Infections in transplants why is it so difficult to collect reasonable data regarding infections?

Infections in transplants why is it so difficult to collect reasonable data regarding infections? Dr Kate Ward k.n.ward@ucl.ac.uk #EBMT2015 www.ebmt.org

Why collect infection data? Along with graft-vs.-host disease (GVHD), infection remains a major source of morbidity and mortality in HSCT recipients 2

Allograft Adapted from Mandell Infectious Diseases

Types of infection & occurrence relative to time after allo-sct Fungi Viruses Candida Aspergillus Herpes simplex/ cytomegalo-, adeno/ varicella-zoster Bacteria Gram-positive Gram-negative encapsulated Pneumonia bacterial non-bacterial* 0 50 Days post-sct 100 >365 * Pneumocystis pneumonia 4

How many infections after allo-sct? 5

REGISTRY & THE NEED TO COLLECT INFECTION DATA To determine the incidence, morbidity & mortality of important infections Specifically to: Generate annual EBMT epidemiology Update guidelines Note trends in relation to procedures e.g. RIC v myeloablative HSCT Basis for designing future studies 6

Currently 90% return What information is collected about infections? 7

Clinical Infectious Diseases 59 (2014) 473-81 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative,

MED-B & infections in the last decade Only ~20% of (allo) CICs report MED-B routinely Even these 20% are often incomplete Reporting bias Information collected generally insufficient for studies for MED-B level studies need to get back to reporting centre for more information Who in the audience has entered infections on Med-B? 9

HIV 28% valid CMV 70% valid EBV 20% valid 10

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O136 Donor EBV status has impact on the incidence of acute and chronic GVHD J. Styczynski 1,*, G. Tridello 2, L. Gil 3, P. Ljungman 4, J. Hoek 5, S. Iacobelli 6, C. Cordonnier 7, H. Einsele 8, K. Ward 9, G. Socie 10, N. Milpied 11, J. H. Veelken 12, P. Chevallier 13, I. Yakoub-Agha 14, J. Maertens 15, D. Blaise 16, J. Cornelissen 17, M. Michallet 18, E. Deconinck 19, E. Petersen 20, J. Passweg 21, H. Greinix 22, R. Duarte 23, N. Kröger 24, P. Dreger 25, A. Nagler 26, S. Cesaro 27 12

Aspergillus Problem 1 Yes 461 No 720 40% incidence BUT unknown 27,896 Is this real?? Aspergillus Problem 2 Definition of documented invasive fungal infection 13

Who has used this reference document? Complication a secondary disease/condition aggravating an already existing one.

How easy is it to find info about a disease (infectious complication) in the patient s charts?

Do you get help from any of the following to identify infection & disease? Nurse Haematologist Microbiologist Virologist 16

Bact/fungi/virus/ 28365 18.7 76.6 parasite Total valid 37047 24.4 100 Total missing 114863 75.6 Total valid + missing 151910 100

Bacteraemia is a better term than bloodstream infection since it means bacteria in the blood emphasising the fact that blood is not, in fact, infected but is merely transporting bacteria. Bacteraemia is not a complication unless it is associated with disease 18

How easy is it to find information about a particular infection in the patient s charts/notes? 19

756 21450 97% other 468 16441 54 207 12,636

ProMISe on Staphylococcus epidermidis 21

What s in a name? 10 Staphylococcus epidermidis Frequency TOTAL 508 1 Staphylococcus epidermidis 162 2 STAPH EPIDERMIDIS 43 3 staphylocoque epidermidis 40 4 staphyloc. epidermidis 35 5 Staph. epidermidis 24 6 S. epidermidis 21 7 Staphylococcus epidermis 21 8 stafylococcus epidermis 16 9 Staph.epidermidis 10 10 St. Epidermidis 8 22

What s in a name? 20 Staphylococcus epidermidis Frequency TOTAL 508 11 Staph epidermis 8 12 staphylococus epidermidis 5 13 staphylocoque épidermidis 5 14 St Epidermidis 4 15 Staphylo epidermidis 4 16 STAPHYLOCOCCI EPIDERMIDIS 4 17 staphylocoque épidermidis méti R 4 18 Staphilococcus epidermidis 3 19 staphylococcen epidermidis 3 20 staphylocoque epidermidis méti R 3 23

