infeksi fungal - yli

8/20/2019 Infeksi Fungal - YLI

1/38

!"#$ &'

()*+,*+ &-./


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.


3/38

!"#$$%&'#()* ), ,-*.% #$$)'%#/01 2%/3 3-4#* %*,0'()*

546')$0$7


4/38

!-/#*0)-$ 8-90:&'%#" ;-*.#"


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 @


6/38

86$/04%' ;-*.#" 11A645#19

• :;6 76


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


8/38


9/38

>01%#/:%' 9)9-"#()*$ #/ :%$? ,): %*@#$%@0 %*,0'()*$


10/38

A%$? ,#'/):$ ,): %*@#$%@0 !#*1%1# %*,0'()*


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


12/38

S>+$ A1MM6 (+@62)>"*+ >1A645#1


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


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.


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


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


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.


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


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.


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.


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.


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


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


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


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


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


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


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.


29/38

C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"

%*,0'()*$ %* 901%#/:%' 9#(0*/$


30/38

C9%104%)").6 #*1 9:0$0*/#()* ), %*@#$%@0 ,-*.#"

%*,0'()*$ %* 901%#/:%' 9#(0*/$


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


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


33/38


34/38


35/38


36/38


37/38


38/38

infeksi fungal - yli

Documents