1. Candidiasis Downloded from www.pharmacy123.blogfa.com

2. Candida sp. albican non-albican: C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. parapsilosis Downloded from www.pharmacy123.blogfa.com

3. Candida infection LOCAL MUCOUS MEMBRANE INFECTIONS INVASIVE FOCAL INFECTIONS CANDIDEMIA AND DISSEMINATED CANDIDIASIS Downloded from www.pharmacy123.blogfa.com

4. Candida sp. Normal flora in the gastrointestinal and genitourinary tracts of humans. Downloded from www.pharmacy123.blogfa.com

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 Downloded from www.pharmacy123.blogfa.co m

6. LOCAL MUCOUS MEMBRANE INFECTIONS Oropharyngeal candidiasis Esophagitis Vulvovaginitis Chronic mucocutaneous candidiasis Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

8. Oropharyngeal candidiasis Signs: Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

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. Downloded from www.pharmacy123.blogfa.co m

11. Esophagitis Rx: – Fluconazole 200 mg once daily then 100 mg for 14 d – Amphotericin B 0.3-0.7 mkd iv for 14 d Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

15. Clinical: severe, recurrent thrush, onychomycosis, vaginitis, and chronic skin lesions (hyperkeratotic, crusted appearance on the face, scalp, and hands) Rx: oral fluconazole,itraconazole Chronic mucocutaneous candidiasis Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

17. INVASIVE FOCAL INFECTIONS Urinary tract infection Endophthalmitis Osteoarticular infections Meningitis Endocarditis Hepatosplenic or chronic disseminated candidiasis Peritonitis and intraabdominal infections Pneumonia Mediastinitis Pericarditis Downloded from www.pharmacy123.blogfa.co m

18. Urinary tract infection BLADDER INFECTION AND COLONIZATION KIDNEY INFECTION Downloded from www.pharmacy123.blogfa.co m

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. Downloded from www.pharmacy123.blogfa.co m

20. 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 Downloded from www.pharmacy123.blogfa.co m

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 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 Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

24. 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 Downloded from www.pharmacy123.blogfa.co m

25. CANDIDEMIA AND DISSEMINATED CANDIDIASIS Candidiemia: presence of Candida sp. in the blood Disseminated candidiasis: several viscera are infected Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

28. 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 Downloded from www.pharmacy123.blogfa.co m

29. Skin lesions CLINICAL MANIFESTATIONS Downloded from www.pharmacy123.blogfa.co m

30. 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 Downloded from www.pharmacy123.blogfa.co m

31. Eye lesions CLINICAL MANIFESTATIONS Downloded from www.pharmacy123.blogfa.co m

32. Muscle abcess –soreness in a discrete muscle group. –warm and swollen CLINICAL MANIFESTATIONS Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

34. Treatment CATHETER REMOVAL ANTIFUNGAL AGENTS –Polyenes: Amphotericin B –Azoles: Fluconazole, Itraconazole and Voriconazole. –Echinocandins:Caspofungin Downloded from www.pharmacy123.blogfa.co m

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 Downloded from www.pharmacy123.blogfa.co m

36. 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 Downloded from www.pharmacy123.blogfa.co m

37. C. parapsilosis ; –very susceptible to most antifungal agents; –caspofungin minimal inhibitory concentrations are higher than for other Candida species DRUG RESISTANCE Downloded from www.pharmacy123.blogfa.co m

38. C. lusitaniae –often resistant to amphotericin therapy; –usually susceptible to azoles and echinocandins DRUG RESISTANCE Downloded from www.pharmacy123.blogfa.co m

39. 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 Treatment Downloded from www.pharmacy123.blogfa.co m