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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