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CANDIDIASIS
Etiologic agents: Candida albicans, new species: C. dubliniensis, C. tropicalis, C. parapsilosis, C. guilliermondii, C. glabrata (formerly Torulopsis glabrata), C. krusei - 4th or 5th most common cause of nosocomial bloodstream infections(through intravascular catheters) in the US. - causes lethal septic shock - are commensals of humans (mouth, stool and vagina) - grow rapidly at 25-37 C on simple media as oval, budding cells - in tissue, both yeasts and pseudohyphae are present Pseudohyphae elongated branching structures with constrictions at the septae. Budding yeasts separate structures or as projections from pseudohyphae. Species: 1. C. glabrata no true hyphae or pseudohyphae in vitro or in infected tissue. 2. C. albicans and C. dubliniensis can form germ tubes in serum, can form chlamydospores (thick walled large spores) in special culture medium. PATHOGENESIS: 1. Deeply invasive candidiasis is often preceded by increased colonization of the mouth,vagina,stool with Candida due to broad-spectrum antibiotic therapy. Local and systemic factors favors infection. Oropahryngeal thrush- occur in neonates and in patients with DM, HIV or dentures. Vulvovalginal candidiasis- 3rd trimester of pregnancy candida from the perineum can enter the urinary tract via an indwelling bladder catheter. Cutaneous candidiasis often involves macerated skin: diapered area of infants, under pendulous breasts, hands constantly in water or covered by occlusive gloves. Deep tissue candidiasis eg. Perforation of the GIT through trauma, surgery or peptic ulceration or by mucosal damage due to cytotoxic agents (cancer chemotherapy) Secretions from the mouth, rectum or vagina; drainage from surgical wounds

or tracheostomy sites contaminate the hub or skin site of a catheter in an umbilical or central vein. 8. IV drug abuse or 3rd degree burns 9. compromised host defense in very low birthweight neonates, neutorpenia or glucocorticoid therapy once candida passed the integumentary barrier. 10. hematogenous seeding in the retina, kidney spleen and liver. CLINICAL MANIFESTATIONS: A. MUCOCUTANEOUS CANDIDIASIS

1. Oral thrush - discrete and confluent adherent white plaques on the oral and pharyngeal mucosa, (mouth and tongue) - painless lesions, but with painful fissuring at the corners of the mouth. - raises possibility of acute HIV infection especially when CD4+ cell count falls, esophageal thrush (CD4+ counts <50/uL) - independent risk factor for vulvovaginal thrush. 2. Cutaneous candidiasis - red macerated intertriginous areas, paronychia, balanitis, or pruritus ani. - candidiasis of the perineal and scrotal skin (discrete pustular lesions on inner aspects of the thighs.) 3. Chronic Mucocutaneous Candidiasis (CMC) or Candidal granuloma - circumscribed hyperkeratotic skin lesions, crumbling dystrophic nails, partial alopecia in areas of scalp lesions, and both oral and vaginal thrush - chronic ringworm, dental dysplasia, and hypofunction of the parathyroid, adrenal and thyroid gland. - with permanent alopecia, severe disfigurement of face and hands - major component of the immune polyendocinopathy syndrome (mutation in the autoimmune regulator gene {AIRE} on chrom 21q22.3 - childhood : autosomal dominant or recessive d/o, or assoc with JOBs Syndrome - adult: assoc with thymoma 4.Vulvovaginal thrush -causes pruritus, discharge and pain on intercourse or urination - speculum exam: inflamed mucosa, thin exudate, often with white curds 5. Esophageal Candidiasis - often asymptomatic

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- can cause substernal pain or a sense of obstruction on swallowing. (mistaken for pain of cardiac origin) - lesions: distal 3rd of esophagus - endoscopy : areas of redness and edema, focal white patches or ulcers -biopsy and brushing required for dx and detection of concomitant infxns (HSV with hema malignancies and CMV infxn in AIDS px) - hema dissemination : neutropenic px B. DEEPLY INVASIVE CANDIDIASIS

