8/20/2019 Infeksi Fungal - YLI
1/38
!"#$ &'
()*+,*+ &-./
8/20/2019 Infeksi Fungal - YLI
2/38
01,2#3*45#1
• Invasive fungal infections
– important causes of morbidity and mortality in
immunocompromised children
–
difficult to diagnose – outcome depends critically on the prompt
initiation of appropriate antifungal chemotherapy
and restoration of host defenses.
8/20/2019 Infeksi Fungal - YLI
3/38
!"#$$%&'#()* ), ,-*.% #$$)'%#/01 2%/3 3-4#* %*,0'()*
546')$0$7
8/20/2019 Infeksi Fungal - YLI
4/38
!-/#*0)-$ 8-90:&'%#" ;-*.#"
8/20/2019 Infeksi Fungal - YLI
5/38
86$/04%' ;-*.#" B 0%##"2"%"25& "))"7&C 81$1#%##"2"%"25&
4$16"3"5/&"&C $6 4; 61,62 ,;6 ?#37 *+*<
>1;1>4"39
–
O6M626 3>++68>1+6+63 @
8/20/2019 Infeksi Fungal - YLI
6/38
86$/04%' ;-*.#" 11A645#19
• :;6 76
8/20/2019 Infeksi Fungal - YLI
7/38
>01%#/:%' 9)9-"#()*$ #/ :%$? ,): %*@#$%@0
%*,0'()*$
Defined by specific predisposing defects in host defenses andseveral additional, non-immunological factors.
–
deficiencies in the number or function of phagocytic cells are associatedwith invasive infections by opportunistic fungi, such as Candida spp.,
Aspergillus spp., zygomyces spp. and a large variety of other, less frequently
encountered yeasts and molds.
–
deficiencies or imbalances of T lymphocyte function are linked tomucocutaneous candidiasis and invasive infections by Cryptococcusneoformans and the dimorphic moulds (Fig. 1).
– Non-immunological factors include the necessary exposure to theorganism, preexisting tissue damage, and, limited to Candida spp., the
presence of indwelling vascular catheters, colonization of mucousmembranes, the use of broad-spectrum antibiotics, parenteral nutrition,and complicated intra-abdominal surgery
8/20/2019 Infeksi Fungal - YLI
8/38
8/20/2019 Infeksi Fungal - YLI
9/38
>01%#/:%' 9)9-"#()*$ #/ :%$? ,): %*@#$%@0 %*,0'()*$
8/20/2019 Infeksi Fungal - YLI
10/38
A%$? ,#'/):$ ,): %*@#$%@0 !#*1%1# %*,0'()*
8/20/2019 Infeksi Fungal - YLI
11/38
A%$? ,#'/):$ ,): %*@#$%@0 B$90:.%"-$ %*,0'()*
• ;68)16+C 6>,;62 @2>8)1+688*1#+*@@26++>M6 ,;626+C
• >88*1#36N4>614>6+C +*4; 4 )2
8/20/2019 Infeksi Fungal - YLI
12/38
S>+$ A1MM6 (+@62)>"*+ >1A645#1
8/20/2019 Infeksi Fungal - YLI
13/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
• The neonate
– Candida spp. colonize the vaginal tract of approximately30% of pregnant women; very rarely, they can become thecause of chorioamnionitis and intrauterine infection.Candida rapidly colonizes the mucocutaneous surfaces]; in
healthy infants, this colonization may result in thrush anddiaper dermatitis].
– In hospitalized, ill neonates, however, Candida has evolvedas important cause of life-threatening invasive infections,particularly in very low birth weight infants.Candida spp.now account for 9–13% of all bloodstream isolates in
NICUs
8/20/2019 Infeksi Fungal - YLI
14/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Invasive candidiasis in preterm infants is most commonly
due to C. Albicans and C. parapsilosis [43, 47] and associated
with prior mucocutaneous colonization, vascular catheters,
the use of broad- spectrum antibiotics and corticosteroids,
and parenteral hyperalimentation. – Most neonates with systemic candidiasis are symptomatic
at the onset of their disease and present with signs and
symptoms that are virtually identical to those of non-fungal
etiological agents.
8/20/2019 Infeksi Fungal - YLI
15/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Malassezia spp. are lipophilic commensal yeasts that
colonize the human skin and may cause pityriasis.
•
may gain access to the bloodstream via percutaneous vascular
catheters to cause a potentially fatal systemic infection in
premature infants receiving parenteral nutritional lipidsupplements.
