Download Infectious Diseases and the Oncology Patient

Infectious Diseases and the
Oncology Patient
Seema Mehta, MD, MS
Faculty
Seema Mehta, MD, MS
Clinical Associate
Johns Hopkins School of Medicine
Baltimore, MD
Learning Objectives
1. Review risk stratification for neutropenic and high
risk patients
2. Review best practices for treatment of febrile
neutropenia
3. Identify organ specific infections in oncology
patients
4. Discuss case examples of complex patients
Definitions
• Fever
– A single oral temperature of >38.3ºC (101ºF) OR
– A temperature of >38ºC (100.4ºF) sustained
for >1 hour
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with
cancer: 2010 update by the infectious diseases society of America. Clin Infec Dis 2011; 52:e56
US Department of Health and Human Services, National Institute of Health, National Cancer Institute. Common terminology criteria
for adverse events (CTCAE)
Definitions
• Neutropenia
– Absolute neutrophil count (ANC) <1500 cells/microL
• Severe neutropenia
– ANC <500 cells/microL (μL) OR
– An ANC that is expected to decrease to <500 cells/µL over
the next 48 hours
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with
cancer: 2010 update b y the infectious diseases society of America. Clin Infec Dis 2011; 52:e56
Risk Stratification of Neutropenic Patients
• Risk of clinically important infections rise
– As neutrophils drop below 500 cells/μL
– As the duration of neutropenia prolongs (>7 days)
• High-risk and low-risk strata
– Infectious Diseases Society of America (IDSA), National
Comprehensive Cancer Network (NCCN) and American
Society of Clinical Oncology (ASCN) have varying
definitions
Febrile Neutropenia: High Risk
• ANY of the following:
–
–
–
–
–
–
–
-Hemodynamic instability
-Oral or GI mucositis
ANC <500 cells/µL* anticipated to last >7 days
-GI symptoms – abd
Alemtuzumab use within the past 2 months pain/n/v/diarrhea
-New neurologic or mental
Inpatient status at the time of fever development
status change
-IVC infection, especially
Uncontrolled or progressive cancer*
catheter tunnel infection
Evidence of hepatic insufficiency (AST, ALT >5x
ULN)
-New pulmonary infiltrate or
hypoxemia
Evidence of renal insufficiency (CrCl <30mL/min)
-Underlying chronic lung
Multinational Association for Supportive Caredisease
in Cancer
(MASCC) risk score <21
-Complex infection at time of
presentation
– Presence of any comorbid disease
Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update b y the infectious diseases society of
America. Clin Infec Dis 2011; 52:e56
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 1.2017
Flowers CR, Seidenfeld J, Bow EJ, et al. Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology
clinical practice guideline. J Clin Oncol 2013
MASCC Score
• Validated tool for measuring the risk for neutropenic
fever-related medical complications
– Burden of illness
• No or mild symptoms = 5
• Moderate symptoms = 3
• Severe symptoms/moribund = 0
– Systolic BP >90 mmHg = 5
– No COPD = 4
BP = blood pressure; COPD = chronic obstructive pulmonary disease
Klastersky J et al. The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer
patients. J Clin Oncol 2000; 13:3038
Paesmans M et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol 2006; 24: 4129
Uys A, et al. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support Care Cancer
2004; 12:555
Klatersky J, et al. Outpatient oral antibiotics for febrile neutropenic cancer patietns using a score predictive for complications. J Clin Oncol 2006; 24:4129
Klastersky J, et al. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score: 10 years of use for identifying low-risk febrile neutropenic cancer
patients. Support Care Cancer 2013; 21:1487
MASCC Score
– Solid tumor or hematologic malignancy WITHOUT prior
history of fungal infections = 4
– No dehydration requiring parenteral fluids = 3
– Outpatient status = 3
– Age <60 years = 2
Klastersky J et al. The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile
neutropenic cancer patients. J Clin Oncol 2000; 13:3038
Paesmans M et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin Oncol 2006; 24: 4129
Uys A, et al. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support
Care Cancer 2004; 12:555
Klatersky J, et al. Outpatient oral antibiotics for febrile neutropenic cancer patietns using a score predictive for complications. J Clin Oncol 2006; 24:4129
Klastersky J, et al. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score: 10 years of use for identifying low-risk febrile
neutropenic cancer patients. Support Care Cancer 2013; 21:1487
MASCC Score
• Max score = 26
• >21  predicts patients at LOW risk for serious
medical complications who can be managed with an
oral empiric antibiotic regimen
• <21  HIGH risk
• Correctly classifies low-risk patients 98% of the time
and high-risk patients 86% of the time
– Sensitivity 95%, Specificity 95%
