Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Werner Heinz1, Dieter Buchheidt2, Maximilian Christopeit3, Marie von Lilienfeld‐Toal4, Oliver A. Cornely5, Hermann Einsele1, Meinolf Karthaus6, Hartmut Link7, Rolf Mahlberg8, Silke Neumann9, Helmut Ostermann10, Olaf Penack11, Markus Ruhnke12, Michael Sandherr13, Xaver Schiel14, Jörg Janne Vehreschild15, Florian Weißinger16, Georg Maschmeyer17
1Department of Internal Medicine II, University of Würzburg Medical Center, Würzburg, Germany
2Department of Internal Medicine-Hematology and Oncology, Mannheim University Hospital, Mannheim, Germany
3Department of Stem Cell Transplantation, University Hospital UKE, Hamburg, Germany
4Department of Hematology and Oncology, University Hospital of Jena, Jena, Germany
5Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany
6Department of Hematology, Oncology and Palliative Care, Klinikum Neuperlach and Klinikum Harlaching, München, Germany
7Hematology and Medical Oncology Private Practice, Kaiserslautern, Germany
8Klinikum Mutterhaus der Borromäerinnen, Trier, Germany
9Medical Oncology, AMO MVZ, Wolfsburg, Germany
10Department of Hematology and Oncology, University of Munich, Munich, Germany
11Internal Medicine, Hematology, Oncology and Tumor Immunology, University Hospital Charité, Campus Virchow Klinikum, Berlin, Germany
12Department of Hematology and Oncology, Paracelsus-Klinik, Osnabrück, Germany
13Hematology and Oncology Practice, Weilheim, Germany
14Department of Hematology, Oncology and Palliative Care, Klinikum Harlaching, Munich, Germany
15German Centre for Infection Research, Partner Site Bonn-Cologne, Cologne, Germany
16Department of Internal Medicine, Hematology, Oncology and Palliative Care, Evangelisches Klinikum Bethel, Bielefeld, Germany
17Department of Hematology, Oncology and Palliative Care, Klinikum Ernst von Bergmann, Potsdam, Germany

Tóm tắt

Từ khóa


Tài liệu tham khảo

Bodey GP (1966) Infectious complications of acute leukemia. Med Times 94(9):1076–1085

Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH (2006) Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106(10):2258–2266. doi: 10.1002/cncr.21847

Link H, Böhme A, Cornely OA, Höffken K, Kellner O, Kern WV, Mahlberg R, Maschmeyer G, Nowrousian MR, Ostermann H, Ruhnke M, Sezer O, Schiel X, Wilhelm M, Auner HW (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). Ann Hematol 82(Suppl 2):S105–S117. doi: 10.1007/s00277-003-0764-4

Penack O, Becker C, Buchheidt D, Christopeit M, Kiehl M, von Lilienfeld-Toal M, Hentrich M, Reinwald M, Salwender H, Schalk E, Schmidt-Hieber M, Weber T, Ostermann H (2014) Management of sepsis in neutropenic patients: 2014 updated guidelines from the Infectious Diseases Working Party of the German Society of hematology and medical oncology (AGIHO). Ann Hematol 93(7):1083–1095. doi: 10.1007/s00277-014-2086-0

Neumann S, Krause SW, Maschmeyer G, Schiel X, von Lilienfeld-Toal M (2013) Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 92(4):433–442. doi: 10.1007/s00277-013-1698-0

Tacke D, Buchheidt D, Karthaus M, Krause SW, Maschmeyer G, Neumann S, Ostermann H, Penack O, Rieger C, Ruhnke M, Sandherr M, Schweer KE, Ullmann AJ, Cornely OA (2014) Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Ann Hematol 93(9):1449–1456. doi: 10.1007/s00277-014-2108-y

Ullmann AJ, Schmidt-Hieber M, Bertz H, Heinz WJ, Kiehl M, Kruger W, Mousset S, Neuburger S, Neumann S, Penack O, Silling G, Vehreschild JJ, Einsele H, Maschmeyer G (2016) Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol 95(9):1435–1455. doi: 10.1007/s00277-016-2711-1

Ruhnke M, Böhme A, Buchheidt D, Cornely O, Donhuijsen K, Einsele H, Enzensberger R, Hebart H, Heussel CP, Horger M, Hof H, Karthaus M, Kruger W, Maschmeyer G, Penack O, Ritter J, Schwartz S (2012) Diagnosis of invasive fungal infections in hematology and oncology—guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German Society for Haematology and Oncology (AGIHO). Ann Oncol 23(4):823–833. doi: 10.1093/annonc/mdr407

Mousset S, Buchheidt D, Heinz W, Ruhnke M, Cornely O, Egerer G, Krüger W, Link H, Neumann S, Ostermann H, Panse J, Penack O, Rieger C, Schmidt-Hieber M, Silling G, Südhoff T, Ullmann A, Wolf H-H, Maschmeyer G, Böhme A (2013) Treatment of invasive fungal infections in cancer patients—updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 93:13–32. doi: 10.1007/s00277-013-1867-1

Maschmeyer G, Carratala J, Buchheidt D, Hamprecht A, Heussel CP, Kahl C, Lorenz J, Neumann S, Rieger C, Ruhnke M, Salwender H, Schmidt-Hieber M, Azoulay E, Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (2015) Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol 26(1):21–33. doi: 10.1093/annonc/mdu192

Vehreschild MJ, Vehreschild JJ, Hubel K, Hentrich M, Schmidt-Hieber M, Christopeit M, Maschmeyer G, Schalk E, Cornely OA, Neumann S (2013) Diagnosis and management of gastrointestinal complications in adult cancer patients: evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Oncol 24(5):1189–1202. doi: 10.1093/annonc/mdt001

