fungal infections, candidiasis, lab diagnosis, esophagitis, treatment of candida infections

1. FUNGAL INFECTIONS

2. Terminology and Microbiology
 classified into specific categories based on both
anatomic location and epidemiology.
 The most common general anatomic categories are
mucocutaneous and deep organ infection.
 The most common general epidemiologic categories
are endemic and opportunistic.
 Although mucocutaneous infections can cause serious
morbidity, they are rarely fatal. Deep organ infections
also cause severe illness in many cases but, in contrast
to mucocutaneous infections, are often fatal.

3.  Endemic mycoses (e.g., coccidioidomycosis) are infections
caused by fungal organisms that are not part of the normal
human microbial flora and are acquired from
environmental sources. In contrast, opportunistic mycoses
are caused by organisms (e.g., Candida and Aspergillus)
that frequently are components of the normal human flora
and whose ubiquity in nature renders them easily acquired
by the immunocompromised host.
 Endemic mycoses cause more severe illness in
immunocompromised patients than in immunocompetent
individuals.

4.  Three other terms frequently used in clinical discussions of
fungal infections are yeast, mold, and dimorphic fungus
 Yeasts are seen as rounded single cells or as budding
organisms: Candida and Cryptococcus
 Molds grow as filamentous forms called hyphae both at
room temperature and when they invade tissue:
Aspergillus, Rhizopus
 Dimorphic is the term used to describe fungi that grow as
yeasts or large spherical structures in tissue but as
filamentous forms at room temperature in the
environment: blastomycosis, paracoccidioidomycosis,
coccidioidomycosis, histoplasmosis, blastomycosis, and
sporotrichosis.

5.  Opportunistic infections have increased in frequency
as a consequence :
 Immunosuppression in organ and stem cell
transplantation and many other diseases,
 Administration of cytotoxic chemotherapy for cancers,
 Liberal use of antibacterial agents.

6. GENUS TYPICAL
GROWTH
SEPTATIONa SEXUAL
FORM
PHYLUM MEDICAL
CLASSIFICAT
ION
Aspergillus Mold + ? Ascomycota Opportunistic
Blastomyces Dimorphic + ? Ascomycota Systemic
Candida Dimorphic + ? Ascomycota Opportunistic
Coccidioides Dimorphic + ? Ascomycota Systemic
Cryptococcus Yeast + Basidiomycota Systemic
Epidermophyton Mold + + Ascomycota Superficial
Histoplasma Dimorphic + + Ascomycota Systemic
Microsporum Mold + + Ascomycota Superficial
Mucor Mold – + Zygomycota Opportunistic
Pneumocystis Cysts ? Ascomycota Opportunistic
Rhizopus Mold – + Zygomycota Opportunistic
Sporothrix Dimorphic + ? Ascomycota Subcutaneous
Trichophyton Mold + + Ascomycota Superficial

7. Diagnosis
 The definitive diagnosis of any fungal infection requires
histopathologic identification of the fungus invading
tissue, accompanied by evidence of an inflammatory
response
 The stains : PAS and GMS.
 Candida, unlike other fungi, is visible on gram-stained
tissue smears. H&E stain is not sufficient to identify
Candida in tissue specimens. When positive, an India ink
preparation of CSF is diagnostic for cryptococcosis. Most
laboratories now use calcofluor white staining coupled
with fluorescent microscopy to identify fungi in fluid
specimens.

8. Diagnosis of deep organ fungal
infections : The most reliable tests are the detection of Ab to C. immitis and
H. capsulatum in serum and CSF, the detection of cryptococcal
polysaccharide Ag in serum and CSF, and the detection of
Histoplasma Ag in urine or serum. The test for galactomannan
approved for diagnosis of aspergillosis.
 Numerous PCR assays to detect Ag are in the developmental
stages, as are nucleic acid hybridization techniques
 lysis-centrifugation technique increases the sensitivity of B/C for
less common organisms (e.g., H. capsulatum) and should be used
when disseminated fungal infection is suspected.
 Candida species can be detected with any of the automated B/C
systems widely used at present.