Klatersky J, et al. Outpatient oral antibiotics for febrile neutropenic cancer patietns using a score predictive for complications. J Clin Oncol 2006; 24:4129
Uys A, et al. Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score. Support
Care Cancer 2004; 12:555
MASCC Score
• May also predict death
– <15 = 29% likelihood of death
– > 15, <21 = 9%
– > 21 = 2%
• Some criticisms of the MASCC Score
– Lack of standardization when defining “burden of febrile
neutropenia”
– Does not include duration of neutropenia
Paesmans M et al. Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications. J Clin
Oncol 2006; 24: 4129
Febrile Neutropenia: Low Risk
• ANC <500 cells/µL for < 7 days AND who have no
active comorbidities or no evidence of renal or
hepatic insufficiency
• Most patients receiving chemotherapy for solid
tumors are deemed low risk
Learning Objectives
1. Review risk stratification for neutropenic and high
risk patients
2. Review best practices for treatment of febrile
neutropenia
3. Identify organ specific infections in oncology
patients
4. Discuss case examples of complex patients
General Principles: Febrile Neutropenia
• Febrile neutropenia (FN) should be considered a
medical emergency
• Broad-spectrum antibiotics should be given as soon
as possible (within 60 minutes of triage)
• Diagnostics should be obtained quickly
Antibiotic Pearls
• Always include appropriate coverage for known/suspected
infections
• Even when a pathogen is known, the antibiotic regimen
should provide broad-spectrum coverage for possibility of
other pathogens
• Moxifloxacin does not penetrate the urinary system
• PCN allergy
– Use clindamycin, doxycycline, trimethoprim/sulfamethoxazole
– Remember that erythromycin resistance for staph aureus indicates
clindamycin will become resistant while on therapy
• Linezolid can induce myelosuppression
– After 2 weeks of use
• Fluoroquinolones -- not good for staph or enterococcus
Learning Objectives
1. Review risk stratification for neutropenic and high
risk patients
2. Review best practices for treatment of febrile
neutropenia
3. Identify organ specific infections in oncology
patients
4. Discuss case examples of complex patients
Organ-specific Infections
• When initially evaluating the patient it is vital to take
a thorough history and physical examination
– Seek out sites suspicious for infection
– Guide selection of cultures and imaging
– Recall that pus is often not found because of lack of
neutrophils
– Abdominal pain may suggest neutropenic enterocolitis (i.e.
typhlitis)
– Perianal or hemorrhoidal tenderness may suggest gramnegative or anaerobic infections
Mouth/Mucosal Membranes: Necrotizing
Ulcerations
• Necrotizing ulceration
– Viral diagnostics
– Culture and gram stains
• Fungal
• Consider leukemic
infiltrates
– Biopsy suspicious
lesions
• Treatment:
– Include anaerobic
coverage
– Consider antiviral (antiHSV) therapy
– Consider systemic
antifungal therapy
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Necrotizing ulcers
Mouth/Mucosal Membranes: Thrush
• Add antifungal therapy
– Fluconazole is first line
therapy
– Voriconaozle,
posaconazole, or
echinocandin if
refractory to fluconazole
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Mouth/Mucosal Membranes: Vesicular
Lesions
• Add Anti-HSV therapy
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Esophagus
• Complaints of
• Consider endoscopy if
retrosternal burning
no response to therapy
• Dysphagia/
• Consider CMV
Odynophagia
esophagitis in high risk
patients
• Consider viral
diagnostics, fungal
culture of oral lesions
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines
in Oncology. Prevention and treatment of cancer-related infections. Version 1.2017
Sino-Nasal Area
• Physical Exam
–
–
–
–
Sinus tenderness
Periorbital cellulitis
Nasal ulcerations
Unilateral eye tearing
• If periorbital cellulitis 
need to add vancomycin
• If CT is suspicious and
high-risk patient  start
liposomal amphotericin B
• HR CT sinuses/orbit
• ENT/ophtho evaluations
(URGENT)
• Culture and stains/ biospy
HR = high-resolution; CT = computed tomography
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Sino-Nasal Area
Lung Infiltrates
• Depending on risk –
must consider the
following:
– Nasal swab/wash for
respiratory viruses/rapid
tests
– Serum Glactomannan or
β-glucan
– CT of chest
– Bronchoscopy
– Diagnostic lung biopsy
• Add azithromycin or
fluoroquinolone to cover
atypical bugs
• Consider adding:
– Mold-active azole
– Antiviral during peak
influenza/RSV season
– Vancomycin or linezolid
if MRSA suspected
– Bactrim if concerned for
Pneumocystis (PJP)
RSV = respiratory syncytial virus
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 1.2017
Abdominal Pain
• Obtain CT (preferred) or
Ultrasound
• Consider treating for
c.difficile
• Check LFTs and
pancreatic enzymes
• Ensure adequate
anaerobic coverage
• Diarrhea?