6. Candida endophthalmitis and purulent folliculitis , with vertebral osteomyelitis - caused by IV injection of impure brown heroin 7. Indolent Arthritis knee in px who have received Glucocorticoid injections into the joint of immunocompromised px, Low BW neonates.; also from infected prosthetic joints 8. Subacute peritonitis from a perforated viscus or from a peritoneal dialysis catheter. 9. Brain abcess or chronic meningitis hematogenous dissemination. DIAGNOSIS 1. Procedure of choice: demonstration of pseudohyphae on wet smear with confirmation by culture. Scrapings for the smear : from skin, nails and oral or vaginal mucosa. Culture of urine, sputum, existing abd. Drains, endotracheal aspirates or the vagina NOT DIAGNOSTIC Recovery of Candida species from multiple superficial sites RISK FACTOR FOR DEEPLY INVASIVE CANDIDIASIS (px with prolonged neutropenia or complicated abd surgery.) 2.Histologic section of biopsies or culture of CSF, blood or joint fluid, CT guided aspirates or surgical specimens dx of deeper lesions 3. Blood cultures dx of Candida endocarditis and IV catheter-induced sepsis serologic tests for antibody or antigen NOT USEFUL PROPHYLAXIS 1. Fluconazole 400 mg daily preventing deeply invasive candidiasis in some high risk post-op px. 2. Fluconazole 3-6mg/kg or Itraconazole solution 5mg/kg recommended daily oral dose
Definition of groups at sufficient risk to benefit from fluconazole depends on the ICU but likely includes px undergoing repeat, complicated abdominal surgery and patients who are both heavily colonized with Candida and immunosuppressed at the time of complicated surgery. The presence of IV Catheters, prolonged stays in the ICU and renal failure increase the risk of candidemia.

1.Obstructed Urinary tract cystitis, pyelitis, or renal papillary necrosis. 2.Candidemia when a colonized Urinary tract is operated or instrumented - may clear when the catheter is removed - focal seeding of the retina can take place even if candidemia clears and the px becomes afebrile - unilateral or bilateral small white retinal exudates (w/in 2 weeks of the onset of candidemia) vitreous humor becomes cloudy, and the px notices blurring, ocular pain, or scotoma retinal detachment, vitreous abcess and extension to the anterior chamber retinal lesions (in 10% of neutropenic px) given systemic antifungal tx 3. Hepatosplenic Candidiasis or Chronic Disseminated Candidiasis - px with acute leukemia who are recovering from profound neutropenia. - originates from intestinal seeding of the portal or venous circulation . - fever, elev. Alkaline phosphatase, multiple small abcesses on US, MRI and CT of the liver, spleen, or kidney. Acute Candidemia in neutropenic px : small erythematous papules may appear in the skin, (figure 187-1 page 1186 in Harrisons), this can develop necrotic center. Punch biopsy to distinguish it from Malassezia folliculitis (similar- appearing but benign condition, involves the cape area of the chest or the extremities of a sweaty febrile px) 4.Candida pneumonia tiny pulmonary nodules 5. Candida endocardidis previously damaged or prosthetic heart valves. Emboli to large arteries, such as iliac or femoral artery .

TREATMENT Table 187-1 page 1187 Type of disease Preferred tx MUCOCUTA-NEOUS Cutaneous Topical Azole Vulvovaginal Azole cream or suppository or oral fluconazole (150 mg) Oropharyn-geal Clotrimazole troche or fluconazole tablet (100mg/d ) or Itraconazole (200 mg/d) Esophageal Fluconazole tablet (100-200 mg/d) or Itraconazole solution (200 mg/d) DEEPLY INVASIVE Nonneutropenic Fluconazole (400 mg/d) or Anphotericin Bb or Caspofungin (70mg once,then 50 mg/d) Neutropenic Anphotericin Bb

Alternatives Topical Nystatin Nystatin suppository Nystatin susp; for azole unresponsive disease: Caspofungin (50mg/d) or amphotericin B (0.3-0.5 mg/kg/d) For azole unresponsive disease: Caspofungin (70mg once,then 50 mg/d) or amphotericin B (0.3-0.5 mg/kg/d)

a Removal of foreign bodies is critical, including plastic catheters for IV fluids, peritoneal dialysis or CSF shunts, prosthetic cardiac valves , and prosthetic joints Bb The dosage of Amphotericin B for eeply invasive candidiasis is 0.5mg/kg daily, although initial doses of 0.7 1.0 mg/kg daily may be appropriate for severely immunocompromised patients. Amphotericin B lipid complex and liposomal amphotericin B are given as 5 mg/kg daily. __________________________________________________________________________________________________

Other tx: 1. Bladder thrush bladder irrigations with Amphotericin B (50 ug/ml for 5 days). If no baldder catheter is in place, Oral Fluconazole can be used to control Candiduria. ( most px w/ candiduria do not have unrelieved uri. Tract obstruction and do not benefit from therapy.) Candida endocarditis on prosthetic or native valves usually relapses unless the valve is replaced. Long term fluconazole- prevent recurrences after valve replacement. Candidemia from suppurative phlebitis of a peripheral vein may not respond until the infected portion of the vein is excised. Therapy for candidemia is continued for 2 weeks after the px becomes afebrile. C. krusei and C. inconspicua resistant to Fluconazole in vitro C. glabrata exhibits intermediate susceptibility to Fluconazole (increase dose to 800 mg), use Amphotericin B or Caspofungin

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Candida endophthalmitis IV Amphotericin B with or w/o Flucytosine Candida vitreous abcess pars plana vitrectomy, injection of amphotericin B into vitreous humor Candida osteolmyelitis debridement, fungal therapy

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