PTID Assignment G1

ASSIGNMENT CASE
STUDY 1
GROUP 1
STUDENT NAME STUDENT ID

Afiq bin Zulanizan 59215121044
Aiza Shahira binti Idris 59215121023
Eikal Syazwan bin Zolkifli 59215121010
Fateehah binti A.H.Hafeez 59215121024
Mohamad Adli bin Mohamad Naser 59215121058
Muhammad Adlan bin Mohd ‘Asri 59215121037
Muhammad Nizar Aiman bin 59215121049

Mohamad Sabri
Muhammad Syafiq Iman bin Sudin 59215121017
Nur Alya Qistyna binti Nazmi 59215121008
Nur Hana Atiqah binti Fairol Azmi 59215121019
Lecturer’s Name
Mr. Nor Safwan Hadi Nor Afendi
Ms. Aina Amanina Abdul Jalil
Dr. Khalid Ahmad Al Ali Sunaidar
7830 Words
Pharmacotherapy of Infectious Disease (RPB 20903)
Table of Contents
1.Introduction of the disease 2

2.Pathophysiology of the disease 3
3.Clinical presentations (sign and symptoms) of the disease 5
4.Risk factors and complications of disease 7
5.Assessment and diagnosis of disease 8
6.Available pharmacological treatment of disease 11
7.Available non-pharmacological treatment of the disease 38
8.Goals of therapy and evaluation of therapeutic outcomes 40
References 43
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1.Introduction of the disease
Pulmonary aspergillosis is a category of diseases caused by the fungus Aspergillus species.

It is most typically caused by the fungus Aspergillus fumigatus. Aspergillus is a fungus that is
prevalent in various surroundings and is usually safe to healthy people. However, Individuals
with significant immunodeficiency face an increased likelihood of developing invasive
pulmonary aspergillosis. The spectrum of pulmonary aspergillosis encompasses mild allergic
responses as well as invasive infections. (Kousha et al., 2011).
There are three distinct classifications of pulmonary aspergillosis: allergic bronchopulmonary

aspergillosis (ABPA), invasive pulmonary aspergillosis (IPA) and chronic pulmonary
aspergillosis (CPA) (Ingle et al., 2016). ABPA is an aspergillus hypersensitivity response that
can elicit asthma-like symptoms, whereas CPA is a persistent infection that can cause lung
damage and respiratory failure. IPA is a severe and often fatal infection that typically occurs
in immunocompromised patients.
A reliable diagnosis is critical for efficient management of pulmonary aspergillosis. Imaging

procedures such as a chest X-ray or a computerised tomography scan (CT scan) are
routinely used for this purpose (Centers of Disease Control and Prevention, n.d.). However,
a paradigm diagnosis would involve examination of lung tissue acquired through
video-assisted thoracoscopic (VATs) or open-lung biopsy for histopathological analysis
(Kousha et al., 2011). The treatment of pulmonary aspergilloma would be determined by the
type and extent of the disease, and could include antifungal medication or surgical
intervention (Centers of Disease Control and Prevention, n.d.).
Pulmonary aspergillosis refers to an infection of the lungs caused by the fungal species,
Aspergillus. It manifests itself in a variety of clinical forms and primarily affects
immunocompromised patients or those with underlying pulmonary diseases. Early detection
and management are critical for improving patient outcomes.
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2.Pathophysiology of the disease
Inhalation of Aspergillus spores

The conidia or spores produced by Aspergillus are abundantly present in the environment as
the air easily disperses them and thus enters the human body through inhalation by the nose
(Taylor & Keller, 2009). People with underlying lung conditions or weakened immune
systems are more prone to inhale this spore.
Adherence and colonisation

After inhalation, the A. fumigatus conidia adhere and bind to the respiratory tract's epithelial
cells and colonize within the airways. Sialic acid residue on the conidia increases the
pathogenicity by promoting stronger adhesion to epithelial cells, thus resulting in
colonization. Products secreted by A. fumigatus, such as serine protease and cysteine
protease, also may facilitate colonization in healthy lung tissue (Taylor & Keller, 2009).The
spores can proceed to germinating stage and form hyphae.
Immune response
The host immune system reacts to Aspergillus presence by activating innate and adaptive
immune responses. The innate responses include phagocytosis by alveolar macrophage
with antimicrobial enzymes (cathepsin D and chitinase), antifungal mechanism and ROS
production by neutrophils, and infection control by NK cells mediated by IFN-γ. In contrast,
the adaptive immune responses resulting from the CD4 helper T cell differentiation triggered
by the innate immunity produces Th1, Th2, Th17 and Treg cells contributing to invasive
aspergillosis protection (Arias et al., 2018). However, these immune responses might be
insufficient to kill the fungal in immunocompromised individuals or lung defect individuals.
Inflammatory response
As the growth and invasion of Aspergillus hyphae in the lung tissue progresses, the immune
system will produce an inflammatory response. The hyphae will release fungal components
and toxic metabolites like mycotoxins and proteases, which can impair the lungs by causing
inflammation and tissue damage. In response to these toxic components, symptoms such as
cough, sputum production and chest discomfort will appear.
Formation of fungus ball

Aspergilloma occurrence in chronic aspergillosis is about 25% (Chakraborty & Baradhi,
2022). Aspergilloma is a composition of Aspergillus hyphae, debris of inflammatory cells and
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mucus in the form of fungus balls (mycetoma) surrounded by fibrous capsules. This
mycetoma is formed in cases of pre-existing cavities or lung tissue damage in which the
hyphae accumulate, producing a dense mass. The aspergilloma continues to grow in the
pre-existing cavity, causing symptoms like chronic cough, haemoptysis and chest pain.
Systemic spread
Individuals with highly weakened immune systems, like those with a history of pulmonary
disease, including Tuberculosis and diabetes mellitus, or those undergoing chemotherapy
and organ transplantation, might have a higher risk of systemic infection spread to other
organs. This condition, known as invasive aspergillosis, is associated with higher mortality
rate and can damage organs like the heart, liver, brain, and kidney.
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3.Clinical presentations (sign and symptoms) of the disease
A respiratory disease known as pulmonary aspergillosis brought on by the fungus

Aspergillus may affect people with compromised immune systems. For a prompt diagnosis
and effective treatment of the disease, it is crucial to comprehend the signs and symptoms of
pulmonary aspergillosis sign and symptoms:
1. Allergic Bronchopulmonary Aspergillosis (ABPA)
A hypersensitive response to Aspergillus spores in the airways causes allergic

bronchopulmonary aspergillosis (ABPA), which can cause repeated attacks of
bronchospasm, coughing, and wheezing. According to the research by Argawal et al.
(2013), typical ABPA warning signs and symptoms include:
● Recurrent asthma-like symptoms: Patients may suffer symptoms like poorly

managed asthma, such as wheezing, coughing, and shortness of breath.
Airway inflammation and bronchospasm are caused by the immune system’s
reaction to Aspergillus antigens.
● Production of sputum: thick, brownish mucus plugs or “brown bronchial
casts,” which are frequently fungus-containing, may be coughed up.
● Chest pain: It is because of the inflammation and accumulation of mucus in
the airways, people with ABPA may feel discomfort or pain in the chest.
● Symptoms that are more common: Some individuals may have systemic
symptoms like fatigue, fever, and weight loss. (American Thoracic Society,
2014)
2. Chronic Pulmonary Aspergillosis (CPA) :
CPA is a slowly progressive fungal infection that typically affects people with
underlying conditions such as tuberculosis, COPD, or bronchiectasis. According to
research by Denning et al. (2003), the key sign and symptoms of CPA include:
● Persistent cough: A chronic cough that lasts longer than eight weeks is a
common symptom of CPA. Sputum production, occasionally involving blood,
may be present in addition to it.
● Breathlessness: Patients may gradually have shortness of breath as the
illness worsens, which might result in respiratory failure in severe situations.
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● Fatigue and weight loss: CPA can cause decreased energy, fatigue, and
unintended weight loss, which are indicators of the overall health effects of
the infection on the patient.
● Fever and night sweats: some people with CPA may develop repeated
low-grade fevers and night sweats, probably because of ongoing
immunological response and chronic inflammation.
3. Invasive Pulmonary Aspergillosis (IPA):
IPA is a severe form of pulmonary aspergillosis that mostly affects

