Kanseri Olan Erişkinlerde Nötropenik Ateş
Özet
Kanserli erişkinlerde nötropenik ateş, kemoterapinin mukozal bariyerler ve bağışıklık sistemi üzerindeki olumsuz etkileri ile altta yatan maligniteye bağlı immünsupresyon neticesinde gelişen, mortalitesi yüksek ciddi bir klinik tablodur. Tanısal olarak ateş, tek bir oral ölçümde 38.3°C veya en az bir saat süren 38.0°C ve üzeri sıcaklık olarak kabul edilirken; nötropeni ise mutlak nötrofil sayısının 500 hücre/mcL'nin altına inmesiyle karakterizedir. Enfeksiyon etkenleri arasında en sık gram-pozitif bakteriler izole edilse de, sepsis riski nedeniyle geniş spektrumlu ampirik antibiyotik tedavisi, periferik ve kateter hatlarından kan kültürleri alınmasını takiben ilk 60 dakika içinde hızla başlanmalıdır. Hastaların yönetiminde ampirik tedavi stratejisini belirlemek amacıyla MASCC ve CISNE gibi doğrulanmış skorlama sistemleri kullanılarak risk sınıflandırması yapılır; düşük riskli hastalar evde oral florokinolon kombinasyonlarıyla izlenebilirken, yüksek riskli hastaların yatırılarak antipsödomonal beta-laktam ajanlarla intravenöz olarak tedavi edilmesi gerekir. Klinik takipte antibiyotiklerin süresi nötrofil sayısının artışına ve odağın varlığına göre belirlenir; 4-7 gün boyunca ateşi düşmeyen yüksek riskli olgulara ampirik antifungal ajanlar eklenmeli, kateter ilişkili dirençli enfeksiyonlarda ise kateterin çıkarılması yoluna gidilmelidir. G-CSF kullanımı ise nötropeni süresini ve hastanede yatış süresini kısaltmaktadır.
Febrile neutropenia in adult cancer patients is a critical clinical condition with high mortality that develops as a result of the negative effects of chemotherapy on mucosal barriers and the immune system, along with underlying malignancy-related immunosuppression. Diagnostically, fever is defined as a single oral temperature measurement of >=38.3°C or >=38.0°C lasting for at least one hour, while neutropenia is characterized by an absolute neutrophil count falling below 500 cells/mcL. Although gram-positive bacteria are most commonly isolated among infectious agents, empirical broad-spectrum antibiotic therapy must be initiated rapidly within the first 60 minutes following blood culture collection from peripheral and catheter lines due to the risk of sepsis. In patient management, risk stratification is performed using validated scoring systems such as MASCC and CISNE to determine the empirical treatment strategy; low-risk patients can be monitored at home with oral fluoroquinolone combinations, whereas high-risk patients require hospitalization and intravenous treatment with antipseudomonal beta-lactam agents. During clinical follow-up, the duration of antibiotics is determined by the increase in neutrophil count and the presence of an infectious source; empirical antifungal agents should be added for high-risk cases with persistent fever for 4-7 days, and catheter removal should be pursued in resistant catheter-related infections. Furthermore, the use of G-CSF shortens the duration of neutropenia and length of hospital stay.
Referanslar
Swati M, Gita N, Sujata B, Farah J, Preeti M. Microbial etiology of febrile neutropenia. Indian J Hematol Blood Transfus. 2010;26(2):49-55.
Safdar A, Armstrong D. Infections in patients with hematologic neoplasms and hematopoietic stem cell transplantation: neutropenia, humoral, and splenic defects. Clin Infect Dis 2011; 53:798.
Taplitz RA, Kennedy EB, Bow EJ, et al. 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. J Clin Oncol 2018; 36:1443.
Willies GH, Woolf CJ. The site of action of corticosteroid antipyresis in the rabbit. J Physiol 1980; 300:1.
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52:e56.
Talcott JA, Siegel RD, Finberg R, Goldman L. Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol 1992; 10:316.
Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 2000; 18:3038.
Carmona-Bayonas A, Jiménez-Fonseca P, Virizuela Echaburu J, et al. Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study. J Clin Oncol 2015; 33:465.
Mohindra R, Mathew R, Yadav S, Aggarwal P. CISNE versus MASCC: Identifying low risk febrile neutropenic patients. Am J Emerg Med. 2020;38(11):2259-63.
Klastersky J. Management of fever in neutropenic patients with different risks of complications, Clin Infect Dis, 2004, vol. 39 Suppl 1(pg. S32-7)
Schmidt-Hieber M, Teschner D, Maschmeyer G, Schalk E. Management of febrile neutropenia in the perspective of antimicrobial deescalation and discontinuation. Expert Rev Anti Infect Ther. 2019;17(12):983-95
Donowitz GR, Harman C, Pope T, Stewart FM. The role of the chest roentgenogram in febrile neutropenic patients. Arch Intern Med 1991;151:701-704. Available at: http://www.ncbi.nlm.nih.gov/pubmed/2012451.
Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36:296.
Rolston KV. Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin Infect Dis 2005; 40 Suppl 4:S246.
Rosa RG, Goldani LZ. Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother 2014; 58:3799.
De Naurois J, Novitzky-Basso I, Gill MJ, Marti Marti F, Cullen MH, Roila F. On behalf of the ESMO Guidelines Working Group. Management of febrile neutropenia: ESMO Clinical Practice Guidelines. Annals of Oncol 2010;21 Suppl 5:v252-6.
Edelsberg J, Weycker D, Bensink M, Bowers C, Lyman GH. Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years. Curr Med Res Opin. 2020;36(3):483-95.
Mhaskar R, Clark OA, Lyman G, et al. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev 2014; :CD003039.
Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2015; 33:3199.
National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology. https://www.nccn.org/professionals/physician_gls (Accessed on December 22, 2021).
Aguilar-Guisado M, Espigado I, Martín-Peña A, et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol 2017; 4:e573.
Snyder M, Pasikhova Y, Baluch A. Early Antimicrobial De-escalation and Stewardship in Adult Hematopoietic Stem Cell Transplantation Recipients: Retrospective Review. Open Forum Infect Dis 2017; 4:ofx226.
Van de Wyngaert Z, Berthon C, Debarri H, et al. Discontinuation of antimicrobial therapy in adult neutropenic haematology patients: A prospective cohort. Int J Antimicrob Agents 2019; 53:781.
Le Clech L, Talarmin JP, Couturier MA, et al. Early discontinuation of empirical antibacterial therapy in febrile neutropenia: the ANTIBIOSTOP study. Infect Dis (Lond) 2018; 50:539.