Hentrich M, Schalk E, Schmidt-Hieber M, Chaberny I, Mousset S, Buchheidt D, Ruhnke M, Penack O, Salwender H, Wolf HH, Christopeit M, Neumann S, Maschmeyer G, Karthaus M, Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (2014) Central venous catheter-related infections in hematology and oncology: 2012 updated guidelines on diagnosis, management and prevention by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology. Ann Oncol 25(5):936–947. doi: 10.1093/annonc/mdt545

Schmidt-Hieber M, Silling G, Schalk E, Heinz W, Panse J, Penack O, Christopeit M, Buchheidt D, Meyding-Lamade U, Hahnel S, Wolf HH, Ruhnke M, Schwartz S, Maschmeyer G (2016) CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). Ann Oncol 27(7):1207–1225. doi: 10.1093/annonc/mdw155

Weissinger F, Auner HW, Bertz H, Buchheidt D, Cornely OA, Egerer G, Heinz W, Karthaus M, Kiehl M, Kruger W, Penack O, Reuter S, Ruhnke M, Sandherr M, Salwender HJ, Ullmann AJ, Waldschmidt DT, Wolf HH (2012) Antimicrobial therapy of febrile complications after high-dose chemotherapy and autologous hematopoietic stem cell transplantation—guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 91(8):1161–1174. doi: 10.1007/s00277-012-1456-8

von Lilienfeld-Toal M, Berger A, Christopeit M, Hentrich M, Heussel CP, Kalkreuth J, Klein M, Kochanek M, Penack O, Hauf E, Rieger C, Silling G, Vehreschild M, Weber T, Wolf HH, Lehners N, Schalk E, Mayer K (2016) Community acquired respiratory virus infections in cancer patients—guideline on diagnosis and management by the Infectious Diseases Working Party of the German Society for Haematology and Medical Oncology. Eur J Cancer (Oxf, Engl: 1990) 67:200–212. doi: 10.1016/j.ejca.2016.08.015

Ullmann AJ, Akova M, Herbrecht R, Viscoli C, Arendrup MC, Arikan-Akdagli S, Bassetti M, Bille J, Calandra T, Castagnola E, Cornely OA, Donnelly JP, Garbino J, Groll AH, Hope WW, Jensen HE, Kullberg BJ, Lass-Florl C, Lortholary O, Meersseman W, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Cuenca-Estrella M (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect 18(Suppl 7):53–67. doi: 10.1111/1469-0691.12041

Klastersky J, Paesmans M, Rubenstein EB, Boyer M, Elting L, Feld R, Gallagher J, Herrstedt J, Rapoport B, Rolston K, Talcott J (2000) 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 18(16):3038–3051. doi: 10.1200/jco.2000.18.16.3038

Kern WV, Cometta A, De Bock R, Langenaeken J, Paesmans M, Gaya H (1999) Oral versus intravenous empirical antimicrobial therapy for fever in patients with granulocytopenia who are receiving cancer chemotherapy. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 341(5):312–318. doi: 10.1056/nejm199907293410502

Kern WV, Marchetti O, Drgona L, Akan H, Aoun M, Akova M, de Bock R, Paesmans M, Viscoli C, 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. J Clin Oncol 31(9):1149–1156. doi: 10.1200/jco.2012.45.8109

Nakagawa Y, Suzuki K, Masaoka T (2009) Evaluation of the risk factors for febrile neutropenia associated with hematological malignancy. J Infect Chemother 15(3):174–179. doi: 10.1007/s10156-009-0683-y

Cherif H, Johansson E, Björkholm M, Kalin M (2006) The feasibility of early hospital discharge with oral antimicrobial therapy in low risk patients with febrile neutropenia following chemotherapy for hematologic malignancies. Haematologica 91(2):215–222

Link H, Maschmeyer G, Meyer P, Hiddemann W, Stille W, Helmerking M, Adam D (1994) Interventional antimicrobial therapy in febrile neutropenic patients. Study Group of the Paul Ehrlich Society for Chemotherapy. Ann Hematol 69(5):231–243

Elting LS, Rubenstein EB, Rolston KV, Bodey GP (1997) Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clin Infect Dis 25(2):247–259

Wisplinghoff H, Cornely OA, Moser S, Bethe U, Stutzer H, Salzberger B, Fatkenheuer G, Seifert H (2003) Outcomes of nosocomial bloodstream infections in adult neutropenic patients: a prospective cohort and matched case-control study. Infect Control Hosp Epidemiol 24(12):905–911. doi: 10.1086/502158

Kirchhoff LV, Sheagren JN (1985) Epidemiology and clinical significance of blood cultures positive for coagulase-negative staphylococcus. Infect Control: IC 6(12):479–486

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 ME, Melillo L, Aversa F, Van Lint MT, Falcucci P, Valentini CG, Girmenia C, Nosari A (2006) The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 91(8):1068–1075

Kern WV, Klose K, Jellen-Ritter AS, Oethinger M, Bohnert J, Kern P, Reuter S, von Baum H, Marre R (2005) Fluoroquinolone resistance of Escherichia coli at a cancer center: epidemiologic evolution and effects of discontinuing prophylactic fluoroquinolone use in neutropenic patients with leukemia. Eur J Clin Microbiol Infect Dis 24(2):111–118. doi: 10.1007/s10096-005-1278-x

Kern WV, Andriof E, Oethinger M, Kern P, Hacker J, Marre R (1994) Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center. Antimicrob Agents Chemother 38(4):681–687

Ruhnke M, Arnold R, Gastmeier P (2014) Infection control issues in patients with haematological malignancies in the era of multidrug-resistant bacteria. Lancet Oncol 15(13):e606–e619. doi: 10.1016/s1470-2045(14)70344-4

