Transcript Current Status of Diagnosis and Mangement of IFI

“Current Status of Diagnosis &
Management of Invasive Fungal
Infection”
Outline of the Presentation

Invasive Fungal Infection

Fungal Pathogens

Fungal infections

Fungal ICU infection

Incidence of ICU acquired candidemia in India

Underlying disease and risk factors

Risk factors for Invasive Fungal Infections in the ICU

Fungal Diagnostic Techniques

Management of Invasive Fungal Infection

Summary of IDSA Guideline for treating Invasive Candidiasis and
Aspergilliosis
Invasive Fungal Infection

Invasive fungal infections (IFIs) have emerged as a major cause of
morbidity and mortality amongst critically ill patients.

Cancer patients admitted to the Intensive Care Unit (ICU) have
multiple risk factors for IFIs.

The vast majority of IFIs in the ICU are due to Candida spp.

The incidence of invasive candidiasis (IC) has increased over recent
decades, especially in the ICU.
Continuing Education in Anaesthesia, Critical Care & Pain j 2013
Fungal Pathogens
Candida sp
Aspergillus sp
Cryptococcus
Fusarium
Pneumocystis
Invasive Fungal infections

Candidiasis: Mucocutaneous, disseminated, UTI,

Cryptococcosis: Central nervous system (CNS), pulmonary,
dematologic, skeletal, and organ-specific disease.

Aspergillosis: Pneumonia, genitourinary, CNS, rhinocerebral,
gastrointestinal, and skin.

Zycomocoses: Rhizopus and Mucor species Pneumocystis
Pneumonia

Histoplasmosis: Pneumonia or disseminated disease
Fungal ICU infection

High mortality rate 35-75%, so early antifungal is essential for
survival

ICU acquired fungal infection patients characteristically have several
underlying medical and surgical risk factors and frequently exposed
to high-risk medications.

Mainly Candidemia in ICU and rarely mold infections.

Rising trend of non-albicans Candida species.

Few multicentric studies on Candidemia from Asian countries.
Chakrabarti et al, Intensive Care Medicine 2015
“Incidence of ICU acquired candidemia in
India” s

Study: 215,112 patients admitted
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27 intensive care units
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North -11, East -3, West-3 Central4, South – 6

11 public sector and 16
private/corporate hospitals

Adult ICU > 18 years

ICU acquired Candidemia after 48
hrs ICU admission
Chakrabarti et al, Intensive Care Medicine 2015
ICU acquired candidemia in India
 Incidence

of candidemia = 6.51/1000 ICU admission •
Highest burden in north India (8.95/1,000) and lowest from
west (3.61/1000 admissions)
 65.2%
were adults with median age of 50 years
 Median
duration of onset of candidemia in ICU – 8 days
 Majority
were non- neutropenic (98.7%)

