Fungal infections can occur due to the increasing use of broad-spectrum antibiotics and patients with immunodeficiency. Some pathogens, such as Cryptococcus, Candida,and Fusarium, rarely cause serious diseases in the normal host, while other endemic fungi, such as Histoplasmosis, Coccidiodes,and Paracoccidiodes can cause disease in a normal host, but has a tendency to be aggressive on immunocompromise. Candida species are normal flora that may be an apportunistic pathogen. Candidiasis occurs in some diseases such as gastrointestinal mucosal esophagitis, a fungal disease associated with the use of catheters and in - patients who have mucosal damage or obtain broad – spectrum antibiotics. Other candidiasis consist of skin candidiasis, funguria candidiasis, disseminated candidiasis and endocarditis candidiasis. Candidemia is the fourth most common cause of nosocomial bloodstream infections in the United States and in many of the developed country. Invasive candidiasis has a significant impact on patient outcomes, and it has been estimated that the mortality of invasive candidiasis is as high as 47%. The mortality rates are 15%-25% for adults and 10%-15% for neonates and children. Diagnostic approach to fungal infection is a priority. The knowledge of the changes in epidemiology and risk factors for fungal infections, has become the main reference to measure optimal treatment of fungal infections.

1. CANDIDIASIS IN FEBRILE NEUTROPENIA
dr. Gina Amanda,
Resident Pulmonology Faculty of Medicine Universitas
Indonesia
Dr. dr. Soroy Lardo, SpPD FINASIM
Division of Tropical Medicine, Indones Army Central
Hospital Gatot Soebroto
Case Report

2. INTRODUCTION
 Febrile neutropenia is one of the most adverse
events in patients with haematological malignancy
or patients who were administered chemotherapy.
 This emergency condition may lead infection which
may progress rapidly and be a life threatening
condition.

3.  Bacteria are the most common pathogen which was
isolated in patients with febrile neutropenia.
Coagulase-negative staphylococci, Staphylococcus aureus,
Enterococcus spp, Viridans group streptococci, Streptococcus
pneumoniae, and Streptococcus pyogenes, and drug-resistant Gram-
negative pathogens.
 Fungal infection especially invasive infection may
cause high mortality in patients with febrile
neutropenia:
1. Candida spp
2. Aspergillus spp.

4. CASE REPORT
 A 62 year old female was admitted to emergency
department with the complaint of diarrhea since
three days before admission.
 Other complaints : fever and nausea
 History :
One week ago, this patient got her first
chemotherapy with docetaxel, doxorubicin, and
cyclophosphamide as the regimen

5. Medical history :
 Breast cancer at 13 months ago and had been
treated with radiation for 27 times.
 Three months later, she got pathologic fracture at
her left hip as the sign of bone metastases and it
was managed with operating procedure.

6. PHYSICAL EXAMINATION
 Vital sign
moderately good general condition,
blood pressure : 120/80 mmHg
heart rate of 85/min
respiratory rate of 24/min
temperature of 37.8 degree of Celcius

7. PHYSICAL EXAMINATION
 Conjunctiva : pale
 Oral thrush.
 On abdominal auscultation, bowel sound was
increased

8. LABORATORY FINDINGS
 Hemoglobin : 9.2 gr/dl
 Leukocyte : 620/μL , 51% of netrofil
 Platelet count : 62.000/μL.
 Hypocalcemia (6.3 mg/dl)
 Hypomagnesemia (1.34 mg/dl)
 Hypokalemia (2.9 mmol/L)

9. DIAGNOSIS
 Febrile neutropenia after chemotherapy
 Breast cancer with bone metastases
 Oral candidiasis
 Gastroenteritis
 Electrolyte imbalance.

10. TREATMENT
 Ceftazidim 1000 mg bid
 Ciprofloxacin 400 mg bid as antibiotic prophylaxis
 Fluconazole 200 mg daily as anti-fungal prophylaxis
agent
 Nystatin drop three times daily for her oral thrush
 Leucogen sub-cutaneous to increase the leukocyte
counts
 Other symptomatic medications.

11.  Day 4th of treatment, the symptoms of diarrhea and
fever, oral thrush, and leukocyte counts were
improved, so we stopped antibiotic and anti-fungal
therapy.
 This patient was discharged on day 13th with good
clinical condition.

12. DISCUSSION
 Epidemiological study  fungal infection as
etiology of sepsis was increased 20% between
1979 and 2000.
 Receiver immunosuppressive therapy or
chemotherapy, suffer hematologic malignancy, and
get allogenic hematopoietic stem cell
transplantation
 Candida spp is the leading cause of invasive fungal
infection where bloodstream infections are caused
by C. albicans, C. glabrata, C. tropicalis or C.
parapsilosis.

13.  In healthy individual
Candida spp is a commensal and colonize in
mucosa and the skin.
 When the homeostasis is disrupted
 disease

14.  Innate immune against Candida is started with the
recognition of invading fungi via PRRs such as Toll-
like receptors (TLRs), C-type lectin receptors
(CLRs), NOD-like receptors, (NLRs) and RIG-I-like
receptors (RLRs)

16.  After the recognition process, it may activate the
immune and non-immune cell populations that
contribute to the antifungal response including
epithelial cells, monocyte, macrophage, neutrophils,
Natural Killer cells, dendritic cells, platelets, and
humoral antifungal mechanism.