immunocompromised people, such as organ transplant recipients. Following are
some IPA warning signs and symptoms:
● Fever: a high-grade, persistent fever that does not subside with antibiotics is
a typical early sign of IPA. It is connected to the infection’s invasiveness.
(Patterson et al., 2016)
● Haemoptysis and cough: patients with IPA may experience cough that are
frequently accompanied by the presence of blood in the sputum. Bleeding
may result from aspergillus blood vessel invasion (Sherif & Segal, 2010)
● Pleuritic chest pain: As the illness worsens, sharp chest discomfort that is
made worse by deep breathing may appear, signifying pleural involvement.
(Azoulay et al., 2006)
● Respiratory distress: IPA can quickly result in acute respiratory distress
syndrome (ARDS), which is characterised by extreme difficulty breathing and
low blood oxygen levels. This illustrates how the infection is pervasive and
how it harms lung tissue. (Koenraad Vandewoude et al., 2006)
Based on the case study, the patient has a productive cough and haemoptysis for 2 months.
So, it is likely to have invasive pulmonary aspergillosis. However, the patient had a history of
Pulmonary Tuberculosis (PTB) and Diabetes Mellitus (DM). People with PTB are usually
easily affected with chronic pulmonary aspergillosis. Based on the sign and symptoms
present by the patient is Chronic Pulmonary Aspergillosis (CPA)
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4.Risk factors and complications of disease
Human pulmonary aspergillosis can be caused by inhaling microscopic Aspergillus

spores from the environment. The vast majority of people routinely breathe in Aspergillus
spores without becoming unwell. People who already have lung illness or a weaker immune
system, on the other hand, are more vulnerable to Aspergillus-related health concerns. Your
chances of having aspergillosis are impacted by your risk of mould exposure as well as your
general health. A variety of factors, including a weakened immune system, make you more
susceptible to infection. People who are on immune-suppressing medicines after undergoing
transplant surgery, particularly those who have had bone marrow or stem cell transplants or
who have specific blood malignancies, are more likely to be impacted by invasive
aspergillosis.
Additionally, people with severe AIDS may be particularly susceptible. Low white
blood cell levels in particular These persons are more vulnerable to invasive aspergillosis as
a result of chemotherapy, organ transplantation, or leukaemia-related declines in white blood
cell counts. It is also permissible to have the immune system cell-affected hereditary illness
known as chronic granulomatous disease.The only other item are the lung cavities.
Aspergillomas are more common in those who have air gaps (cavities) in their lungs.
Aspergillus mould allergies are more common in people with cystic fibrosis or asthma,
especially if their lung conditions are severe or challenging to manage. The risk of
opportunistic infections may increase with long-term corticosteroid therapy, depending on the
underlying illness being treated and the additional drugs being used.
Different forms of aspergillosis can cause a variety of serious consequences.

Aspergillomas and invasive aspergillosis can both induce fatal pulmonary haemorrhage.
When invasive aspergillosis spreads to other organs, particularly the brain, heart, and
kidneys, it is the most lethal. Invasive aspergillosis can spread quickly, providing a severe
risk to the individual.
It is quite challenging to completely avoid Aspergillus exposure. On the other hand,

people who have had a transplant or are through chemotherapy ought to stay away from
places like building sites, compost pits and grain storage facilities. Your doctor might suggest
that you use a face mask to protect yourself from Aspergillus and other potentially harmful
airborne pathogens if you have a damaged immune system.
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5.Assessment and diagnosis of disease
A set of respiratory illnesses brought on by the fungus Aspergillus are referred to as

pulmonary aspergillosis. A typical variety of mould found in the environment is Aspergillus,
which can be found in soil, decomposing organic materials, and indoor settings. The majority
of people regularly come into contact with Aspergillus spores without any negative
consequences. However, pulmonary aspergillosis is more likely to affect people with
compromised immune systems or specific underlying lung problems. The assessment and
diagnosis test of pulmonary aspergillosis is very difficult to do, this is because the
assessment and diagnostic test for the pulmonary aspergillosis are not in advanced
methods. The current diagnostic test methods suffer from a lack of sensitivity and specificity,
resulting in a prolonged waiting period for doctors to obtain test results in clinical settings.
This delay in obtaining results ultimately leads to a delay in providing treatment to patients. It
is well-established that delayed diagnosis hinders prompt treatment, making faster diagnosis
a crucial factor in achieving better outcomes for patients.
Next, from the previous journal and research stated that, even though the clinician use
sputum that being infected by the Aspergillus it will not necessarily show the result of
infection and also the clinician should take note and caution about interpretation of antigen
test, polymerase chain reaction (PCR) and also superficial cultures as the result of these
diagnostic test maybe difficult to be interpret. Direct examination or cultures from sterile sites
are the golden standard but conventional diagnostic tests maybe insensitive and late positive
(Florl, 2019, 155-160)
For the assessment of pulmonary aspergillosis we can use a spirometry test also known as
a pulmonary function test. This test is a very common test to know and determine the
condition and workflow of our lungs. This test also functioning well to estimate the amount of
air in our lung. The function of this test is to estimate the capacity of the lung, detect narrow
airways, show exposure of certain substances that change the lung function, etc. In this test,
spirometry or pulmonary function test will measure a few indicator that will indicate the lung
whether the lung have problem or not:
1. Tidal volume = represents the volume of air typically inhaled and exhaled during regular
breathing.
2. Minute volume = total volume of air exhaled in one minute.
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3. Vital capacity = maximum volume of air that can be exhaled after a full inhalation,
corresponding to the maximum capacity of the lungs.
4. Functional residual capacity = amount of air that remains in the lungs after a normal
exhalation.
5. Residual volume = amount of air that remains in the lungs after exhaling as much as
possible.
6. Forced vital capacity = amount of air exhaled forcefully and rapidly after a deep
inhalation.
7. Forced expiratory volume = amount of air expired during specific time intervals, typically
the first, second, and third seconds of the Forced Vital Capacity (FVC) test.
Figure 5.1: Shows the chart to assess a patient's pulmonary test.
In the diagnostic process, doctors typically begin by conducting several tests to further
investigate a patient's disease. One of the initial tests is a blood test, which can be
particularly helpful in early disease detection, especially for individuals with weakened
immune systems. Another important test is a fungal culture, which is crucial for clinicians to
identify the specific fungal species that has invaded the patient's body, such as Aspergillus.
To culture the fungal specimen, various mediums can be used, including uvitex 2b, Gomori's
methenamine silver stain, fluorescent substances like calcoflour white, and Blancophor.
Culturing the specimen provides evidence of the infection, although it may not always be
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sufficient to differentiate Aspergillus from other filamentous fungi. However, the

micromorphology observed in the culture can offer valuable information about the fungal
class. Culturing clinical specimens is considered the gold standard for diagnosing pulmonary
conditions, as it helps determine the most effective antifungal medication to treat the
disease.
Additionally, antigen testing is another important diagnostic tool. It is typically used as an

add-on test to complement culture and microscopy tests.
Besides, tests are usually done for the pulmonary Aspergillosis, Aspergillus antibody testing.
This test use of antibody detection is very useful for the immunocompromised patient. The
serum sample from the pulmonary cavities patient will be tested, this test is to diagnose the
total of immunoglobulin E (IgE) and Aspergillus - specific IgE. In addition, we can use Pan -
fungal detection B- Glucan (BG). (1→3)-β-d-glucan (BG) is a polysaccharide fungal cell wall
component that being released by the Aspergillus fungi or other like Fusarium, Acremonium,
Candida, and Pneumocystis during the infection. B- Glucan is a panfungal marker and its
specificity depends on the fungal pathogen and underlying patient populations examined.
Both tests from Aspergillus antibody testing and Pan- fungal detection B- Glucan are very
new methods to be used due to the advance development in biotechnology.
Next, Imaging method also can be used to diagnose pulmonary Aspergillosis, but even
though this method can be used, chest radiography is of little use in the early stage of the
disease due to the nonspecific changes. The use of chest computed tomography combined
with high- resolution images can be used to further diagnostic tests for bronchoscopy and
open-lung biopsy. This method can produce more clearer and detailed images that reveal
fungal mass and also characteristic signs of invasive Aspergillosis.
We can also use bronchoscopy and bronchoalveolar Lavage (BAL), this is a procedure that
inserts a tiny camera into the airways. A bronchoscopy may occasionally be carried out to
collect a lung sample. A bronchoscope — a thin, flexible tube with a camera—is inserted into
the airways during this treatment. During bronchoscopy, a bronchoalveolar lavage may be
performed, in which a tiny amount of sterile fluid is injected and subsequently removed for
laboratory testing.
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6.Available pharmacological treatment of disease
Management of Pulmonary Aspergillosis consists of the removal of Aspergillosis nodules

through surgery or with the combination of triazoles, to reduce hemoptysis (for symptomatic
patients), and improve lung functions.
For the first line treatment, usage of triazoles (Itraconazole and Voriconazole) was
reported effective against Aspergillus sp. except for Fluconazole which does not have effect
on said microorganism in treating Aspergillosis.
However, in the rare cases of drug toxicity, resistance, intolerant or clinical failures,
Posaconazole and Isavuconazole are approved by FDA for the treatment of Aspergillosis,
other than their high cost, they show better tolerability and lesser side effects compared to
those mentioned earlier.
As a last resort, intravenous treatment is used in salvage therapy. But it was
mentioned, they can be used in exceptional situations or severe cases as first line treatment.
(Maghrabi and Denning 2017). Choices of intravenous treatment consist of either
Amphotericin B which is widely preferred, or Echinocandins namely, Caspofungin or
Micafungin.
(MIMS 2022)
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(Maghrabi and Denning 2017)
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6.1 TRIAZOLES
Drug name : Itraconazole
(SPORANOX, Itraconazole 100mg capsules, by JANSSEN-CILAG)

