2Candida sp.albicannon-albican: C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. parapsilosis
3Candida infection LOCAL MUCOUS MEMBRANE INFECTIONS INVASIVE FOCAL INFECTIONSCANDIDEMIA AND DISSEMINATED CANDIDIASIS
4Candida sp.Normal flora in the gastrointestinal and genitourinary tracts of humans.
5Candida infectionImmune response is an important determinant of the type of infection.Benign infections: local overgrowth on mucous membranesMore extensive persistent mucous membrane infections: deficiencies in cell-mediated immunity.Invasive focal infections: after hematogenous spread or when anatomic abnormalities or devices
7Oropharyngeal 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
9Oropharyngeal 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
10Esophagitis AIDS-defining illness Clinical: odynophagia or pain on swallowingDx: endoscopyConfirmatory biopsy shows the presence of yeasts and pseudohyphae invading mucosal cells, and culture reveals Candida.
11Esophagitis Rx: Fluconazole 200 mg once daily then 100 mg for 14 d Amphotericin B mkd iv for 14 d
12VulvovaginitisRisk: associated with increased estrogen levels, antibiotics, corticosteroids, diabetes mellitus, HIV infection, intrauterine devices, and diaphragm useSymptoms: 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
13Vulvovaginitis Dx: Wet mount or KOH preparation of vaginal secretions Rx:clotrimazole 100 mg vg suppo. for 7 dfluconazole 150 mg oralsingle dose
14Chronic mucocutaneous candidiasis A rare syndromeOnset in childhoodSome have autosomal recessive polyglandular autoimmune syndrome type I, referred to as the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndromemanifested by chronic mucocutaneous candidiasis and endocrine disorders, such as hypoparathyroidism, adrenal insufficiency, and primary hypogonadism
15Chronic 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
16RISK FACTORS FOR INVASIVE INFECTION immunosuppressed patientsHematologic malignanciesRecipients of solid organ or hematopoietic stem cell transplantsThose given chemotherapeutic agents for a variety of different diseasesintensive care patientsTrauma and Burn patients,Neonatal unitsCentral venous cathetersTotal parenteral nutritionBroad-spectrum antibioticsHigh APACHE II scoresRenal failure requiring hemodialysisAbdominal surgical proceduresGastrointestinal tract perforations and anastomotic leaks
17INVASIVE FOCAL INFECTIONS Urinary tract infectionEndophthalmitisOsteoarticular infectionsMeningitisEndocarditisHepatosplenic or chronic disseminated candidiasisPeritonitis and intraabdominal infectionsPneumoniaMediastinitisPericarditis
18Urinary tract infection BLADDER INFECTION AND COLONIZATIONKIDNEY INFECTION
19BLADDER 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.
20BLADDER 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.
21BLADDER INFECTION AND COLONIZATION Recommendations: IDSAAsymptomatic 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 withintravenous amphotericin B mg/kg per day for 1-7 days
22KIDNEY INFECTION Most commonly occurs in patients with disseminated Acute infectionBilateral, consisting of multiple microabscesses in the cortex and medullaChronic infectionInvolve 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
23KIDNEY INFECTION Rx: Amphotericin B (0.5 to 1.0 mg/kg/day) Fluconazole (400 mg/day adjusted for renal function).At least 2 weeksremoval and replacement of all intravenous catheters
24EndocarditisRisk: prosthetic heart valves, IVDU, indwelling central venous catheters and prolonged fungemia.Dx: Duke criteriaRx: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
25CANDIDEMIA AND DISSEMINATED CANDIDIASIS Candidiemia: presence of Candida sp. in the bloodDisseminated candidiasis: several viscera are infected
26PATHOGENESISthree major routes by which Candida gain access to the bloodstream:Through the gastrointestinal tract mucosal barrierVia an intravascular catheterFrom a localized focus of infection, such as pyelonephritis
27CLINICAL MANIFESTATIONS Vary from minimal fever to a full-blown sepsis syndromeClinical 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
28CLINICAL 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.
30CLINICAL MANIFESTATIONS Eye lesions:Exogenous: following trauma or surgery on the eyeEndogenous: 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
32CLINICAL MANIFESTATIONS Muscle abcesssoreness in a discrete muscle group.warm and swollen
33DIAGNOSIS 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 symptomsCulture and stain of biopsy material
34Treatment CATHETER REMOVAL ANTIFUNGAL AGENTS Polyenes: Amphotericin B Azoles: Fluconazole, Itraconazole and Voriconazole.Echinocandins:Caspofungin
35DRUG 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 Bsusceptible to voriconazoleincreased doses of amphotericin B
36DRUG RESISTANCEC. 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 vitrousing high doses of fluconazole, amphotericin B
37DRUG RESISTANCE C. parapsilosis ; very susceptible to most antifungal agents;caspofungin minimal inhibitory concentrations are higher than for other Candida species
38DRUG RESISTANCE C. lusitaniae often resistant to amphotericin therapy; usually susceptible to azoles and echinocandins
39Treatment Fluconazole 400 mg or 800 mg of daily Amphotericin B 0.7 mg/kg per dayCaspofungin is 50 mg/day after a loading dose of 70 mgVoriconazole 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 BDuration of therapy for candidemia :A minimum of two weeks of therapy after blood cultures become negative