How to prevent infections in HSCT recipients
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- Lionel Chambers
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1 How to prevent infections in HSCT recipients J Peter Donnelly PhD FRCPath Department of Haematology Radboud University Medical Centre Nijmegen, The Netherlands
2 Malignancies, microbes and antimicrobials Microbes and man Immune defences Mucosal barrier Infectious complications Prevention
3 Microbes and man
4 Body surfaces and their resident microbial flora Infections In The Immunocompromised Host: General Principles Donnelly, Blijlevens & van der Velden In Principles And Practice Of Infectious Diseases, 8th Edition
5 Body surfaces and their resident microbial flora ~10 14 bacteria inhabit the human adult i.e. 10 x the number of human cells in the body 1-3% of the body weight i.e kg the vast majority of bacteria live in the large intestine 500 to 1,000 different species of bacteria about ½ the weight of faeces Infections In The Immunocompromised Host: General Principles Donnelly, Blijlevens & van der Velden In Principles And Practice Of Infectious Diseases, 8th Edition
6 Body surfaces and their resident microbial flora ~10 14 bacteria inhabit the human adult i.e. 10 x the number of human cells in the body 1-3% of the body weight i.e kg the vast majority of bacteria live in the large intestine 500 to 1,000 different species of bacteria about ½ the weight of faeces Infections In The Immunocompromised Host: General Principles Donnelly, Blijlevens & van der Velden In Principles And Practice Of Infectious Diseases, 8th Edition
7 More microbes than man
8 More microbes than man Viridans streptococci. Escherichia coli Staphylococcus epidermidis
9 Immune defences
10 Immune disintegration
11 Immune disintegration Mucosal barriers
12 Immune disintegration Mucosal barriers Innate immunity
13 Immune disintegration Mucosal barriers Innate immunity Cellular immunity
14 Immune disintegration Underlying disease Haematological malignancies GvHD Mucosal barriers Innate immunity Cellular immunity
15 Immune disintegration Underlying disease Haematological malignancies GvHD Mucosal barriers Chemotherapy Cystostatics Innate immunity Cellular immunity
16 Immune disintegration Underlying disease Haematological malignancies GvHD Mucosal barriers Chemotherapy Cystostatics Innate immunity Irradiation Local Total body Cellular immunity
17 Immune disintegration Underlying disease Haematological malignancies GvHD Mucosal barriers Drugs Steroids Monoclonal antibodies Immunesuppressants Chemotherapy Cystostatics Innate immunity Irradiation Local Total body Cellular immunity
18 Immune disintegration Underlying disease Haematological malignancies GvHD Mucosal barriers Drugs Steroids Monoclonal antibodies Immunesuppressants Chemotherapy Cystostatics Innate immunity Infections CMV EBV Irradiation Local Total body Cellular immunity
19 Infectious complications Exogenous microorganisms
20 Exogenous microorganisms
21 Exogenous microorganisms fungi Aspergillus Fusarium Candida
22 Exogenous microorganisms fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile
23 Exogenous microorganisms fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile viruses viruses VZV RSV Hepatitis B
24 Exogenous microorganisms air Ventilation systems, air conditioners, building materials fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile viruses viruses VZV RSV Hepatitis B
25 Exogenous microorganisms air Ventilation systems, air conditioners, building materials water Tap water, ice, vaporizers, humidifiers, sink drains, toilets, baths, showers, cut flowers fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile viruses viruses VZV RSV Hepatitis B
26 Exogenous microorganisms air Ventilation systems, air conditioners, building materials water Tap water, ice, vaporizers, humidifiers, sink drains, toilets, baths, showers, cut flowers food Dairy products, fresh fruits & vegetables, uncooked/unprocessed foods, dried foodstuffs, meats fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile viruses viruses VZV RSV Hepatitis B
