Neutropenic Fever 1 Outpatient Treatment For Solid Tumor Patients (18 years and older)
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1 Page 1 of 6 Patient presents with fever to MDACC Complete physical exam Start IV fluids CBC with differential and platelets, BMP, lactic acid Blood cultures (with a set collected from each lumen simultaneously if CVC present and 1 peripheral site); other cultures (e.g., sputum culture, urinalysis with culture and sensitivity) only if clinically indicated Chest x-ray or other tests as clinically indicated Calculate MASCC score (See Appendix A) Patient must meet all of the following criteria for outpatient treatment: Solid tumor Has access to transportation and telephone at Able to tolerate oral medications residence Able to tolerate fluids 18 years of age or older Does not use feeding tube as primary route for No quinolone allergy for oral regimens nutrition and medications Patient is considered low risk (i.e., MASCC No confirmed focus of infection score greater than or equal to 21 and no other Lives within 1 hour travel time of MD Anderson complicating factors present) Has a 24 hour caregiver No colonization with fluoroquinolone-resistant Not currently on antibiotics or multi-drug resistant organisms Criteria met? Yes No First dose of each antibiotic should be given STAT in the EC for all febrile neutropenic patients Patient should be observed 4 hours prior to discharge Selection of antimicrobials should be performed after careful review of antimicrobial allergies, recent antimicrobial exposure, past infections and microbiological studies Combination therapy is preferred: Ciprofloxacin 750 mg PO twice daily and amoxicillin/clavulanic acid 875 mg PO twice daily each for 7 days Combination therapy if true penicillin allergy: Clindamycin 600 mg PO three times daily and ciprofloxacin 750 mg PO twice daily each for 7 days Monotherapy (No randomized control trials): Levofloxacin 750 mg PO daily for 7 days) or Moxifloxacin 400 mg PO daily for 7 days Note: Doses indicated are for patients with normal renal/hepatic function Refer to Neutropenic Fever Inpatient Adult Treatment (Solid Tumors, Lymphoma, Myeloma) Algorithm Schedule outpatient visit for Days 2, 3 and 7 and phone follow-up for Days 4, 5 and 6 Day 2: CBC with differential; repeat creatinine if baseline greater than 1.2 mg/dl Day 3: CBC with differential, repeat creatinine Day 7: CBC with differential, repeat creatinine or phone follow-up if NF has resolved If unable to adhere to or if patient experiences persistent fever, refer to Neutropenic Fever Inpatient Adult Treatment (Solid Tumors, Lymphoma, Myeloma) Algorithm NF = neutropenic fever 1 ANC less than 1 K/microliter and temperature greater than or equal to 38.3 o C or equal to 38 o C for 1 hour or longer
2 Page 2 of 6 APPENDIX A: Multinational Association for Supportive Care in Cancer (MASCC) Risk Index Score MASCC Score Characteristic Weight Burden of illness: no or mild symptoms 5 No hypotension 5 No chronic obstructive pulmonary disease 4 Solid tumor 4 No dehydration 3 Burden of illness: moderate symptoms 3 Outpatient status 3 Age less than 60 years 2 Burden of illness not cumulative Patients with score of 21 or greater are considered low risk