INDICATIONS :
FDA-Labeled Indications: Aspergillosis, Invasive, salvage therapy

Non-FDA Labeled Indications: Allergic bronchopulmonary aspergillosis, Aspergillosis,
Invasive, in high-risk patients; Prophylaxis, Pulmonary aspergillosis, Chronic (cavitary or
necrotizing)
MECHANISM OF ACTION
According to (Merative, 2023, Mechanism of Action section), Itraconazole hinders the

process of 14C-demethylation of ergosterol, an essential element found in fungal cell
membranes, through the inhibition of cytochrome P450.
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DOSAGE
200 mg PO/IV 12-24 hourly or 200-400 mg PO 24 hourly x 2-5 months.
May be increased to 200 mg PO 12 hourly
ADVERSE REACTION
Common adverse reactions according to (Merative, 2023, Adverse Effect section)

are:
● Cardiovascular: Dema (4%), Hypertension (3%)

● Dermatologic: Pruritus (3% to 5%), Rash (3% to 9%)
● Gastrointestinal: Abdominal pain (1.7% to 4%), Diarrhea (1.7% to 4%), Nausea
(3% to 11%), Vomiting (5%)
● Hepatic: Abnormal liver function (3%)
● Neurologic: Dizziness (1.2% to 4%), Headache (2.2% to 10%)
● Respiratory: Rhinitis (up to 9%), Sinusitis (2% to 7%), Upper respiratory
infection (up to 8%)
● Other: Fatigue (1.5% to 3%), Fever (2% to 3%)
According to MIMS Malaysia (2022),
Gastrointestinal symptoms, including dyspepsia, abdominal pain, nausea, vomiting,

constipation, and diarrhea, as well as elevated liver enzyme levels, hepatitis, and
cholestatic jaundice, are potential side effects of this medication. It may also cause
central nervous system effects like headaches and dizziness. Allergic reactions such as
itching, rash, hives, and angioedema can occur. Additionally, other effects may include
increased levels of triglycerides, hair loss, swelling, and hypokalaemia with prolonged
use.
CONTRAINDICATIONS AND PRECAUTION
Based on (Merative, 2023, Contraindications/Warning section),
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● Using avanafil, cisapride, disopyramide, dofetilide, dronedarone, eplerenone,

ergot alkaloids (such as dihydroergotamine, ergometrine [ergonovine],
ergotamine, isavuconazole, levacetylmethadol [levomethadyl], lomitapide,
methylergometrine [methylergonovine]), naloxegol, felodipine, irinotecan,
lovastatin, lurasidone, methadone, oral midazolam, nisoldipine, pimozide,
quinidine, ranolazine, simvastatin, ticagrelor, triazolam, and ivabradine together
with this medication may have adverse effects due to their interaction with
CYP3A4.
● If you are a poor or intermediate metabolizer of CYP2D6, or if you are taking
strong or moderate CYP2D6 inhibitors, avoid using this medication alongside
eliglustat.
● When initiating and gradually increasing the dosage of venetoclax in patients with
chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), do not
co-administer it with this medication.
● For patients with renal or hepatic impairment, using this medication alongside
colchicine, fesoterodine, solifenacin, or telithromycin may lead to complications.
● If you are hypersensitive to itraconazole or any other component of this product,
avoid using it.
● This medication should not be used by pregnant women or women planning to
become pregnant for the treatment of onychomycosis.
Pregnancy Category
Contraindicated (MDX)
Special Instructions
o Use with caution in patients with history of liver & renal diseases.
o In patients with hypochlorhydria, absorption may be improved by

administering the drug with an acidic drink (for example: cola)
DRUG INTERACTION
(MIMS Malaysia, 2023) stated the drug-drug interaction and food-drug interaction as
follows:
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● The absorption of itraconazole capsules may be reduced when taken together

with medications that neutralize stomach acid, such as aluminum hydroxide,
H2-receptor antagonists, and proton pump inhibitors.
● Certain drugs like rifampicin, rifabutin, isoniazid, carbamazepine, phenytoin,
phenobarbital, nevirapine, and efavirenz can decrease the levels of itraconazole
in the bloodstream.
● On the other hand, ciprofloxacin, clarithromycin, erythromycin, ritonavir-boosted
darunavir, ritonavir-boosted fosamprenavir, indinavir, ritonavir, telaprevir, and
cobicistat can increase the levels of itraconazole in the bloodstream.
● Itraconazole may also affect the plasma concentrations of various medications,
including tamsulosin, certain opioid analgesics, digoxin, certain anticoagulants,
repaglinide, saxagliptin, praziquantel, certain antihistamines, certain
antineoplastics, certain antipsychotics, anxiolytics and hypnotics, verapamil,
nadolol, aliskiren, bosentan, riociguat, aprepitant, certain corticosteroids,
salmeterol, certain immunosuppressants, certain urological drugs, cinacalcet,
mozavaptan, tolvaptan, delamanid, artemether and lumefantrine, simeprevir,
atorvastatin, and alitretinoin.
● Additionally, itraconazole may decrease the plasma concentration of meloxicam
FDI
St. John's wort can lower the plasma concentration of itraconazole. Grapefruit or
grapefruit juice can affect the serum levels of itraconazole. When taking itraconazole
capsules, absorption may be improved when taken with food and acidic beverages.
However, the oral solution of itraconazole may have a slower and reduced absorption
rate when taken with food.
Drug name: Voriconazole
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(VFEND, Voriconazole 200mg tablets, by PFIZER)
Class: Antifungal, Triazoles (Merative, 2023, Drug Name Info section)
Indication:
FDA-Labelled Indications: Aspergillosis,Invasive
Non-FDA Labelled Indications: Allergic bronchopulmonary aspergillosis, Aspergillosis

-Invasive; Prophylaxis, Pulmonary aspergillosis, Chronic (cavitary or necrotizing)
MECHANISM OF ACTION
17
Voriconazole is an antifungal drug from the triazole class that works by inhibiting the
synthesis of ergosterol, a crucial component of fungal cell walls. It achieves this by
targeting the cytochrome P450 enzyme responsible for 14-alpha-sterol demethylation,
ultimately leading to a depletion of ergosterol in the fungal cells (Merative, 2023,
Mechanism of Action section),
DOSAGE
Loading dose : 6 mg/kg IV 12 hourly x 24 hours or <40 kg: 200 mg PO 12 hourly & >40
kg: 400 mg PO 12 hourly followed by
Maintenance doses :
Children: 7 mg/kg IV 12 hourly
Adult: 4 mg/kg I2 hourly
ADVERSE REACTION
According to (Merative, 2023, Adverse Effects section), the common adverse reactions
of voriconazole are:
Cardiovascular: Hypertension (Adult, less than 2%; pediatric, 11%), Peripheral edema
(Adult, less than 2%; pediatric, 9%)
Dermatologic: Rash (Adult, 7%; pediatric, 13%)
Endocrine metabolic: Hypokalemia (11%)
Gastrointestinal: Abdominal pain (12%), Diarrhea (Adult, less than 2%; pediatric, 11%),
Nausea (Adult, 5.4%; pediatric, 13%), Vomiting (Adult, 4.4%; pediatric, 20%)
Hematologic: Thrombocytopenia (10%)
Neurologic: Headache (Adult, 3%; pediatric, 10%)
Ophthalmic: Photophobia (6%), Visual disturbance (Adult, approximately 21%; pediatric,

