INFECTION DATA: WHY, WHEN, AND WHAT TO REPORT?

Marcie Riches, MD, MS

Associate Member, BMT

Moffitt Cancer Center

Scientific Director, CIBMTR INWC

February 10, 2015

Overview

• Why is infection data important?

• Why is it so complicated?

• What to report

Can infections be prevented? • Updated guidelines published in 2009 for

infection prophylaxis1

• 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

Acute

Neutropenia, barrier

breakdown (mucositis,

central venous access

devices)

Impaired cellular and

humoral immunity;

NK cells recover first, CD8 T

cell numbers increasing but

restricted T cell repertoire

Impaired cellular and

humoral immunity; B cell

& CD4 T cell numbers recover

slowly and repertoire diversifies

Bacte

rial

Fungal

Viral

Gram positive organisms Encapsulated bacteria

Gastrointestinal Streptococci species

Varicella Zoster virus

Aspergillus species Aspergillus species

Candida species

Pneumocystis

Phase I: Pre-engraftment Phase III: Late phase Phase II: Post-engraftment

Day 0 Day 15-45 Day 100 Day 365 and beyond

Mo

re c

om

mo

n

Les

s c

om

mo

n

(Seasonal/intermittent)

Graft-versus-host-disease:

Chronic

Gram negative bacilli

Herpes Simplex virus Cytomegalovirus

Respiratory and enteric viruses

EBV PTLD Other viruses eg. HHV

Immune Recovery following HCT

Storek, Expert Opinion on Biologic Therapy 2008

0

20

40

60

80

100

120

140

Imm

un

e c

ell c

ou

nts

(%

no

rma

l) Neutrophils, Monocytes, NK cells

B cells, CD8 T cells

CD4 T cells

Plasma cells, Dendritic cells

Upper normal limit

Lower normal limit

Weeks Months Years post HCT

Immune Reconstitution

• Quantitative Immunoglobulins—made by B-cells – IgG – IgM – IgA

• Immunodeficiency Panels – CD3 count (all T cells) – CD4 count (T cells) – CD8 count (T cells) – CD 19/20 count (B cells) – CD 56 count (NK cells)

• None of these assess FUNCTION of the cells

2100 R3, q55 - 76

Why are infection data so complicated?

• Numerous possible infections

• Antimicrobial medications used as

– Prophylaxis

– Pre-emptive therapy

– Empiric therapy

– Treatment of documented infection

• Multiple cultures and samples drawn

– What is really an infection?

Infectious disease markers

• Look for prior exposure! • Antibodies

– IgM: indicates recent infection—first antibody to develop with exposure • Ex. CMV IgM—new infection

– IgG: indicates prior infection—memory! • Ex. CMV IgG—past exposure

• What we check – EBV - Hepatitis B – CMV - Hepatitis C – HSV 1 and 2 - HTLV – VZV - HIV – Toxoplasma - WNV – Chaga’s - RPR

Exposure vs Infection

• Prior exposure – May or may not have caused symptoms

– Virus lies dormant • Can reactivate and cause symptoms in immune compromised

person

– Antibody markers (IgG)

• Infection – Active viral (infection) replication with/without disease

• **generally always treated**

– Assess with test to measure viral loads • Usually PCR

Where is the data to assess infection?

• Microbiology section: contains culture results

• Molecular pathology/immunology: PCR results for viral loads

• Pathology: histopathology or other tissue diagnoses for various infections

• Radiology: imaging studies, particularly for CT scan findings for fungal infections

• Progress notes

Infection Prophylaxis

• Usually include: – Antibiotics

• Quinolones

• Bactrim (TMP/SMX)

– Antifungals

– Antivirals

• Generally started about the time of conditioning to PREVENT infections

• Most centers have specific infection prophylaxis protocols/SOPs

Infection Prophylaxis 2100, R 3.0 Questions 260 – 289

How common are infections?

• >90% of patients likely to have at least one infection

• Many patients will have multiple infections

• 174/190 (91.6%) patients experienced 442 infectious episodes (1 – 11/patient)1

1Cordonnier et al, Transplantation 2006

“Clinically Significant Infection”

• Identified infections that result in a change of therapy with systemic antimicrobial agents

• Suspected infections with supporting clinical or radiographic findings (i.e. pulmonary infiltrate on chest CT)

– NOTE: Fever without documented infection (i.e. culture negative neutropenic fever) is NOT an infection

Infection Reporting

Sites of Infection

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

So What’s NOT an Infection?