9.  Serodiagnosis: Except in the cases of
coccidioidomycosis, cryptococcosis, and
histoplasmosis, there are no fully validated and widely
used tests for serodiagnosis of disseminated fungal
infection.
 Skin tests for the endemic mycoses are no longer
available.

10. Treatment
 Amphotericin B (AmB)(The lipid formulations include liposomal AmB
(L-AB; 3-5 mg/kg per day) and AmB lipid complex (ABLC; 5 mg/kg per day)
side effects: nephrotoxicity
• Azoles: Fluconazole, Voriconazole(first-line drug of choice for
treatment of aspergillosis), Itraconazole, Posaconazole
• Echinocandins: caspofungin, anidulafungin, and
micafungin
• Flucytosine (5-Fluorocytosine)
• Griseofulvin and Terbinafine
• Topical Antifungal Agents :clotrimazole, econazole, miconazole,
oxiconazole, sulconazole, ketoconazole, tioconazole, butaconazole,
and terconazole, Nystatin, ciclopirox olamine, halprogin, terbinafine,
naftifine, tolnaftate, and undecylenic acid.

11. Candidiasis

12. Candidiasis
 The genus Candida encompasses more than 150
species, only a few of which cause disease in humans,
human pathogens are C. albicans, C. guilliermondii, C.
krusei, C. parapsilosis, C. tropicalis, C. kefyr, C.
lusitaniae, C. dubliniensis, and C. glabrata
 They inhabit the GI tract (including the mouth and
oropharynx), the female genital tract, and the skin
 In the USA, these species are the 4th most common
isolates from the blood of hospitalized patients.

13. Candidiasis
 Candida is a small, thin-walled, ovoid yeast that
measures 4–6 μm in diameter and reproduces by
budding
 occur in three forms in tissue: blastospores,
pseudohyphae, and hyphae
 Candida grows readily on simple medium; lysis
centrifugation enhances its recovery from blood

15.  A Few Common Risk Factors for Candidal
Infections:
Hiv and other immunodeficiency states
Antibiotics
Topical or oral steroids
Skin trauma or occlusion
Diabetes and other endocrinopathies
Nutritional deiciencies
Age (very young or very old)
Malignancies

16. Clinical Manifestations
 Mucocutaneous Candidiasis:
Thrush: white, adherent, painless, discrete or confluent patches in
the mouth, tongue, or esophagus . The occurrence of thrush in a
young, otherwise healthy-appearing person should prompt an
investigation for underlying HIV infection
Vulvovaginal candidiasis: pruritus, pain, and vaginal discharge
paronychia: painful swelling at the nail-skin interface
onychomycosis
Intertrigo: erythematous irritation with redness and pustules in the
skin folds
Balanitis: erythematous-pustular infection of the glans penis

17.  Mucocutaneous Candidiasis
erosio interdigitalis blastomycetica: Infection between the
digits of the hands or toes;
folliculitis, with pustules developing most frequently in the area of
the beard
perianal candidiasis: a pruritic, erythematous, pustular infection
surrounding the anus
diaper rash: a common erythematous-pustular perineal infection in
infants
Generalized disseminated cutaneous candidiasis: occurs
primarily in infants, is characterized by widespread eruptions over the
trunk, thorax, and extremities

18.  Mucocutaneous Candidiasis
 Chronic mucocutaneous candidiasis: infection of the hair,
nails, skin, and mucous membranes that persists despite intermittent
therapy

19.  Deeply Invasive Candidiasis
Nonhematogen:
Deep esophageal infection
joint or deep wound infection
kidney infection
infection of intraabdominal organ
gallbladder infection

20.  Deeply Invasive Candidiasis
Hematogenous: The brain, chorioretina , heart, and kidneys are
most commonly infected and the liver and spleen less commonly so
(most often in neutropenic patients). In fact, nearly any organ can
become involved, including the endocrine glands, pancreas, heart
valves (native or prosthetic), skeletal muscle, joints (native or
prosthetic), bone, and meninges.

