Predictive and risk factor analysis for bloodstream infection in high-risk hematological patients with febrile neutropenia: post-hoc analysis from a prospective, large-scale clinical study
Tóm tắt
Bloodstream infection (BSI) is a frequent complication observed in patients with febrile neutropenia (FN). BSI risk factors and incidence vary depending on chemotherapy types and prophylactic antimicrobial agents. We clarified these issues by post-hoc analysis of a prospective clinical trial cohort for severe FN in hematological malignancy. We performed an intention-to-treat analysis of 413 high-risk patients and 1272 blood culture sets. Overall, 356 patients (86.2%) developed FN, and 20.8% had BSI complications. Prophylactic antimicrobials did not prevent complications of FN and BSI, but the incidence of BSIs of Gram-negative (GN) bacteria was lower than in the non-prophylaxis group (23.8% vs. 56.7%). Multinational Association of Supportive Care in Cancer (MASCC) scores < 20 were significantly correlated with the incidence of BSI, whereas MASCC scores > 21 were not (41.7% vs. 17.2%). The only significant risk factors were hypotension and dehydration. axillary temperatures were higher in GN-caused BSIs than in Gram-positive-caused BSIs and in patients with negative blood culture results (38.7 °C vs. 38.2 °C vs. 38.0 °C). The higher the fever, the higher the incidence of BSI and GN bacteremia. MASCC score and axillary temperature are strong predictors of BSI. Non-administration of prophylactic antimicrobials and GN-caused BSI are correlated. UMIN00010411.
Tài liệu tham khảo
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, 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:e56-93.
Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, et al. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica. 2013;98:1826–35.
Taplitz RA, Kennedy EB, Bow EJ, Crews J, Gleason C, Hawley DK, et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Oncol Pract. 2018;14:692–5.
Bodey GP, Jadeja L, Elting L. Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med. 1985;145:1621–9.
Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis. 2003;36:1103–10.
Gudiol C, Bodro M, Simonetti A, Tubau F, González-Barca E, Cisnal M, et al. Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients. Clin Microbiol Infect. 2013;19:474–9.
Montassier E, Batard E, Gastinne T, Potel G, de La Cochetière MF. Recent changes in bacteremia in patients with cancer: a systematic review of epidemiology and antibiotic resistance. Eur J Clin Microbiol Infect Dis. 2013;32:841–50.
Holland T, Fowler VG Jr, Shelburne SA 3rd. Invasive gram-positive bacterial infection in cancer patients. Clin Infect Dis. 2014;59:S331–4.
Mikulska M, Viscoli C, Orasch C, Livermore DM, Averbuch D, Cordonnier C, et al. Aetiology and resistance in bacteraemias among adult and paediatric haematology and cancer patients. J Infect. 2014;68:321–31.
Perez F, Adachi J, Bonomo RA. Antibiotic-resistant gram-negative bacterial infections in patients with cancer. Clin Infect Dis. 2014;59(Suppl 5):S335–9.
Trecarichi EM, Tumbarello M. Antimicrobial-resistant Gram-negative bacteria in febrile neutropenic patients with cancer: current epidemiology and clinical impact. Curr Opin Infect Dis. 2014;27:200–10.
Kato H, Fujita H, Akiyama N, Kimura SI, Hiramoto N, Hosono N, et al. Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001–2005 using the Japan Adult Leukemia Study Group AML201 protocols. Support Care Cancer. 2018;26:4187–98.
Kanda Y, Kimura SI, Iino M, Fukuda T, Sakaida E, Oyake T, et al. D-index-guided early antifungal therapy versus empiric antifungal therapy for persistent febrile neutropenia: a randomized controlled noninferiority trial. J Clin Oncol. 2020;38:815–22.
Kimura SI, Kanda Y, Iino M, Fukuda T, Sakaida E, Oyake T, et al. Efficacy and safety of micafungin in empiric and D-index-guided early antifungal therapy for febrile neutropenia; a subgroup analysis of the CEDMIC trial. Int J Infect Dis. 2020;100:292–7.
Klastersky 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 identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18:3038–51.
Kimura SI, Gomyo A, Hayakawa J, Tamaki M, Akahoshi Y, Harada N, et al. Clinical significance of repeat blood cultures during febrile neutropenia in adult acute myeloid leukaemia patients undergoing intensive chemotherapy. Infect Dis. 2017;49:748–57.
Koenig C, Bodmer N, Agyeman PKA, Niggli F, Adam C, Ansari M, et al. 39.0 °C versus 38.5 °C ear temperature as fever limit in children with neutropenia undergoing chemotherapy for cancer: a multicentre, cluster-randomised, multiple-crossover, non-inferiority trial. Lancet Child Adolesc Health. 2020;4:495–502.
Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.
Cruciani M, Rampazzo R, Malena M, Lazzarini L, Todeschini G, Messori A, et al. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis. 1996;23:795–805.
Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol. 1998;16:1179–87.
Cruciani M, Malena M, Bosco O, Nardi S, Serpelloni G, Mengoli C. Reappraisal with meta-analysis of the addition of Gram-positive prophylaxis to fluoroquinolone in neutropenic patients. J Clin Oncol. 2003;21:4127–37.
Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. N Engl J Med. 2005;353:977–87.
Gafter-Gvili A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Ann Intern Med. 2005;142:979–95.
Perez-Simon JA, Garcia-Escobar I, Martinez J, Vazquez L, Caballero D, Canizo C, et al. Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation. Bone Marrow Transplant. 2004;33:183–7.
Slavin MA, Grigg AP, Schwarer AP, Szer J, Spencer A, Sainani A, et al. A randomized comparison of empiric or pre-emptive antibiotic therapy after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;40:157–63.
Hamadah A, Schreiber Y, Toye B, McDiarmid S, Huebsch L, Bredeson C, et al. The use of intravenous antibiotics at the onset of neutropenia in patients receiving outpatient-based hematopoietic stem cell transplants. PLoS ONE. 2012;7:e46220.
Bow EJ. Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients. Curr Opin Infect Dis. 2011;24:545–53.
Wingard JR, Eldjerou L, Leather H. Use of antibacterial prophylaxis in patients with chemotherapy-induced neutropenia. Curr Opin Hematol. 2012;19:21–6.
Ahn S, Lee YS, Lim KS, Lee JL. Adding procalcitonin to the MASCC risk-index score could improve risk stratification of patients with febrile neutropenia. Support Care Cancer. 2013;21:2303–8.
Combariza JF, Lombana M, Pino LE, Arango M. C-reactive protein and the MASCC risk index identify high-risk patients with febrile neutropenia and hematologic neoplasms. Support Care Cancer. 2015;23:1009–13.
Vazquez L, Henze L, Kiehl M, Liebregts T, von Lilienfeld-Toal M, Classen A, et al. Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO). Ann Hematol. 2019;98:1051–69.
Tafuro P, Colbourn D, Gurevich I, Schoch P, Wachs H, Krystofiak S, et al. Comparison of blood cultures obtained simultaneously by venepuncture and from vascular lines. J Hosp Infect. 1986;7:283–8.