17. There are two types of Candida infection:
 Mucosal
 Systemic infection

18.  Oral candidiasis is frequently found in cancer
patients who receive chemotherapy and/or radiation
for all cancer treatment.
 The prevalence of clinical oral fungal infection was
7.5% in pretreatment, 39.1% during treatment, and
32.6% after the end of cancer therapy.
 Study in Iran revealed that among neutropenia
patients which are caused by mediacation,
iatrogenic factors, stem cell disorder, and infection,
the oral candidiasis is occurred in 8.7% cases.

19. TREATMENT FOR ORAL CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
MILD disease
Recommendation:
 Clotrimazole troches, 10 mg 5 times daily
or
 Miconazole mucoadhesive buccal 50 mg tablet
applied to the mucosal surface over the canine
fossa once daily for 7–14 days

20. TREATMENT FOR ORAL CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
MILD disease
Alternatives
 Nystatin suspension (100 000 U/mL) 4–6 mL 4
times daily
or
 1–2 nystatin pastilles (200 000 U each) 4 times
daily for 7–14 days
or
 moderate to severe disease, oral fluconazole, 100–
200 mg daily, for 7–14 days

21. TREATMENT FOR ORAL CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
MODERATE TO SEVERE disease
Recommendations
 Oral fluconazole, 100–200 mg daily, for 7–14 days

22. SYSTEMIC CANDIDIASIS
 a serious complication mainly in neutropenia patient
 high morbidity and mortality index
 Mohammadi et al. :
- 7.1% of 309 patients with cancer and neutropenia
had candidiasis
- Candida albicans was the most prevalent etiology
of candidiasis among neutropenia patients.
- Mortality rate in cancer patients was 13.6% vs
5.2% in control group

23.  In acute neutropenia patients
digestive tract is the main entrance of Candida
spp.
 Impaired of gut function may lead invasif
candidiasis.
 Total body irradion or cytotoxic chemotherapy may
disrupt the barrier of digestive tract spread
Candida spp to the bloodstream
disseminates to visceral organs.

24. TREATMENT FOR INVASIVE CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
Non-neutropenia
Recommendation as initial therapy
 Echinocandin (caspofungin: loading dose 70 mg,
then 50 mg daily
or
 micafungin: 100 mg daily
or
 anidulafungin: loading dose 200 mg, then 100 mg
daily)

25. TREATMENT FOR INVASIVE CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
Non-neutropenia
Alternatives
 Fluconazole, intravenous or oral, 800-mg (12
mg/kg) loading dose, then 400 mg (6 mg/kg) daily

26. TREATMENT FOR INVASIVE CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
Neutropenia
Recommendation as initial therapy
 Echinocandin (caspofungin: loading dose 70 mg,
then 50 mg daily
or
 Micafungin: 100 mg daily
or
 Anidulafungin: loading dose 200 mg, then 100 mg
daily)

27. TREATMENT FOR INVASIVE CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
Neutropenia
Alternatives
 Lipid formulation AmB, 3–5 mg/kg daily, but it has a
potential toxicity.
 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.

28. TREATMENT FOR INVASIVE CANDIDIASIS BASED ON
INFECTIOUS DISEASES SOCIETY OF AMERICA
(IDSA)
Neutropenia
Alternatives
 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.
 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.
 Voriconazole can also be used as step-down therapy
during neutropenia in clinically stable patients who have
had documented bloodstream clearance and isolates
that are susceptible to voriconazole.

29. ANTI-FUNGAL PROPHYLAXIS IN FEBRILE
NEUTROPENIA
 The choice of anti-fungal treatment is fluconazole.
 Several meta-analyses and randomized trials
fluconazole was effective to prevent Candida
infections in high risk patients.
 Among lower risk patients, severe candidiasis is
rare, so they don’t need prophylaxis treatment.

30. ANTI-FUNGAL PROPHYLAXIS IN FEBRILE
NEUTROPENIA
 Fluconazole has :
• High systemic activity
• Excellent tolerability
• Cheap
• Less toxic
• Prevent all species of Candida except C. kruesei
and C. galbrata.
o Alternatives agents for candidiasis are itraconazole,
voriconazole, posaconazole, and caspofungin.

31.  In our case, this patient suffered oral candidiasis
when febrile neutropenia had occurred (neutrophil
counts: 316 cells).
 She treated with nystatin drop and the lesion was
improved after 4 days of treatment.
 Anti-fungal prophylaxis was also administered to
prevent systemic fungal infection. We chose
fluconazole for prophylaxis.

32. SUMMARY
 Candidiasis is the most prevalent fungal infection in
febrile neutropenia patients either systemic or
mucosal infection.
 Prophylaxis agents for mold infection should be
given to this group since it might be a life
threatening condition with high mortality rate.

33. THANK YOU