Transcript Candidiasis - ::: อายุรศาสตร์

Candidiasis
C. Charunee
9/4/50
Candida sp.
• albican
• non-albican: C. glabrata, C. krusei, C.
parapsilosis, C. tropicalis, C.
parapsilosis
Candida infection
• LOCAL MUCOUS MEMBRANE INFECTIONS
• INVASIVE FOCAL INFECTIONS
• CANDIDEMIA AND DISSEMINATED
CANDIDIASIS
Candida sp.
• Normal flora in the gastrointestinal
and genitourinary tracts of humans.
Candida infection
• Immune response is an important
determinant of the type of infection.
– Benign infections: local overgrowth on
mucous membranes
– More extensive persistent mucous membrane
infections: deficiencies in cell-mediated
immunity.
– Invasive focal infections: after hematogenous
spread or when anatomic abnormalities or
devices
LOCAL MUCOUS MEMBRANE
INFECTIONS
• Oropharyngeal candidiasis
• Esophagitis
• Vulvovaginitis
• Chronic mucocutaneous candidiasis
Oropharyngeal candidiasis
• A common local infection.
• Host: infants, older adults who wear
dentures, patients treated with antibiotics,
chemotherapy, or radiation therapy to the
head and neck, and cellular immune
deficiency states.
• Symptoms: cottony feeling, loss of taste,
pain on eating and swallowing,
asymptomatic
Oropharyngeal candidiasis
• Signs:
Oropharyngeal candidiasis
• Diagnosis: Gram stain or KOH preparation
on the scrapings. Budding yeasts with or
without pseudohyphae.
• Rx:
– Clotrimazole troche
(10 mg troche dissolved five times per day)
– Nystatin suspension
(400,000 to 600,000 units four times per day)
- Nystatin troche (200,000 to 400,000 units four
to five times per day),
- For 7 to 14 days
Esophagitis
• AIDS-defining illness
• Clinical: odynophagia or
pain on swallowing
• Dx: endoscopy
– Confirmatory biopsy
shows the presence of
yeasts and pseudohyphae
invading mucosal cells,
and culture reveals
Candida.
Esophagitis
• Rx:
– Fluconazole 200 mg once daily then
100 mg for 14 d
– Amphotericin B 0.3-0.7 mkd iv for 14 d
Vulvovaginitis
• Risk: associated with increased estrogen
levels, antibiotics, corticosteroids, diabetes
mellitus, HIV infection, intrauterine
devices, and diaphragm use
• Symptoms: itching and discharge.
Dyspareunia, dysuria, and vaginal
irritation.
• Signs: vulvar erythema and swelling and
vaginal erythema and discharge, which is
classically white and curd-like but may be
watery
Vulvovaginitis
• Dx: Wet mount or KOH
preparation of vaginal
secretions
• Rx:
– clotrimazole 100 mg vg suppo.
for 7 d
– fluconazole 150 mg oral
single dose
Chronic mucocutaneous
candidiasis
• A rare syndrome
• Onset in childhood
• Some have autosomal recessive polyglandular
autoimmune syndrome type I, referred to as the
autoimmune polyendocrinopathy-candidiasisectodermal dystrophy (APECED) syndrome
• manifested by chronic mucocutaneous candidiasis
and endocrine disorders, such as
hypoparathyroidism, adrenal insufficiency, and
primary hypogonadism
Chronic mucocutaneous
candidiasis
• Clinical: severe, recurrent
thrush, onychomycosis,
vaginitis, and chronic skin
lesions (hyperkeratotic,
crusted appearance on the
face, scalp, and hands)
• Rx:
oral fluconazole,itraconazole
RISK FACTORS FOR
INVASIVE INFECTION
• immunosuppressed patients
– Hematologic malignancies
– Recipients of solid organ or hematopoietic stem cell
transplants
– Those given chemotherapeutic agents for a variety of
different diseases
• intensive care patients
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Trauma and Burn patients,
Neonatal units
Central venous catheters
Total parenteral nutrition
Broad-spectrum antibiotics
High APACHE II scores
Renal failure requiring hemodialysis
Abdominal surgical procedures
Gastrointestinal tract perforations and anastomotic leaks
INVASIVE FOCAL INFECTIONS
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Urinary tract infection
Endophthalmitis
Osteoarticular infections
Meningitis
Endocarditis
Hepatosplenic or chronic disseminated candidiasis
Peritonitis and intraabdominal infections
Pneumonia
Mediastinitis
Pericarditis
Urinary tract infection
• BLADDER INFECTION AND COLONIZATION
• KIDNEY INFECTION
BLADDER INFECTION AND
COLONIZATION
• Risk factors: urinary tract drainage devices; prior
antibiotic therapy; diabetes; urinary tract
pathology and malignancy.
• Most patients with candiduria are asymptomatic.
• It is difficult to differentiate between colonization
and bladder infection.
• Infected patients may have dysuria, frequency,
and suprapubic discomfort, no symptoms.
• Pyuria with a chronic indwelling bladder catheter
that it cannot be used to indicate infection.
BLADDER INFECTION AND
COLONIZATION
• Ascending involvement of the
kidneys is uncommon but can occur
in urinary tract obstruction or renal
transplantation.
• Candiuria can be seen in systemic
infection, it is accompanied by many
other signs and symptoms of
disseminated infection.