What s in a name? 30 Staphylococcus epidermidis Frequency TOTAL 508 21 Epidermidis staphylococcus 2 22 Staphyl. epidermidis 2 23 staphyloccocus epidermidis 2 24 staphylococcu epidermidis 2 25 staphylococcus epidermidis meti-r 2 26 staphylococcus epidermidus 2 27 Staphylococcus Epididermis 2 28 staphylocoque epidermidis meti-s 2 29 E. Epidermidis 1 30 Epidermidis 1 24

What s in a name? 40 Staphylococcus epidermidis Frequency TOTAL 508 31 MRSE (staphylococcus epidermidis) 1 32 s. epidermis 1 33 S.EPIDERMIDIS 1 34 Saph epidermidis 1 35 St. epidermidis and St. simulans 1 36 staff epidermidis 1 37 Stafilococus epidermidis 1 38 Stafilokok epidermis sepsis 1 39 stafylococcus epidermis+mitis 1 40 STAP.-EPIDERMIDIS, STREP.SANQUIS 1 25

What s in a name? 50 Staphylococcus epidermidis Frequency TOTAL 508 41 stapfylococcus epidermidis 1 42 staph epidermidis et enterocoque 1 43 staph hémolytique +épidermidis méti R 1 44 Staph hominis + epidermidis 1 45 Staph. epiderm 1 46 staph. epidermides 1 47 Staph. épidermidis meti R 1 48 Staph. epidermidis, Staph. koag.negat. 1 49 Staph. epidermidis, Streptococcus oralis 1 50 Staph. Epidermidis; Strep. Sanguinis 1 26

What s in a name? 60 Staphylococcus epidermidis Frequency TOTAL 508 51 Staph. epidermis 1 52 staphiloccoque epidermidis 1 53 Staphilococcus eoidermidis 1 54 staphilococo epidermidis 1 55 staphlococcus epidermidis 1 56 STAPHULOCOCCUS EPIDERMIS 1 57 staphy. epidermidis 1 58 STAPHYCOCOCCUS EPIDERMIDIS 1 59 STAPHYCOLOCCUS EPIDERMIS 1 60 Staphylcoccus epididermis 1 27

What s in a name? 70 Staphylococcus epidermidis Frequency TOTAL 508 61 Staphyllo epidermidis meti-resistant 1 62 Staphyllococcus epidermidis 1 63 Staphyllococcus Epidermis 1 64 Staphylo. epidermidis 1 65 Staphyloc. epiderm. 1 66 Staphyloc. epidermidids 1 67 Staphyloc. epidermidis, Diffteroidi 1 68 Staphyloc. epidermidis, Difteroidi 1 69 staphyloccus epidermidis 1 70 staphyloccus epidermis 1 28

What s in a name? 80 Staphylococcus epidermidis Frequency TOTAL 508 71 staphylococcus apidermidis 1 72 staphylococcus epidermdis 1 73 staphylococcus epidermicus 1 74 Staphylococcus epidermides 1 75 Staphylococcus épidermidis 1 76 Staphylococcus epidermidis + haemolyticu 1 77 STAPHYLOCOCCUS EPIDERMIDIS GROWTH 1 78 Staphylococcus epidermidis methi-r 1 79 Staphylococcus epidermidis Meti R 1 80 Staphylococcus epidermis Meti R 1 29

What s in a name? 90 Staphylococcus epidermidis Frequency TOTAL 508 81 Staphylococcus Epidermis Oxa S 1 82 Staphylococcus epidermitus 1 83 Staphylococcus Epidermus 1 84 STAPHYLOCOCCUS EPIDERMUS GROWTH 1 85 STAPHYLOCOCCUS EPYDERMIDIS 1 86 Staphylococcus, Epidermitis, Venco R 1 87 staphylocoque épidermdis méti R 1 88 staphylocoque épidermidis méti S 1 89 Staphylocoque epidermidis meti-r 1 90 staphylocoque epidermidis multi R 1 30

