The assesment and

Management of
lung Mycosis
Pulmonary mycosis: candiosis
Invasive pulmonary aspergillosis
 Mikosis Paru

• Adalah Gangguan Paru (termasuk saluran Napas) yang

disebabkan oleh infeksi, kolonisasi jamur, maupun reaksi
hipersensitif terhadap jamur
• Meningkat seiring peningkatan pasien dengan gangguan sitem
imun :
– Keganasan - transplantasi organ
• kkk
 Diagnosis mikosis paru biasanya terlambat

35
Hospital mortality (%)

30
25
20
15
10
5
0
< 12 12–24 24–48 > 48

Penundaan memulai terapi antijamur (Jam)

Morrell M, et al. Antimicrob Agents Chemother 2005; 49:3640–5

 Late
diagnosis
Relatively 
 limited  toxic drugs

Late antfungal treatment

diagnostic low doses of
options antifungals

Poor treatment results
Initial situation
colonization

invasion infecton

invasion
disease

integument damage
Systemic mycosis: candidemia, pneumonia
 MODEL FOR INVASIVE CANDIDIASIS
Blijlevens, Donnelly, De Pauw. Brit J Haematol 2002;117:259-64

Central venous catheter GI tract
Antibiotics
insult Anti-cancer

Normal
commensal
flora

injury selection

infection Candida species

translocation

Disease
 Respiratory candidiasis

• Candida is the most common

inhabitant of oropharyngeal cavity
• May be invasive in various
immunocompromised conditions
• Nosocomial infection, frequently
overlooked
 Phaller et al: J Clin Microbiol 2005,43 548-59

• Isolate from respiratoty/alimentary/genital

tract, skin, soft tissue, inner tissues, blood
and normally sterile body fluid
• From Asia, Europe, Middle East,
Latin and North America in 6,5 yrs
(June 1997- December 2003)
• Total isolates of Candida >20000 (134715+75810),
non Candida >9500 (6052+3533)
 Phaller et al: J Clin Microbiol 2005, 43: 548-59

• Candida per year: 97,5%, Candida albicans 66,2%

• Total C. albicans per year dicreases 10%
• Accompanied by increase n ia number of
other Candida: C. tropicalis and C.parapsilosis.

• C. glabrata and C. krusei are relatively constant

• Others: Cryptococcus neoformans (21%), Saccharomyces
spp (6,8), Trichosporon spp (6,5%) and Rhodotorula spp
(2,3%)
Risk factor for Nosocomial Invasive Candida Infections
Ruhnke, Current Drug Targets, 2006,7,495-504
Immunosuppressive therapy
*Inpatients with HIV Infection,
With corticosteroids, Cytotoxic chemotherapy for cancer
Prolonged therapy with broad-spectrum antibiotics  2 weeks*
Central venous or arterial catheters *
Parenteral nutrition
Ongoing invasive ventilation  10 days
Colonization with Candida species  2 body regions *
Haemodialysis *
Recurrent gastrointestinal perforations, surgery for acute pancreatitis *
High “score” (APACHE II/III > 20)
Acute renal failure *
Neutropenia
Length of stay on the ICU  9 days
Extensive requirement of blood transfusions
* “independent” risk factor from multivariate analysis
 Respiratory candidiasis
Candida pneumonia
(Papas: CID 2004:38,161-89)

• Aspiration of oropharyngeal materials

• Hematologenic spread, multiple organ
involvement
• Firm diagnosis: histological examination;
diagnosis solely based on
microbiologic data is often incorrect
• Therapy: Amphotericin B 0,7-1g/day
 *Pulmonary aspergillosis
• Frequent infection in the lung
accompanying chronic lung diseases:
*aspergilloma: fungus ball in cavity
or lung abscess
causing hemoptysis/chronic cough

