Infection Data: Form Updates

Marcie Riches, MD, MS Associate Professor University of North Carolina Scientific Director, Infection and Immune Reconstitution WC Overview

• Why is infection data important?

• Why is it so complicated?

• What to report • Infections account for 7 – 17% of the primary cause of death as reported to the CIBMTR

• The incidence of infection in transplant patients is much higher, with nearly 70% or more patients having at least one infection in the post-transplant period Can infections be prevented? • Guidelines published in 2009 for infection prevention1 • Prophylaxis and new antimicrobials have decreased early serious infections2 – CMV disease decreased by 48% – GN bacteremia decreased by 39% – Invasive mold infections decreased by 51% – Invasive Candida infections decreased by 88% • Later infections continue to remain a problem

1Tomblyn et al, BBMT and BMT, 2009 2Gooley et al, NEJM 2010 Prior Infection Prophylaxis Data

Collected y/n for all drugs received after the start of the conditioning regimen

* Results in data documenting patients receiving multiple drugs of the same class with no information on sequence/overlap* Revised Infection Prophylaxis Data • Collect medication prophylaxis data by antimicrobial type (i.e. bacterial, viral, fungal) • Key change: – Collect only the first drug started closest to the start of the preparative regimen – Only in the antibacterial group can more than one drug be selected • Both drugs must start at the same time! 2100 v 4.0 q 407 – 418 Antibacterial Medications 2100 v 4.0 q 419 – 421 Antiviral Medications

• The option of “None” means the patient did not receive any antiviral drug from the start of the preparative regimen through Day +45

• Clinically, this would be highly unusual 2100 v 4.0 q 422 – 424 Antifungal Medications 2100 v 4.0 q 425 – 427 Anti-pneumocystis Medications Why the change • Understanding the anti-microbial medications at the time of transplant is useful to understand subsequent infections • Pros: – Data is discrete (single drug) – Can use to study prophylaxis patterns • Cons: – Doesn’t provide information on changes in prophylaxis or therapy within an individual patient Infection Reporting • Changes: – Organism list updated • Focused on viral and fungal infections • Rare/serious bacterial infections – Site list refined – Addition of questions for SIRS and Septic Shock

• Manual updated – What not to report – Examples Infection reporting

Bacterial Organisms: 2100 v4.0

• Acinetobacter • Legionella pneumophilia • Nocardia • Bordatella pertussis • Legionella non-pneumophilia • Pasteurella multocida • Burkholderia cepacia • Leptospira • Proteus • Campylobacter • Leptotrichia buccalis • Pseudomonas aeruginosa • Capnocytophaga • Leuconostoc • Pseudomonas non-aeruginosa • Chlamydia pneumoniae • Listeria • Rhodococcus • Citrobacter • Micrococcus • Rickettsia • Clostridium (not difficile) • Mycobacterium abscessus • Salmonella • Clostridium difficile • Mycobacterium avium • Serratia marcescens • Corynebacterium jeikeium intracellulare (MAI) • Shigella • Enterobacter • Mycobacterium cheloneae • Staphylococcus aureus • Enterococcus (VRE) • Mycobacterium fortuitum (Methicillin Resistant) • Enterococcus (not VRE) • Mycobacterium haemophilum • Staphylococcus aureus • Escherichia/E. coli • Mycobacterium kansasii (Methicillin Sensitive) • Fusobacterium • Mycobacterium marinum • Stenotrophomonas maltophilia • Haemophilus influenzae • Mycobacterium mucogenicum • Stomatococcus • Haemophilus non-influenzae • Mycobacterium Tb • Streptococcus, alpha-hemolytic • Klebsiella • Mycoplasma • Streptococcus, Group B • Lactobacillus • Neisseria gonorrhea • Streptococcus pneumoniae • Neisseria meningitidis • Treponema (syphillis) • Vibrio (all spp)