BLADDER INFECTION AND
COLONIZATION
Recommendations: IDSA
• Asymptomatic candiduria rarely requires antifungal therapy,
if kidney transplantation, neutropenia, low birth-weight
neonates, or urinary tract manipulation.
• Asymptomatic candiduria may respond to risk factor
reduction by removal of bladder catheters or urologic
stents, and discontinuation of antibiotics ]. If it is not
possible, placement of new devices or intermittent bladder
catheterization may be beneficial.
• Symptomatic candiduria should always be treated.
• Rx:
– Fluconazole 200 mg/day 7- 14 days,
– Azole-resistant yeast can be treated with
intravenous amphotericin B 0.3-0.7 mg/kg per day for 1-7 days
KIDNEY INFECTION
• Most commonly occurs in patients with
disseminated
• Acute infection
– Bilateral, consisting of multiple microabscesses
in the cortex and medulla
• Chronic infection
– Involve the renal pelvis and medulla with
sparing of the cortex, which reflects ascending
infection.
– The kidney is usually the only organ involved
and the infection tends to be unilateral
KIDNEY INFECTION
• Rx:
– Amphotericin B (0.5 to 1.0 mg/kg/day)
– Fluconazole (400 mg/day adjusted for
renal function).
– At least 2 weeks
– removal and replacement of all
intravenous catheters
Endocarditis
• Risk: prosthetic heart valves, IVDU,
indwelling central venous catheters and
prolonged fungemia.
• Dx: Duke criteria
• Rx:
– Amphotericin B 0.7-1 MKD at least 6 weeks.
with fluconazole being substituted for
amphotericin B as follow-up therapy.
– Resection of the valve and any associated
abscesses
CANDIDEMIA AND
DISSEMINATED CANDIDIASIS
• Candidiemia: presence of Candida
sp. in the blood
• Disseminated candidiasis: several
viscera are infected
PATHOGENESIS
• three major routes by which Candida
gain access to the bloodstream:
– Through the gastrointestinal tract
mucosal barrier
– Via an intravascular catheter
– From a localized focus of infection,
such as pyelonephritis
CLINICAL MANIFESTATIONS
• Vary from minimal fever to a full-blown
sepsis syndrome
• Clinical clues:
– characteristic eye lesions (chorioretinitis,
endophthalmitis),
– skin lesions,
– much less commonly, muscle abscesses.
– signs of multiorgan system failure may present:
kidneys, heart, liver, spleen, lungs, eyes, and
brain
CLINICAL MANIFESTATIONS
• Skin lesions:
– Suddenly as clusters of painless pustules on an
erythematous base; occur on any area of the
body.
– The lesions vary from tiny pustules or nodular;
several centimeters in diameter; and appear
necrotic in the center.
– In severely neutropenic patients, the lesions
may be macular rather than pustular.
– Dx: by a punch biopsy.
CLINICAL MANIFESTATIONS
• Skin lesions
CLINICAL MANIFESTATIONS
• Eye lesions:
– Exogenous: following trauma or surgery on the
eye
– Endogenous: through hematogenous seeding of
the retina and choroid as a complication of
candidemia.
– Primary presenting symptoms: pain and gradual
decrease in visual acuity.
– The classic findings of chorioretinal involvement:
focal, glistening, white, infiltrative, often
mound-like lesions on the retina, a vitreal haze
is present; sometimes fluffy white balls or
"snowballs" in the vitreous
CLINICAL MANIFESTATIONS
• Eye lesions
CLINICAL MANIFESTATIONS
• Muscle abcess
– soreness in a discrete muscle group.
– warm and swollen
DIAGNOSIS
• Gold standard: candidemia is a
positive blood culture
• Blood cultures: H/C +ve 50 % of
patients who were found to have
disseminated candidiasis at autopsy.
• Ophthalmologic evaluation: Once
H/C+ve, whether or not they have
ocular symptoms
• Culture and stain of biopsy material
Treatment
• CATHETER REMOVAL
• ANTIFUNGAL AGENTS
– Polyenes: Amphotericin B
– Azoles: Fluconazole, Itraconazole and
Voriconazole.
– Echinocandins:Caspofungin
DRUG RESISTANCE
• C. albicans; resistance is extremely
low
• C. krusei; intrinsically resistant to
fluconazole due to an altered
cytochrome P-450 isoenzyme,
sometimes demonstrates decreased
susceptibility to amphotericin B
– susceptible to voriconazole
– increased doses of amphotericin B
DRUG RESISTANCE
• C. glabrata; many are also resistant
to the azoles due to changes in drug
efflux, Amphotericin B also has
delayed killing kinetics against C.
glabrata in vitro
– using high doses of fluconazole,
amphotericin B
DRUG RESISTANCE
• C. parapsilosis ;
– very susceptible to most antifungal
agents;
– caspofungin minimal inhibitory
concentrations are higher than for other
Candida species
DRUG RESISTANCE
• C. lusitaniae
– often resistant to amphotericin therapy;
– usually susceptible to azoles and
echinocandins
Treatment
• Fluconazole 400 mg or 800 mg of daily
• Amphotericin B 0.7 mg/kg per day
• Caspofungin is 50 mg/day after a loading dose of
70 mg
• Voriconazole is 3 mg/kg twice daily after a
loading dose of 6 mg/kg twice daily for one day.
• C. glabrata and C. krusei, higher doses of
amphotericin B (1 mg/kg daily of standard
amphotericin B
• Duration of therapy for candidemia :
– A minimum of two weeks of therapy after blood cultures
become negative