21. Diagnosis
 visualization of pseudohyphae or hyphae on wet
mount (saline and 10% KOH), tissue Gram's stain, PAS
stain, or methenamine silver stain in the presence of
inflammation; the presence of ocular or macronodular
skin lesions is highly suggestive of widespread
infection of multiple deep organs.
 Recovery of Candida from sputum, urine, or peritoneal
catheters may indicate mere colonization rather than
deep-seated infection

22. Treatment: Treatment of Mucocutaneous Candidal
Infections
DiseasePreferred TreatmentAlternatives
CutaneousTopical azoleTopical nystatin
VulvovaginalOral fluconazole (150
mg) or azole cream or
suppository
Nystatin suppository
ThrushClotrimazole trochesNystatin
EsophagealFluconazole tablets
(100–200 mg/d) or
itraconazole solution
(200 mg/d)
Caspofungin,
micafungin, or
amphotericin B

23. Treatment:
 Candidemia and Suspected Hematogenously
Disseminated Candidiasis: because there is no
reliable way to distinguish benign candidemia from
deep-organ infection, and because antifungal drugs
less toxic than amphotericin B are available, it has
become the standard of practice to treat all patients
with candidemia, whether or not there is clinical
evidence of deep-organ involvement, and if an
indwelling intravascular catheter may be involved,
it is best to remove or replace the device whenever
possible.

24.  Unless azole resistance is considered likely,
fluconazole is the agent of choice for the treatment
of candidemia and suspected disseminated
candidiasis in nonneutropenic, hemodynamically
stable patients

25. AgentRoute of AdministrationComment
Amphotericin B deoxycholateIV onlyBeing replaced by lipid
formulations
Amphotericin B lipid formulationsNot FDA approved as primary
therapy, but used commonly
because less toxic than
amphotericin B deoxycholate;
ABCD associated with frequent
infusion reactions
Liposomal (AmBisome, Abelcet)IV only
Lipid complex (ABLC)IV only
Colloidal dispersion (ABCD)IV only
Azoles
FluconazoleIV and oralMost commonly used
VoriconazoleIV and oralMultiple drug interactions
EchinocandinsBroad spectrum against Candida
species
CaspofunginIV onlyApproved for disseminated
candidiasis
AnidulafunginIV onlyApproved for disseminated
candidiasis
MicafunginIV onlyUnder evaluation for disseminated
candidiasis

26.  Recovery of Candida from sputum is almost never
indicative of underlying pulmonary candidiasis and
does not by itself warrant antifungal treatment.

27.  Candida in the urine of a patient with an
indwelling bladder catheter may represent
colonization only rather than bladder or kidney
infection; however, the threshold for systemic
treatment is lower in severely ill patients in this
category since it is not possible to distinguish
colonization from lower or upper urinary tract
infection.

28. The significance of the recovery of Candida
from abdominal drains in postoperative
patients is also unclear, but again, the
threshold for treatment is generally low
because most of the affected patients have
been subjected to factors predisposing to
disseminated candidiasis.

29. Removal of the infected valve and long-term
antifungal therapy constitute appropriate
treatment for Candida endocarditis

30.  All patients with candidemia should undergo
ophthalmologic examination because of the relatively
high frequency of this ocular complication. Not only
can this examination detect a developing eye lesion
early in its course; in addition, identification of a
lesion signifies a probability of ~90% of deep-organ
abscesses and may prompt prolongation of therapy for
candidemia beyond the recommended 2 weeks after
the last positive blood culture.
 .

31. Recommended treatment for Candida
meningitis is a polyene plus flucytosine

34. Typical oral thrush with curdlike
white patches over the tongue

35. Numerous Candida plaques
seen in the duodenum
(upper panels) and
esophagus (lower panels).

36. Severe Candida folliculitis in beard
distribution

39. Macronodular lesions
of disseminated
candidiasis.

40. Candida spinal osteomyelitis.

41. Candida abscesses in the liver, kidney, and spleen
on magnetic resonance imaging.

42. Advanced hematogenous
Candida endophthalmitis.