Saito T, Yoshioka S, Iinuma Y, Takakura S, Fujihara N, Ichinohe T, Ishikawa T, Uchiyama T, Ichiyama S (2008) Effects on spectrum and susceptibility patterns of isolates causing bloodstream infection by restriction of fluoroquinolone prophylaxis in a hematology-oncology unit. Eur J Clin Microbiol Infect Dis 27(3):209–216. doi: 10.1007/s10096-007-0428-8

Bossaer JB, Hall PD, Garrett-Mayer E (2010) Incidence of vancomycin-resistant enterococci (VRE) infection in high-risk febrile neutropenic patients colonized with VRE. Support Care Cancer 19(2):231–237. doi: 10.1007/s00520-009-0808-y

Matar MJ, Safdar A, Rolston KV (2006) Relationship of colonization with vancomycin-resistant enterococci and risk of systemic infection in patients with cancer. Clin Infect Dis 42(10):1506–1507. doi: 10.1086/503675

Charbonneau P, Parienti JJ, Thibon P, Ramakers M, Daubin C, du Cheyron D, Lebouvier G, Le Coutour X, Leclercq R (2006) Fluoroquinolone use and methicillin-resistant Staphylococcus aureus isolation rates in hospitalized patients: a quasi experimental study. Clin Infect Dis 42(6):778–784. doi: 10.1086/500319

Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS (2005) Fluoroquinolone prescribing in the United States: 1995 to 2002. Am J Med 118(3):259–268. doi: 10.1016/j.amjmed.2004.09.015

Goossens H, Ferech M, Vander Stichele R, Elseviers M (2005) Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet (Lond, Engl) 365(9459):579–587. doi: 10.1016/s0140-6736(05)17907-0

Liss BJ, Vehreschild JJ, Cornely OA, Hallek M, Fätkenheuer G, Wisplinghoff H, Seifert H, Vehreschild MJGT (2012) Intestinal colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and oncological malignancies. Infection 40(6):613–619. doi: 10.1007/s15010-012-0269-y

Cumpston A, Craig M, Hamadani M, Abraham J, Hobbs GR, Sarwari AR (2013) Extended follow-up of an antibiotic cycling program for the management of febrile neutropenia in a hematologic malignancy and hematopoietic cell transplantation unit. Transpl Infect Dis 15(2):142–149. doi: 10.1111/tid.12035

Vehreschild MJ, Hamprecht A, Peterson L, Schubert S, Hantschel M, Peter S, Schafhausen P, Rohde H, Lilienfeld-Toal MV, Bekeredjian-Ding I, Libam J, Hellmich M, Vehreschild JJ, Cornely OA, Seifert H (2014) A multicentre cohort study on colonization and infection with ESBL-producing Enterobacteriaceae in high-risk patients with haematological malignancies. J Antimicrob Chemother 69(12):3387–3392. doi: 10.1093/jac/dku305

Ng ES, Liew Y, Koh LP, Hsu LY (2010) Fluoroquinolone prophylaxis against febrile neutropenia in areas with high fluoroquinolone resistance—an Asian perspective. J Formos Med Assoc 109(9):624–631. doi: 10.1016/s0929-6646(10)60102-7

Jones BM, Bland CM (2017) Penicillin skin testing as an antimicrobial stewardship initiative. Am J Health Syst Pharm 74(4):232–237. doi: 10.2146/ajhp160233

Macy E, Khan DA, Castells MC, Lang DM (2017) Penicillin allergy testing: a key component of antibiotic stewardship. Clin Infect Dis 64(4):531–532. doi: 10.1093/cid/ciw795

Rimawi RH, Cook PP, Gooch M, Kabchi B, Ashraf MS, Rimawi BH, Gebregziabher M, Siraj DS (2013) The impact of penicillin skin testing on clinical practice and antimicrobial stewardship. J Hosp Med 8(6):341–345. doi: 10.1002/jhm.2036

Maertens J, Theunissen K, Verbeken E, Lagrou K, Verhaegen J, Boogaerts M, Eldere JV (2004) Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol 126(6):852–860. doi: 10.1111/j.1365-2141.2004.05140.x

Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Boogaerts M (2001) Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 97(6):1604–1610

Pazos C, Ponton J, Del Palacio A (2005) Contribution of (1->3)-beta-d-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. J Clin Microbiol 43(1):299–305. doi: 10.1128/jcm.43.1.299-305.2005

Senn L, Robinson JO, Schmidt S, Knaup M, Asahi N, Satomura S, Matsuura S, Duvoisin B, Bille J, Calandra T, Marchetti O (2008) 1,3-Beta-d-glucan antigenemia for early diagnosis of invasive fungal infections in neutropenic patients with acute leukemia. Clin Infect Dis 46(6):878–885. doi: 10.1086/527382

Mengoli C, Cruciani M, Barnes RA, Loeffler J, Donnelly JP (2009) Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis 9(2):89–96. doi: 10.1016/s1473-3099(09)70019-2

Marr KA, Laverdiere M, Gugel A, Leisenring W (2005) Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Clin Infect Dis 40(12):1762–1769. doi: 10.1086/429921

Reinwald M, Hummel M, Kovalevskaya E, Spiess B, Heinz WJ, Vehreschild JJ, Schultheis B, Krause SW, Claus B, Suedhoff T, Schwerdtfeger R, Reuter S, Kiehl MG, Hofmann WK, Buchheidt D (2012) Therapy with antifungals decreases the diagnostic performance of PCR for diagnosing invasive aspergillosis in bronchoalveolar lavage samples of patients with haematological malignancies. J Antimicrob Chemother 67(9):2260–2267. doi: 10.1093/jac/dks208

Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM (2014) Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 42(8):1749–1755. doi: 10.1097/ccm.0000000000000330

Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34(6):1589–1596. doi: 10.1097/01.ccm.0000217961.75225.e9

Legrand M, Max A, Peigne V, Mariotte E, Canet E, Debrumetz A, Lemiale V, Seguin A, Darmon M, Schlemmer B, Azoulay E (2012) Survival in neutropenic patients with severe sepsis or septic shock. Crit Care Med 40(1):43–49. doi: 10.1097/CCM.0b013e31822b50c2

Perron T, Emara M, Ahmed S (2014) Time to antibiotics and outcomes in cancer patients with febrile neutropenia. BMC Health Serv Res 14:162. doi: 10.1186/1472-6963-14-162

Lee A, Mirrett S, Reller LB, Weinstein MP (2007) Detection of bloodstream infections in adults: how many blood cultures are needed? J Clin Microbiol 45(11):3546–3548. doi: 10.1128/jcm.01555-07

Cockerill FR 3rd, Wilson JW, Vetter EA, Goodman KM, Torgerson CA, Harmsen WS, Schleck CD, Ilstrup DM, Washington JA 2nd, Wilson WR (2004) Optimal testing parameters for blood cultures. Clin Infect Dis 38(12):1724–1730. doi: 10.1086/421087

Guembe M, Rodriguez-Creixems M, Sanchez-Carrillo C, Perez-Parra A, Martin-Rabadan P, Bouza E (2010) How many lumens should be cultured in the conservative diagnosis of catheter-related bloodstream infections? Clin Infect Dis 50(12):1575–1579. doi: 10.1086/652766

Blot F, Nitenberg G, Chachaty E, Raynard B, Germann N, Antoun S, Laplanche A, Brun-Buisson C, Tancrede C (1999) Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet (Lond, Engl) 354(9184):1071–1077

Seifert H, Cornely O, Seggewiss K, Decker M, Stefanik D, Wisplinghoff H, Fätkenheuer G (2003) Bloodstream infection in neutropenic cancer patients related to short-term nontunnelled catheters determined by quantitative blood cultures, differential time to positivity, and molecular epidemiological typing with pulsed-field gel electrophoresis. J Clin Microbiol 41(1):118–123

Tissari P, Zumla A, Tarkka E, Mero S, Savolainen L, Vaara M, Aittakorpi A, Laakso S, Lindfors M, Piiparinen H, Maki M, Carder C, Huggett J, Gant V (2010) Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study. Lancet (Lond, Engl) 375(9710):224–230. doi: 10.1016/s0140-6736(09)61569-5

von Lilienfeld-Toal M, Lehmann LE, Raadts AD, Hahn-Ast C, Orlopp KS, Marklein G, Purr I, Cook G, Hoeft A, Glasmacher A, Stuber F (2009) Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia. J Clin Microbiol 47(8):2405–2410. doi: 10.1128/jcm.00491-09

Mancini N, Clerici D, Diotti R, Perotti M, Ghidoli N, De Marco D, Pizzorno B, Emrich T, Burioni R, Ciceri F, Clementi M (2008) Molecular diagnosis of sepsis in neutropenic patients with haematological malignancies. J Med Microbiol 57(Pt 5):601–604. doi: 10.1099/jmm.0.47732-0

Guido M, Quattrocchi M, Zizza A, Pasanisi G, Pavone V, Lobreglio G, Gabutti G, De Donno A (2012) Molecular approaches in the diagnosis of sepsis in neutropenic patients with haematological malignances. J Prev Med Hyg 53(2):104–108

Desmet S, Maertens J, Bueselinck K, Lagrou K (2016) Broad-range PCR coupled with electrospray ionization time of flight mass spectrometry for detection of bacteremia and Fungemia in patients with neutropenic fever. J Clin Microbiol 54(10):2513–2520. doi: 10.1128/jcm.01066-16

Lamoth F, Jaton K, Prod'hom G, Senn L, Bille J, Calandra T, Marchetti O (2010) Multiplex blood PCR in combination with blood cultures for improvement of microbiological documentation of infection in febrile neutropenia. J Clin Microbiol 48(10):3510–3516. doi: 10.1128/jcm.00147-10

von Lilienfeld-Toal M, Dietrich MP, Glasmacher A, Lehmann L, Breig P, Hahn C, Schmidt-Wolf IG, Märklein G, Schroeder S, Stuber F (2004) Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein. Eur J Clin Microbiol Infect Dis 23(7):539–544. doi: 10.1007/s10096-004-1156-y

Persson L, Soderquist B, Engervall P, Vikerfors T, Hansson LO, Tidefelt U (2005) Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia. Eur J Haematol 74(4):297–303. doi: 10.1111/j.1600-0609.2004.00387.x

de Bont ES, Vellenga E, Swaanenburg JC, Fidler V, Visser-van Brummen PJ, Kamps WA (1999) Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia. Br J Haematol 107(2):375–380

Prat C, Sancho JM, Dominguez J, Xicoy B, Gimenez M, Ferra C, Blanco S, Lacoma A, Ribera JM, Ausina V (2008) Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk & Lymphoma 49(9):1752–1761. doi: 10.1080/10428190802258956

Steinmetz HT, Herbertz A, Bertram M, Diehl V (1995) Increase in interleukin-6 serum level preceding fever in granulocytopenia and correlation with death from sepsis. J Infect Dis 171(1):225–228

Wu CW, Wu JY, Chen CK, Huang SL, Hsu SC, Lee MT, Chang SS, Lee CC (2015) Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis. Support Care Cancer 23(10):2863–2872. doi: 10.1007/s00520-015-2650-8