27 Exogenous microorganisms air Ventilation systems, air conditioners, building materials water Tap water, ice, vaporizers, humidifiers, sink drains, toilets, baths, showers, cut flowers food Dairy products, fresh fruits & vegetables, uncooked/unprocessed foods, dried foodstuffs, meats fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile viruses viruses VZV RSV Hepatitis B catheters IV solutions, blood products, indwelling catheters, drainage tubes, endoscopes, tapes, plasters
28 Exogenous microorganisms air Ventilation systems, air conditioners, building materials water Tap water, ice, vaporizers, humidifiers, sink drains, toilets, baths, showers, cut flowers food Dairy products, fresh fruits & vegetables, uncooked/unprocessed foods, dried foodstuffs, meats fungi Aspergillus Fusarium Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus Clostridium difficile viruses viruses VZV RSV Hepatitis B catheters IV solutions, blood products, indwelling catheters, drainage tubes, endoscopes, tapes, plasters contacts Health care workers, other patients, visitors, objects including thermometers & toiletries, bed linen
29 Infectious complications Endogenous microorganisms
30 Endogenous microorganisms
31 Endogenous microorganisms fungi Candida
32 Endogenous microorganisms fungi Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus epidermidis Viridans streptococci Enterococcus species
33 Endogenous microorganisms fungi Candida bacteria enterobacteriaceae Pseudomonas aeruginosa Staphylococcus epidermidis Viridans streptococci Enterococcus species viruses viruses HSV CMV EBV
34 Infectious complications Neutropenia
35 Neutropenia
36 Temperature [ C] Neutropenia- infectious complications Fever 35
37 Temperature [ C] Neutropenia- infectious complications Fever 35 Bacteraemia
38 Temperature [ C] Neutropenia- infectious complications Fever 35 Bacteraemia Devices
39 Temperature [ C] Neutropenia- infectious complications Fever 35 Bacteraemia Devices Pulmonary infiltrates
40 Temperature [ C] Neutropenia- infectious complications Fever 35 Bacteraemia Devices neutrophils lymphocytes Pulmonary infiltrates thrombocytocytes mucosal barrier injury
41 Mucosal barrier
42 Department of Cancer Mucosal Treatment Defences Adapted from Donnelly, 1998
43 Department of Mucosal Defences Hello. I m mucositis Adapted from Donnelly, 1998
44 Department of Mucosal Defences Oops! I mean MBI Adapted from Donnelly, 1998
45 Pathobiology of Mucosal Barrier Injury Initiation Upregulation & Message Gen Signaling & Amplification Ulceration Healing Adapted from Sonis, 2004 Nat Rev Cancer
46 Pathobiology of Mucosal Barrier Injury Initiation Upregulation & Message Gen Signaling & Amplification Ulceration Healing Cytotoxic drugs ± irradiation Adapted from Sonis, 2004 Nat Rev Cancer
47 Pathobiology of Mucosal Barrier Injury Initiation Upregulation & Message Gen Signaling & Amplification Ulceration Healing Cytotoxic drugs ± irradiation NF- B I B I B NF- B Adapted from Sonis, 2004 Nat Rev Cancer
48 Pathobiology of Mucosal Barrier Injury Initiation Upregulation & Message Gen Signaling & Amplification Ulceration Healing Cytotoxic drugs ± irradiation NF- B I B translocation NF- B I B infection Adapted from Sonis, 2004 Nat Rev Cancer
49 Pathobiology of Mucosal Barrier Injury Initiation Upregulation & Message Gen Signaling & Amplification Ulceration Healing Cytotoxic drugs ± irradiation NF- B I B translocation NF- B I B infection Epithelial restitution Endogenous KGF Matrix metalloproteinases Adapted from Sonis, 2004 Nat Rev Cancer
50 Signs and symptomsmucosal barrier injury diarrhoea vomiting nausea bowel cramps pain bleeding malabsorption gut mouth redness oedema ulceration pain saliva dysfunction bleeding dysphagia inability of oral intake Blijlevens 2008
51 Oral mucositis Signs and symptoms redness 1-3 oedema 1-3 ulceration 1-3 pain 1-3 dysphagia 1-3 Daily Mucositis Score 5-15
52 Mean OM WHO score Proportion of patients with fever Mean OM WHO score and fever patients OM WHO score Patients with fever Day of assessment Blijlevens et al. Blood 2006;108:Abstr 46
53 Mean WHO mucositis score Oral mucositis and different conditioning regimens MEL-TBI MEL Wardley et al Brit J Haematol 110,
54 Mean WHO mucositis score Oral mucositis and different conditioning regimens BUS BUS-C Wardley et al Brit J Haematol 110,
55 Mean WHO mucositis score Oral mucositis and different conditioning regimens C-TBI C-BCNU CVB Wardley et al Brit J Haematol 110,