26%)
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Psychiatric: Hallucinations (Adult, 2.4% to 16.6%; pediatric, 5%)
Respiratory: Bleeding from nose (16%), Cough (10%), Upper respiratory infection (5%)
Other: Fever (Adult, 5.7%; pediatric, 25%), Inflammatory disease of mucous membrane
(6%)
CONTRAINDICATIONS AND PRECAUTIONS
Hypersensitivity (MIMS Malaysia, 2023). Caution should be exercised when

co-administering voriconazole with medications metabolized by the CYP3A4 enzyme,
such as terfenadine, astemizole, cisapride, pimozide, quinidine, rifampicin,
carbamazepine, long-acting barbiturates (e.g., phenobarbital, mephobarbital), ergot
alkaloids (e.g., ergotamine and dihydroergotamine), efavirenz (at a dose of ≥400 mg
once daily), ritonavir (at a dose of ≥400 mg twice daily), sirolimus, rifabutin, and St.
John's wort (MIMS Malaysia, 2023).
Special precautions should be taken into account, as mentioned in the Malaysia Medical
Index of Medicines (MIMS) for 2023. These precautions include monitoring patients with
conditions that may potentially cause irregular heart rhythms (proarrhythmic conditions)
and assessing the risk of acute pancreatitis. Before initiating treatment, it is important to
correct any electrolyte imbalances, such as hypokalemia, hypomagnesemia, and
hypocalcemia. Consideration should also be given to individuals with different CYP2C19
metabolizer status (ultrarapid, intermediate, and poor metabolizers), as well as patients
with hepatic and renal impairment. The use of voriconazole during pregnancy and
lactation should be approached with caution and under medical supervision.
DRUG INTERACTION
(MIMS Malaysia, 2023) stated the drug-drug interaction and food-drug interaction as
follows:
Drug-drug interaction
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Voriconazole can lengthen the prothrombin time when taken with oral anticoagulants. It
may also raise the levels of ciclosporin and tacrolimus in the bloodstream, as well as
certain long-acting opiates (such as oxycodone and methadone), NSAIDs (such as
ibuprofen and diclofenac), omeprazole, and short-acting opiates (such as alfentanil and
fentanyl). When voriconazole is used concurrently with phenytoin, it can decrease the
plasma concentration of voriconazole and increase the plasma concentration of
phenytoin. Additionally, voriconazole may increase the plasma concentration of oral
contraceptives.
Food-drug interaction
Voriconazole levels can be reduced when taken together with St. John's wort.
Additionally, the absorption of voriconazole may be decreased when taken with food.
Drug name: POSACONAZOLE
NOXAFIL, Posaconazole 100mg tablet, by Merck Sharp & Dohme)
Indication:
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FDA-Labelled Indications: Aspergillosis,Invasive
Non-FDA Labelled Indications: Allergic bronchopulmonary aspergillosis, Aspergillosis

-Invasive; Prophylaxis, Pulmonary aspergillosis, Chronic (cavitary or necrotizing)
MECHANISM OF ACTION
A triazole antifungal which inhibits the synthesis of ergosterol, a component of the fungal
cell membrane, by inhibition of the CYP450-dependent enzyme lanosterol
14-alpha-demethylase which results in accumulation of methylated sterol precursors
and depletion of ergosterol within the fungal cell membrane
DOSAGE
Oral Suspension :Adult- 400 milligram BD, with food. (200mg QID if unable tolerate food)
Tablet or IV :Adult- Loading dose 300 milligram BD on the first day, then 100 milligram
OD for 13 days, with food.
(Salvage therapy, suspension) 200 mg orally three times daily for 6 to 12 weeks
depending on disease site, disease improvement, and level of
immunosuppression.
The recommended salvage treatment involves taking tablets or receiving an IV

injection of 300 mg twice daily on the first day, followed by a daily dosage of 300
mg for a period of 6 to 12 weeks, depending on factors such as the location of the
disease, improvement of the disease, and the level of immune system
suppression.
ADVERSE REACTION
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Common
● Endocrine metabolic: Hypokalemia (Prophylaxis, 14% to 30% )

● Gastrointestinal: Diarrhoea (Adult prophylaxis, 29% to 42%; oropharyngeal
candidiasis, 10%; refractory oropharyngeal candidiasis, 13% ; paediatric
prophylaxis, 18% to 22% ), Nausea (Adult prophylaxis, 19% to 38%;
oropharyngeal candidiasis, 9%; refractory oropharyngeal candidiasis, 29% ;
paediatric prophylaxis, 16% to 18% ), Vomiting (Adult prophylaxis, 12% to
29%; oropharyngeal candidiasis, 7%; refractory oropharyngeal candidiasis,
28% ; paediatric prophylaxis, 24% to 26%; invasive aspergillosis, 18.1% )
● Neurologic: Headache (Adult prophylaxis, 14% to 28%; oropharyngeal
candidiasis, 8%; refractory oropharyngeal candidiasis, 20% ; paediatric
prophylaxis, 12% to 14% )
● Other: Fever (Prophylaxis, 21% to 45%; oropharyngeal candidiasis, 6%;
refractory oropharyngeal candidiasis, 34% )
Serious
● Cardiovascular: Prolonged QT interval (1% to 2% ), Torsades de pointes

(Less than 5% )
● Hepatic: Cholestasis (Rare ), Liver failure (Rare )
CONTRAINDICATIONS
Hypersensitivity to posaconazole or other azole antifungals
Taking together with sirolimus
Taking together with CYP3A4 substrates that prolong the QT interval
Taking together with HMG-CoA reductase inhibitors primarily metabolized by CYP3A4
Taking together with ergot alkaloids
Taking together with VENCLEXTA at initiation and during the ramp-up phase in patients
with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL)
Delayed-release oral suspension: Known or suspected hereditary fructose intolerance

(HFI)
22
PRECAUTIONS
Administration: Avoid IV administration with moderate or severe renal impairment (GFR

less than 50 mL/min/1.73 m(2)) unless benefit outweighs risk; monitoring recommended
if use is necessary.
Taking together with calcineurin-inhibitor: Will increase plasma midazolam

concentrations which could prolong hypnotic and sedative effects. Patients must be
monitored closely for adverse effects associated with high plasma concentrations of
midazolam and benzodiazepine receptor antagonists must be available to reverse these
effects.
Concomitant use with vincristine: Coadministration increases risk of neurotoxicity and

other serious adverse events; reserve combined use when no other alternatives are
available.
Cardiovascular: QT interval prolongation, including cases of torsade de pointes, has

been reported; correct potassium, magnesium, and calcium levels prior to initiating
therapy.
Cardiovascular: Preexisting proarrhythmic conditions.
Endocrine and metabolic: Electrolyte disturbances, especially potassium, magnesium,

and calcium require monitoring and correction before and during therapy.
Hepatic: Potentially serious or fatal hepatic reactions, including elevations in liver

enzymes, hepatitis, cholestasis, or hepatic failure, have been reported; monitoring
recommended and discontinuation may be necessary.
Immunologic: Breakthrough fungal infections may occur; monitoring recommended.
Renal: Severe renal impairment (GFR less than 20 mL/min/1.73 m(2)); monitoring
recommended with delayed-release tablets, oral suspension, and delayed-release oral
suspension.
23
DRUG INTERACTION
Concurrent use of EFAVIRENZ and POSACONAZOLE may result in decreased

posaconazole peak concentration and exposure and increased risk of QT interval
prolongation.
Concurrent use of FENTANYL and CYP3A4 INHIBITORS may result in increased risk of
fentanyl toxicity.
Concurrent use of ESOMEPRAZOLE and POSACONAZOLE may result in decreased

posaconazole plasma levels.
Concurrent use of NIFEDIPINE and STRONG CYP3A4 INHIBITORS may result in

Increased risk of hypotension, bradycardia, or acute renal injury.
Concurrent use of POSACONAZOLE and WARFARIN may result in an increased risk of

bleeding.
24
Drug name: ISAVUCONAZOLE
(CRESEMBA, Isavuconazole 100mg capsules, by PFIZER)
MECHANISM OF ACTION
Isavuconazole weakens the fungal cell membrane structure and function by inhibiting
lanosterol 14-alpha-demethylase which prevents the conversion to ergosterol, part of the
fungal cell membrane.
DOSAGE
Adult:
Loading dosage, 372 milligram orally (2 capsules) or IV every 8 hours for 6 doses
25
Maintenance dosage, 372 milligram orally (2 capsules) or IV once daily , starting

12 to 24 hours AFTER the last loading dose
Duration, 6 to 12 weeks depending on disease site, disease improvement, and

level of immunosuppression.
ADVERSE REACTION
Common
● Cardiovascular: Peripheral edema (15.2% )

● Endocrine metabolic: Hypokalemia (19.1% )
● Gastrointestinal: Constipation (14% ), Diarrhoea (23.7% ), Nausea (27.6% ),
Vomiting (25% )
● Musculoskeletal: Backache (10.1% )
● Neurologic: Headache (16.7% )
● Respiratory: Cough (12% ), Dyspnea (17.1% )
Serious
● Hepatic: Cholestasis, Hepatitis (Up to 5% ), Increased liver function test

