Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

Invasive Fungal Infection in Febrile Patients with Hematologic Malignancies Undergoing Chemotherapy in Iran

Author(s): Saba Sheikhbahaei, Alireza Mohammadi, Roya Sherkat*, Alireza Emami Naeini, Majid Yaran and Somaye Najafi

Volume 19 , Issue 3 , 2019

Page: [302 - 307] Pages: 6

DOI: 10.2174/1871530319666190211163245

Price: $65


Background: Patients with hematological malignancies undergoing cytotoxic chemotherapy are susceptible to develop invasive fungal infections particularly Aspergillus and Candida spp. Early detection of these infections is required to start immediate antifungal therapy and increase the survival of these patients.

Method: Our study included consecutive patients of any age with hematologic malignancies who were hospitalized to receive chemotherapy and suffer from persistent fever (rectal temperature >38.5°C) for more than 5 days despite receiving broad-spectrum antibiotics. A whole blood sample was taken and sent for blood culture. PCR was also conducted for Aspergillus and Candida species.

Results: One hundred and two patients were investigated according to the inclusion criteria. The most common hematologic malignancy was AML affecting 38 patients (37.2%). Six patients were diagnosed with invasive fungal infections (A. fumigatus n=3, C. albicans n=2, A. flavus n=1) by PCR (5.8%) while blood culture showed fungus only in 1 patient. Three more cases were known as probable IFI since they responded to antifungal therapy but the PCR result was negative for them. AML was the most prevalent malignancy in IFI patients (83.3%) and odds ratio for severing neutropenia was 21.5. Odds for each of the baseline characteristics of patients including gender, age>60, diabetes mellitus, previous IFI, history of using more than 3 antibiotics, antifungal prophylaxis, episodes of chemotherapy> 8 and chemotherapy regimen of daunarubicin+cytarabine were calculated.

Conclusion: We found that multiplex real-time PCR assay is more accurate than blood culture in detecting fungal species and the results are prepared sooner. Among all factors, the only type of cancer (AML) and severe neutropenia, were found to be risk factors for the development of fungal infections in all hematologic cancer patients and previous IFI was a risk factor only AML patients.

Keywords: Invasive fungal infection, Aspergillus, Candida, hematologic cancer, chemotherapy, acute myeloid leukemia.

