candidiasis in febrile neutropenia

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

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.

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.

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

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.

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

PHYSICAL EXAMINATION

Conjunctiva : pale

Oral thrush.

On abdominal auscultation, bowel sound was

increased

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)

DIAGNOSIS

Febrile neutropenia after chemotherapy

Breast cancer with bone metastases

Oral candidiasis

Gastroenteritis

Electrolyte imbalance.

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.

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.

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.

In healthy individual

Candida spp is a commensal and colonize in

mucosa and the skin.

When the homeostasis is disrupted

disease

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)

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.

There are two types of Candida infection:

Mucosal

Systemic infection

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.

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



(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



(IDSA)

MODERATE TO SEVERE disease

Recommendations

Oral fluconazole, 100–200 mg daily, for 7–14 days

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

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.

TREATMENT FOR INVASIVE CANDIDIASIS BASED ON


(IDSA)

Non-neutropenia

Recommendation as initial therapy

Echinocandin (caspofungin: loading dose 70 mg,

then 50 mg dailyor

micafungin: 100 mg dailyor

anidulafungin: loading dose 200 mg, then 100 mg

daily)



(IDSA)

Non-neutropenia

Alternatives

Fluconazole, intravenous or oral, 800-mg (12

mg/kg) loading dose, then 400 mg (6 mg/kg) daily



(IDSA)

Neutropenia

Recommendation as initial therapy

Echinocandin (caspofungin: loading dose 70 mg,

then 50 mg dailyor

Micafungin: 100 mg dailyor

Anidulafungin: loading dose 200 mg, then 100 mg

daily)



(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.



(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.

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.

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.

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.

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.

THANK YOU

candidiasis in febrile neutropenia

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