Median APACHE II score of 17.0 at admission
Chakrabarti et al, Intensive Care Medicine 2015
Underlying disease and risk factors
Underlying respiratory illness (25.0%):
 Pneumonia (32.9%)
 ARDS (17.9%)
 COPD (15.4%)
Underlying renal disease (22.9%)
 Acute (61.2%) or chronic renal failure (30.1%)
Malignancy (12.8%)
 Solid organ (82.9%) and haematological (17.1%)
 47.9% gastrointestinal, 60.7% were intraperitoneal
Surgical procedure (37.3%) within 30 days
 Gastrointestinal, hepatobiliary and pancreatic surgeries (48.4%)
Chakrabarti et al, Intensive Care Medicine 2015
Risk factors for Invasive Fungal Infections in the
ICU
Adult Patients
Solid Organ Transplant
Recipients
Patients with Malignancy
Candida Colonization
All Transplant recipient
All patients with Malignancy
Diabetes Mellitus
Immunocomsupresnats medications
Neutropenia: duration and severity
Kidney Failure
Corticosteroids
Mucosal Damage
Hemodialysis
Recipients of more than one organ
Concomitant viral infection
Severe Acute Pancreatitis
Acute or Chronic rejection
Recent Chemotherapy
High APACHE II Score
Advance donor age
Prolonged Stay in Mechanical
Ventilation
CMV Infection
“Fungal Infection in the intensive care unit”
Risk factors for Invasive Fungal Infections in
the ICU
Adult Patients
Solid Organ Transplant Recipients
Patients with Malignancy
Central venous or urinary
catheter
Liver Transplant recipient
HSCT recipients
Prolonged stay in ICU
Intraoperative blood requirement > 40
Units
Graft vs Host Disease
Broad Spectrum Antibacterial
Choledochojejunostomay
Prior Invasive Fungal Infection
Parenteral Nutrition
Retransplantation
Delayed engraftment
Major Surgery
Reexploreation
Underlying malignancy
Burns
Length of Transplant operation
Induction with Cytarbine
Fluminat hepatic Failure
“Fungal Infection in the intensive care unit”
Risk factors for Invasive Fungal Infections in
the ICU
Adult Patients
Solid Organ Transplant Recipients
Patients with Malignancy
Lung transplant recipients
Delayed chest closure
Bronchiolitis obliterans
Heart transplant recipients
Delayed chest closure
“Fungal Infection in the intensive care unit”
APACHE II= Acute Physiological and Chronic health Evaluation II scale, CMV Cytomegalovirus,HSCT=
hematopoietic stem cell transplantation, ICU = Intensive care unit
Fungal Diagnostic Techniques
Traditional Methods
Method
Pathogen(s)
detected
Comments
Culture
All
Replication time is longer for fungi than for bacteria: may take a long
time to complete; may be negative for certain fungal pathogens in
blood; unable to differentiate colonization form true infection may
require invasive specimen.
Histopathology
All
Cannot identify specific pathogens and may be difficult to distinguish
from bacterial or other causes; lack of immune response in
immunosuppressed patients results ; delay in symptoms related to
infection.
Radiology
All
“Fungal Infection in the intensive care unit”
Fungal Diagnostic Techniques
Rapid Diagnostic Tools
Method
Pathogen(s) detected
Comments
Galactomannan
Aspergillus only
False positive with B lactum antibiotics: low sensitivity in solid
organ transplant recipients; Controversy regarding positive test
cut-off.
Beta-Glucan
Candida Spp.and
Aspergillus only
False positive with dialysis filters gauze sponges, albumins,
immune globulin; controversy regarding positive test cut-off.
Fungal PCR
All; test is specific to
organism
Not Commercially available.
PNA FISH
Candida albicans and
candida glabrata
“Fungal Infection in the intensive care unit”
PCR= polymerase chain reaction,PNA FISH= peptide nucleic acid fluorescence in situ hybridization.
Other Diagnostic Techniques

Chest X –Ray

In case of Aspergillus ling Disease the Presence of aspergillomas
or “air crescent” formation on chest CT cab be diagnostic if
present.

Funsoscopy may revels cotton-wool ball changes within the
retina if candida chrorodorentitis is present.
“Fungal Infection in the intensive care unit”
Management of Invasive Fungal Infection
Spectrum of action of systemic antifungal agents
Mayo Clin Proc. • August 2011;86(8):805-817
Treatment Strategies
Prophylactic
Pre-emptive
Empiric
Strategies
Prophylactic Therapy

Prophylaxis therapy provides antifungal agents to a broad populations
of patients to prevent disease.
 Fluconazole (Azoles) as Prophylaxis in various ICU patients.
 If Azole resistant candida spp. or the emergence of disease with
pathogens inherently resistant to fluconazole
Prophylaxis Be Used to Prevent Invasive Candidiasis in the Intensive
Care Unit Setting as per IDSA 2015
 Fluconazole, 800-mg (12 mg/kg) loading dose, then 400 mg (6
mg/kg) daily, could be used in high-risk patients in adult ICUs with a
high rate (>5%) of invasive candidiasis
 An alternative is to give an echinocandin
“Fungal Infection in the intensive care unit”
Clin Infect Dis. (2015) doi: 10.1093/cid/civ933
Pre Emptive Antifungal therapy

Early Intervention in the course of Disease.