3 Page 3 of 6 SUGGESTED READINGS Beguin, Y., Benoit, Y., Crokaert, F., Selleslag, D., Vandercam, B., & National Fund for Scientific Research. (2002). Outpatient and home parenteral antibiotic therapy (OHPAT) in low-risk febrile neutropenia: Consensus statement of a belgian panel. Acta Clinica Belgica, 57(6), Carstensen, M., & Sorensen, J. B. (2008). Outpatient management of febrile neutropenia: Time to revise the present treatment strategy. Journal of Supportive Oncology, 6(5), Chamilos, G., Bamias, A., Efstathiou, E., Zorzou, P. M., Kastritis, E., Kostis, E., & Dimopoulos, M. A. (2005). Outpatient treatment of low risk neutropenic fever in cancer patients using oral moxifloxacin. Cancer, 103(12), doi: /cncr Cooper, M., Durand, C., Beaulac, M., & Steinberg, M. (2011). Single-agent, broad-spectrum fluoroquinolones for the outpatient treatment of low-risk febrile neutropenia. Annals of Pharmacotherapy, 45(9), doi: /aph.1q147 Cornely, O. A., Wicke, T., Seifert, H., Bethe, U., Schwonzen, M., Reichert, D., & Fätkenheuer, G. (2004). Once-daily oral levofloxacin monotherapy versus Piperacillin/Tazobactam three times a day: A randomized controlled multicenter trial in patients with febrile neutropenia. International Journal of Hematology, 79(1), doi: /bf Elting, L. S., Lu, C., Escalante, C. P., Giordano, S. H., Trent, J. C., Cooksley, C., & Rolston, K. (2008). Outcomes and cost of outpatient or inpatient management of 712 patients with febrile neutropenia. Journal of Clinical Oncology, 26(4), doi: /jco Escalante, C. P., Rubenstein, E. B., & Rolston, K. V. I. (1996). Outpatient antibiotic treatment in low-risk febrile neutropenic cancer patients. Supportive Care in Cancer, 4(5), doi: /bf Escalante, C. P., Weiser, M. A., Manzullo, E., Benjamin, R., Rivera, E., Lam, T., & Rolston, K. (2004;2003;). Outcomes of treatment pathways in outpatient treatment of low risk febrile neutropenic cancer patients. Supportive Care in Cancer, 12(9), doi: /s 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), doi: /jco Freifeld, A. G., Bow, E. J., Sepkowitz, K. A., Boeckh, M. J., Ito, J. I., Mullen, C. A., & Wingard, J. R. (2011). Executive summary: Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clinical Infectious Diseases, 52(4), doi: /cid/ciq147 Freifeld, A. G., Bow, E. J., Sepkowitz, K. A., Boeckh, M. J., Ito, J. I., Mullen, C. A., & Wingard, J. R. (2011). Executive summary: Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clinical Infectious Diseases, 52(4), doi: /cid/ciq147 Freifeld, A., Marchigiani, D., Walsh, T., Chanock, S., Lewis, L., Hiemenz, S., & Pizzo, P. A. (1999). A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. The New England Journal of Medicine, 341(5), doi: /nejm Freifeld, A., Sankaranarayanan, J., Ullrich, F., and Sun, J. (2008). Clinical practice patterns of managing low-risk adult febrile neutropenia during cancer chemotherapy in the USA. Supportive Care in Cancer, 16(2), doi: /s x Gardembas-Pain, M., Desablens, B., Sensebe, L., Lamy, T., Ghandour, C., and Boasson, M. (1991). Home treatment of febrile neutropenia: An empirical oral antibiotic regimen. Annals of Oncology, 2(7), doi: /oxfordjournals.annonc.a Continued on Next Page
4 Page 4 of 6 SUGGESTED READINGS - continued Gillis, S., Dann, E. J., and Rund, D. (1996). Selective discharge of patients with acute myeloid leukemia during chemotherapy induced neutropenia. American Journal of Hematology, 51(1), doi: /(sici) (199601)51:1<26::aid-ajh5>3.3.co;2-8 Hidalgo, M., Hornedo, J., Lumbreras, C., Trigo, J. M., Colomer, R., Perea, S., & Cortés-Funes, H. (1999). Outpatient therapy with oral ofloxacin for patients with low risk neutropenia and fever: A prospective, randomized clinical trial. Cancer, 85(1), doi: /(sici) ( )85:1<213::aid-cncr29>3.0.co;2-d Hughes, W. T., Armstrong D., Bodey G. P., Bow E. J., Brown, A. E., Calandra T., Feld, R., Pizzo, P. A., Rolston, K. V., Shenep, J. L.,... Young, L. S. Clin