56 Mean WHO mucositis score Oral mucositis and different conditioning regimens MEL-TBI BUS MEL C-TBI BUS-C C-BCNU CVB Wardley et al Brit J Haematol 110,
57 GRANULOCYTES {log(10 9 /L)} Grade of mucositis Mucositis and Neutropenia in HSCT Mucositis 0 Days after transplant Neutropenia 0.1
58 Mucosal barrier injury - gut Signs and symptoms vomiting 0-3 nausea 0-3 diarrhoea 0-3 volume 0-3 incontinency 0-3 abdominal pain 0-3 Daily Gut Score grade grade grade Blijlevens et al. Support Care Cancer (2004) 12;227-33
59 Citrullus vulgaris
60 Mucosal barrier injury citrulline Gut luminal side glutamate glutamine ornithine citrulline citrulline
61 Mucosal barrier injury citrulline Gut luminal side cytotoxic therapy glutamate glutamine ornithine citrulline citrulline
62 Plasma citrulline Citrulline and allogeneic HSCT recipients Days after start Blijlevens et al. Bone Marrow Transplant (2004)
63 Plasma citrulline Citrulline and allogeneic HSCT recipients normal Days after start Blijlevens et al. Bone Marrow Transplant (2004)
64 Plasma citrulline Citrulline and allogeneic HSCT recipients normal partial atrophy Days after start Blijlevens et al. Bone Marrow Transplant (2004)
65 Plasma citrulline Citrulline and allogeneic HSCT recipients normal partial atrophy proximal total atrophy Days after start Blijlevens et al. Bone Marrow Transplant (2004)
66 Plasma citrulline Citrulline and allogeneic HSCT recipients normal partial atrophy proximal total atrophy diffuse total atrophy Days after start Blijlevens et al. Bone Marrow Transplant (2004)
67 High -risk patients 10 Host defences 1 neutrophils Blijlevens et al. 2004
68 High -risk patients 60 Gut barrier injury 40 citrulline Host defences neutrophils Blijlevens et al. 2004
69 High -risk patients Inflammation 100 CRP Gut barrier injury 40 citrulline Host defences neutrophils Blijlevens et al. 2004
70 High -risk patients Inflammation 100 CRP Gut barrier injury 40 citrulline Host defences neutrophils Blijlevens et al. 2004
71 High -risk patients Inflammation 100 CRP Gut barrier injury 40 citrulline Host defences neutrophils Blijlevens et al. 2004
72 Endogenous origin of infection Skin Mucosa
73 Endogenous origin of infection Skin chemotherapy Mucosa injury
74 Endogenous origin of infection Skin chemotherapy Mucosa antibiotics Normal commensal flora injury
75 Endogenous origin of infection Skin chemotherapy Mucosa antibiotics Normal commensal flora injury selection Potential pathogen
76 Endogenous origin of infection Skin chemotherapy Mucosa antibiotics Normal commensal flora injury selection infection Potential pathogen translocation
77 Endogenous origin of infection Skin chemotherapy Mucosa antibiotics Systemic infection injury selection Normal commensal flora Potential pathogen infection translocation
78 Endogenous origin of infection Skin chemotherapy Mucosa antibiotics Catheter colonisation Systemic infection injury selection Potential pathogen Normal commensal flora infection translocation
79 Infectious complications HSCT recipient
80 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Neutrophils, monocytes, NK cells Plasma Dendritic cells CD4 T cells Transplant Days Weeks Months
81 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Neutrophils, monocytes, NK cells Transplant Days Weeks Months
82 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT stem cells Neutrophils, monocytes, NK cells Transplant Days Weeks Months
83 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells Transplant Days Weeks Months
84 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells CD4 T cells Transplant Days Weeks Months
85 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
86 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
87 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Graft-versus-host disease stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
88 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Graft-versus-host disease stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
89 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) 41 Common bacteria (endogenous) streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Graft-versus-host disease stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