Empiric antifungal therapy should be started as soon as
possible in patients who have the risk factors and who have
clinical signs Fungal Infection.
Echinocandin:
(caspofungin: loading dose of 70 mg, then 50
mg daily; micafungin: 100 mg daily;
anidulafungin: loading dose of 200 mg, then
100 mg daily)
Fluconazole, 800-mg (12 mg/kg) loading dose,
then 400 mg (6 mg/kg) daily,
Lipid formulation AmB, 3–5 mg/kg daily, is an
alternative if there is intolerance to other
antifungal agent
Treatment for fungal Infection
Category
Drug
Formulation Main Indication
Azoles
(Trizoles)
Fluconazole
PO/IV
Candida albicans
Itraconzole
PO/IV
Posaconzole
PO
Voriconzole
PO/IV
Balstomycosis, histoplasmosis, aspergillosis,
candidiasis, cryptococcal meningitis
Aspergillus (alternative treatment),
zygomycosis, fluconazole-resistant Candida
spp.
Invasive aspergillosis, non-albicans
candidaemia, coccidioidomycosis,
fluconazole-resistant Candida spp.
“Fungal Infection in the intensive care unit”
Treatment for fungal Infection
Category
Drug
Formulations
Echinocandin Anidulofungi IV
s
n
Caspofungin IV
Micafungin
Polyenes
Main Indication
Candida Species
Most Candida Infections, Potential salvage
treatment for Aspergillus.
IV
Amphoterici IV
nB
Liposomal
IV
amphotericin
Active against most systemic fungal infection
including aspergillosis.
Treatment for fungal Infection
Category
Drug
Formulatio
n
Main Indication
Other
Flucytosine
IV
Cryptococcal meningitis (Used in combination
with Amphotericin)
Other topical
antifungal agents
Amorolfine
Benzoic acid
Griseofulvein
Nystatin
Terbinafine
Undecantoes
“Fungal Infection in the intensive care unit”
Treatment of Fungal Infection
Candidiasis: Fluconazole; or if a resistant Candida species is likely: an
Echinocandin or an Amphotericin.
Aspergillosis: Voriconazole, an Amphotericin, or both.
Zygomycosis: an Amphotericin+posaconazole.
Cryptococcosis: An amphotericin with flucytosine, followed by fluconazole.
Blastomycosis: Itraconzole, fluconazole, or an amphotericin (depending on
the site and severity of the disease).
Continuing Education in Anaesthesia, Critical Care & Pain j 2013
Treatment of Fungal Infection
Histoplasmosis: itraconazole or an amphotericin (possibly with steroids in acute
pulmonary disease).
Coccidioidosis: Fluconazole or an Amphotericin.
Paracoccidioidosis: Co-trimoxazole (fluconazole or an amphotericin if cotrimoxazole not tolerated).
Pneumocystis pneumonia: co-trimoxazole (with steroids); alternatively, if co-
trimoxazole is not tolerated: pentamidine or primaquine/atovaquone with clindamycin.
Continuing Education in Anaesthesia, Critical Care & Pain j 2013
Summary of IDSA (2008) Guideline for treating Invasive
Candidiasis and Aspergilliosis
Disease State
First line Treatment
Alternative Regimen(s)
Invasive Aspergillosis Voriconazole 6 mg/kg Iv q 12 h for 2
doses then 4 mg/kg IV q 12 h or 200
mg PO q 12 h
Lipid Amphotericin B 3-5 mg/kg IV q 24 h
Caspofungin 70 mg IV loading dose then
50 mg/kg/day IV
Micafungin 100-150 mg/day/IV
Posaconazole 800 mg/day PO 2-4 divided
doses
Itraconzole dose depends on formulation
Candidemia
(Non-Neutropenic
patient moderatesevere illness)
Caspofungin 70 mg IV loading dose
then 50 mg/day IV
Micafungin 100 mg/day IV
Anidulafungin 200 mg IV loading
dose the 100mg/day IV
Fluconazole 800 mg IV loading dose then
400 mg/day IV or PO
Candidemia
(Neutropenic)
Caspofungin 70 mg IV loading dose