Korones DN (2004) Is routine chest radiography necessary for the initial evaluation of fever in neutropenic children with cancer? Pediatr Blood Cancer 43(7):715–717. doi: 10.1002/pbc.20226

Navigante AH, Cerchietti LC, Costantini P, Salgado H, Castro MA, Lutteral MA, Cabalar ME (2002) Conventional chest radiography in the initial assessment of adult cancer patients with fever and neutropenia. Cancer Control 9(4):346–351

Oude Nijhuis CS, Gietema JA, Vellenga E, Daenen SM, De Bont ES, Kamps WA, Groen HJ, van der Jagt EJ, van der Graaf WT (2003) Routine radiography does not have a role in the diagnostic evaluation of ambulatory adult febrile neutropenic cancer patients. Eur J Cancer (Oxf, Engl: 1990) 39(17):2495–2498

Talbot GH, Huang A, Provencher M (1991) Invasive Aspergillus rhinosinusitis in patients with acute leukemia. Rev Infect Dis 13(2):219–232

Camus V, Edet-Sanson A, Bubenheim M, Hitzel A, Becker S, David M, Stamatoullas A, Lenain P, Jardin F, Contentin N, Fontoura ML, Cardinael N, Vaudaux S, Dubois S, Tilly H, Vera P, Lepretre S (2015) (1)(8)F-FDG-PET/CT imaging in patients with febrile neutropenia and Haematological malignancies. Anticancer Res 35(5):2999–3005

Gafter-Gvili A, Paul M, Bernstine H, Vidal L, Ram R, Raanani P, Yeshurun M, Tadmor B, Leibovici L, Shpilberg O, Groshar D (2013) The role of (1)(8)F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia. Leuk Res 37(9):1057–1062. doi: 10.1016/j.leukres.2013.06.025

Guy SD, Tramontana AR, Worth LJ, Lau E, Hicks RJ, Seymour JF, Thursky KA, Slavin MA (2012) Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients. Eur J Nucl Med Mol Imaging 39(8):1348–1355. doi: 10.1007/s00259-012-2143-7

Vos FJ, Donnelly JP, Oyen WJ, Kullberg BJ, Bleeker-Rovers CP, Blijlevens NM (2012) 18F-FDG PET/CT for diagnosing infectious complications in patients with severe neutropenia after intensive chemotherapy for haematological malignancy or stem cell transplantation. Eur J Nucl Med Mol Imaging 39(1):120–128. doi: 10.1007/s00259-011-1939-1

Bavaro MF (2002) Neutropenic enterocolitis. Curr Gastroenterol Rep 4(4):297–301

Gorschlüter M, Mey U, Strehl J, Ziske C, Schepke M, Schmidt-Wolf IG, Sauerbruch T, Glasmacher A (2005) Neutropenic enterocolitis in adults: systematic analysis of evidence quality. Eur J Haematol 75(1):1–13. doi: 10.1111/j.1600-0609.2005.00442.x

van Vliet M, Potting CM, Sturm PD, Donnelly JP, Blijlevens NM (2011) How prompt is prompt in daily practice? Earlier initiation of empirical antibacterial therapy for the febrile neutropenic patient. Eur J Cancer Care 20(5):679–685. doi: 10.1111/j.1365-2354.2011.01264.x

Yahav D, Paul M, Fraser A, Sarid N, Leibovici L (2007) Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis 7(5):338–348. doi: 10.1016/s1473-3099(07)70109-3

Kim PW, Wu YT, Cooper C, Rochester G, Valappil T, Wang Y, Kornegay C, Nambiar S (2010) Meta-analysis of a possible signal of increased mortality associated with cefepime use. Clin Infect Dis 51(4):381–389. doi: 10.1086/655131

Research UFaDACfDEa (2009) Statistical review and evaluation. Clinical studies NDA number 50-679. Drug name: Maxipime 04/22/2009

McCullough BJ, Wiggins LE, Richards A, Klinker K, Hiemenz JW, Wingard JR (2014) Aztreonam for febrile neutropenia in patients with beta-lactam allergy. Transpl Infect Dis 16(1):145–152. doi: 10.1111/tid.12148

Raad II, Whimbey EE, Rolston KV, Abi-Said D, Hachem RY, Pandya RG, Ghaddar HM, Karl CL, Bodey GP (1996) A comparison of aztreonam plus vancomycin and imipenem plus vancomycin as initial therapy for febrile neutropenic cancer patients. Cancer 77(7):1386–1394. doi: 10.1002/(sici)1097-0142(19960401)77:7<1386::aid-cncr25>3.0.co;2-x

Nesher L, Tverdek FP, Mahajan SN, Chemaly RF, Rolston KV (2015) Ertapenem usage in cancer patients with and without neutropenia: a report on 97 cases from a comprehensive cancer center. Infection 43(5):545–550. doi: 10.1007/s15010-015-0784-8

Toya T, Nannya Y, Narukawa K, Ichikawa M, Kurokawa M (2012) A comparative analysis of meropenem and doripenem in febrile patients with hematologic malignancies: a single-center retrospective study. Jpn J Infect Dis 65(3):228–232

Hachem R, Reitzel R, Rolston K, Chaftari AM, Raad I (2017) Antimicrobial activities of ceftazidime-avibactam and comparator agents against clinical bacteria isolated from patients with cancer. Antimicrob Agents Chemother 61 (4). doi: 10.1128/aac.02106-16