90 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) 41 Common bacteria (endogenous) streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Viruses CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Fungi Aspergillus spp. (airways) P. jerovecii(airways) Protozoa T. gondiii Graft-versus-host disease stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
91 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Viruses CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Fungi Aspergillus spp. (airways) P. jerovecii(airways) Protozoa T. gondiii Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
92 Infectious complications HSCT recipient PREVENTION
93 Physical preventative measures
94 Guidelines on infection prevention in HSCT
95 Guidelines on infection prevention in HSCT Room ventilation Construction, renovation and building cleaning Isolation and barrier precautions Hand hygiene Equipment Plants, play areas and toys Health-care personnel HCT center visitors Patient skin and oral care Preventing intravascular catheter-associated infections Prevention and control of specific health-care-associated infections Infection control surveillance
96 E00 adult haematology ward
97 E00 adult haematology ward
98 E00 adult haematology ward
99 HEPA/LAF and survival Hahn et al 2002 Infect Control Hosp Epidemiol 23:
100 Measures to minimise infection risk air HEPA-filtered medications Aseptic preparation furnishing Clean & disinfected food Freshly cooked Low-microbial content drink contact Single-use containers No tap water Bottled water ice-cubes Personal effects Dedicated toothbrush and paste Dedicated cups HWC compliant with hygiene Close family & friends bedding Clean & laundered accommodation Single-use On-suite sanitation
101 Prophylaxis against bacterial infections
102 Gram-negative bacilli because infection can:- develop from cryptic colonisation progress rapidly lead to shock fulminate AND effective treatment is available
103 Elements of the gut flora
104 Selective Gut Decontamination SELECTIVE GUT DECONTAMINATION
105 Elements of the gut flora Selective Gut Decontamination
106 Impairment of colonization resistance by antibiotics Impairment antibiotics high moderate low no effect rifampicin, penicillin V, cloxacillin, clindamycin, erythromycin, bacitracin ampicillin, piperacillin, azlocillin, cefoperazone, (po) gentamicin, (po) amikacin, (po) vancomycin cefuroxime, cefotaxime, moxalactam, cefoxitin aztreonam, imipenem, neomycin, doxycycline cotrimoxazole, polymyxins, quinolones, ceftazidime, meropenem
107 Selective oral antimicrobial prophylaxis SYSTEMIC PROPHYLAXIS SYSTEMIC PROPHYLAXIS SELECTIVE GUT DECONTAMINATION
108 Selective oral antibacterial prophylaxis
109 Fluoroquinolone versus control regimens Dekker 1987 Karp 1987 Bow 1988 Arning 1990 Liang 1990 Orlandi 1990 Winston 1990 Kern 1991 Lew 1991 Donnelly 1992 Talbot 1993 Jansen 1994 Pooled Gram negative bacteraemia (2% vs 11.4%) significant Favours fluoroquinolone Favours control regimen co-trimoxazole nonabsorbabale placebo Fluoroquinolone n=619 Control regimens n= log [Odds Ratio] Cruciani et al 1996Clin Infect Dis 23;795
110 All-Cause mortality - quinolones vs placebo Gafter-Gvili, A. et. al. Ann Intern Med 2005;142:
111 All-Cause mortality - quinolones vs placebo Favours quinolone Gafter-Gvili, A. et. al. Ann Intern Med 2005;142:
112 Overview of antibacterial prophylaxis studies Fever Clinically defined infections Microbiologically defined infections Gram-negative infections Gram-positive infections Bacteraemia Risk for infection-related death Fungal infections Adverse events Relative Risk of treatment over placebo Gafter-Gvili, A. et. al. Ann Intern Med 2005;142:
113 Downside
114 Absorption of ciprofloxacin after chemotherapy pre chemorx 7-8d 0 pre 1h 2h hours after 500mg dose 3h 4h 10-12d 13-15d 18d days after start of chemotherapy Johnston et al ( J Antimicrob Chemother 1990:25, )
115 Absorption of ciprofloxacin after chemotherapy Mucosal barrier injury pre chemorx 7-8d 0 pre 1h 2h hours after 500mg dose 3h 4h 10-12d 13-15d 18d days after start of chemotherapy Johnston et al ( J Antimicrob Chemother 1990:25, )
116 Absorption of ciprofloxacin after chemotherapy Mucosal barrier injury bacteraemia 7-8d pre chemorx 0 pre 1h 2h hours after 500mg dose 3h 4h 10-12d 13-15d 18d days after start of chemotherapy Johnston et al ( J Antimicrob Chemother 1990:25, )