then 50 mg/day IV
Micafungin 100 mg IV daily
Anidulafungin 200 mg IV loading
dose then 100 mg /day IV
Fluconazole 800mg IV loading dose then
400 mg/day IV or PO
Voriconazole if mold coverage desired
Voriconazole 6 mg/kg IV q 12 h for doses
then 4 mg kg IV q 12 h or 200 mg PO q 12 h
Continuing Education in Anaesthesia, Critical Care & Pain j 2013
Summary of IDSA Guideline for treating Invasive
Candidiasis and Aspergilliosis
Candida glabrata
Echinocandin
Fluconazole or Voriconazole with
susceptibility testing
Candida Parpsilos
Fluconazole
Echinocandin if already responding
to therapy
Solid organ transplant
Recipient (prophylaxis ) Fluconazole 200-400 mg/day IV or PO for 7-14
days
ICU Prophylaxis (High
Risk Patient only )
Liposomal amphotericin B 1-2
mg/kg/day IV for 7-14 days
Fluconazole 400 mg/day IV or PO
Clin Infect Dis. (2015) doi: 10.1093/cid/civ933
The 2016 Revised Recommendations for the Management of Candidiasis
The Treatment for Candidemia in Neutropenic Patients
Strong recommendation;
moderate-quality evidence
Strong recommendation;
low-quality evidence
Weak recommendation;
low-quality evidence
An echinocandin as initial therapy
Caspofungin: loading dose 70 mg, then
50 mg daily;
Micafungin: 100 mg daily;
Anidulafungin: loading dose 200 mg,
then 100 mg daily
For infections due to C. krusei
An echinocandin, lipid formulation AmB, or
voriconazole is recommended
Fluconazole, 800-mg (12 mg/kg) loading
dose, then 400 mg (6 mg/kg) daily is
An alternative for patients who are not critically
ill and have had no prior azole exposure
Lipid formulation AmB 3–5 mg/kg daily,
is an effective but less attractive
alternative because of the potential for
toxicity.
Recommended minimum duration of therapy
for candidemia without metastatic
complications is
2 weeks after documented clearance of Candida
from the bloodstream, provided neutropenia and
symptoms attributable to candidemia have
resolved
Fluconazole, 400 mg (6 mg/kg) daily
Can be used for stepdown therapy during
persistent neutropenia in clinically stable
patients who have susceptible isolates and
documented bloodstream clearance
Ophthalmological findings of choroidal and
vitreal infection are minimal until recovery from
neutropenia; therefore, dilated funduscopic
examinations should be performed within the
first week after recovery from neutropenia
Voriconazole, 400 mg (6 mg/kg) twice daily
for 2 doses, then 200–300 mg (3–4 mg/kg)
twice daily, Can be used in situations in which
additional mold coverage is desired
Clin Infect Dis. (2015) doi: 10.1093/cid/civ933
The Treatment for Candidemia in Neutropenic Patients
Strong recommendation;
moderate-quality evidence
Strong recommendation;
low-quality evidence
Weak recommendation;
low-quality evidence
In the neutropenic patient, sources of Voriconazole Can also be used as
step-down therapy during neutropenia
candidiasis other than a CVC (eg, in clinically stable patients who have
gastrointestinal tract) predominate. had documented bloodstream
clearance and isolates that are
Catheter
removal
should
be susceptible to voriconazole
considered on an individual basis
Granulocyte colony-stimulating
factor (G-CSF)–mobilized
granulocyte transfusions Can be
considered in cases of persistent
candidemia with anticipated
protracted neutropenia
Clin Infect Dis. (2015) doi: 10.1093/cid/civ933
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