1. Candidiasis
C. Charunee
9/4/50

2. Candida sp.
albican
non-albican: C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. parapsilosis

3. Candida infection LOCAL MUCOUS MEMBRANE INFECTIONS
INVASIVE FOCAL INFECTIONS
CANDIDEMIA AND DISSEMINATED CANDIDIASIS

4. Candida sp.
Normal flora in the gastrointestinal and genitourinary tracts of humans.

5. 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

6. LOCAL MUCOUS MEMBRANE INFECTIONS
Oropharyngeal candidiasis
Esophagitis
Vulvovaginitis
Chronic mucocutaneous candidiasis

7. 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

8. Oropharyngeal candidiasis
Signs:

9. 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

10. 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.

11. Esophagitis Rx: Fluconazole 200 mg once daily then 100 mg for 14 d
Amphotericin B mkd iv for 14 d

12. 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

13. 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

14. Chronic mucocutaneous candidiasis
A rare syndrome
Onset in childhood
Some have autosomal recessive polyglandular autoimmune syndrome type I, referred to as the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome
manifested by chronic mucocutaneous candidiasis and endocrine disorders, such as hypoparathyroidism, adrenal insufficiency, and primary hypogonadism

15. 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

16. 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
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

17. INVASIVE FOCAL INFECTIONS
Urinary tract infection
Endophthalmitis
Osteoarticular infections
Meningitis
Endocarditis
Hepatosplenic or chronic disseminated candidiasis
Peritonitis and intraabdominal infections
Pneumonia
Mediastinitis
Pericarditis

18. Urinary tract infection
BLADDER INFECTION AND COLONIZATION
KIDNEY INFECTION

19. 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.

20. 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.

21. 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 days,
Azole-resistant yeast can be treated with
intravenous amphotericin B mg/kg per day for 1-7 days

22. 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

23. 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

24. Endocarditis
Risk: prosthetic heart valves, IVDU, indwelling central venous catheters and prolonged fungemia.
Dx: Duke criteria
Rx:
Amphotericin B MKD at least 6 weeks. with fluconazole being substituted for amphotericin B as follow-up therapy.
Resection of the valve and any associated abscesses

25. CANDIDEMIA AND DISSEMINATED CANDIDIASIS
Candidiemia: presence of Candida sp. in the blood
Disseminated candidiasis: several viscera are infected

26. 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

27. 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

28. 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.

29. CLINICAL MANIFESTATIONS
Skin lesions

30. 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

31. CLINICAL MANIFESTATIONS
Eye lesions

32. CLINICAL MANIFESTATIONS
Muscle abcess
soreness in a discrete muscle group.
warm and swollen

33. 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

34. Treatment CATHETER REMOVAL ANTIFUNGAL AGENTS Polyenes: Amphotericin B
Azoles: Fluconazole, Itraconazole and Voriconazole.
Echinocandins:Caspofungin

35. 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

36. 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

37. DRUG RESISTANCE C. parapsilosis ;
very susceptible to most antifungal agents;
caspofungin minimal inhibitory concentrations are higher than for other Candida species

38. DRUG RESISTANCE C. lusitaniae often resistant to amphotericin therapy;
usually susceptible to azoles and echinocandins

39. 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