(17.1% ), Liver failure (Up to 5% )
● Immunologic: Anaphylaxis, Hypersensitivity reaction (Up to 5% )
● Renal: Renal failure (10.1% )
● Respiratory: Acute respiratory failure (7.4% )
● Other: Infusion reaction (6.2% )
CONTRAINDICATIONS
Taking together with strong CYP3A4 inhibitors
Taking together with strong CYP3A4 inducers
Hypersensitivity to isavuconazole
26
PRECAUTIONS
Administration: Precipitate may form after dilution of IV formulation; administer through

an in-line filter
Dermatologic: Severe skin reactions, such as Stevens Johnson syndrome, have been
reported with other azole antifungals; discontinue and provide supportive care if severe
cutaneous reaction develops
Hepatic: Hepatitis, cholestasis, hepatic failure, and death have been reported in patients
with serious underlying medical disease (eg, hematologic malignancy); monitoring
recommended and discontinuation may be necessary
Immunologic: Anaphylactic reactions, including fatalities, have been reported, often soon
after initiation of treatment; discontinue and provide supportive treatment if necessary
Infusion reactions: Hypotension, dyspnea, chills, dizziness, paresthesia, and

hypoesthesia have been reported during IV administration; discontinuation may be
necessary
Reproductive: Drug may cause foetal harm; contraception recommended during

treatment and for 28 days after final dose
DRUG INTERACTION
Taking ISAVUCONAZONIUM SULFATE and MIDAZOLAM together may result in

increased midazolam exposure.
Taking ISAVUCONAZONIUM SULFATE and ATORVASTATIN together may result in

increased atorvastatin exposure.
Taking ISAVUCONAZONIUM SULFATE and RITONAVIR together may result in

increased isavuconazole exposure. And decrease ritonavir exposure
6.2 POLYENES
Drug name : AMPHOTERICIN B
27
Class: Antifungal, Polyene (Merative, 2023, Drug Name Info section)
Indications :
FDA-Labelled Indications : Aspergillosis, Invasive
Non-FDA Labelled Indications : Aspergillosis , Invasive - HIV Infection.
MECHANISM OF ACTION
Amphotericin B exerts its effect on vulnerable fungi by attaching to sterols present in the
cell membrane. This interaction causes changes in membrane permeability, leading to
the leakage of intracellular components (Merative, 2023, Mechanism of Action section).
The fungistatic or fungicidal activity of amphotericin B depends on the susceptibility of
the specific organism and the concentration achieved in bodily fluids (Merative, 2023,
Mechanism of Action section).
DOSAGE
According to National Antimicrobial Guidelines (2019),
ABCD (amphotericin B colloidal dispersion) = 3-4 mg/kg (6 mg/kg/day for IA) q24h
ABLC (amphotericin B lipid complex) = 5 mg/kg q24h
Ampho B deoxycholate (conventional) = 0.7-1.0mg/kg q24h
Liposomal ampho B = 3-5 mg/kg q24h
ADVERSE REACTIONS
28
According to MIMS Malaysia (2022), the adverse effects are:
● GI effects (nausea and vomiting, diarrhea, GI hemorrhage, abdominal pain); CV

effects (hypotension, cardiac arrest); Respiratory effects (respiratory failure,
dyspnoea, pneumonia); Renal failure; Other effects (headache, rash,
bilirubinemia, hypokalemia, acidosis)
● Nephrotoxicity & infusion-related hyperpyrexia, rigors & chills are reduced relative
to Amphotericin B deoxycholate.
According to (Merative, 2023, Adverse Effects section), the common adverse reactions
of Amphotericin B are:
Cardiovascular: Hypotension, Thrombophlebitis
Dermatologic: Injection site pain
Gastrointestinal: Diarrhea, Indigestion, Loss of appetite, Nausea, Vomiting
Hematologic: Anemia, Normochromic, Normocystic
Musculoskeletal: Arthralgia, Myalgia
Neurologic: Headache
Respiratory: Tachypnea
Other: Fever, Infusion reaction, Malaise, Shivering.
29
For contraindications and precautions, (Merative, 2023, Contraindications/Warning

section) stated:
- Hypersensitivity to amphotericin B or any other component of the product.
Precautions
Cardiovascular: Increased risk of potentially fatal cardiac or cardiopulmonary arrest at

doses above 1.5 mg/kg/day
Immunologic: Acute reactions (for example: fever and chills, hypotension, anorexia,
tachypnoea may occur within 1 to 3 hours of initiation and are more severe with first few
doses.
Immunologic: Reserved for treatment of patients with progressive, potentially

life-threatening fungal infections due to susceptible organisms.
Neurologic: Leukoencephalopathy has been reported; total body irradiation may

increase risk.
Pulmonary: Acute pulmonary reactions have been reported during or shortly after
leukocyte transfusions; monitoring and separation of infusions as far as possible
recommended.
Renal: Use with caution in patients with renal impairment due to risk of nephrotoxicity;
monitoring recommended.
DRUG INTERACTION
30
(MIMS Malaysia, 2023) stated the drug-drug interaction as follows:
● There is a potential for increased kidney damage when amphotericin B is used

together with nephrotoxic medications like ciclosporin.
● When used in combination with antineoplastic drugs, there is an elevated risk of
hypotension, bronchospasm, and kidney damage.
● The use of amphotericin B alongside corticosteroids, corticotropin, loop diuretics,
and thiazide diuretics may increase the likelihood of developing hypokalemia (low
potassium levels).
● Amphotericin B may also amplify the toxicity of flucytosine and digitalis (a drug
used to treat heart conditions).
● Additionally, it can enhance the muscle-relaxing effects of skeletal muscle
relaxants like tubocurarine.
31
6.3 ECHINOCANDINS
Drug name: CASPOFUNGIN
(CANCIDAS, Caspofungin IV, by Merck Sharp & Dohme)
Indication :
FDA-Labelled Indications : Aspergillosis, Invasive, salvage therapy
Non-FDA Labelled Indications : Aspergillosis, Invasive, initial therapy
32
MECHANISM OF ACTION
Caspofungin is an antifungal medication belonging to the class of semisynthetic

echinocandins which works by inhibiting the synthesis of beta (1,3)-D-glucan, a critical
component of the cell wall in susceptible organisms such as Aspergillus and Candida
species (Merative, 2023, Mechanism of Action section).
DOSAGE
70 mg loading dose, followed by 50 mg q24h (MIMS Online, 2022)
ADVERSE REACTIONS
According to MIMS Malaysia (2023), the possible adverse reactions of caspofungin

include diarrhea, nausea, vomiting, flushing, headache, fever, chills, joint pain,
inflammation of veins (phlebitis), rapid heart rate (tachycardia), rash, redness of the skin
(erythema), facial swelling, itching (pruritus), excessive sweating (hyperhidrosis), warm
sensation, difficulty breathing (dyspnea), and bronchospasm. Additionally, it may cause
excessive sweating, low potassium levels (hypokalemia), elevated liver enzymes and
alkaline phosphatase, and reduced levels of red and white blood cells. In more severe
cases, it can lead to pulmonary edema, adult respiratory distress syndrome (ARDS), and
radiographic infiltrates, particularly in cases of invasive aspergillosis.
For contraindications and precautions, (Merative, 2023, Contraindications/Warning

section) stated:
Contraindications
33
If you have a hypersensitive reaction (such as anaphylaxis) to caspofungin acetate or

any ingredient in the product, avoid using it.
Precautions
Dermatologic: Cases of Stevens-Johnson syndrome and toxic epidermal necrolysis,

including instances that resulted in death, have been documented in relation to this
medication. If you experience any initial signs or symptoms of these conditions, it is
important to stop using the medication immediately.
Hepatic: Liver function test abnormalities have been reported, especially with
concomitant cyclosporine use; monitoring recommended.
Hepatic: Hepatic dysfunction, hepatitis, and hepatic failure have been reported in
patients with serious underlying conditions who were receiving multiple concomitant
medications; monitoring recommended.
Immunologic: Hypersensitivity reactions have been reported, including anaphylaxis and

histamine-mediated adverse reactions (for example: rash, facial swelling, angioedema,
pruritus, sensation of warmth, or bronchospasm); discontinue at first sign or symptom.
DRUG INTERACTION
When taken together with rifampicin and other cytochrome P450 enzyme inducers,
caspofungin may result in reduced plasma concentrations (MIMS Malaysia, 2023). There
is a possibility of increased hepatic enzyme levels when caspofungin is used in
combination with ciclosporin (MIMS Malaysia, 2023). Furthermore, the blood
concentration of tacrolimus may be decreased when co-administered with caspofungin
(MIMS Malaysia, 2023).
34
Drug name: MICAFUNGIN
(MYCAMINE, Micafungin IV 100mg, by ASTELLAS)
Indication :
MECHANISM OF ACTION
semisynthetic lipopeptide (echinocandin) antifungal agent, synthesised by a chemical

modification that inhibits the synthesis of 1,3 beta-D-glucan, a fundamental constituent of
fungal cell walls
DOSAGE
Adult
35
100 to 150 milligram IV once daily for at least 6 to 12 weeks
Paeds
(4 months or older, 40 kg or less) 2 to 3 milligram/kg IV once daily for at least 6 to 12

weeks
(4 months or older, more than 40 kg) 100 to 150 mg IV once daily for at least 6 to 12
weeks
ADVERSE REACTIONS
Common
● Endocrine metabolic: Acidosis (Pediatric, 20% ), Hypokalemia (Pediatric, 25% )

