CASE

A 41-year-old man, previously healthy and without any prior history of hospitalization, was admitted
associated with multiple episodes of vomiting during this period and recurrent high fever and suspect
with meningitis. One day before admission he noticed paresthesia in his right fingers. On physical
examination, left facial palsy and neck stiffness. The patient also had several whitish plaques in the oral
cavity, consistent with severe oropharyngeal candidiasis. Cardiopulmonary auscultation and abdominal
examination were normal. Complete blood count showed normal levels of haemoglobin and platelets.
There was leukopenia with 2.930 cells /ml blood (normal range: 4000–10000), with a severe
lymphopenia of 279 lymphocytes/ml blood (normal range: 800–4500).
Because meningitis was suspected, the patient underwent lumbar puncture for microbiologic
examination. The cerebrospinal fluid (CSF) was clear in appearance, with transparent supernatant and
fast drip, which reflects increased intracranial pressure. There were 43% lymphocytes, 2% monocytes
and 55% neutrophils per ml, and only one red blood cell per ml was observed. The glucose concentration
was 52 mg/dl (lower than normal). Under microscopic examination using Gram staining, oval yeast
without capsules were found, many of which presented budding cells.
The treatment was initiated with fluconazole 50 mg per day, but four days after admission the patient’s
general condition was not improve. The CSF culture showed growth of creamy and smooth white
colonies, and reported as C. parapsilosis.

Seorang pria 41 tahun, yang sebelumnya sehat dan tanpa riwayat rawat inap, selama periode ini
mengalami episode muntah dan demam tinggi yang berulang berulang yang diduga berkitan dengan
meningitis. Satu hari sebelum masuk rumah sakit ia mengalami paresthesia (sensasi abnormal berupa
kesemutan, tertusuk, atau terbakar pada kulit yang umumnya dirasakan di tangan, kaki, lengan, dan
tungkai) di jari kanannya. Pada pemeriksaan fisik, meninggalkan wajah palsy (kelumpuhan otot-otot
salah satu sisi wajah, sehingga wajah menjadi asimetris, karena salah satu sisi wajah tampak melorot/
mencong) dan leher kaku. Pasien juga memiliki beberapa plak keputihan di rongga mulut, konsisten
dengan kandidiasis orofaringeal parah. Auskultasi cardiopulmonary dan pemeriksaan perut yang normal.
Hitungan darah lengkap menunjukkan hemoglobin dan trombosit tingkat normal. Ada leukopenia
dengan 2.930 sel/ml darah (rentang normal: 4000-10000), dengan limfopenia parah dari 279 limfosit /
ml darah (rentang normal: 800-4500).Karena meningitis diduga, pasien menjalani pungsi lumbal untuk
pemeriksaan mikrobiologis. Cairan serebrospinal (CSF) jelas dalam penampilan, dengan supernatan
transparan dan tetes cepat, yang mencerminkan peningkatan tekanan intrakranial. Ada 43% limfosit, 2%
monosit dan 55% neutrofil per ml, dan hanya satu sel darah merah per ml diamati. Konsentrasi glukosa
adalah 52 mg/dl (lebih rendah dari normal). Di bawah pemeriksaan mikroskopis menggunakan
pewarnaan Gram, ragi oval tanpa kapsul ditemukan, banyak yang disajikan tunas sel. Perawatan dimulai
dengan flukonazol 50 mg per hari, tapi empat hari setelah masuk kondisi umum pasien tidak membaik.
Budaya CSF menunjukkan pertumbuhan koloni putih lembut dan halus, dan dilaporkan sebagai C.
parapsilosis.
TUGAS:

Selesaikan kasus diatas sesuai acuan S O A P !