• Culture-negative neutropenic fever without clear source

• Upper respiratory infections that are presumed viral but no virus identified

• Stool/Oral Candida

• Toe nail Fungus

What is the same infection? (i.e. don’t report again)

Bacteria Virus Fungal

≤7 days

• All bacteria (except Clostridium Difficile)

≤30 days

• Clostridium Difficile

≤ 365 days

• Helicobacter pylori

≤14 days

• VZV

• HZV

• Adenovirus

• Enterovirus

• Influenza virus

• Parainfluenza

• Rhinovirus

≤60 days

• CMV

• HSV

• Polyomavirus

• EBV

≤14 days

• Yeasts

Candida

Cryptococcus

≤90 days

• Molds

Aspergillus

Fusarium

Mucor

Infections with Supplemental Data

• Mold infections (2046/2146)

– Aspergillus - Fusarium

– Mucormycosis - Rhizopus

– Zygomycetes

• Viral Hepatitis (2047/2147)

– Hepatitis B

– Hepatitis C

• HIV (2048/2148)

Definitions of Fungal Infection

• Proven – Organism seen on pathology with associated tissue damage

– Organism identified by culture from a sterile procedure from a sterile area with associated clinical/radiologic findings of infection

• Probable – Requires 1 host factor + 1 clinical factor + 1 microbiologic factor

• Possible – Requires 1 host factor + 1 clinical factor

– No microbiologic factor needed

Clin Infect Dis. 2008 June 15; 46(12): 1813–1821

Host Factors

• Recent neutropenia for >10 days associated with the onset of fungal disease

• Receipt of allogeneic transplant

• Steroid use of >0.3mg/kg/day for >3 wks

• Treatment with T-cell immune suppressive meds in prior 90 days – i.e. Cyclosporine, CAMPATH, Fludarabine

• Inherited severe immune deficiency

Clin Infect Dis. 2008 June 15; 46(12): 1813–1821

Clinical Factors

• Lower Resp Tract –CT findings of well-defined

nodule, wedge shaped infiltrate, air-crescent, or cavity, OR

–Nonspecific nodule(s) with pleural rub, pleural pain, or hemoptysis

• Tracheobronchitis –Ulceration, nodule,

pseudomembrane, eschar, or plaque seen on bronch

• Sinonasal Infection – Imaging with sinusitis plus

either acute localized pain, nasal ulcer or black eschar, or extension beyond bony borders

• CNS –Focal CNS lesions

–Meningeal enhancement

• Disseminated candidiasis –Target lesions in liver and/or

spleen

Clin Infect Dis. 2008 June 15; 46(12): 1813–1821

Microbiologic Factors

Cytology, Direct Microscopy, or Culture – Sputum, BAL, or bronchial

brush findings with fungal elements by culture or direct observation

– Sinus aspirate with findings of fungal elements by culture or direct observation

– Skin ulcerations require both culture and direct observation of fungal elements

Detection of Antigen, cell wall, or nucleic acids –Galactomannan: single positive

in serum, plasma, pleural fluid, BAL, or CSF

–Beta-D-glucan: single serum sample positive

–PCR for nucleic acids are NOT considered

Clin Infect Dis. 2008 June 15; 46(12): 1813–1821

Fungal Insert

• To obtain more specific information about mold infections

• Requests detailed information of

– Diagnosis

• Date of infection, site of infection, diagnostic tests

– Prophylaxis and Therapy • Fungal drugs at the time of diagnosis

• Therapy up to 6 months after diagnosis

Mold infection (2046/2146)

Therapy Example

*If treatment held for less than 7 consecutive days and then restarted, do not consider as “Therapy Stopped”

Viral Hepatitis Insert (2047/2147)

• Viral Hepatitis may be a chronic infection of the liver

–Viral particles can be found in the blood stream

–May lead to cirrhosis or hepatocellular carcinoma

–May be lymphomagenic

• Goal: Collect detailed information on antiviral therapy and viral loads in HCT patients

Viral Hepatitis B • HBsAb = Hepatitis B surface antibody

– Develops in patients immunized against HBV – Develops in patients infected with HBV

• HBcAb = Hepatitis B core antibody – NOT seen in patients immunized – Occurs in a patient infected with HBV who successfully made antibodies – Often not seen in chronic HBV hepatitis

• HBsAg = Hepatitis B surface antigen – NOT seen in patients immunized – Indicates ongoing viral replication with potential to infect others

• HBV DNA = Hepatitis B viral load – Ongoing viral replication – PCR test

Example

• Patient AB:

– HBcAb positive

– HBsAb positive

– HBsAg negative

• Patient YZ:

– HBcAb negative

– HBsAb positive

– HBsAg negative

Which patient had a prior infection with Hepatitis B?

Viral Hepatitis C

• HCAb = Hepatitis C antibody

– Prior exposure to hepatitis C

– **NO Immunization available**

• HCV RNA = Hepatitis C viral load

– Ongoing viral replication

– Infective potential

• Diagnostic test

• Viral Load levels

• Treatment

• CD4 counts (HIV only)

• Liver pathology (Viral Hepatitis Only)

Key Data Elements: Hepatitis and HIV forms

Questions