Infect Dis Mar 15;34(6): Epub 2002 Feb guidelines for the use of antimicrobial agents in neutropenic patients with cancer. see comment. Clin Infect Dis. 34(6): Innes, H. E., Smith, D. B., O'Reilly, S. M., Clark, P. I., Kelly, V., and Marshall, E. (2003). Oral antibiotics with early hospital discharge compared with in-patient intravenous antibiotics for low-risk febrile neutropenia in patients with cancer: A prospective randomised controlled single centre study. British Journal of Cancer, 89(1), doi: /sj.bjc Johnson, T. N., De Jesus, Y. A., McMahon, L., Rolston, K. V. I., & Row, M. B. (2008). Outpatient management of febrile neutropenia: Is it safe yet? Journal of Supportive Oncology, 6(5), Kamana, M., Escalante, C., Mullen, C. A., Frisbee Hume, S., and Rolston, K. V. I. (2005). Bacterial infections in low risk, febrile neutropenic patients. Cancer, 104(2), doi: / cncr Kern, W. V. (2006). Risk assessment and treatment of low-risk patients with febrile neutropenia. Clinical Infectious Diseases, 42(4), doi: / Kern, W. V., Cometta, A., de Bock, R., Langenaeken, J., Paesmans, M., Zanetti, G., & European Org Res Treatment Canc. (1999). Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. The New England Journal of Medicine, 341(5), doi: /nejm Kern, W. V., Marchetti, O., Drgona, L., Akan, H., Aoun, M., Akova, M., & Calandra, T. (2013). Oral antibiotics for fever in low-risk neutropenic patients with cancer: a double-blind, randomized, multicenter trial comparing single daily moxifloxacin with twice daily ciprofloxacin plus amoxicillin/clavulanic acid combination therapy EORTC infectious diseases group trial XV. Journal of clinical oncology, 31(9), Klastersky, J., Paesmans, M., Georgala, A., Muanza, F., Plehiers, B., Dubreucq, L., & Barette, M. (2006). Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. Journal of Clinical Oncology, 24(25), doi: /jco Klastersky, J., Paesmans, M., Rubenstein, E. B., Boyer, M., Elting, L., Feld, R., & for the Study Section on Infections of Multinational Association for Supportive Care in Cancer. (2000). The multinational association for supportive care in cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. Journal of Clinical Oncology, 18(16), doi: /jco Link, H., Böhme, A., Cornely, O. A., Höffken, K., Kellner, O., Kern, W. V., & Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). (2003). Antimicrobial therapy of unexplained fever in neutropenic patients: Guidelines of the infectious diseases working party (AGIHO) of the german society of hematology and oncology (DGHO), study group interventional therapy of unexplained fever, arbeitsgemeinschaft supportivmassnahmen in der onkologie (ASO) of the deutsche krebsgesellschaft (DKG- German cancer society). Annals of Hematology, 82(S2), S105-S117. doi: /s Continued on Next Page
5 Page 5 of 6 SUGGESTED READINGS - continued Malik, I. A., Khan, W. A., Aziz, Z., & Karim, M. (1994). Self-administered antibiotic therapy for chemotherapy-induced, low-risk febrile neutropenia in patients with nonhematologic neoplasms. Clinical Infectious Diseases, 19(3), doi: /clinids/ Malik, I. A., Khan, W. A., Karim, M., Aziz, Z., and Ata Khan, M. (1995). Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: Results of a prospective randomized trial. The American Journal of Medicine, 98(3), doi: /s (99) Niho, S., Ohe, Y., Goto, K., Ohmatsu, H., Matsumoto, T., Kubota, K., & Nishiwaki, Y. (2004). Randomized trial of oral versus intravenous antibiotics in low-risk febrile neutropenic patients with lung cancer. Japanese Journal of Clinical Oncology, 34(2), doi: /jjco/hyh019 Petrilli, A. S., Carlesse, F. A., and Pereira, C. A. P. (2007). Oral gatifloxacin in the outpatient treatment of children with cancer fever and neutropenia. Pediatric Blood and Cancer, 49(5), doi: /pbc Rolston K. V. (1999). New trends in patient management: risk-based therapy for febrile patients with neutropenia. Clin Infect Dis. 29(3): Rolston K. V., Frisbee-Hume S. E., Patel, S., Manzullo E. F., and Benjamin, R. S. (2010). Oral moxifloxacin for outpatient treatment of low-risk, febrile neutropenic patients. Support Care Cancer. in press Jan;18(1): doi: /s Epub 2009 Apr 22. Rolston, K. V. I., Manzullo, E. F., Elting, L. S., Frisbee-Hume, S. E., McMahon, L., Theriault, R. L., & Benjamin, R. S. (2006). Once daily, oral, outpatient quinolone monotherapy for low-risk cancer patients with fever and neutropenia: A pilot study of 40 patients based on validated risk-prediction rules. Cancer, 106(11), doi: /cncr Rubenstein, E. B., Rubenstein, E. B., Rolston, K., Rolston, K., Benjamin, R. S., Escalante, C., & Benjamin, R. S. (1993). Outpatient treatment of febrile episodes in low risk neutropenic patients with cancer. Cancer, 71(11), doi: / ( )71:11<3640::aid-cncr >3.0.co;2-h Blot, E., Héron, F., Lishner, M., Rubenstein, E. B., Rolston, K. V. I., Kim, Y. J., & Talcott, J. A. (2000). Oral antibiotics for febrile patients with neutropenia due to cancer chemotherapy. The New England Journal of Medicine, 342(1), doi: /nejm Sebban, C., Dussart, S., Fuhrmann, C., Ghesquieres, H., Rodrigues, I., Geoffrois, L., & Biron, P. (2008). Oral moxifloxacin or intravenous ceftriaxone for the treatment of low-risk neutropenic fever in cancer patients suitable for early hospital discharge. Supportive Care in Cancer, 16(9), doi: /s z Talcott, J. A., Finberg, R., Mayer, R. J., & Goldman, L. (1988). The medical course of cancer patients with fever and neutropenia: Clinical identification of a low-risk subgroup at presentation. Archives of Internal Medicine, 148(12), doi: /archinte Talcott, J. A., Siegel, R. D., Finberg, R., and Goldman, L. (1992). Risk assessment in cancer patients with fever and neutropenia: A prospective, two-center validation of a prediction rule. Journal of Clinical Oncology, 10(2), doi: /jco Talcott, J. A., Whalen, A., Clark, J., Rieker, P. P., and Finberg, R. (1994). Home antibiotic therapy for low-risk cancer patients with fever and neutropenia: A pilot study of 30 patients based on a validated prediction rule. Journal of Clinical Oncology, 12(1), doi: /jco Vidal, L., Paul, M., Ben-Dor, I., Pokroy, E., Soares-Weiser, K., and Leibovici, L. (2004). Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients. Cochrane Database of Systematic Reviews (Online), (4), CD doi: / cd pub2
6 Page 6 of 6 DEVELOPMENT CREDITS This practice consensus algorithm is based on majority expert opinion of the Neutropenic Fever Work Group at the University of Texas MD Anderson Cancer Center. It was developed using a multidisciplinary approach that included input from the following core group members: Samuel L. Aitken, PharmD (Pharmacy Clinical Programs) Ŧ Patrick Chaftari, MD (Emergency Medicine) Tami N. Johnson, PharmD (Pharmacy Clinical Programs) Victor E. Mulanovich, MD (Infectious Diseases) Ŧ Terry W. Rice, MD (Emergency Medicine) Kenneth V. Rolston, MD (Infectious Diseases) Ŧ Frank P. Tverdek, PharmD (Pharmacy Clinical Programs) Anita M. Williams, BS Sonal Yang, PharmD Ŧ Core Development Team Lead Clinical Effectiveness Development Team
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