Infections remain a threat for patients with haematological malignancies. In accordance with the European Hematology Association roadmap we provide a concise overview regarding the most relevant current challenges in infectious diseases for haematologists. These include bacterial infections and the need for antibiotic stewardship as well as infections with community-acquired respiratory viruses, infections in patients receiving targeted therapies, re-activations of latent infections and vaccination strategies. The following review intends to summarise the most relevant information for clinicians currently caring for patients with haematological malignancies. Recommendations given are based on the guidelines published by the Infectious Diseases Working Party of the German Society of Haematology and Medical Oncology.

1.
Bower H, Andersson TM, Bjorkholm M, Dickman PW, Lambert PC, Derolf AR: Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life. Blood Cancer J 2016;6:e390.
[PubMed]
2.
Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM: Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 2016;34:2851-2857.
[PubMed]
3.
Engert A, Balduini C, Brand A, Coiffier B, Cordonnier C, Dohner H, de Wit TD, Eichinger S, Fibbe W, Green T, de Haas F, Iolascon A, Jaffredo T, Rodeghiero F, Salles G, Schuringa JJ: The European Hematology Association roadmap for European hematology research: a consensus document. Haematologica 2016;101:115-208.
[PubMed]
4.
Satlin MJ, Jenkins SG, Walsh TJ: The global challenge of carbapenem-resistant Enterobacteriaceae in transplant recipients and patients with hematologic malignancies. Clin Infect Dis 2014;58:1274-1283.
[PubMed]
5.
Alevizakos M, Gaitanidis A, Nasioudis D, Tori K, Flokas ME, Mylonakis E: Colonization with vancomycin-resistant enterococci and risk for bloodstream infection among patients with malignancy: a systematic review and meta-analysis. Open Forum Infect Dis 2017;4:ofw246.
[PubMed]
6.
Ford CD, Lopansri BK, Haydoura S, Snow G, Dascomb KK, Asch J, Bo Petersen F, Burke JP: Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia. Infect Control Hosp Epidemiol 2015;36:47-53.
[PubMed]
7.
De Rosa FG, Corcione S, Motta I, Petrolo A, Filippini C, Pagani N, Fossati L, Cavallo R, Di Perri G: Risk factors for mortality in patients with Staphylococcus aureus bloodstream infection. J Chemother 2016;28:187-190.
[PubMed]
8.
Lubbert C, Becker-Rux D, Rodloff AC, Laudi S, Busch T, Bartels M, Kaisers UX: Colonization of liver transplant recipients with KPC-producing Klebsiella pneumoniae is associated with high infection rates and excess mortality: a case-control analysis. Infection 2014;42:309-316.
[PubMed]
9.
Kola A, Kohler C, Pfeifer Y, Schwab F, Kuhn K, Schulz K, Balau V, Breitbach K, Bast A, Witte W, Gastmeier P, Steinmetz I: High prevalence of extended-spectrum-beta-lactamase-producing Enterobacteriaceae in organic and conventional retail chicken meat, Germany. J Antimicrob Chemother 2012;67:2631-2634.
[PubMed]
10.
Tumbarello M, Trecarichi EM, Tumietto F, Del Bono V, De Rosa FG, Bassetti M, Losito AR, Tedeschi S, Saffioti C, Corcione S, Giannella M, Raffaelli F, Pagani N, Bartoletti M, Spanu T, Marchese A, Cauda R, Viscoli C, Viale P: Predictive models for identification of hospitalized patients harboring KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2014;58:3514-3520.
[PubMed]
11.
Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M: 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;98:1826-1835.
[PubMed]
12.
Heinz WJ, Buchheidt D, Christopeit M, von Lilienfeld-Toal M, Cornely OA, Einsele H, Karthaus M, Link H, Mahlberg R, Neumann S, Ostermann H, Penack O, Ruhnke M, Sandherr M, Schiel X, Vehreschild JJ, Weissinger F, Maschmeyer G: 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). Ann Hematol 2017;96:1775-1792.
[PubMed]
13.
Tokars JI: Predictive value of blood cultures positive for coagulase-negative staphylococci: implications for patient care and health care quality assurance. Clin Infect Dis 2004;39:333-341.
[PubMed]
14.
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: 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 2015;26:21-33.
[PubMed]
15.
Aguilar-Guisado M, Espigado I, Martin-Pena A, Gudiol C, Royo-Cebrecos C, Falantes J, Vazquez-Lopez L, Montero MI, Rosso-Fernandez C, de la Luz Martino M, Parody R, Gonzalez-Campos J, Garzon-Lopez S, Calderon-Cabrera C, Barba P, Rodriguez N, Rovira M, Montero-Mateos E, Carratala J, Perez-Simon JA, Cisneros JM: 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-e583.
[PubMed]
16.
Heudorf U, Krackhardt B, Karathana M, Kleinkauf N, Zinn C: Multidrug-resistant bacteria in unaccompanied refugee minors arriving in Frankfurt am Main, Germany, October to November 2015. Euro Surveill 2016;21.
[PubMed]
17.
Rachow T, Schluter V, Bremer-Streck S, Lindig U, Scholl S, Schlattmann P, Kiehntopf M, Hochhaus A, von Lilienfeld-Toal M: Measurement of piperacillin plasma concentrations in cancer patients with suspected infection. Infection 2017.
[PubMed]
18.
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: 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 2016;67:200-212.
[PubMed]
19.
Hermann B, Lehners N, Brodhun M, Boden K, Hochhaus A, Kochanek M, Meckel K, Mayer K, Rachow T, Rieger C, Schalk E, Weber T, Schmeier-Jurchott A, Schlattmann P, Teschner D, von Lilienfeld-Toal M: Influenza virus infections in patients with malignancies - characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO). Eur J Clin Microbiol Infect Dis 2017;36:565-573.
[PubMed]
20.
Chemaly RF, Vigil KJ, Saad M, Vilar-Compte D, Cornejo-Juarez P, Perez-Jimenez C, Mubarak S, Salhab M, Jiang Y, Granwehr B, Adachi JA, Raad, II: A multicenter study of pandemic influenza A (H1N1) infection in patients with solid tumors in 3 countries: early therapy improves outcomes. Cancer 2012;118:4627-4633.
[PubMed]
21.
Shah DP, Shah PK, Azzi JM, Chemaly RF: Parainfluenza virus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: a systematic review. Cancer Lett 2016;370:358-364.
[PubMed]
22.
Lehners N, Schnitzler P, Geis S, Puthenparambil J, Benz MA, Alber B, Luft T, Dreger P, Eisenbach C, Kunz C, Benner A, Buchholz U, Aichinger E, Frank U, Heeg K, Ho AD, Egerer G: Risk factors and containment of respiratory syncytial virus outbreak in a hematology and transplant unit. Bone Marrow Transplant 2013;48:1548-1553.
[PubMed]
23.
Drexler JF, Helmer A, Kirberg H, Reber U, Panning M, Muller M, Hofling K, Matz B, Drosten C, Eis-Hubinger AM: Poor clinical sensitivity of rapid antigen test for influenza A pandemic (H1N1) 2009 virus. Emerg Infect Dis 2009;15:1662-1664.
[PubMed]
24.
Lehners N, Tabatabai J, Prifert C, Wedde M, Puthenparambil J, Weissbrich B, Biere B, Schweiger B, Egerer G, Schnitzler P: Long-term shedding of influenza virus, parainfluenza virus, respiratory syncytial virus and nosocomial epidemiology in patients with hematological disorders. PLoS One 2016;11:e0148258.
[PubMed]
25.
Mayer JL, Lehners N, Egerer G, Kauczor HU, Heussel CP: CT-morphological characterization of respiratory syncytial virus (RSV) pneumonia in immune-compromised adults. Rofo 2014;186:686-692.
[PubMed]
26.
Aguayo-Hiraldo PI, Arasaratnam RJ, Tzannou I, Kuvalekar M, Lulla P, Naik S, Martinez CA, Piedra PA, Vera JF, Leen AM: Characterizing the Cellular Immune Response to Parainfluenza Virus 3. J Infect Dis 2017;216:153-161.
[PubMed]
27.
Tzannou I, Nicholas SK, Lulla P, Aguayo-Hiraldo PI, Misra A, Martinez CA, Machado AA, Orange JS, Piedra PA, Vera JF, Leen AM: Immunologic Profiling of Human Metapneumovirus for the Development of Targeted Immunotherapy. J Infect Dis 2017;216:678-687.
[PubMed]
28.
Marjuki H, Mishin VP, Chesnokov AP, De La Cruz JA, Fry AM, Villanueva J, Gubareva LV: An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality. J Infect Dis 2014;210:435-440.
[PubMed]
29.
Garg R, Latimer L, Gerdts V, Potter A, van Drunen Littel-van den Hurk S: Intranasal immunization with a single dose of the fusion protein formulated with a combination adjuvant induces long-term protective immunity against respiratory syncytial virus. Hum Vaccin Immunother 2017:0.
[PubMed]
30.
Blimark C, Holmberg E, Mellqvist UH, Landgren O, Bjorkholm M, Hultcrantz M, Kjellander C, Turesson I, Kristinsson SY: Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica 2015;100:107-113.
[PubMed]
31.
Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Cervantes F, Jones MM, Sun K, McQuitty M, Stalbovskaya V, Gopalakrishna P, Barbui T: Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia 2016;30:1701-1707.
[PubMed]
32.
Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J, Jordan K: Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28:iv119-iv142.
[PubMed]
33.
Getahun H, Matteelli A, Chaisson RE, Raviglione M: Latent Mycobacterium tuberculosis infection. N Engl J Med 2015;372:2127-2135.
[PubMed]
34.