*Allergic bronchopulmonary aspergillosis fungus

grows on bronchial surface in
bronchiectasis, COPD, cystic fibrosis etc causing
hypersensitivity reaction resembling asthma
Other forms
*chronic necrotizing pnemonia *Invasive pulmonary aspergillosis: fatal
disease
Pulmonary aspergillosis
Aspergilloma
fungus grows in a tb cavity or lung
abscess, forming a ball of hyphae
(mycetoma)
causing
granulomatous tissue reaction
in the cavity wall, which is rich of
capillary tissue.
Pulmonary aspergillosis: Aspergilloma
Symptoms:
*chronic cough,
*hemoptysis, frequently massive
(600ml or > in 24 hrs).
Hemoptysis is the most frequent reason for
lobectomy in Persahabatan Hospital Jakarta,
after Tb, lung cancer and bronchiectasis.
 Pulmonary aspergillosis
Allergic bronchopulmonary aspergillosis
Fungus grows on bronchial surface in
bronchiectasis, cystic fibrosis etc

causing
hypersensitivity reaction

resembling symptoms & signs of asthma

in atopic patients
 Cryptococcal Pulmonary Infection

• Immunocompetent/
immunocompromised patients
• Nonspecific symptoms: malaise,
cough, fever. Maybe accompanied
by meningitis
• 20% asymptomatic.
• In HIV positive patients,
pneumonia is common and
usually progressive and severe
 Phaller et al: J Clin Microbiol 2005,43 548-59

• Isolate from respiratoty/alimentary/

genital tract, skin, soft tissue, inner
tissues, blood and normally sterile
body fluid
• From Asia, Europe, Middle East,
Latin and North America in 6,5 yrs
(June 1997- December 2003)
• Cryptococcus neoformans (21%),
Saccharomyces spp (6,8),
Trichosporon spp (6,5%)
and Rhodotorula spp (2,3%)
 The Manangement of Invasive
Pulmonary Mycosis

• To suspect the presence of invasive fungal

infection
• To establish the presence of fungus in the organ:
diagnosis
• To treat the fungal infection
 To suspect
the presence of
Invasive Pulmonary Mycosis

• To recognize the conditions which

underlie the possibility of invasive
mycosis
• The most important step in good
management of invasive mycosis
 To Diagnose
Invasive Pulmonary Mycosis

• To establish the presence of fungus in

the organ: diagnosis
• To recognize the conditions which
underlie the possibility of invasive
mycosis
Diagnosis of Pulmonary Mycosis
*symptoms&signs
•physical findings
•chest X-ray features
Host factors

+ tissue
Clinical
features
Mycology:
*serologic exam
*direct smear
*culture:sputum
 Problems in diagnosis
• Symptoms & signs: chronic cough, fever,
malaise, dyspnea, wheezing, hemoptysis,
resemble those of other pulmonary
disorders
• physical findings: nonspecific
• chest X-ray features of the majority of
respiratory fungal infections mimic
other lung diseases  have limited value
in predicting the causative organism
 Radiographic Features
• Part of the evid- • cavitary lesions,
ence contributing fungus ball in cavity,
to the diagnosis • honeycomb structure
(bronchiectasis)
• Interstitial infiltrate
bronchopneumonia, • multiple nodules,
masses,
consolidation,
segmental • pleural effusion. etc
peumonia
Candida pneumonia Invasive Aspergillosis

AJR 1982;138: 645 – 648

Heart & Lung 1998;27(1): 63 - 66
Clinical • High resolution CT: halo
& Imaging sign or crescent sign in
Studies neutropenic or allogeineic
in HSCT
Invasive resoluton
• Othre imaging of lung,
Aspergillosis
brain, sinus
• Otherwise unexplained
fever and/or local
symptoms in
immunosupressi=ed
probability patients
 Radiologic Diagnosis
• Halo of low attenuation
surrounding a nodular lesion
is an early finding in
invasive pulmonary aspergillosis
• An air-crescent is also suggestive of
invasive aspergillosis but it is a late
finding
• Lancet 2005;366: 1013-25
 Chest X-ray picture: Cryptococcal Pulmonary Infection

Radiology 1990;175: 725 – 728

Diagnosis of Pulmonary Mycosis
*symptoms&signs
•physical findings
•chest X-ray features
Host factors

+ tissue
Clinical
features
Mycology:
*serologic exam
*direct smear
*culture:sputum
Mycology Diagnosis of Invasive Mycosis

Problems in diagnosis: procedures to obtain

specimens from respiratory organs for
mycologic investigations
• Sputum, blood
• Bronchoscopy, bronchial washing,
tissue biopsy or needle aspiration
• Fine needle aspiration biopsy
• Transthoracic needle aspiration biopsy
• Transbronchial lung biopsy
 DIAGNOSTIC TESTS
FOR INVASIVE PULMONARY MYCOSIS

  specificity

fr
culture

eq
histology

ue
antgen

nc
antbody

y
enolase
mannan

of
oc
PCR

cu
1-3-ß-D-glucan

rr
en
ce
C-Reactve Protein (CRP),
procalcitonin (PCT),
interleukin-6 (IL-6)
Mycology Diagnosis of
Invasive Aspergillosis
Diagnosis of Pulmonary Mycosis
tissue