117 LOG 2 [MIC] Plasma levels and MICs of ciprofloxacin viridans streptococci staphylococci enterobacteria non-fermenters 16 4 plasma level S.mitis S.sanguis enterococcus unspeciated S.epidermidis unspeciated S.aureus P. aeruginosa other G -ve bacilli E.coli/Citrobacter spp Klebsiella spp E. cloacae
118 Ciprofloxacin comes out in the sweat Resistant Staphylococcus epidermidis Days (mean, range) from start First isolation Last isolation Axilla 2.7 (1-7) 37 (7-62) Nose 18 (8-24) 39 (20-62) Ciprofloxacin MIC (mg/l) Resistance Pre-study none Post-study 4-12 MET >32 MET-ERY-SUL-TRI-GEN 6 volunteers took 750 mg bd ciprofloxacin for 7 days Høiby et al, Lancet 1997, 349;167
119 Incidence of ofloxacin resistant E.coli in Ulm No prophylaxis Kern et al 2005 Eur J Clin Microbiol Infect Dis 24;111
120 Antimicrobial prevention of infection - problems Side effects symptomatic skin rash diarrhoea pharmacological drug absorption drug interactions toxicity bone marrow major organ Compliance tolerability unpalatable Ecological selective pressure Gram +ve cocci acquired resistance E.coli Gould et al 1994
121 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) Gram-negative streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Viruses CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Fungi Aspergillus spp. (airways) P. jerovecii(airways) Protozoa T. gondiii Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
122
123 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) Fungi streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Fungi Viruses Fungi CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Aspergillus spp. (airways) P. jerovecii(airways) Protozoa T. gondiii Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
124 Recommendations for allogeneic HSCT recipients (2013) Update: ECIL 5, 2013 Antifungal prophylaxis* Preengraftment Low risk for moulds Pre-engraftment High risk for moulds GvHD Fluconazole A-I A-III - against A-III against Itraconazole B-I B-I B-I Voriconazole B-I B-I B-I Posaconazole OS/Tablet B-II B-II A-I Micafungin B-I C-I C-II Caspofungin /anidulafungin No data No data No data Liposomal Amphotericin B C-II C-II C-II Aerosolized amphotericin B plus fluconazole C-III B-II No data *For doses & need for Therapeutic Drug Monitoring: please refer to slides 21 and 22
125 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Viruses Viruses CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Fungi Protozoa Aspergillus spp. (airways) P. jerovecii(airways) T. gondiii Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
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127 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Viruses CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Fungi Aspergillus spp. (airways) P. jerovecii(airways) Protozoa T. gondiii Pneumocystis Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
128
129 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Fungi Candida spp. (mucosa) Aspergillus spp.(airways) Viruses HSV (reactivation) RSV Viruses CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Fungi Aspergillus spp. (airways) P. jerovecii(airways) Protozoa T. gondiii Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii Vaccination stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
130 Vaccnination Bone Marrow Transplantation (2009) 44,
131 Immune cell counts (% of normal) Temperature C Infectious phases following transplant PRE-TRANSPLANT ENGRAFTMENT EARLY POST-ENGRAFTMENT LATE POST-ENGRAFTMENT Common bacteria (endogenous) Viruses staphylococci (skin) Gram-negative bacilli (gut) HSV (reactivation) Common bacteria (endogenous) Gram-negative Fungi Viruses streptococci (oral) staphylococci (skin) Gram-negative bacilli (gut) Clostridium difficile (gut) Candida spp. (mucosa) Aspergillus spp.(airways) HSV (reactivation) RSV Fungi Viruses Fungi Viruses Protozoa CMV (reactivation) VZV (reactivation) HHV-6 Adenovirus RSV Aspergillus spp. (airways) P. jerovecii(airways) T. gondiii Pneumocystis Graft-versus-host disease Bacteria (encapsulated) S. pneumoniae S. aureus Viruses VZV (reactivation) CMV (reactivation) RSV Fungi P. jerovecii(airways) Protozoa T. gondiii Vaccination stem cells Neutrophils, monocytes, NK cells Plasma Dendritic cells B cells CD4 T cells Transplant Days Weeks Months
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