● Gastrointestinal: Diarrhoea (Treatment, 7% to less than 15%; prophylaxis, 51%
to 77% ), Nausea (Treatment, 7% to 10%; prophylaxis, 70% to 71% ), Vomiting
(Treatment, 7% to 18%; prophylaxis, 65% to 66% )
● Hematologic: Thrombocytopenia (Treatment, 9% to 25%; prophylaxis, 72% to
75% )
● Neurologic: Headache (Treatment, 9%; prophylaxis, 44% )
● Respiratory: Oxygen saturation below reference range (Pediatric, 15% )
● Other: Fever (7% to 61% ), Sepsis (Pediatric, 20% )
Serious
● Cardiovascular: Atrial fibrillation (Adult, 3% to 5% )

● Hematologic: Anaemia (Treatment, 15% to 18%; prophylaxis, 51% ),
Hemoglobinuria, Hemolysis, Hemolytic anaemia, Intravascular hemolysis
● Hepatic: Hepatitis, Liver failure (Adult, less than 5% )
● Immunologic: Anaphylaxis, Hypersensitivity reaction (Adult, less than 5% ),
Non-allergic anaphylaxis
● Renal: Acute renal failure (Pediatric, less than 15% )
36
CONTRAINDICATIONS
Hypersensitivity to micafungin, any excipients of the product, or other echinocandins
PRECAUTIONS
Hematologic: Reports have indicated the occurrence of hemolytic anemia and significant
hemolysis, including acute intravascular hemolysis.
Hepatic: Abnormalities in liver function tests, significant impairment of liver function,

hepatitis, and hepatic failure have been observed.
Immunologic: Hypersensitivity reactions, such as anaphylaxis and shock, have been

documented.
Immunologic: Infusion reactions, including rash, itching, facial swelling, and widening of
blood vessels, have been reported. If a reaction occurs, it is advised to slow down the
infusion rate.
Immunologic: Injection site reactions, such as inflammation of the veins (phlebitis) and
blood clot-related inflammation (thrombophlebitis), have been reported in patients
receiving doses of 50 to 150 mg/day. These reactions are more common in patients
receiving micafungin via a peripheral intravenous (IV) line.
Renal: Significant hemolysis (including hemoglobinuria) has been reported
Renal: Renal dysfunction (eg, BUN or creatinine elevations, significant renal impairment,
acute renal failure) has been reported
DRUG INTERACTION
Taking METHOTREXATE and HEPATOTOXIC AGENTS together may result in

increased methotrexate exposure, an increased risk of methotrexate-related severe
adverse reactions, reduced active metabolite formation and possibly reduced drug
efficacy.
37
7.Available non-pharmacological treatment of the disease
There are few non-pharmacological treatments that are indicated for chronic pulmonary
aspergillosis.One of the treatments is surgical resection, either by conventional lobectomy or
a video-assisted thoracic surgical (VATS) procedure is recommended to remove the fungus
ball and should be considered in all patients with severe haemoptysis. However, the surgical
resection planning must consider the pulmonary function of the patient (Kousha et al., 2011).
Patients with insufficient pulmonary function are not recommended to undergo surgical
resection. The aspergilloma must be completely removed throughout the procedure without
any fungal components spilling into the pleural area for the procedure to be successful
(Denning et al., 2016).
Next non-pharmacological treatment is granulocyte transfusions (Kousha et al., 2011), in

which it can be used to treat invasive fungal infections. It involves the infusion of
granulocytes, which is a type of white blood cells into the patient’s blood. This treatment
provides functional neutrophils to fight against the bacteria or fungi that caused the
infections. Granulocyte transfusion is indicated for neutropenic patients, which has absolute
neutrophil count less than 0.5 x 103 /µl, with fungal or bacterial infections who are
unresponsive to antimicrobial or antifungal therapies for at least 24 to 48 hours. The patient
also must have an expectation of neutrophil recovery (Manjee & Gniadek, 2020).
Other than that, transbronchial removal of mycetoma is also an option to treat chronic
aspergillosis. This method uses a CT scan with virtual bronchoscopy reconstruction for
pre-procedural planning, flexible bronchoscope access using a rigid bronchoscope or
double-lumen endotracheal tube, and biopsy forceps and a basket retrieval device to remove
aspergillomas. However, patients without a straight airway leading to the aspergilloma
cannot use the method (Lang et al., 2020).
Furthermore, bronchial artery embolization (BAE) can also be an option to control massive
or recurrent haemoptysis in patients with pulmonary aspergilloma. This procedure is usually
performed in individuals who are not good surgical candidates or who have advanced
disease (Maghrabi & Denning, 2017). Successful embolization stops the haemorrhage by
semi-permanently blocking arteries that caused haemoptysis (Lang et al., 2020).
Last but not least, radiotherapy is also a treatment option especially when BAE failed to
manage haemoptysis in those who cannot undergo surgical procedure. Without altering the
38
fungus's growth, radiotherapy causes the arteries that line the aspergilloma chamber to
become occluded (Lang et al., 2020).
39
8.Goals of therapy and evaluation of therapeutic outcomes
Goals of Therapy
It has been determined from the case study that the patient has chronic pulmonary
aspergillosis with aspergilloma. In light of its extensive occurrence, chronic pulmonary
aspergillosis is a catastrophic, substantial fungal pulmonary infection. Given the frequently
multiple related concurrent medical conditions, multifaceted scientific representation,
pharmaceutical reactions, adverse reactions, and intolerance (Maghrabi & Denning, 2017).
Although a certain diagnosis would be preferred before starting therapy, due to the disease's
high mortality, treatment should start as soon as it is suspected. Of course, a definitive
diagnosis should be sought in order to apply the most effective antifungal regimen (Jennings
& Hardin, 1993). In the case of chronic pulmonary aspergillosis, the major objectives are to
reduce respiratory symptoms as well as to stop additional lung damage and the onset of
lung fibrosis (Warris & Armstrong-James, 2022).
Eradicating the fungal is the major objective of treatment for chronic pulmonary aspergillosis
in order to provide patients with symptomatic relief and provide survival against the disease.
Resolution of immunosuppression, particularly an upsurge of neutrophil count in severely
neutropenic patients, is thought to be the most crucial indicator of survival (Jennings &
Hardin, 1993). Symptomatic relief be accomplished such as by using oral triazoles like
itraconazole as the disease's first line treatment. By preventing the transformation of
lanosterol to ergosterol, which in turn damages the Aspergillus cell membrane, oral triazoles
act as antifungal medicines. This will kill the fungal while also allowing for the management
and mitigation of the patient's symptoms (Maghrabi & Denning, 2017). It is anticipated that
the symptoms experienced by the patient such as productive cough and haemoptysis for 2
weeks might be alleviated after taking antifungal medications. Other than that, antifungal
drugs may reinforce the resilience of immune defences by preventing the spread of the
fungal throughout the body. This lessens the amount of fungal in the body, resulting in fewer
symptoms and a quicker recovery (Mazu et al., 2016).
In addition to treating the symptoms and preventing them from growing worse, the next
therapeutic objective for chronic pulmonary aspergillosis is to ensure radiological
improvement. By amalgamating imaging and medical outcomes a few months following
examination, responses to therapy were reported as generally evolved, in keeping with
previously published cohort studies (Camara et al., 2015). Reduced pleural and cavitary
thickness, decreased cavity size or number, and stability of radiological characteristics on
subsequent chest CT scans were all considered signs of radiological improvement.
40
According to the doctor's clinic records, clinical improvement was understood to mean a
decrease in symptoms, consolidation of respiratory or physiological symptoms like coughing,
hemoptysis, fever, dyspnea, weight gain of less than 3 kg, greater energy, and increased
exercise tolerance (Camara et al., 2015). To put it another way, overall progress denotes
stability or improvement of the aforementioned characteristics without decline (El-Ashram et
al., 2016).
Besides treating with antifungal agents, surgery is also one of the therapies that is taken into
consideration when there are issues such as adverse effects, drug resistance, or an
unavoidable recurrence after drug withdrawal. Surgery gives patients with localised lesions a
chance of recovery, but only in rare occasions (Changming et al., 2022). There are
numerous accounts of persistent greater success alongside longevity soon after surgical
treatment rather than medical intervention solely in patients with symptomatic disease,
regardless of the truth that there is no refusion that surgical procedure comes with an
elevated possibility of negative consequences, notably severe haemorrhage, bronchopleural
fistula and death from respiratory failure (Kumar et al., 2017). The primary surgical approach
has been open thoracotomy, with lobectomy being the most frequent operation. The
damaged lung lobe is removed during this treatment. It is typically carried out when a lung
cavity or localised fungal tumour is unresponsive to previous therapies (Kay, 1997). A
lobectomy is the best course of action for pulmonary aspergilloma because it quickly controls
the symptoms and stops additional haemoptysis. In addition, it can lessen the fungal burden
and perhaps even slow the disease's course (Rergkliang et al., 2004).
Evaluation of therapeutic outcomes