+ Clinical +
Host
feature Mycology
factors = Proven
s

+
Clinical +
Host
feature Mycology = Probable
factors
s

Clinical Negativ
Host + e
factors + feature =
s + or
Not
done Possible
Negative
Host +
+ or Mycology
factors Not done
=
 Treatment

4
1
40
Temperature (°C)

39
38
37
CT
36

PCR
PCR +
Disease likelihood

Galactomannan
Galactomannan + Culture + Tissue+
Tissue
10
Granulocytes (log10x109/L)

0.1

-14 -7 0 7 14 21 28 35 42 49 56 63
Days after transplant
Diagnostic Strategies for Pulmonary Mycosis
Treatment

4
1
40
Temperature (°C)

39
38
37
CT
36

PCR
PCR +
Disease likelihood

Galactomannan
Galactomannan + Culture + Tissue+
Tissue
10
Granulocytes (log10x109/L)

0
Proven
1

0.1

-14 -7 0 7 14 21 28 35 42 49 56 63
Days after transplant
Diagnostic Strategies for Pulmonary Mycosis
Treatment

4
1
40
Temperature (°C)

39
38
37
CT
36

PCR
PCR +
Disease likelihood

Galactomannan
Galactomannan + Culture + Tissue+
Tissue
10
Granulocytes (log10x109/L)

0
Remote Possible Probable disease Proven
1

0.1

-14 -7 0 7 14 21 28 35 42 49 56 63
Days after transplant
Antifungal Therapeutic Strategies
for Pulmonary Mycosis

Diagnostic
Treatment

4
1
40
Temperature (°C)

39
38
37
CT
36

PCR
PCR +
Disease likelihood

Galactomannan
Galactomannan + Culture + Tissue+
Tissue
10
Granulocytes (log10x109/L)

0
Remote Possible Probable disease Proven
1

0.1

-14 -7 0 7 14 21 28 35 42 49 56 63
Days after transplant
Antifungal Therapeutic Strategies
for Pulmonary Mycosis

Empirical Pre-emptive Diagnostic

Treatment

4
1
40
Temperature (°C)

39
38
37
CT
36

PCR
PCR +
Disease likelihood

Galactomannan
Galactomannan + Culture + Tissue+
Tissue
10
Granulocytes (log10x109/L)

0
Remote Possible Probable disease Proven
1

0.1

-14 -7 0 7 14 21 28 35 42 49 56 63
Days after transplant
Antifungal Therapeutic Strategies
for Pulmonary Mycosis

4Prophylaxis Empirical Pre-emptive Diagnostic

Treatment

1
40
Temperature (°C)

39
38
37
CT
36

PCR
PCR +
Disease likelihood

Galactomannan
Galactomannan + Culture + Tissue+
Tissue
10
Granulocytes (log10x109/L)

0
Remote Possible Probable disease Proven
1

0.1

-14 -7 0 7 14 21 28 35 42 49 56 63
Days after transplant
 Treatment of
Invasive Pulmonary Mycosis

• The best treatment should be according to

the etiology (result of culture)
• While waiting for identification of the
causative fungus, treatment can be
administered according to the risk factors,
clinical features and the epidemiologic data
available
• Thus treatment can be empirical,
preemptive or preventive
Anti Fungal Treatment Concept

Definitive Therapy
• Infection signs are present
• fungal infection diagnosis is
proven by histopathology
examination (fungemia)
specificity >95%
Anti Fungal Treatment Concept

Empiric therapy
 Antifungal therapy is given
 based on patients risk factors,
 sign of infection are present,
 but the etiology is not clear
FACTORS SUGGESTING
POSSIBLE FUNGAL LUNG INFECTION
Limper, AH: The Changing Spectrum of Fungal Infections In Pulmonary and Critical Care
Practice, Clinical Approach To Diagnosis. Proceedings of the American Thoracic Society Vol 7, 2010

• Patent has traditonal immune suppression (significant

neutropenia, hematological malignancy, transplant,
or chemotherapy)
• Patent has emerging immune-compromising conditons
(cortcosteroid use, novel biological immune suppression,
cirrhosis, renal insufficiency, COPD, diabetes)
• Exposure or recent travel to endemic geographical regions
• Nonresolving lung infiltrates and fever despite antbacterial
antbiotcs
• May or may not have associated adenopathy
• May have associated skin, bone, CNS finding
Anti Fungal
Treatment Concept:
Empiric therapy