Graphical Abstract
Suresh, A.V.; Varma, P.P.; Sinha, S.; Deepika, S.; Raman, R.; Srinivasan, M.; Mandapal, T.; Reddy, C.O.; Anand, B.B. Risk-scoring system for predicting mucositis in patients of head and neck cancer receiving concurrent chemoradiotherapy [rssm-hn]. J. Cancer Res. Ther., 2010, 4, 448-451.
Pagano, L.; Caira, M.; Candoni, A.; Offidani, M.; Fianchi, L.; Martino, B.; Pastore, D.; Picardi, M.; Bonini, A.; Chierichini, A.; Fanci, R.; Caramatti, C.; Invernizzi, R.; Mattei, D.; Mitra, M.E.; Melillo, L.; Aversa, F.; Van Lint, M.T.; Falcucci, P.; Valentini, C.G.; Girmenia, C.; Nosari, A. The epidemiology of fungal infections in patients with hematologic malignancies: The SEIFEM-2004 study. Haematologica, 2006, 91, 1068-1075.
Carrigan, S.D.; Scott, G.; Tabrizian, M. Toward resolving the challenges of sepsis diagnosis. Clin. Chem., 2004, 8, 1301-1314.
Morrell, M.; Fraser, V.J.; Kollef, M.H. Delaying the empiric treatment of Candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob. Agents Chemother., 2005, 49, 3640-3645.
Hugonnet, S.; Sax, H.; Eggimann, P.; Chevrolet, J.C.; Pittet, D. Nosocomial bloodstream infection and clinical sepsis. Emerg. Infect. Dis., 2004, 10, 76-81.
Avolio, M.; Diamante, P.; Zamparo, S.; Modolo, M.L.; Grosso, S.; Zigante, P.; Tosoni, N.; De Rosa, R.; Stano, P.; Camporese, A. Molecular identification of bloodstream pathogens in patients presenting to the emergency department with suspected sepsis. Shock, 2010, 34, 27-30.
Lehmann, L.E.; Hunfeld, K.P.; Emrich, T.; Haberhausen, G.; Wissing, H.; Hoeft, A.; Stüber, F. A multiplex real-time PCR assay for rapid detection and differentiation of 25 bacterial and fungal pathogens from whole blood samples. Med. Microbiol. Immunol., 2008, 197, 313-324.
von Lilienfeld-Toal, M.; Lehmann, L.E.; Raadts, A.D.; Hahn-Ast, C.; Orlopp, K.S.; Marklein, G.; Purr, I.; Cook, G.; Hoeft, A.; Glasmacher, A.; Stüber, F. Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia. J. Clin. Microbiol., 2009, 47, 2405-2410.
Sun, Y.; Huang, H.; Chen, J.; Li, J.; Ma, J.; Li, J.; Liang, Y.; Wang, J.; Li, Y.; Yu, K.; Hu, J.; Jin, J.; Wang, C.; Wu, D.; Xiao, Y.; Huang, X. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumour Biol., 2015, 36, 757-767.
Erjavec, Z. Kluin-Nele mans, H.; Verweij, P. E. Trends in invasive fungal infections, with emphasis on invasive aspergillosis. Clin. Microbiol. Infect., 2009, 15, 625-633.
Warnock, D.W. Trends in epidemiology of invasive fungal infections. Jpn. J. Med. Mycol, 2007, 48, 1-12.
Donhujisen, K.; Petersen, P.; Schmid, K.W. Trend reversal in the frequency of mycoses in hematological neoplasias. Dtsch. Arztebl. Int., 2008, 105, 501-506.
Ruhnke, M. Epidemiology of Candida albicans infections and role of non-Candida -albicans yeasts. Curr. Drug Targets, 2006, 7(4), 495-504.
Marr, K.A. Invasive Candida infections: the changing epidemiology. Oncology, 2004, 18, 9-14.
Marr, K.A.; Carter, R.A.; Crippa, F.; Wald, A.; Corey, L. Epidemiology and outcome of mold infections in hematopoietic stem cell transplantation recipients. Clin. Infect. Dis., 2002, 34, 909-917.
Bow, E.J.; Laverdière, M.; Lussier, N.; Rotstein, C.; Cheang, M.S.; Ioannou, S. Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer, 2002, 94, 3230-3246.
Leroy, O.; Gangneux, J.P.; Montravers, P.; Mira, J.P.; Gouin, F.; Sollet, J.P.; Carlet, J.; Reynes, J.; Rosenheim, M.; Regnier, B.; Lortholary, O. AmarCand Study Group. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006). Crit. Care Med., 2009, 37, 1612-1618.
Mauro, M.V.; Cavalcanti, P.; Perugini, D.; Noto, A.; Sperlì, D.; Giraldi, C. Diagnostic utility of Light Cycler SeptiFast and procalcitonin assays in the diagnosis of bloodstream infection in immunocompromised patients. Diagn. Microbiol. Infect. Dis., 2012, 73, 308-311.
Paolucci, M.; Stanzani, M.; Melchionda, F.; Tolomelli, G.; Castellani, G.; Landini, M.P.; Varani, S.; Lewis, R.E.; Sambri, V. Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients. Diagn. Microbiol. Infect. Dis., 2013, 75, 130-134.
Grace, C.J.; Lieberman, J.; Pierce, K.; Littenberg, B. Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. Clin. Infect. Dis., 2001, 32, 1651-1655.
Serody, J.S.; Berrey, M.M.; Albritton, K.; O’Brien, S.M.; Capel, E.P.; Bigelow, S.H.; Weber, D.J.; Gabriel, D.A.; Wiley, J.M.; Schell, M.J.; Gilligan, P.H.; Shea, T.C. Utility of obtaining blood cultures in febrile neutropenic patients undergoing bone marrow transplantation. Bone Marrow Transplant., 2000, 26, 533-538.
Paolucci, M.; Stanzani, M.; Melchionda, F.; Tolomelli, G.; Castellani, G.; Landini, M.P.; Varani, S.; Lewis, R.E.; Sambri, V. Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients. Diagn. Microbiol. Infect. Dis., 2013, 75, 130-134.
Jiang, H.H.; Zhang, H.; She, G.R.; Zhang, J.W.; Zhang, D. Historical and geography studies on deep mycosis in China since 1950 to 2007. Chin. J. Mycol. (Chin), 2010, 5, 148-153.
Martino, R.; Subira, M. Invasive fungal infections in hematology: new trends. Ann. Hematol., 2002, 81, 233-243.
Reynolds, L.; McKee, M. Factors influencing antibiotic prescribing in China: an exploratory analysis. Health Policy, 2009, 90, 32-36.
Caira, M.; Trecarichi, E.M.; Mancinelli, M.; Leone, G.; Pagano, L. Uncommon mold infections in hematological patients: epidemiology, diagnosis and treatment. Expert Rev. Anti Infect. Ther., 2011, 9, 881-892.
Rammaert, B.; Lanternier, F.; Poirée, S.; Kania, R.; Lortholary, O. Diabetes and mucormycosis: a complex interplay. Diabetes Metab., 2012, 38, 193-204.
Guinea, J.; Torres-Narbona, M.; Gijón, P.; Muñoz, P.; Pozo, F.; Peláez, T.; de Miguel, J.; Bouza, E. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin. Microbiol. Infect., 2010, 16, 870-877.
Chang, S.S.; Hsieh, W.H.; Liu, T.S.; Lee, S.H.; Wang, C.H.; Chou, H.C.; Yeo, Y.H.; Tseng, C.P.; Lee, C.C. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis. PLoS One, 2013, 8, e62323.
El-Mahallawy, H.A.; Shaker, H.H.; Ali Helmy, H.; Mostafa, T. Razak, Abo-Sedah. A. Evaluation of pan-fungal PCR assay and Aspergillus antigen detection in the diagnosis of invasive fungal infections in high risk paediatric cancer patients. Med. Mycol., 2006, 44, 733-739.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy