How to prevent Infections in Patients undergoing allo-hsct? Olaf Penack EBMT Course, 29 Sept 1 Oct 2014, Naples, Italy #EBMT2014 www.ebmt.org
Prevention of Infections Epidemiology and risk factors for infections Prevention of bacterial infections Prevention of fungal infections Prevention of viral infections 2 2
Not within the Scope... Protective Environment Ullmann & Donnelly 3 3
Not within the Scope... Microbiome and GVHD Bone marrow GVHD T cells Van Bekkum et al, J Natl Cancer Inst. 1967 Beelen et al, Blood. 1999 4 4
Levels of Prevention Primary prevention - avoidance of disease immunisations,donor selection, primary prophylaxis Secondary prevention early detection and treatment CMV PCR, chest CT-scan Tertiary prevention management of existing conditions 5 5
Prevention of Infections Epidemiology and risk factors for infections Prevention of bacterial infections Prevention of fungal infections Prevention of viral infections 6 6
Immunreconstitution post allo-hsct Biol Blood Marrow Transplant 15:1143-1238, 2009 7 7
Infections during allo-hsct Biol Blood Marrow Transplant 15:1143-1238, 2009 8 8
Cause of Infection-Related Death IDWP Analyses: Bone Marrow Transplantation (2005) 36, 757 769 9 9
Late Infections after allo-sct 196 long term survivors 30 patients died after day +360 Causes of death after day +360 Relapse = 30% Infections = 65% (mostely related to cgvhd) Risk factors for late infectious mortality Irradiation, CMV status, extensive cgvhd Socié et al., Biology of Blood and Marrow Transplantation 13:1304-1312 (2007) 10 10
Risk Factors for IFD Graft type Disease status HLA mismatch I. Ruiz Camps / International Journal of Antimicrobial Agents 32 Suppl. 2 (2008) S119 S123 11 11
Incidence of IFI % Risk Factors Duration of Neutropenia L-AmB prophylaxis No systemic prophylaxis 50 45 40 35 30 25 20 15 10 5 0 46,4 17,8 6,3 2,8 0 4,3 <10 days 10-20 days > 20 days Duration of neutropenia Ann Oncol. 2006 Aug;17(8):1306-12 12 12
Prevention of Infections Epidemiology and risk factors for infections Prevention of bacterial infections Prevention of fungal infections Prevention of viral infections 13 13
ECIL 4 Survey Bloodstream Infections in Hematology Patients in Europe 14 14
ECIL 4 Survey Bloodstream Infections in Hematology Patients in Europe 15 15
Lokal Epidemiology in Berlin BC = 1619, BC+ = 172 (aprox. 10%) BC Isolates Hem/Onk CVK 2013 5 4 3 21 25 24 10 80 Koag neg Staph Streptokokken Enterokokken E. coli Candida Klebsiellen Stenotrophomonas Andere 16 16
Prophylaxis with Antibiotics Advantages: - Less Infections - Potentially shorter hospital stay Disadvantages: - Survival benefit not shown - Selection of resistant bacteria 17 17
Prophylaxis with Antibiotics Levofloxacin prophylaxis was discontinued Mortality rates 33.3% without vs 2.9% with fluoroquinolone prophylaxis Fewer gram-negative bacteremia during the baseline period (4.8%) than during the discontinuation period (44.4%) Incidence of bacteremia and mortality rate back to baseline after levofloxacin prophylaxis was reintroduced Escherichia coli isolated during the discontinuation period was susceptible to levofloxacin in vitro, whereas all E. coli isolates isolated during both prophylaxis periods were resistant Clinical Infectious Diseases 2005; 40:1087 93 18 18
Prophylaxis with Antibiotics N Engl J Med 2005:353:977 987 19 19
Prophylaxis with Antibiotics Infection associated mortality is significantly reduced Cochrane Database Syst Rev 2012: 1:CD004386 20 20
Prophylaxis with Antibiotics Guidelines Ann Hematol. 2013 Apr;92(4):433-42 21 21
Prophylaxis with Antibiotics Open Questions Does prophylaxis induce resistance? If so, do resistant bacteria cause disease? Is mortality higher in infections by resistant bacteria? Should prophylaxis only be used in centers with a low resistance pattern? 22 22
Is mortality higher in infections by resistant bacteria? * five of six patients with VRE bacteremia died prior to day +100 Bone Marrow Transplantation (2008) 41, 385 392 23 23
Prevention of Infections Risk factors for infections Prevention of bacterial infections Prevention of fungal infections Prevention of viral infections 24 24
Prevention Aspergillus Infection 80 hematology Patients undergoing intensive therapies. No impact of masks on the incidence of aspergillosis Biol Blood Marrow Transplant 2012 Dec;18(12):1927-34 25 25
Prevention Aspergillus Infection IgG responses against 6 purified recombinant Aspergillus fumigatus proteins before allo-hsct or Chemotherapy for acute Leukemia. 73 subjects, including 19 patients who subsequently developed proven or probable IA and 54 uninfected controls. IgG responses prior to allo-hsct were significantly higher in the patients developing IA compared with controls. Colonization or ongoing Aspergillus infections before imunosuppression? Biol Blood Marrow Transplant 2012 Dec;18(12):1927-34 26 26
Anti Fungal Prophylaxis Guidelines 27 27
Anti Fungal Prophylaxis Guidelines 28 28
Anti Fungal Prophylaxis Guidelines 29 29
Anti Fungal Prophylaxis Guidelines Ann Hematol. 2014 Jun 21 30 30
PjP Prevention 31 31
PjP Prevention 32 32
PjP Prevention 33 33
PjP Prevention 34 34
PjP Prevention 35 35
PjP Prevention 36 36
Prevention of Infections Risk factors for infections Prevention of bacterial infections Prevention of fungal infections Prevention of viral infections 37 37
Visiting young children should be restricted from HSCT wards (BII). All visitors and HCWs with RTI should be restricted from access to patients and wards (AII). Inside care facilities, infection control measures should be applied to HSCT patients with RTI (AII). Outpatients with RTI should be seen and treated in accordance with infection control measures (AII). Clinical Infectious Diseases 2013;56(2):258 66 38 38
Post-exposure antiviral prophylaxis, currently with oseltamivir, for at least 10 days is advised for HSCT recipients who are <12 months after transplant, or substantially immunocompromised, regardless of vaccination history, after exposure to a confirmed or probable case of influenza. (C-III) Yearly vaccination with seasonal trivalent inactivated influenza vaccine is recommended in allogeneic and autologous HSCT recipients. (A-II) 39 39
CMV Prevention Blood, 2004. 103(6): p. 2003-8 A CMV IgG- donor should be chosen for a CMV IgG- recipient (IA). A CMV IgG+ donor should be chosen for a CMV IgG+ recipient (1A). Primary prophylaxis with ganciclovir is not generally recommended as toxicity outweighs efficacy in HSCT patients (Grade 1B). I.V. immunoglobulin is not recommended for prophylaxis of CMV (Grade 1A). Monitoring of CMV load should be undertaken at least weekly for the first 3 months post-hsct (Grade 2C). British Journal of Haematology, 2013, 162, 25 39 40 40
HSV Prevention Lancet, 1983. 2(8352): p. 706-8 41 41
VZV Prevention AGIHO 2014 42 42
Vaccination Bone Marrow Transplantation (2009) 44, 521 526 43 43
How to prevent Infections in Patients undergoing allo-hsct? Olaf Penack EBMT Course, 29 Sept 1 Oct 2014, Naples, Italy #EBMT2014 www.ebmt.org