Infection Data: Form UpdatesMarcie Riches, MD, MSAssociate ProfessorUniversity of North CarolinaScientific 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 tothe CIBMTR

• The incidence of infection in transplantpatients 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 problem1Tomblyn et al, BBMT and BMT, 20092Gooley 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 – 418Antibacterial Medications

2100 v 4.0 q 419 – 421Antiviral Medications

• The option of “None” meansthe patient did not receive anyantiviral drug from the start ofthe preparative regimen throughDay +45

• Clinically, this would be highly unusual

2100 v 4.0 q 422 – 424Antifungal Medications

2100 v 4.0 q 425 – 427Anti-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• Bordatella pertussis• Burkholderia cepacia• Campylobacter• Capnocytophaga• Chlamydia pneumoniae• Citrobacter• Clostridium (not difficile)• Clostridium difficile• Corynebacterium jeikeium• Enterobacter• Enterococcus (VRE)• Enterococcus (not VRE)• Escherichia/E. coli• Fusobacterium• Haemophilus influenzae• Haemophilus non-influenzae• Klebsiella• Lactobacillus

• Legionella pneumophilia• Legionella non-pneumophilia• Leptospira• Leptotrichia buccalis• Leuconostoc• Listeria• Micrococcus• Mycobacterium abscessus• Mycobacterium avium

intracellulare (MAI)• Mycobacterium cheloneae• Mycobacterium fortuitum• Mycobacterium haemophilum• Mycobacterium kansasii• Mycobacterium marinum• Mycobacterium mucogenicum• Mycobacterium Tb• Mycoplasma• Neisseria gonorrhea• Neisseria meningitidis

• Nocardia• Pasteurella multocida• Proteus• Pseudomonas aeruginosa• Pseudomonas non-aeruginosa• Rhodococcus• Rickettsia• Salmonella• Serratia marcescens• Shigella• Staphylococcus aureus

(Methicillin Resistant)• Staphylococcus aureus

(Methicillin Sensitive)• Stenotrophomonas maltophilia• Stomatococcus• Streptococcus, alpha-hemolytic• Streptococcus, Group B• Streptococcus pneumoniae• Treponema (syphillis)• Vibrio (all spp)

Removed several bacterial organisms we are unlikely to study

Viral Organisms: 2100 v4.0• Adenovirus• BK Virus• Coronavirus• CMV• Chikaungunya• Dengue• Enterovirus (ECHO,

Coxsackie)• Enterovirus D68 (EV-D68)• Enterovirus (polio)• Enterovirus NOS• EBV

• Hepatitis A• Hepatitis B• Hepatitis C• Hepatitis E• Herpes Simplex• HHV-6• HIV 1/HIV 2• Human metapneumovirus• HPV• HTLV 1/2• Influenza NOS• Influenza A• Influenza B

• JC Virus• Measles (rubeola)• Mumps• Norovirus• PML• Parainfluenza• RSV• Rhinovirus• Rotavirus• Rubella• Varicella• WNV

Several new viruses addedSplit out certain viruses into 2 categories based upon infections

Fungi and Parasites: 2100 v4.0

• Aspergillus NOS• Aspergillus flavus• Aspergillus fumigatus• Aspergillus niger• Aspergillus terreus• Aspergillus ustus• Blastomycosis• Candida albicans• Candida non-albicans• Coccidiomycosis

• Cryptococcus gattii• Cryptococcus neoformans• Fusarium spp• Histoplasmosis• Mucormycosis• Pneumocystis• Rhizopus• Scedosporium• Zygomycetes, NOS• Suspected Fungal

Infection

• Chaga's• Cryptosporidium• Giardia• Helminths• Strongyloides• Toxoplasma

Fungi Parasites

Combined all Candida spp into 2 groupsExpanded out AspergillusAdded new organisms of importance

Sites of Infection (prior)

**Disseminated infections must have the organism identified at 3 or more non-contiguous sites

• Blood• Bone• CNS• Eyes• Genital• GI tract, upper• GI tract, lower• Joints

• Liver/Spleen• Lung• Skin/Cellulitis• Skin, necrotizing

fasciitis• Sinuses/Upper

respiratory tract• Urinary tract, upper• Urinary tract, lower

Site: Changes 2100 v4

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• All bacteria (except Clostridium Difficile)

≤30 days• Clostridium Difficile

≤ 365 days• Helicobacter pylori

≤14 days• Adenovirus• Enterovirus• Herpes/Varicella zoster• Influenza virus• Parainfluenza• Rhinovirus• Respiratory syncytial virus≤60 days• Cytomegalovirus • Herpes simplex virus• Polyomavirus• Epstein-Barr virus

≤14 days• Yeasts

Candida sppCryptococcus

≤90 days• Molds

AspergillusFusariumMucor

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)

• 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

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