Aitken SL, Kontoyiannis DP, DePombo AM, Bhatti MM, Tverdek FP, Gettys SC, Nicolau DP, Nunez CA (2016) Use of Ceftolozane/Tazobactam in the treatment of multidrug-resistant Pseudomonas aeruginosa bloodstream infection in a pediatric leukemia patient. Pediatr Infect Dis J 35(9):1040–1042. doi: 10.1097/inf.0000000000001228

Nakane T, Tamura K, Hino M, Tamaki T, Yoshida I, Fukushima T, Tatsumi Y, Nakagawa Y, Hatanaka K, Takahashi T, Akiyama N, Tanimoto M, Ohyashiki K, Urabe A, Masaoka T, Kanamaru A (2015) Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: a multicenter prospective randomized trial. J Infect Chemother 21(1):16–22. doi: 10.1016/j.jiac.2014.08.026

Bucaneve G, Micozzi A, Picardi M, Ballanti S, Cascavilla N, Salutari P, Specchia G, Fanci R, Luppi M, Cudillo L, Cantaffa R, Milone G, Bocchia M, Martinelli G, Offidani M, Chierichini A, Fabbiano F, Quarta G, Primon V, Martino B, Manna A, Zuffa E, Ferrari A, Gentile G, Foa R, Del Favero A (2014) Results of a multicenter, controlled, randomized clinical trial evaluating the combination of piperacillin/tazobactam and tigecycline in high-risk hematologic patients with cancer with febrile neutropenia. J Clin Oncol 32(14):1463–1471. doi: 10.1200/jco.2013.51.6963

Schwab KS, Hahn-Ast C, Heinz WJ, Germing U, Egerer G, Glasmacher A, Leyendecker C, Märklein G, Nellessen CM, Brossart P, von Lilienfeld-Toal M (2014) Tigecycline in febrile neutropenic patients with haematological malignancies: a retrospective case documentation in four university hospitals. Infection 42(1):97–104. doi: 10.1007/s15010-013-0524-x

Paul M, Yahav D, Bivas A, Fraser A, Leibovici L (2010) Anti-pseudomonal beta-lactams for the initial, empirical, treatment of febrile neutropenia: comparison of beta-lactams. Cochrane Database Syst Rev 11:CD005197. doi: 10.1002/14651858.CD005197.pub3

Tamma PD, Cosgrove SE, Maragakis LL (2012) Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev 25(3):450–470. doi: 10.1128/cmr.05041-11

Furno P, Bucaneve G, Del Favero A (2002) Monotherapy or aminoglycoside-containing combinations for empirical antibiotic treatment of febrile neutropenic patients: a meta-analysis. Lancet Infect Dis 2(4):231–242

Paul M, Soares-Weiser K, Grozinsky S, Leibovici L (2003) Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropaenia. Cochrane Database Syst Rev 3:CD003038. doi: 10.1002/14651858.cd003038

Marcus R, Paul M, Elphick H, Leibovici L (2011) Clinical implications of beta-lactam-aminoglycoside synergism: systematic review of randomised trials. Int J Antimicrob Agents 37(6):491–503. doi: 10.1016/j.ijantimicag.2010.11.029

Mavros MN, Polyzos KA, Rafailidis PI, Falagas ME (2011) Once versus multiple daily dosing of aminoglycosides for patients with febrile neutropenia: a systematic review and meta-analysis. J Antimicrob Chemother 66(2):251–259. doi: 10.1093/jac/dkq451

Vardakas KZ, Samonis G, Chrysanthopoulou SA, Bliziotis IA, Falagas ME (2005) Role of glycopeptides as part of initial empirical treatment of febrile neutropenic patients: a meta-analysis of randomised controlled trials. Lancet Infect Dis 5(7):431–439. doi: 10.1016/s1473-3099(05)70164-x

Zaas AK, Song X, Tucker P, Perl TM (2002) Risk factors for development of vancomycin-resistant enterococcal bloodstream infection in patients with cancer who are colonized with vancomycin-resistant enterococci. Clin Infect Dis 35(10):1139–1146. doi: 10.1086/342904

Lisboa LF, Miranda BG, Vieira MB, Dulley FL, Fonseca GG, Guimaraes T, Levin AS, Shikanai-Yasuda MA, Costa SF (2015) Empiric use of linezolid in febrile hematology and hematopoietic stem cell transplantation patients colonized with vancomycin-resistant enterococcus spp. Int J Infect Dis 33:171–176. doi: 10.1016/j.ijid.2015.02.001

Teuffel O, Ethier MC, Alibhai SM, Beyene J, Sung L (2011) Outpatient management of cancer patients with febrile neutropenia: a systematic review and meta-analysis. Ann Oncol 22(11):2358–2365. doi: 10.1093/annonc/mdq745

Innes HE, Smith DB, O'Reilly SM, Clark PI, Kelly V, 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. Br J Cancer 89(1):43–49. doi: 10.1038/sj.bjc.6600993

Grillon A, Schramm F, Kleinberg M, Jehl F (2016) Comparative activity of ciprofloxacin, levofloxacin and moxifloxacin against Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia assessed by minimum inhibitory concentrations and time-kill studies. PLoS One 11(6):e0156690. doi: 10.1371/journal.pone.0156690

Rolston KV, Frisbee-Hume S, LeBlanc B, Streeter H, Ho DH (2003) In vitro antimicrobial activity of moxifloxacin compared to other quinolones against recent clinical bacterial isolates from hospitalized and community-based cancer patients. Diagn Microbiol Infect Dis 47(2):441–449

Rubenstein EB, Rolston K, Benjamin RS, Loewy J, Escalante C, Manzullo E, Hughes P, Moreland B, Fender A, Kennedy K et al (1993) Outpatient treatment of febrile episodes in low-risk neutropenic patients with cancer. Cancer 71(11):3640–3646