The primary organ affected by chronic pulmonary aspergillosis (CPA) is the lung. CPA is a
progressive and frequently challenging fungal infection. The efficiency of therapy
approaches and the improvement of patient outcomes depend strongly on the therapeutic
effects of CPA (Bongomin et al., 2018). Monitoring the progress of the disease, measuring
lung function, and taking into consideration the effect on quality of life are all part of
evaluating therapeutic outcomes.
Controlling the infection and slowing the progression of the disease are two of the main
objectives of treating CPA. The primary method of treatment is antifungal therapy,
specifically with drugs like voriconazole, itraconazole, or posaconazole (Dening et al., 2016).
Assessing the effectiveness treatment of antifungal in terms of minimising the fungal load
41
and stopping the spread of infection is part of the evaluation of therapeutic outcomes.
Clinical improvement, stabilization or resolution of lung lesions, and a drop in
Aspergillusspecific biomarkers in the blood or sputum are all options to assess this
(Cadranel J, et al., 2019)
In assessing the efficacy of treatment, radiological imaging including chest X-rays and
computed tomography (CT) scans is necessary to keep track of alterations in fibrosis,
nodules, or lung cavities . These serial imaging investigations are carried out. The evaluation
involves identifying the size, quantity, and distribution of infections and comparing those
results with those from earlier imaging studies (Denning et al., 2016). A positive therapy
response is indicated by the regression or recovery of the pulmonary lesions.
Another crucial component of assessing the effectiveness of CPA therapy is monitoring lung
function. To evaluate respiratory function, pulmonary function tests such as spirometry,
diffusion capacity measures, and lung volumes are used (Bongomin et al., 2020). An
improvement in lung function measurements indicates that the infection has been controlled
and signals a favorable response to treatment. In order to track changes over time and
evaluate the effect of therapy on lung health, these tests are repeated at regular intervals.
Besides that, A study found out that a patient’s survival rate will be higher when receiving
antifungal treatment within 3 months of diagnosis compared to patients who receive
treatment after 3 months of a diagnosis. This proves that early diagnosis and treatment are
essential in order to improve the outcomes (Bongomin et al., 2018).
In conclusion, monitoring the development of the disease using radiological imaging,

assessing lung function, and taking into consideration the effect on the patient's quality of life
are all important components of evaluating therapeutic outcomes in chronic pulmonary
aspergillosis. Control of the infection, healing or stabilization of lung infections, improvement
in lung function, and improvement in overall quality of life are examples of successful
therapeutic outcomes. To keep an eye out for relapses and guarantee the ongoing efficacy
of treatment initiatives, long-term follow-up is essential.
42
References
Agarwal, R. P., Chakrabarti, A., Shah, A. M., D. Bakshi Gupta, Meis, J. F., R. Guleria,
Moss, R. A., & Denning, D. W. (2013). Allergic bronchopulmonary aspergillosis: review
of literature and proposal of new diagnostic and classification criteria. 43(8), 850–873.
https://doi.org/10.1111/cea.12141
American Thoracic Society. (2014). What is Allergic Bronchopulmonary Aspergillosis

(ABPA)?
https://www.thoracic.org/patients/patient-resources/resources/allergic-bronchopulm-as
pergillosis.pdf
Arias, M., Santiago, L., Matxalen Vidal-García, Redrado, S., Lanuza, P. M., Comas, L.,
Domingo, M., Rezusta, A., & Galvez, E. M. (2018). Preparations for Invasion:
Modulation of Host Lung Immunity During Pulmonary Aspergillosis by Gliotoxin and
Other Fungal Secondary Metabolites. 9. https://doi.org/10.3389/fimmu.2018.02549
Azoulay, E., Jean-François Timsit, Tafflet, M., Arnaud de Lassence, Darmon, M., Zahar,
J.-R., Christophe Adrie, Maité Garrouste-Orgeas, Cohen, Y., Mourvillier, B., &
Schlemmer, B. (2006). Candida Colonization of the Respiratory Tract and Subsequent
Pseudomonas Ventilator-Associated Pneumonia. 129(1), 110–117.
https://doi.org/10.1378/chest.129.1.110
Aspergillosis. Centers for Disease Control and Prevention.

https://www.cdc.gov/fungal/diseases/aspergillosis/index.html. Accessed Jan. 8, 2020.
Bongomin, F., Harris, C., Hayes, G., Kosmidis, C., & Denning, D. W. (2018).
Twelve-month clinical outcomes of 206 patients with chronic pulmonary aspergillosis.
13(4), e0193732–e0193732. https://doi.org/10.1371/journal.pone.0193732
Bongomin, F., Lucy Grace Asio, Joseph Baruch Baluku, Kwizera, R., & Denning, D. W.
(2020). Chronic Pulmonary Aspergillosis: Notes for a Clinician in a Resource-Limited
Setting Where There Is No Mycologist. 6(2), 75–75. https://doi.org/10.3390/jof6020075
43
Camara, B., Reymond, E., Saint-Raymond, C., Roth, H., Marie-Pierre Brenier-Pinchart,
Pinel, C., Cadranel, J., Ferretti, G., Hervé Pelloux, & Pison, C. (2015). Characteristics
and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary
hospital registry. 9(1), 65–73. https://doi.org/10.1111/crj.12105
Changming, S., Qiao, G., Wang, C., Jin, F., & Zhang, Y. (2022). Outcomes of surgery for
different types of chronic pulmonary aspergillosis: results from a single-center,
retrospective cohort study. 22(1). https://doi.org/10.1186/s12890-022-01836-z
Chakraborty, R. K., & Baradhi, K. M. (2022, December 19). Aspergilloma. Nih.gov;

StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK546668/
Centers for Disease Control and Prevention. (n.d.). Diagnosis and testing of aspergillosis.
Retrieved from https://www.cdc.gov/fungal/diseases/aspergillosis/diagnosis.html
Denning, D. W., Cadranel, J., Beigelman-Aubry, C., Ader, F., Chakrabarti, A., Blot, S.,
Ullmann, A. J., Dimopoulos, G., & Lange, C. (2016). Chronic pulmonary aspergillosis:
rationale and clinical guidelines for diagnosis and management. European
Respiratory
Journal, 47(1), 45–68. https://doi.org/10.1183/13993003.00583-2015
Denning, D. W., Konstantinos Riniotis, Dobrashian, R., & Sambatakou, H. (2003). Chronic
Cavitary and Fibrosing Pulmonary and Pleural Aspergillosis: Case Series, Proposed
Nomenclature Change, and Review. 37(s3), S265–S280.
https://doi.org/10.1086/376526
Denning, D. W., Cadranel, J., Beigelman-Aubry, C., Ader, F., Chakrabarti, A., Blot, S.,
Ullmann, A. J., Dimopoulos, G., & Lange, C. (2016). Chronic pulmonary aspergillosis:
rationale and clinical guidelines for diagnosis and management. 47(1), 45–68.
https://doi.org/10.1183/13993003.00583-2015
Despois, O., Sharon C.-A. Chen, Gilroy, N., Jones, M. P., Wu, P. K., & Beardsley, J. (2022).
Chronic Pulmonary Aspergillosis: Burden, Clinical Characteristics and Treatment
Outcomes at a Large Australian Tertiary Hospital. 8(2), 110–110.
https://doi.org/10.3390/jof8020110
Ingle, A. P., Shende, S., Pandit, R., Paralikar, P., Tikar, S., Kon, K., & Rai, M. (2016).
Nanotechnological applications for the control of pulmonary infections. In Elsevier
eBooks (pp. 223–235). https://doi.org/10.1016/b978-0-12-804543-5.00015-4
44
Jennings, T. A., Thompson, D. F. (2016). Treatment of Aspergillosis with Itraconazole -

Dennis F. Thompson, Marsha A. Raebel, Thomas C. Hardin, 1993. Annals of
Pharmacotherapy. https://journals.sagepub.com/doi/10.1177/106002809302701011
Kay, P. H. (1997). Surgical management of pulmonary aspergilloma. Thorax, 52(9), 753–754.

https://doi.org/10.1136/thx.52.9.753
Koenraad Vandewoude, Blot, S., Depuydt, P., Benoit, D., Temmerman, W., Colardyn, F., &
Vogelaers, D. (2006). 10(1), R31–R31. https://doi.org/10.1186/cc4823
Kousha, M., Tadi, R., & Soubani, A. O. (2011). Pulmonary aspergillosis: a clinical review.
European Respiratory Review, 20(121), 156–174.
https://doi.org/10.1183/09059180.00001011
Kumar, A., Belal Bin Asaf, Harsh Vardhan Puri, Lingaraju, V. C., Siddiqui, S., Pulle Mohan
Venkatesh, & Sood, J. (2017). Video-assisted thoracoscopic surgery for pulmonary
aspergilloma. 34(4), 318–318. https://doi.org/10.4103/0970-2113.209232
Lang, M., Lang, A. L., Chauhan, N., & Gill, A. (2020). Non-surgical treatment options for
pulmonary aspergilloma. Respiratory Medicine, 164, 105903.
https://doi.org/10.1016/j.rmed.2020.105903
Maghrabi, F., & Denning, D. W. (2017). The Management of Chronic Pulmonary

