patients with hematologic malignancies and low-risk febrile neutropenia. Ann Hematol. 2007;86(4):263-70.

14. Baskaran ND, Gan GG, Adeeba K. Applying the Multinational Association for Supportive Care in Cancer risk scoring in predictingoutcome of febrile neutropenia patients in a cohort of patients. Ann Hematol. 2008;87(7):563-9.

15. De Lalla F. Outpatient therapy for febrile neutropenia: clinical and economic implications. Pharmacoeconomics. 2003;21(6):397-413.

16. Lima SS, França SM, Godoi CC, Martinho GH, Jesus LA, Romanelli RM et al. Neutropenic patients and their infectious complications at a University Hospital. Rev Bras Hematol Hemoter. 2013;35(1):18-22.

Submitted: 4/8/2012

Accepted: 7/31/2012

Conflict-of-interest disclosure: The author declares no competing financial interest

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Publication Dates

• Publication in this collection
  05 Apr 2013
• Date of issue
  2013