Download infection data: why, when, and what to report?

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
Phase I: Pre-engraftment
Phase II: Post-engraftment
Phase III: Late phase
Chronic
Graft-versus-host-disease:
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
Gram negative bacilli
Less common
Encapsulated bacteria
Gram positive organisms
Gastrointestinal Streptococci species
Viral
Herpes Simplex virus
Cytomegalovirus
Respiratory and enteric viruses
(Seasonal/intermittent)
Varicella Zoster virus
Other viruses eg. HHV
EBV PTLD
Fungal
Aspergillus species
Aspergillus species
Candida species
Pneumocystis
Day 0
Day 15-45
Day 100
Day 365 and beyond
More common
Bacterial
Neutropenia, barrier
breakdown (mucositis,
central venous access
devices)
Acute
Immune Recovery following HCT
Immune cell counts (% normal)
140
120
Neutrophils, Monocytes, NK cells
B cells, CD8 T cells
100
CD4 T cells
Plasma cells, Dendritic cells
Upper normal limit
80
Lower normal limit
60
40
20
0
Weeks
Months
Years post HCT
Storek, Expert Opinion on Biologic Therapy 2008
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
CMV
HSV 1 and 2
VZV
Toxoplasma
Chaga’s
- Hepatitis B
- Hepatitis C
- HTLV
- HIV
- WNV
- 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
≤7 days
• All bacteria
(except Clostridium
Difficile)
Virus
≤14 days
• VZV
• HZV
• Adenovirus
• Enterovirus
≤30 days
• Influenza virus
• Clostridium
• Parainfluenza
Difficile
• Rhinovirus
≤60 days
≤ 365 days
• CMV
• Helicobacter pylori
• HSV
• Polyomavirus
• EBV
Fungal
≤14 days
• Yeasts
Candida
Cryptococcus
≤90 days
• Molds
Aspergillus
Fusarium
Mucor
Infections with Supplemental Data
• Mold infections (2046/2146)
– Aspergillus
– Mucormycosis
– Zygomycetes
- Fusarium
- Rhizopus
• 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
• Sinonasal Infection
• Lower Resp Tract
– Imaging with sinusitis plus
either acute localized pain,
nasal ulcer or black eschar, or
extension beyond bony borders
– CT findings of well-defined
nodule, wedge shaped
infiltrate, air-crescent, or
cavity, OR
– Nonspecific nodule(s) with
pleural rub, pleural pain, or
hemoptysis
• CNS
– Focal CNS lesions
– Meningeal enhancement
• Tracheobronchitis
– Ulceration, nodule,
pseudomembrane, eschar, or
plaque seen on bronch
• 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
Key Data Elements:
Hepatitis and HIV forms
•
•
•
•
•
Diagnostic test
Viral Load levels
Treatment
CD4 counts (HIV only)
Liver pathology (Viral Hepatitis Only)
Questions