Aspergillosis: The UK National Aspergillosis Centre Approach. Current Fungal
Infection
Reports, 11(4), 242–251. https://doi.org/10.1007/s12281-017-0304-7
Malcolm, D. R., David, W. W., (2003). Fungal Infection Diagnosis and Management 3rd
Edition. Blackwell Publishing.
Manjee, K., & Gniadek, T. J. (2020). Educational Case: Granulocyte Transfusion. Academic
Pathology, 7, 237428952090950. https://doi.org/10.1177/2374289520909500
Marshall, H. M., Jones, S., & Williams, A. J. (2010). Chronic pulmonary aspergillosis -
longterm follow-up over 20 years, a case report. https://doi.org/10.3941/jrcr.v4i2.350
45
Mayo Clinic . (2022, January 06). Aspergillosis . Retrieved from

http://mayoclinic.org/diseases-conditions/aspergillosis/symptoms-causes/syc-2036961
9#:~:text=People%20who%20have%20air%20spaces,allergic%20response%20to%20
aspergillus%20mold
Mazu, T., Bricker, B. A., Flores-Rozas, H., & Ablordeppey, S. Y. (2016). The Mechanistic
Targets of Antifungal Agents: An Overview. Mini-reviews in Medicinal Chemistry, 16(7),
555–578. https://doi.org/10.2174/1389557516666160118112103
Patterson, T. L., Thompson, G. H., Denning, D. W., Fishman, J. A., Hadley, S., Raoul
Herbrecht, Kontoyiannis, D. P., Marr, K. A., Morrison, V. A., Nguyen, M., Segal, B. H.,
Steinbach, W. J., Stevens, D. A., Walsh, T. J., Wingard, J. R., Anne, J., & Bennett, J.
M. (2016). Practice Guidelines for the Diagnosis and Management of Aspergillosis:
2016 Update by the Infectious Diseases Society of America. 63(4), e1–e60.
https://doi.org/10.1093/cid/ciw326
Rergkliang, C., Chetpaophan, A., Chittithavorn, V., & Vasinanukorn, P. (2004). Surgical
Management of Pulmonary Cavity Associated with Fungus Ball. Asian Cardiovascular
and Thoracic Annals, 12(3), 246–249. https://doi.org/10.1177/021849230401200314
‌Sherif, R., & Segal, B. H. (2010). Pulmonary aspergillosis: clinical presentation, diagnostic
tests, management and complications. 1–1.
https://doi.org/10.1097/mcp.0b013e328337d6de
Taylor, & Keller, N. P. (2009). Pathogenesis of Aspergillus fumigatus in Invasive

Aspergillosis. 22(3), 447–465. https://doi.org/10.1128/cmr.00055-08
Warris, A., & Armstrong-James, D. (2022). Antifungal therapy for chronic pulmonary
aspergillosis. The Lancet Infectious Disease, 22(7), 924–926.
https://doi.org/10.1016/s1473-3099(22)00126-8
Zarif A, Thomas A, Vayro A. (2021) .Chronic Pulmonary Aspergillosis: A Brief Review. Yale J
Biol Med. 29;94(4):673-679. PMID: 34970105; PMCID: PMC8686779
Itraconazole (2023). In Micromedex Drug Reference (electronic version). Retrieved May

13, 2023 from https://www.micromedexsolutions.com/.
46
MIMS Malaysia. (2023). Itraconazole. In MIMS Online. Retrieved May 13, 2023 from
https://www.mims.com/malaysia/
Voriconazole (2023). In Micromedex Drug Reference (electronic version). Retrieved May

13, 2023 from https://www.micromedexsolutions.com/
MIMS Malaysia. (2023). Voriconazole. In MIMS Online. Retrieved May 13, 2023 from
MIMS Malaysia. (2023). Amphotericin B. In MIMS Online. Retrieved May 13, 2023 from
Amphotericin B (2023). In Micromedex Drug Reference (electronic version). Retrieved May

13, 2023 from https://www.micromedexsolutions.com/
Caspofungin (2023). In Micromedex Drug Reference (electronic version). Retrieved May 13,
2023 from https://www.micromedexsolutions.com/
MIMS Malaysia. (2023). Caspofungin. In MIMS Online. Retrieved May 13, 2023 from
MIMS Online. (2022). TreatmentGuideline Attachment MIMS Malaysia. Auth.mims.com.

https://www.mims.com/malaysia/treatmentguideline/attachment/17_Aspergillosis_MRG
_MID_20220408_3_Boxview.pdf?_gl=1
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ASSIGNMENT CASE

STUDENT NAME STUDENT ID

Aiza Shahira binti Idris 59215121023

Eikal Syazwan bin Zolkifli 59215121010

Fateehah binti A.H.Hafeez 59215121024

Mohamad Adli bin Mohamad Naser 59215121058

Muhammad Adlan bin Mohd ‘Asri 59215121037

Muhammad Nizar Aiman bin 59215121049

Muhammad Syafiq Iman bin Sudin 59215121017

Nur Alya Qistyna binti Nazmi 59215121008

Nur Hana Atiqah binti Fairol Azmi 59215121019

1.Introduction of the disease 2

1.Introduction of the disease

Pulmonary aspergillosis is a category of diseases caused by the fungus Aspergillus species.

There are three distinct classifications of pulmonary aspergillosis: allergic bronchopulmonary

A reliable diagnosis is critical for efficient management of pulmonary aspergillosis. Imaging

2.Pathophysiology of the disease

Inhalation of Aspergillus spores

Adherence and colonisation

Formation of fungus ball

3.Clinical presentations (sign and symptoms) of the disease

A respiratory disease known as pulmonary aspergillosis brought on by the fungus

1. Allergic Bronchopulmonary Aspergillosis (ABPA)

A hypersensitive response to Aspergillus spores in the airways causes allergic

● Recurrent asthma-like symptoms: Patients may suffer symptoms like poorly

2. Chronic Pulmonary Aspergillosis (CPA) :

3. Invasive Pulmonary Aspergillosis (IPA):

IPA is a severe form of pulmonary aspergillosis that mostly affects

4.Risk factors and complications of disease

Human pulmonary aspergillosis can be caused by inhaling microscopic Aspergillus

Different forms of aspergillosis can cause a variety of serious consequences.

It is quite challenging to completely avoid Aspergillus exposure. On the other hand,

5.Assessment and diagnosis of disease

A set of respiratory illnesses brought on by the fungus Aspergillus are referred to as

Figure 5.1: Shows the chart to assess a patient's pulmonary test.

sufficient to differentiate Aspergillus from other filamentous fungi. However, the

Additionally, antigen testing is another important diagnostic tool. It is typically used as an

6.Available pharmacological treatment of disease

Management of Pulmonary Aspergillosis consists of the removal of Aspergillosis nodules

(Maghrabi and Denning 2017)

Drug name : Itraconazole

(SPORANOX, Itraconazole 100mg capsules, by JANSSEN-CILAG)

FDA-Labeled Indications: Aspergillosis, Invasive, salvage therapy

According to (Merative, 2023, Mechanism of Action section), Itraconazole hinders the

200 mg PO/IV 12-24 hourly or 200-400 mg PO 24 hourly x 2-5 months.

May be increased to 200 mg PO 12 hourly

Common adverse reactions according to (Merative, 2023, Adverse Effect section)

● Cardiovascular: Dema (4%), Hypertension (3%)

According to MIMS Malaysia (2022),

Gastrointestinal symptoms, including dyspepsia, abdominal pain, nausea, vomiting,

CONTRAINDICATIONS AND PRECAUTION

Based on (Merative, 2023, Contraindications/Warning section),

● Using avanafil, cisapride, disopyramide, dofetilide, dronedarone, eplerenone,

o ﻿In patients with hypochlorhydria, absorption may be improved by

● The absorption of itraconazole capsules may be reduced when taken together

Drug name: Voriconazole

(VFEND, Voriconazole 200mg tablets, by PFIZER)

Class: Antifungal, Triazoles (Merative, 2023, Drug Name Info section)

FDA-Labelled Indications: Aspergillosis,Invasive

Non-FDA Labelled Indications: Allergic bronchopulmonary aspergillosis, Aspergillosis

Children: 7 mg/kg IV 12 hourly

Adult: 4 mg/kg I2 hourly

Dermatologic: Rash (Adult, 7%; pediatric, 13%)

o In patients with hypochlorhydria, absorption may be improved by