•
Similar to Candida, the most probable mode of acquisition is via the
hands of health care workers, but direct contamination through
contaminated intravenous (IV) solutions and catheters has also
been reported.
•
Special media containing olive oil are required for isolation
8/20/2019 Infeksi Fungal - YLI
16/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Infections by Aspergillus species and zygomyces
• very rare in the neonatal setting.
• they tend to have a predilection for the skin, and, in thecase of the zygomycetes, for the gastrointestinal tract,
resulting in necrotizing skin lesions and devastatingnecrotizing gastroenterocolitis, respectively.
• Potential sources of the organism are contaminatedwater, contaminated ventilation systems andcontaminated dressing materials or infusion boards
8/20/2019 Infeksi Fungal - YLI
17/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
• The infant –
Disseminated histoplasmosis is a classical example for the potentiallydismal course of a primary infection by an endemic fungus inapparently healthy infants that were exposed to the organisms.
• The disease is fatal if not detected and treated.
•
Its clinical manifestations include prolonged fevers, failure to thrive,hepatosplenomegaly, pancytopenia, and ultimately, DIC and multiorganfailure.
– Not much is known about blastomycosis and cocidioidomycosis in thisage group, but ultimately fatal cases have been reported
–
Conceptually, primary infection by endemic fungi during infancy isreminiscent of the infantile form of pulmonary pneumocystosis, which
is associated with young age, malnutrition, and endemic exposure.
8/20/2019 Infeksi Fungal - YLI
18/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Candida albicans is a ubiquitous agent of diaperdermatitis, which may be precipitated by moisture,occlusion, fecal contact and urinary pH.
• Its classical presentation is that of an erythema
bordered by a collarette of scale with satellite papulesand pustules.
• Concomitant dermatophytosis may occasionally bepresent.
• Treatment consists of the correction of physiological
factors and topical antifungal treatment
8/20/2019 Infeksi Fungal - YLI
19/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
• Children with congenital immunodeficiencies
– Inherited immunodeficiencies involving the number or function of Tlymphocytes predispose to mucocutaneous and, occasionally, invasivecandidiasis, and conceptually, to cryptococcosis and histoplasmosis
–
The role of Ig in host defenses against fungi is important against
cryptococcosis and possibly mucosal and invasive candidiasis. Childrenwith inherited deficits of B lymphocytes appear to be not at increasedrisk for fungal infection, unless there is a concomitant disorder of Tlymphocytes or phagocytosis.
• This includes individuals with the x-linked hyper-IgM syndrome, andpatients with the hyper-IgE syndrome, which is associated with chronic
mucocutaneous candidiasis, and possibly with cryptococcosis andaspergillosis.
8/20/2019 Infeksi Fungal - YLI
20/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
• Children with acquired immunodeficiencies
• Iatrogenic immunosuppression
– Treatment with glucocorticosteroids rapidly provides a
functional impairment of phagocytosis by mono- and PMNleukocytes. Such therapy is one of the most important
reasons for the increased susceptibility to invasive mycoses
of children with immunosuppressive therapy for
immunological disorders, solid organ transplantation, and
for graft-vs.-host disease (GVHD) following HSCT.
8/20/2019 Infeksi Fungal - YLI
21/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
• Cancer
– Prolonged, profound granulocytopenia is the single most
important risk factor for opportunistic fungal infections in
children and adolescents with cancer.
– Other well-known, but notable risk factors include
chemotherapy-induced mucositis, extended courses of
broad-spectrum antibiotics, the presence of indwelling
central venous lines, and, particularly in children with acute
leukemia, the therapeutic use of glucocorticosteroid.
8/20/2019 Infeksi Fungal - YLI
22/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Oropharyngeal candidiasis (OPC) may occur in up to 15%of children undergoing intensive chemotherapy or bonemarrow transplantation despite various forms of topical orsystemic antifungal prophylaxis.
– Esophageal candidiasis is also not uncommon, even in theabsence of conspicuous OPC, and Candida epiglottitis andlaryngeal candidiasis may emerge in neutropenic childrenas life- threatening causes of airway obstruction.
– Candida- and Aspergillus spp are the most common causesof invasive fungal infections in children with cancer
8/20/2019 Infeksi Fungal - YLI
23/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Invasive candidiasis in neutropenic children maypresent as catheter-associated candidemia, acutedisseminated candidiasis, and deep single organcandidiasis
•
Catheter-associated fungemia is most commonly causedby C. Albicans
• Acute disseminated candidiasis occurs typically ingranulocytopenic children and manifests with persistentfungemia, hemodynamic instability, multiple cutaneous
and visceral lesions and high mortality despite antifungaltherapy
8/20/2019 Infeksi Fungal - YLI
24/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Invasive aspergillosis has emerged as important cause formorbidity and mortality in children with hematologicalmalignancies or undergoing bone marrow transplantation
•
the lungs are the most frequently affected site, and disseminateddisease is found in approximately 30% of cases
•
primary cutaneous aspergillosis has been preferentially reported inassociation with lacerations by armboards, tape, and electrodes andat the insertion site of peripheral or central venous catheters
•
With combined surgical and medical therapy, primary cutaneousaspergillosis has a comparatively more favorable prognosis
8/20/2019 Infeksi Fungal - YLI
25/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Similar to histoplasmosis [121, 122], cryptococcal meningoencephalitisor pneumonitis are rare opportunistic infections in children withcancer
• HIV infection
–
mucosal as well as invasive fungal infections are major causes of
morbidity and mortality in advanced stages of the disease
– OPC is the most prevalent opportunistic infection in HIV-infectedchildren
–
Esophageal candidiasis in the era prior to HAART occurred
–
in approximately 10% of patients and was associated with recurrent
OPC, low CD4+ counts, and use of broad-spectrum antibiotics
8/20/2019 Infeksi Fungal - YLI
26/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– In the absence of significant immunological reconstitution,oropharyngeal and esophageal candidiasis have an exceedingly highpropensity to recur. The chronic use of fluconazole under thesecircumstances has been associated with the emergence of fluconazole-resistant Candida strains; it has been shown that such resistant strainscan be exchanged among HIVinfected family members.
–
HIV-related impairment of phagocytosis by mono- andpolymorphonuclear leukocytes [145, 146] makes a major contributionto the increased susceptibility of patients with advanced HIV infectionto invasive aspergillosis
8/20/2019 Infeksi Fungal - YLI
27/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
– Compared to adults, HIV-infected children have lower rates ofcryptococcal infections, and, with the exception of disseminatedpenicilliosis, data on histoplasmosis and other endemic mycoses arevery limited
• Children with severe acute illnesses
–
Invasive procedures, indwelling vascular and urinary catheters, use ofbroad-spectrum antibiotics and corticosteroids, mechanical ventilationand parenteral feeding as well as length of stay and severity of theunderlying condition, all contribute to a heightened risk of deeplyinvasive Candida infections in critically ill patients requiring intensivecare
8/20/2019 Infeksi Fungal - YLI
28/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
• Children with chronic pulmonary diseases
– Mycoses may occur in children and adolescents with
chronic sinopulmonary infection and lung destruction, as it
may be associated with congenital B cell defects, the hyper-
IgE syndrome, and, most commonly, cystic fibrosis.
– Non-invasive fungal diseases associated with the
colonization of the respiratory tract by Aspergillus spp. and
other moulds such as allergic bronchopulmonary
aspergillosis and aspergilloma formation clearly
predominate in this setting.
8/20/2019 Infeksi Fungal - YLI
29/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
8/20/2019 Infeksi Fungal - YLI
30/38
C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"
%*,0'()*$ %* 901%#/:%' 9#(0*/$
8/20/2019 Infeksi Fungal - YLI
31/38
A0'0*/ #1@#*'0$ %* 0#:"6 1%#.*)$%$ #*1
9:0049(@0 /30:#96
• Early diagnosis and rapid initiation of effective
antifungal chemotherapy is paramount to the
successful management of invasive mycoses
–
Improved blood culture detection technique – HRCT
– MRI
– nucleic acid amplification based systems
8/20/2019 Infeksi Fungal - YLI
32/38
>01%#/:%' 93#:4#')").6 ), 0$/#D"%$301
#*(,-*.#" #.0*/$
• Amphotericin B deoxycholate
– Primarily acts by binding to ergosterol in the fungal cell
membrane, leading to pore formation and ultimately, cell
death
–
Possesses a broad spectrum of antifungal activity thatincludes most fungi pathogenic in humans. However, some
of the emerging pathogens such as A. terreus, Tr. beigelii ,
Scedosporium prolificans and certain Fusarium spp. may be
microbiologically and clinically resistant
8/20/2019 Infeksi Fungal - YLI
33/38
8/20/2019 Infeksi Fungal - YLI
34/38
8/20/2019 Infeksi Fungal - YLI
35/38
8/20/2019 Infeksi Fungal - YLI
36/38
8/20/2019 Infeksi Fungal - YLI
37/38
8/20/2019 Infeksi Fungal - YLI
38/38
Top Related