Removed several bacterial organisms we are unlikely to study Viral Organisms: 2100 v4.0

• Adenovirus • Hepatitis A • JC Virus • BK Virus • Hepatitis B • Measles (rubeola) • Coronavirus • Hepatitis C • Mumps • CMV • Hepatitis E • Norovirus • Chikaungunya • Herpes Simplex • PML • Dengue • HHV-6 • Parainfluenza • Enterovirus (ECHO, • HIV 1/HIV 2 • RSV Coxsackie) • Human metapneumovirus • Rhinovirus • Enterovirus D68 (EV-D68) • HPV • Rotavirus • Enterovirus (polio) • HTLV 1/2 • Rubella • Enterovirus NOS • Influenza NOS • Varicella • EBV • Influenza A • WNV • Influenza B

Several new viruses added Split out certain viruses into 2 categories based upon infections Fungi and Parasites: 2100 v4.0

Fungi Parasites

• Aspergillus NOS • Cryptococcus gattii • Chaga's • Aspergillus flavus • Cryptococcus neoformans • Cryptosporidium • Aspergillus fumigatus • Fusarium spp • Giardia • Aspergillus niger • Histoplasmosis • Helminths • Aspergillus terreus • Mucormycosis • Strongyloides • Aspergillus ustus • Pneumocystis • Toxoplasma • Blastomycosis • Rhizopus • Candida albicans • Scedosporium • Candida non-albicans • Zygomycetes, NOS • Coccidiomycosis • Suspected Fungal Infection

Combined all Candida spp into 2 groups Expanded out Aspergillus Added new organisms of importance Sites of Infection (prior)

**Disseminated infections must have the organism identified at 3 or more non-contiguous sites Site: Changes 2100 v4 • Blood • Liver/Spleen • Bone • Lung • CNS • Skin/Cellulitis • Eyes • Skin, necrotizing • Genital fasciitis • GI tract, upper • Sinuses/Upper • GI tract, lower respiratory tract • Joints • Urinary tract, upper • Urinary tract, lower SIRS/Septic Shock

• SIRS: a clinical syndrome of dysregulated inflammation with 2 or more abnormalities in temp, HR, RR, or WBC – Does not have to have an organism identified – May also be labeled “sepsis”

• Septic Shock: Sepsis (life-threatening organ dysfunction) associated with circulatory collapse requiring vasopressors and a lactate of >2 mmol/L associated with an infection – Does not have to have an organism identified – Higher risk of death compared to SIRS/Sepsis alone What not to report at all! • Culture negative neutropenic fever – Note: if SIRS/sepsis or Septic Shock occurred, this will be reported separately • Suspected but unconfirmed viral or bacterial infections – Includes URI presumed viral but no virus identified • Candida spp found only in oropharynx or stool • Toe nail fungus (onychomycoses) What not to report because it’s the same infection: Bacteria Virus Fungal ≤7 days ≤14 days ≤14 days • All bacteria (except • Adenovirus • Yeasts Clostridium Difficile) • Enterovirus Candida spp • Herpes/Varicella zoster Cryptococcus ≤30 days • Influenza virus • Clostridium Difficile • Parainfluenza • Rhinovirus ≤90 days ≤ 365 days • Respiratory syncytial virus • Molds • Helicobacter pylori ≤60 days Aspergillus • Cytomegalovirus Fusarium • Herpes simplex virus Mucor • Polyomavirus • Epstein-Barr virus Additional changes in process • Revisions to 2046/2146 Fungal Infection forms (planned ~April 2017) • Additional forms – Respiratory virus form 2149 (~April 2017) – CMV/HHV-6/EBV/Adenovirus forms (~July 2017) • Planned: – Revisions to 2047/2147 Hepatitis viral forms – Revisions to 2048/2148 HIV forms – Addition of PJP form 2046/2146 Changes • Need data regarding diagnostic testing – Allows for researchers to categorize infections as possible/probable/proven • Need data regarding treatment – Set specific times for assessment of drugs – Only request start date • Form 2146 required for any fungal infection (including suspected) reported on 2100/2200 Form 2046/2146: Diagnostic tests • Mark if the test was considered “positive” to support the diagnosis of fungal infection • Sections for: – Radiology (CXR, CT scan, MRI) – Pathology (biopsy or cytology) – Cultures – Stains (KOH/Calcofluor/Giemsa) – Assays (Galactomannan, Fungitell) • Under the test type, specific sites/sample sources requested – Set up as skip patterns with the ability to copy and paste to report multiple sites within a specific test Form 2046/2146: Diagnostic tests (ex) Form 2146: Lab data • Request data on specific labs at the date of diagnosis of the infection (+/- 7 days) • Blood counts – WBC – % neutrophils – % lymphocytes – % monocytes – Platelets Form 2046/2146: Treatment • Request data on all antifungal medications (list provided) from 7 days prior to the diagnosis of the infection until the end of the reporting period – Request start date • 2046: Note this may be unknown • 2146: Generally the HCT center is involved so should be able to find/estimate – For each drug received, asks if the patient is still receiving the drug 30 days (+/-3) from date of diagnosis Form 2046/2146: Treatment