Antifungal therapy
is given based on
patients risk factors,

Signs of infection
are present,
but the etiology
is not
clear
• Candidemia: biakan
jamur dari darah
• Pneumonia: cairan
bilasan bronkus
Systemic mycosis: candidemia, pneumonia

Gejala dan tanda

 Pada pasien sakit berat
atau rawat di ICU
 Demam, tidak hilang
setelah
pemberian anti-
biotika yang adekuat
 Gejala dan tanda infeksi
lainnya
 Pengobatan Candidemia
IDSA Guideline 2009

Without neutropenia With neutropenia

 Fluconazole • An echinocandin
loading *anidulafungin,
dose 800mg (12mg /kg daily), loading
then 400 mg (6 dose 200mg/day, then 100 mg/day
mg/kg) daily, or *mycafungin
100mg/day
*caspofungin,
 an echinocandin
*mycafungin: 100 mg loading dose 70mg/day,
daily then 50mg/day
*anidulafungin: • Fluconazole, for patients
loading dose 200 mg, who are less critically ill and
then 100 mg daily) who have had no recent azole
exposure. Loading dose of 800
*caspofungin: mg (12 mg/kg/day then 400 mg
loading dose of 70 mg, then (6 mg/kg)/ day
50 mg daily;
 Indikasi ekinokandin
IDSA Guideline 2009

• Severely ill and • For patients who have

initially received
fluconazole/voticonazole,
moderately are clinically improved,
severe ill patients, and whose follow-up
or culture results are
negative,
• patients who have continuing use of an
had recent azole azole to completion of
exposure (A-III) therapy is reasonable
 Indikasi ekinokandin
IDSA Guideline 2009

• Transition from • Transition to flu-

an echinocandin to conazole or vori-
fluconazole: patients conazole is not
who have isolates that
recommended in
are likely to be
susceptible to
patients with infection
fluconazole due to C. glabrata.
(e.g. Candida albicans) without confirmation
of isolate
and who are susceptibility
clinically stable (A-II). (B-III).
 Duration of therapy
• The recommended duration of therapy for
candidemia without obvious metastatic
complications is for 2 weeks after
documented clearance of Candida from the
bloodstream and resolution of symptoms
attributable to candidemia (A-III).
• Intravenous catheter removal is strongly
recommended for nonneutropenic patients
with candidemia (A-II).
Anaissie EJ, Rex JH, Uzun O, Vartivarian S. Predictors of adverse
outcome in cancer patients with candidemia. Am J Med 1998;
104:238–45.
,
• An extremely important factor influ-
encing the outcome of candidemia in
neutropenic patients is the recovery of
neutrophils during therapy.
• In a large retrospective cohort of 476 pts
with cancer who had candidemia, persistent
neutropenia was associated with a greater
chance of treatment failure
 Pulmonary aspergillosis

• Pulmonary • The 4 commonly des-cribed

aspergillosis is a categories are;
general term for - allergic aspergillosis (ABPA)
the lung disease - colonizing aspergillosis (CNPA)
caused by the - aspergilloma
genus - invasive aspergillosis
Aspergilllus  Panackal AA, Bennet JE, Williamson PR. Treatment
optons in invasive aspergillosis. Current treatment
optons in infectous disease (2014) 6:309-25
Clinical Spectrum of Pulmonary Aspergillosis

Soubani AO, et al. Chest 2002;121:1988-99

 Pengobatan aspergiloma
Pengobatan aspergiloma bergantung
kepada faktor2 sbb:
• Gejala (hemoptsis)
• Besarnya lesi
• Faal paru
• Risiko prognostk dan penyakit yang
mendasari

Terapi
• Terapi definitif: Reseki paru
(lobektomi)
• BAE (Bronchial artery embolizaton)

Panackal AA, Bennet JE, Williamson PR. Treatment optons in

invasive aspergillosis. Current treatment optons in infectous
disease (2014) 6:309-25
 Pengobatan aspergiloma

Kousha et al. Pulmonary aspergillosis: aclinical review. Eur Respir Rev 2011;20:121.
 Allergic Bronchopulmonary Aspergillosis