Sipsas NV, Kosmas C, Ziakas PD, Karabelis A, Vadiaka M, Skopelitis E, Kordossis T, Tsavaris N (2007) Comparison of two oral regimens for the outpatient treatment of low-risk cancer patients with chemotherapy-induced neutropenia and fever: ciprofloxacin plus cefuroxime axetil versus ciprofloxacin plus amoxicillin/clavulanate. Scand J Infect Dis 39(9):786–791. doi: 10.1080/00365540701367769

Ortega M, Rovira M, Almela M, de la Bellacasa JP, Carreras E, Mensa J (2004) Measurement of C-reactive protein in adults with febrile neutropenia after hematopoietic cell transplantation. Bone Marrow Transplant 33(7):741–744. doi: 10.1038/sj.bmt.1704409

Hatzistilianou M, Rekliti A, Athanassiadou F, Catriu D (2010) Procalcitonin as an early marker of bacterial infection in neutropenic febrile children with acute lymphoblastic leukemia. Inflamm Res 59(5):339–347. doi: 10.1007/s00011-009-0100-0

Sakr Y, Sponholz C, Tuche F, Brunkhorst F, Reinhart K (2008) The role of procalcitonin in febrile neutropenic patients: review of the literature. Infection 36(5):396–407. doi: 10.1007/s15010-008-7374-y

Secmeer G, Devrim I, Kara A, Ceyhan M, Cengiz B, Kutluk T, Buyukpamukcu M, Yetgin S, Tuncer M, Uludag AK, Tezer H, Yildirim I (2007) Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia. J Pediatr Hematol Oncol 29(2):107–111. doi: 10.1097/MPH.0b013e3180320b5b

Robinson JO, Lamoth F, Bally F, Knaup M, Calandra T, Marchetti O (2011) Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever? PLoS One 6(4):e18886. doi: 10.1371/journal.pone.0018886

Engel A, Knoll S, Kern P, Kern WV (2005) Interleukin-8 serum levels at fever onset in patients with neutropenia predict early medical complications. Infection 33(5–6):380–382. doi: 10.1007/s15010-005-5068-2

El-Maghraby SM, Moneer MM, Ismail MM, Shalaby LM, El-Mahallawy HA (2007) The diagnostic value of C-reactive protein, interleukin-8, and monocyte chemotactic protein in risk stratification of febrile neutropenic children with hematologic malignancies. J Pediatr Hematol Oncol 29(3):131–136. doi: 10.1097/MPH.0b013e3180308770

Buyukberber N, Buyukberber S, Sevinc A, Camci C (2009) Cytokine concentrations are not predictive of bacteremia in febrile neutropenic patients. Med Oncol (Northwood, London, England) 26(1):55–61. doi: 10.1007/s12032-008-9081-z

Tromp YH, Daenen SM, Sluiter WJ, Vellenga E (2009) The predictive value of interleukin-8 (IL-8) in hospitalised patients with fever and chemotherapy-induced neutropenia. Eur J Cancer (Oxf, Engl: 1990) 45(4):596–600. doi: 10.1016/j.ejca.2008.10.041

Heussel CP, Kauczor HU, Heussel G, Fischer B, Mildenberger P, Thelen M (1997) Early detection of pneumonia in febrile neutropenic patients: use of thin-section CT. AJR Am J Roentgenol 169(5):1347–1353. doi: 10.2214/ajr.169.5.9353456

Heussel CP, Kauczor HU, Heussel GE, Fischer B, Begrich M, Mildenberger P, Thelen M (1999) Pneumonia in febrile neutropenic patients and in bone marrow and blood stem-cell transplant recipients: use of high-resolution computed tomography. J Clin Oncol 17(3):796–805. doi: 10.1200/jco.1999.17.3.796

Bow EJ, Rotstein C, Noskin GA, Laverdiere M, Schwarer AP, Segal BH, Seymour JF, Szer J, Sanche S (2006) A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies. Clin Infect Dis 43(4):447–459. doi: 10.1086/505393

Cometta A, Kern WV, De Bock R, Paesmans M, Vandenbergh M, Crokaert F, Engelhard D, Marchetti O, Akan H, Skoutelis A, Korten V, Vandercam M, Gaya H, Padmos A, Klastersky J, Zinner S, Glauser MP, Calandra T, Viscoli C (2003) Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy. Clin Infect Dis 37(3):382–389. doi: 10.1086/376637

Cometta A, Calandra T, Gaya H, Zinner SH, de Bock R, Del Favero A, Bucaneve G, Crokaert F, Kern WV, Klastersky J, Langenaeken I, Micozzi A, Padmos A, Paesmans M, Viscoli C, Glauser MP (1996) Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto Infection Program. Antimicrob Agents Chemother 40(5):1108–1115

Erjavec Z, de Vries-Hospers HG, Laseur M, Halie RM, Daenen S (2000) A prospective, randomized, double-blinded, placebo-controlled trial of empirical teicoplanin in febrile neutropenia with persistent fever after imipenem monotherapy. J Antimicrob Chemother 45(6):843–849

Link H, Hiddemann W, Maschmeyer G, Buchheidt D, Glass B, Cornely O, Wilhelm M, Helmerking M, Adam D (1997) Antimicrobial therapy in neutropenic patients with unexplained fever, PEG-study II. Onkologie 20(Suppl 1):132

Schiel X, Link H, Maschmeyer G, Glass B, Cornely OA, Buchheidt D, Wilhelm M, Silling G, Helmerking M, Hiddemann W, Ostermann H, Hentrich M (2006) A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich Society for Chemotherapy (PEG) multicenter trial II. Infection 34(3):118–126. doi: 10.1007/s15010-006-5113-9