What s in a name? 97 Staphylococcus epidermidis Frequency TOTAL 508 91 STAPHYLOCOQUE EPIDERMIS 1 92 Staphylocoque Epidermis Méti R 1 93 staphylocoques épidermidis 1 94 Staphylocoques epidermidis et streptocoq 1 95 Statphylocoque épidermidis OXA R 1 96 Streptococcus epidermidis 1 97 STREPTOCOCO EPIDERMIDIS 1 31

Common bacterial infections Gram-positive bacteria (n=10) Gram-negative bacteria (n=18) Staphylococcus aureus Escherichia coli Staphylococcus epidermidis Klebsiella spp Coagulase-negative staphylococci Enterobacter spp Enterococcus faecalis Serratia spp. Enterococcus faecium Citrobacter freundii Streptococcus pneumoniae Salmonella spp Viridans group streptococci Pseudomonas aeruginosa Streptococcus bovis Pseudomonas fluorescens Listeria monocytogenes Pseudomonas putida Corynebacterium spp. Pseudomonas stutzeri Ralstonia picketti Acinetobacter spp. Alcaligenes faecalis Burkholderia cepacia Ortega et al Ann Hematol (2005) 84: 40 47 32

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What does CMV viraemia mean? CMV DNA in blood or CMV antigen in blood Regularly tested for because, if detected antiviral drugs given to PREVENT the complications of CMV pneumonia, retinitis etc CMV disease is RARE but detection of CMV is common. 34

How easy is it to find the start date of a particular infection in the patient s charts/notes? 35

It is difficult to get the infection data out of the database without a start date for the infection J Hoek

Current problems re infection & Med B Data managers insufficient expertise Use of case definitions document June 2012 infections in Promise 100,000 in 37,507 ptts Before, at or after transplant? No exact dates for infections Little information on hospitalisation List of names for infections/pathogens huge 21,000 other infections 37

QUESTION Who has used the information on infectious complications and published the results? Almost noone! So we need your suggestions how to make it work! 38

WE NEED to STOP THIS! 39

What is the Remedy for infections? 40

Pick your cherry Hey. Pick me! 41

IDWP New Data Structure Med A+ CMV Limited to centres with a clear interest Med A MED A+ H1N1 Limited to survey participants MED A+ Antibiotic resistance Limited to study participants 42

Common bacterial infections Gram-positive bacteria (n=10) Staphylococcus aureus Staphylococcus epidermidis Coagulase-negative staphylococci Enterococcus faecalis Enterococcus faecium Streptococcus pneumoniae Viridans group streptococci Streptococcus bovis Listeria monocytogenes Corynebacterium spp. Gram-negative bacteria (n=18) Escherichia coli Klebsiella spp Enterobacter spp Serratia spp. Citrobacter freundii Salmonella spp Pseudomonas aeruginosa Pseudomonas fluorescens Pseudomonas putida Pseudomonas stutzeri Ralstonia picketti Acinetobacter spp. Alcaligenes faecalis Burkholderia cepacia Ortega et al Ann Hematol (2005) 84: 40 47 43

Common bacterial infections Gram-positive bacteria (n=10) Staphylococcus aureus Staphylococcus epidermidis Coagulase-negative staphylococci Enterococcus faecalis Enterococcus faecium Streptococcus pneumoniae Viridans group streptococci Streptococcus bovis Listeria monocytogenes Corynebacterium spp. Gram-negative bacteria (n=18) Escherichia coli Klebsiella spp Enterobacter spp Serratia spp. Citrobacter freundii Salmonella spp Pseudomonas aeruginosa Pseudomonas fluorescens Pseudomonas putida Pseudomonas stutzeri Ralstonia picketti Acinetobacter spp. Alcaligenes faecalis Burkholderia cepacia Antibiotic resistant Ortega et al Ann Hematol (2005) 84: 40 47 44

Non-interventional prospective study The resistance pattern of Gram-negative bacteria isolated from blood of HSCT recipients. Ongoing c90 centres participating 45

Survey H1N1 Haematologica 96, 1231-1235 (2011)

What next? The Remedy is specific modules for infection rather than Med-B Design forms for infection module e.g. CMV disease & new antiviral drugs Should be as brief as possible Data managers & physicians work together to solve 48

Thanks to Jennifer Hoek, Study coordinator Peter Donnelly, Microbiologist 49