Only for 2146 Form 2046/2146: Response to Therapy • Form 2046

• Form 2146 Form 2149: Respiratory Virus Form • Triggered in the following circumstances: – Organism of either RSV, PIV, Influenza NOS/A/B or metapneumovirus – Organism Rhinovirus or Coronovirus only if the site of infection includes “LUNG” • Rationale: – Respiratory viruses can be fatal in the immunocompromised patient – Data to understand in our patient population is needed • Goal: – Collect information on diagnosis, risk factors, and treatment/response to therapy Form 2149: Diagnosis • Collect information on tests with a positive result supporting the diagnosis

• Tests performed 7 days before and up to 14 days after the reported date of infection – Allows us to have global picture of certainty of diagnosis Form 2149: Diagnosis Form 2149: Clinical Factors

• Lab parameters (+/- 7 days of infection diagnosis) – WBC, % neutrophils, % lymphocytes, % monocytes, platelets – IgG level Form 2149: Therapy and Response • Specific antiviral drugs from 7 days prior to date of infection until 14 days after diagnosis • IVIG use: y/n Form 2150: CMV/EBV/ADV/HHV-6 • Triggered in the following circumstances: – Organism of ADV or EBV, regardless of site – Organism CMV or HHV-6 if at any site other than just blood • Rationale – Serious infections that need additional study • Goal: – Collect information on diagnosis, risk factors, and treatment/response to therapy Form 2150: Diagnosis • Collect information on tests with a positive result supporting the diagnosis

• Tests performed 7 days before and up to 14 days after the reported date of infection – Allows us to have global picture of certainty of diagnosis – Because of the range of infections, there are several questions but the skip pattern is built into the form Form 2150: Diagnosis Form 2150: Symptoms at diagnosis • Symptoms +/- 1 day of diagnosis – O2 requirement: y/n – Liver/spleen/LN enlargement: y/n (for each) – Diarrhea (y/n) – Neurologic symptoms (y/n)

• Lab parameters (+/- 7 days of infection diagnosis) – WBC, % neutrophils, % lymphocytes, % monocytes, platelets – IgG level – Creatinine, ALT (SGPT) Form 2150: Treatment • Request data on all antiviral medications (list provided) from 7 days prior to the diagnosis of the infection until the end of the reporting period • Date medication started • If therapy was still being received 30 days (+/- 3 days) from diagnosis. Form 2150: Treatment and Response • Include information on chemotherapy, immunotherapy, IVIG, virus specific T cells – If CTLs given, will trigger Form 4000 Summary • Infection data is important to continue to improve post-HCT outcomes for our patient • The data you provide is critical, particularly for the rare and/or serious infections