Goldberg E, Gafter-Gvili A, Robenshtok E, Leibovici L, Paul M (2008) Empirical antifungal therapy for patients with neutropenia and persistent fever: systematic review and meta-analysis. Eur J Cancer (Oxf, Engl: 1990) 44(15):2192–2203. doi: 10.1016/j.ejca.2008.06.040

Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, Dhedin N, Isnard F, Ades L, Kuhnowski F, Foulet F, Kuentz M, Maison P, Bretagne S, Schwarzinger M (2009) Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis 48(8):1042–1051. doi: 10.1086/597395

Maschmeyer G, Heinz WJ, Hertenstein B, Horst HA, Requadt C, Wagner T, Cornely OA, Löffler J, Ruhnke M (2013) Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study. Eur J Clin Microbiol Infect Dis 32(5):679–689. doi: 10.1007/s10096-012-1794-4

Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, Pappas P, Seibel N, Greenberg RN, Dummer S, Schuster M, Holcenberg JS (1999) Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study group. N Engl J Med 340(10):764–771. doi: 10.1056/nejm199903113401004

Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, dePauw BE (2004) Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 351(14):1391–1402. doi: 10.1056/NEJMoa040446

Aguilar-Guisado M, Espigado I, Cordero E, Noguer M, Parody R, Pachon J, Cisneros JM (2010) Empirical antifungal therapy in selected patients with persistent febrile neutropenia. Bone Marrow Transplant 45(1):159–164. doi: 10.1038/bmt.2009.125

Girmenia C, Micozzi A, Gentile G, Santilli S, Arleo E, Cardarelli L, Capria S, Minotti C, Cartoni C, Brocchieri S, Guerrisi V, Meloni G, Foa R, Martino P (2010) Clinically driven diagnostic antifungal approach in neutropenic patients: a prospective feasibility study. J Clin Oncol 28(4):667–674. doi: 10.1200/jco.2009.21.8032

Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, Wilmer A, Verhaegen J, Boogaerts M, Van Eldere J (2005) Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: a prospective feasibility study. Clin Infect Dis 41(9):1242–1250. doi: 10.1086/496927

Schneider T, Halter J, Heim D, Passweg J, Stern M, Tichelli A, Weisser M, Gerull S (2012) Pre-emptive diagnosis and treatment of fungal infections—evaluation of a single-centre policy. Clin Microbiol Infect 18(2):189–194. doi: 10.1111/j.1469-0691.2011.03589.x

Tan BH, Low JG, Chlebicka NL, Kurup A, Cheah FK, Lin RT, Goh YT, Wong GC (2011) Galactomannan-guided preemptive vs. empirical antifungals in the persistently febrile neutropenic patient: a prospective randomized study. Int J Infect Dis 15(5):e350–e356. doi: 10.1016/j.ijid.2011.01.011

Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J (2002) Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 346(4):225–234. doi: 10.1056/nejm200201243460403

Boogaerts M, Winston DJ, Bow EJ, Garber G, Reboli AC, Schwarer AP, Novitzky N, Boehme A, Chwetzoff E, De Beule K (2001) Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann Intern Med 135(6):412–422

Toubai T, Tanaka J, Ota S, Shigematsu A, Shono Y, Ibata M, Hashino S, Kondo T, Kakinoki Y, Masauzi N, Kasai M, Iwasaki H, Kurosawa M, Asaka M, Imamura M (2007) Efficacy and safety of micafungin in febrile neutropenic patients treated for hematological malignancies. Intern Med (Tokyo, Japan) 46(1):3–9

Yanada M, Kiyoi H, Murata M, Suzuki M, Iwai M, Yokozawa T, Baba H, Emi N, Naoe T (2006) Micafungin, a novel antifungal agent, as empirical therapy in acute leukemia patients with febrile neutropenia. Intern Med (Tokyo, Japan) 45(5):259–264

Kubiak DW, Bryar JM, McDonnell AM, Delgado-Flores JO, Mui E, Baden LR, Marty FM (2010) Evaluation of caspofungin or micafungin as empiric antifungal therapy in adult patients with persistent febrile neutropenia: a retrospective, observational, sequential cohort analysis. Clin Ther 32(4):637–648. doi: 10.1016/j.clinthera.2010.04.005

Jeong SH, Kim DY, Jang JH, Mun YC, Choi CW, Kim SH, Kim JS, Park JS (2016) Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study. Ann Hematol 95(2):337–344. doi: 10.1007/s00277-015-2545-2

Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, Goldberg JM, Khatcheressian JL, Leighl NB, Perkins CL, Somlo G, Wade JL, Wozniak AJ, Armitage JO (2015) Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 33(28):3199–3212. doi: 10.1200/jco.2015.62.3488

Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR (2011) 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 52(4):e56–e93. doi: 10.1093/cid/cir073

Cornelissen JJ, Rozenberg-Arska M, Dekker AW (1995) Discontinuation of intravenous antibiotic therapy during persistent neutropenia in patients receiving prophylaxis with oral ciprofloxacin. Clin Infect Dis 21(5):1300–1302

Slobbe L, Waal L, Jongman LR, Lugtenburg PJ, Rijnders BJ (2009) Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: a prospective observational safety study. Eur J Cancer (Oxford, England: 1990) 45(16):2810–2817. doi: 10.1016/j.ejca.2009.06.025

Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M (2013) 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 98(12):1826–1835. doi: 10.3324/haematol.2013.091025

Averbuch D, Cordonnier C, Livermore DM, Mikulska M, Orasch C, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M (2013) Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European conference on infections in leukemia (ECIL-4, 2011). Haematologica 98(12):1836–1847. doi: 10.3324/haematol.2013.091330