• Perempuan,
40th, batuk
berbulan2,
sesak napas
tadak mem-
baik dengan
pengobatan
asma
Uji galaktomanan
Ditemukan hifa
positf, dari bahan
dalam sputum
sputum
Terapi aspergilosis bronkopulmoner alergik
 Terapi aspergilosis bronkopulmoner alergik

Kousha et al. Pulmonary aspergillosis: aclinical review. Eur Respir Rev 2011;20:121.
 Interacton of Aspergillus with the host
A unique microbial-host interaction

ABPA

Frequency of aspergillosis
Frequency of aspergillosis

Acute IA
Severe asthma with
fungal sensitsaton
Subacute IA Allergic sinusits

Aspergilloma
Chronic pulmonary

Immune dysfuncton Immune hyperactvity

. After Casadevall & Pirofski, Infect Immun 1999;67:3703
 Chronic Necrotzing Aspergillosis
• Amphotericin B (IV) memberi hasil yang baik
• Itrakonazol dapat dipilih sebagai alternatf
• Reseksi bedah ~ untuk pasien muda & faal paru
yang baik (Binder dkk ~ 10% - 90% respons baik
dengan tndakan bedah)
• Prognosis ~ tdak jelas - 73% ~ hidup 1 – 2 th terapi
(kematan krn sebab lain)
 ANTIFUNGAL FOR INVASIVE ASPERGILOSIS
Panackal AA, Bennet JE, Williamson PR. Treatment options in invasive aspergillosis. Current treatment options in infectious disease (2014) 6:309-25.
 Konsensus Rekomendasi Terapi Aspergilosis invasif
Hail MA, Adel FA. Clinical practice guidelines for the treatment of invasive Aspergillus infections in adults in the
Middle East region: Expert panel recommendtaions. Journal of infection and Public Health.2014

• Vorikonazol (A) sangat dianjurkan sebagai terapi primer

• Antijamur lain: amfoterisin B (B), kaspofungin (B), mikafungin
(B), posakonazol (B), itrakonazol (B) terapi alternatif
• Pada pasien yang mendapat terapi imunosupresif jangka
panjang, terapi antijamur harus dilanjutkan (B)
• Pencegahan nfeksi berulang dengan melanjutkan terapi
antijamur pada pasien yang berhasil diobati untuk aspergilosis
invasif masa lalu risiko neutropenia (B)
• Penghentian/pengurangan dosis kortikosteroid dianjur-kan
pada pasien aspergilosis invasif (C)
 TAKE HOME MESSAGE
The Manangement of Invasive Pulmonary Mycosis
• To suspect the presence of invasive fungal
infection: risk factors, immunocompromise
patients
• To establish the presence of fungus in the organ:
diagnosis: mycologic tests
• To treat the fungal infection: empirical,
preemptive, diagnostic.
• Choice of drug: according to type of disease and
fungus
 TAKE HOME MESSAGE
• The diagnosis of pulmonary mycosis should
be made on the basis of clinical symptoms,
(fever, malaise, chronic cough, dyspnea,
wheezing, hemoptysis, etc) in individuals
with predesposing factors, radiological
findings, plus mycological and / or
pathologic as well as serologic results.
 TAKE HOME MESSAGE
• The diagnosis may be categorized as
remote, possible, probable or proven.
• Awareness concerning the
predisposing factor and
the knowledge of the frequent
type of fungus in the relevant
condition may help in making early
diagnosis and hence early treatment of
lung mycosis.
 TAKE HOME MESSAGE
• Pengobatan aspergilosis paru tergantung
bentuk kelainan klinisnya yakni: aspergiloma,
allergic bronchopulmonary aspergillosis,
chronic necrotzing aspergilosis
aspergilosis paru invasif.
 TAKE HOME MESSAGE
• Aspergiloma: observasi  reseksi.
Obat ant jamur belum tentu dibutuhkan
• Allergic bronchopulmonary aspergillosis Obat
utama : kortkosteroid Obat
antjamur dapat memperbaiki hasil pengobatan
• Aspergilosis invasif dan chronic necrotizing
pneumonia: Vorikonazol, amfoterisin B,
itrakonazol
 TAKE HOME MESSAGE
• Status imunokompromis harus ditangani
dengan maksimal, terutama pada
aspergilosis paru invasif
• Pengobatan OAJ dapat dimulai segera
setelah ada dugaan asper-gilosis,
dilanjutkan selama pencarian agen penyebab,
sampai dgn 2 minggu setelah biakan jamur
negatf
 • THANK YOU
• THANK YOU
• Thank you