1. S: Muntah, demam tinggi, wajah palsi, leher kaku, plak keputihan di rongga mulut
2. O:
a. Hemoglobin dan trombosit tingkat normal.
b. Ada leukopenia dengan 2.930 sel/ml darah (rentang normal: 4000-10000), dengan
limfopenia parah dari 279 limfosit/ml darah (rentang normal: 800-4500).
c. There were 43% lymphocytes, 2% monocytes and 55% neutrophils per ml, and only
one red blood cell per ml was observed. The glucose concentration was 52 mg/dl
(lower than normal). Under microscopic examination using Gram staining, oval yeast
without capsules were found, many of which presented budding cells
3. A:
a) Pasien tsb. mengalami infeksi jamur jenis infeksi apa? Jelaskan alasan saudara!
C. parapsilosis, didasarkan pada hasil kultur yang telah dilakukan
b) Untuk mendukung jawaban pada pertanyaan a), pemeriksaan apa yang perlu dilakukan?
Dilakukan kultur
c) Mengapa pasien tsb. mengalami limphopenia? Jelaskan !
Mucocutaneous candidiasis occurs in 3 forms in persons with HIV infection: oropharyngeal,
esophageal, and vulvovaginal disease. Oropharyngeal candidiasis (OPC) was among the
initial manifestations of HIV-induced immunodeficiency to be recognized (1,2) and typically
affects the majority of persons with advanced untreated HIV infection. Presenting months or
years before more severe opportunistic illnesses, OPC may be a sentinel event indicating the
presence or progression of HIV disease.(3-5) Although usually not associated with severe
morbidity, OPC can be clinically significant. Severe OPC can interfere with the administration
of medications and adequate nutritional intake, and may spread to the esophagus.(6)
Esophageal candidiasis remains one of the most common opportunistic infections in
countries where combination antiretroviral therapy (ART) is a routine part of the standard of
care.(7) Vulvovaginal candidiasis is an important concern for women with HIV infection,
although the relationship of vulvovaginal candidiasis to HIV infection remains unclear.(8) In
resource-poor nations, mucocutaneous candidiasis is a formidable problem.(9,10) Despite
the frequency of mucosal disease, disseminated or invasive infections with Candida and
related yeasts are surprisingly uncommon
Over 90% of patients with AIDS will develop oropharyngeal candidiasis (OPC) at some time
during their illness. HIV Meruapakan kondisi imunodefiensi yang dapat mengakibatkan
limphopenia
d) Mengapa jamur bisa resisten terhadap obat antijamur? Jelaskan !
The mechanism of resistance to azoles is related to their mode of action (11,14). Azoles are
inhibitors of P450 cytochrome dependent on C14 demethylase, an important enzyme which
synthesizes the ergosterol of the fungal cell. Resistance of yeasts to these drugs may be due
 to alterations in the C14 demethylase or to a lower capacity of the azoles to bind to P450
cytochrome oxidase. Mekanisme resistensi termasuk mutasi titik dalam gen ERG11
menyebabkan penurunan afinitas obat target enzim dan up - regulasi gen yang mengkode
pompa penghabisan ( MDR dan CDR ). Perubahan gen pengkode target enzim dari antijamur,
azol terhadap jalur biosinesis ergosterol yaoitu ERG11, overekspresi gen pompa efluks
termasuk CDR1, CDR2, dan MDRI
4. p:
a. Bagaimana anda merencanakan manajemen terapi agar kondisi pasien tersebut membaik?
b. Bagaimana anda memberikan KIE kepada keluarga pasien ?
c. Apa rencana monitoring yang perlu dilakukan terkait terapi yang diberikan?
Candidiasis in immunosuppressed patients. The treatment of esophageal candidiasis has
not been studied so well as the treatment of OPC. Most experts recommend systemic
therapy because of the significant morbidity of esophageal candidiasis and the absence of
evidence supporting the use of topical therapy. Response rates to systemic therapies
generally are quite good. Fluconazole has proved to be more effective than ketoconazole in
one trial.(80) There have been no comparative studies of itraconazole in tablet or solution vs
fluconazole. Itraconazole solution probably is equivalent to fluconazole for treating
esophageal candidiasis.
As it is often not possible to correct the underlying predisposing conditions that would
prevent candidiasis in these patients, infections are usually more severe and generally do not
respond well to topical imidazole treatment. Oral Fluconazole [100-400 mg/day for 1-2
weeks] is currently the drug of choice for controlling oropharangeal candidiasis in AIDS
patients. However, indefinite maintenance treatment with Fluconazole [150-300 mg/week]
is required, and intermittent dosing depending on symptoms has now been advocated to
prevent the emergence of Fluconazole resistant strains of C. albicans.
Neutropenic patients with invasive candidiasis require high dose Amphotericin B treatment
[1.0 mg/kg/day] often given in combination with 5- Flucytosine [150 mg/kg/day]. With the
use of 5-Flucytosine blood levels should be monitored and antifungal susceptibility tests
performed. These patients present a major diagnostic problem for the clinician, primarily
due to the inadequacies of current diagnostic methods. Thus empiric treatment with
Amphotericin B is usually initiated in patients with persistent antibacterial resistant fever for
greater than 72-96 hours duration. High dose Fluconazole [400-800 mg/day] and Liposomal
Amphotericin B [3-5 mg/kg/day] have also been used with success, especially in cases of
hepatosplenic candidiasis. More recently, the combined use of Fluconazole with 5-
Flucytosine and Fluconazole with Amphotericin B have been used to treat some patients
with systemic candidiasis. In addition, haematopoietic growth factors such as G-CSF, GM-CSF
and M-CSF have been used to stimulate neutrophil and/or monocyte-macrophage
production in order to boost the host immune system.