Kusumoto S, Tobinai K: Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy. Hematology Am Soc Hematol Educ Program 2014;2014:576-583.
[PubMed]
35.
Sandherr M, Hentrich M, von Lilienfeld-Toal M, Massenkeil G, Neumann S, Penack O, Biehl L, Cornely OA: Antiviral prophylaxis in patients with solid tumours and haematological malignancies-update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). Ann Hematol 2015;94:1441-1450.
[PubMed]
36.
Torres HA, Hosry J, Mahale P, Economides MP, Jiang Y, Lok AS: Hepatitis C virus reactivation in patients receiving cancer treatment: a prospective observational study. Hepatology 2018;67:36-47.
[PubMed]
37.
Zhou X, Lisenko K, Lehners N, Egerer G, Ho AD, Witzens-Harig M: The influence of rituximab-containing chemotherapy on HCV load in patients with HCV-associated non-Hodgkin's lymphomas. Ann Hematol 2017;96:1501-1507.
[PubMed]
38.
Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, Abergel A, Mangia A, Lai CL, Chan HL, Mazzotta F, Moreno C, Yoshida E, Shafran SD, Towner WJ, Tran TT, McNally J, Osinusi A, Svarovskaia E, Zhu Y, Brainard DM, McHutchison JG, Agarwal K, Zeuzem S: Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015;373:2599-2607.
[PubMed]
39.
Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M: Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015;373:2608-2617.
[PubMed]
40.
Mallet V, van Bommel F, Doerig C, Pischke S, Hermine O, Locasciulli A, Cordonnier C, Berg T, Moradpour D, Wedemeyer H, Ljungman P: Management of viral hepatitis in patients with haematological malignancy and in patients undergoing haemopoietic stem cell transplantation: recommendations of the 5th European Conference on Infections in Leukaemia (ECIL-5). Lancet Infect Dis 2016;16:606-617.
[PubMed]
41.
Baylis SA, Gartner T, Nick S, Ovemyr J, Blumel J: Occurrence of hepatitis E virus RNA in plasma donations from Sweden, Germany and the United States. Vox Sang 2012;103:89-90.
[PubMed]
42.
Versluis J, Pas SD, Agteresch HJ, de Man RA, Maaskant J, Schipper ME, Osterhaus AD, Cornelissen JJ, van der Eijk AA: Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation. Blood 2013;122:1079-1086.
[PubMed]
43.
Hottinger AF, George AC, Bel M, Favet L, Combescure C, Meier S, Grillet S, Posfay-Barbe K, Kaiser L, Siegrist CA, Dietrich PY: A prospective study of the factors shaping antibody responses to the AS03-adjuvanted influenza A/H1N1 vaccine in cancer outpatients. Oncologist 2012;17:436-445.
[PubMed]
44.
Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, Bousvaros A, Dhanireddy S, Sung L, Keyserling H, Kang I: 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014;58:309-318.
[PubMed]
45.
Verstovsek S, Gotlib J, Mesa RA, Vannucchi AM, Kiladjian JJ, Cervantes F, Harrison CN, Paquette R, Sun W, Naim A, Langmuir P, Dong T, Gopalakrishna P, Gupta V: Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol 2017;10:156.
[PubMed]
46.
Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S: Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med 2015;372:426-435.
[PubMed]
47.
Byrd JC, Furman RR, Coutre SE, Burger JA, Blum KA, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Shaw Y, Bilotti E, Zhou C, James DF, O'Brien S: Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015;125:2497-2506.
[PubMed]
48.
Lionakis MS, Dunleavy K, Roschewski M, Widemann BC, Butman JA, Schmitz R, Yang Y, Cole DE, Melani C, Higham CS, Desai JV, Ceribelli M, Chen L, Thomas CJ, Little RF, Gea-Banacloche J, Bhaumik S, Stetler-Stevenson M, Pittaluga S, Jaffe ES, Heiss J, Lucas N, Steinberg SM, Staudt LM, Wilson WH: Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma. Cancer Cell 2017;31:833-843 e835.
[PubMed]
49.
Jones JA, Robak T, Brown JR, Awan FT, Badoux X, Coutre S, Loscertales J, Taylor K, Vandenberghe E, Wach M, Wagner-Johnston N, Ysebaert L, Dreiling L, Dubowy R, Xing G, Flinn IW, Owen C: Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial. Lancet Haematol 2017;4:e114-e126.
[PubMed]
50.
Maertens J, Cesaro S, Maschmeyer G, Einsele H, Donnelly JP, Alanio A, Hauser PM, Lagrou K, Melchers WJ, Helweg-Larsen J, Matos O, Bretagne S, Cordonnier C: ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother 2016;71:2397-2404.
[PubMed]
51.
Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, Kipps TJ, Anderson MA, Brown JR, Gressick L, Wong S, Dunbar M, Zhu M, Desai MB, Cerri E, Heitner Enschede S, Humerickhouse RA, Wierda WG, Seymour JF: Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med 2016;374:311-322.
[PubMed]
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