LFTs = liver function tests
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Perirectal Pain
• Physical examination
• Consider CT
• Ensure adequate
anaerobic coverage
• Consider enterococcal
coverage
• Consider local wound
care
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Diarrhea
• Send c.difficile assay
• Consider evaluation for
viral pathogens,
bacterial cultures,
and/or parasite
examination
• Start oral vancomycin
(preferred) or
metronidazole if
c.difficile is highly
suspected or confirmed
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Urinary Tract Symptoms
• Send for urinalysis and
urine culture
• Identify specific
pathogen and start
therapy/tailor antibiotics
accordingly
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Skin
• Cellulitis/Skin and soft tissue
infection
– Treat based on clinical
evaluation
– Can consider biopsy or culture
of drainage
– Ensure gram positive coverage
• Clindamycin,
trimethoprim/sulfamethoxazole,
cephalexin, doxycycline
National Comprehensive Cancer Network (NCC) Clinical Practice
Guidelines in Oncology. Prevention and treatment of cancer-related infections. Version 1.2017
Skin
• Vesicular lesions
– Aspirate or scrape for
VZV or HSV PCR (can
do a DFA or culture if
PCR unavailable)
– If scraping the vesicle –
remember to take
sample from edge as
that is where the virus
lives
• Start treatment with
anti-viral agent:
– Acyclovir/Valacyclovir
– Famciclovir
– Recall that
ValGanciclovir is the only
oral antiviral active
against CMV
VZV = varicella-zoster virus, HSV = herpes simplex virus, PCR = polymerase chain reaction, DFA = direct fluorescentantibody, CMV = cytomegalovirus
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Disseminated papules or other lesions
• Aspiration or biopsy
• Consider evaluation for
VZV
• Consider vancomycin
addition
• Consider mold-active
azole in high-risk
patients
National Comprehensive Cancer Network (NCC) Clinical Practice Guidelines in Oncology. Prevention and treatment of cancer-related
infections. Version 1.2017
Learning Objectives
1. Review risk stratification for neutropenic and high
risk patients
2. Review best practices for treatment of febrile
neutropenia
3. Identify organ specific infections in oncology
patients
4. Discuss case examples of complex patients
Case #1
• 67 yo woman w/ a hx of relapsed AML receiving
Vidaza while awaiting SCT.
• Presented to clinic C2D10 with baseline chronic
pancytopenias.
– ANC 0.5, Hgb 8.8, Plts 22,000
• Notes a new, small bullous lesion on her hand
• What would you treat with?
Three Days Later…
• Presented to the ER for increased pain and swelling.
• Taken to OR that night by ortho for I&D
• Intraoperative findings show seropurulent fluid and
multiple indurated purpuric lesions
• What would you treat with empirically at this time?
Cultures and beyond
• Cultures grew MRSA – would this change your
management?
• Required repeat I&D 5 days later to debride necrotic
tissue. Cultures negative
• Required 5 weeks of wound care/antibiotics which
delayed SCT
• 1 year outcome: doing well! Seen in clinic Feb 2017
Case 2
• 58yo woman w/ classical Hodgkin’s lymphoma
presenting to clinic C1D8 of ABVD w/ day 2
pegfilgrastim complaining of ear drainage, h/a, and
low grade fevers x 3 days
• ANC 0.5. Afebrile in clinic. Right ear with black
drainage.
• Seen by PCP earlier that week – given
clarithromycin
• Allergies: Sulfa, PCN, fluoroquinolones
• What would you do at this time?
Work up and Cultures
• CT sinuses – nonspecific right middle ear mastoid
disease, incompletely visualized
• Cultures – growing mold
• What would you do at this time?
Outcome
• Direct admission for ENT and ID services for
presumed invasive fungal OE and mastoiditis
• 48h after admission, cultures resulted: Aspergillus
spp, not fumigatus
• MRI confirmed no mastoiditis
• What would you treat with?