Candidiasis

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Candidiasis

• C. Charunee
• 9/4/50

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Candida sp.

• albican
• non-albican C. glabrata, C. krusei, C.
  parapsilosis, C. tropicalis, C. parapsilosis

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Candida infection

• LOCAL MUCOUS MEMBRANE INFECTIONS
• INVASIVE FOCAL INFECTIONS
• CANDIDEMIA AND DISSEMINATED CANDIDIASIS

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Candida sp.

• Normal flora in the gastrointestinal and
  genitourinary tracts of humans.

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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

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LOCAL MUCOUS MEMBRANE INFECTIONS

• Oropharyngeal candidiasis
• Esophagitis
• Vulvovaginitis
• Chronic mucocutaneous candidiasis

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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

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Oropharyngeal candidiasis

• Signs

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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

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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.

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Esophagitis

• Rx
• Fluconazole 200 mg once daily then 100 mg for 14
  d
• Amphotericin B 0.3-0.7 mkd iv for 14 d

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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

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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

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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-ectoderm
  al dystrophy (APECED) syndrome
• manifested by chronic mucocutaneous candidiasis
  and endocrine disorders, such as
  hypoparathyroidism, adrenal insufficiency, and
  primary hypogonadism

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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

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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

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INVASIVE FOCAL INFECTIONS

• Urinary tract infection
• Endophthalmitis
• Osteoarticular infections
• Meningitis
• Endocarditis
• Hepatosplenic or chronic disseminated candidiasis
• Peritonitis and intraabdominal infections
• Pneumonia
• Mediastinitis
• Pericarditis

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Urinary tract infection

• BLADDER INFECTION AND COLONIZATION
• KIDNEY INFECTION

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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.

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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.

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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

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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

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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

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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

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CANDIDEMIA AND DISSEMINATED CANDIDIASIS

• Candidiemia presence of Candida sp. in the blood
• Disseminated candidiasis several viscera are
  infected

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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

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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

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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.

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CLINICAL MANIFESTATIONS

• Skin lesions

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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

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CLINICAL MANIFESTATIONS

• Eye lesions

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CLINICAL MANIFESTATIONS

• Muscle abcess
• soreness in a discrete muscle group.
• warm and swollen

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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/Cve, whether
  or not they have ocular symptoms
• Culture and stain of biopsy material

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Treatment

• CATHETER REMOVAL
• ANTIFUNGAL AGENTS
• Polyenes Amphotericin B
• Azoles Fluconazole, Itraconazole and
  Voriconazole.
• EchinocandinsCaspofungin

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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

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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

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DRUG RESISTANCE

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

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DRUG RESISTANCE

• C. lusitaniae
• often resistant to amphotericin therapy
• usually susceptible to azoles and echinocandins

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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