CANDIDIASIS

Presenter:
SITI NORAISAH KIFLI
 INTRODUCTION
 a fungal infection (mycosis) of any of the Candida species, of which
Candida albicans is the most common

 Candida is a genus of “yeast-like fungi” which exist as part of the

normal flora of the mouth, gastro-intestinal tract and vagina.
Candidiasis occurs when there is a disturbance of local condition or
impairment of immune system.

 Infections can occur anywhere and are most common in skinfolds

and web spaces, on the genitals, cuticles, and oral mucosa.

 Most candidal infections are of the skin and mucous membranes, but
invasive candidiasis is common in immunosuppressed patients and
can be life threatening
 PATHOPHYSIOLOGY
Candida is a unicellular yeast whose cells reproduce by budding.

This organism can flourish in most environments. It frequently

colonizes the oropharynx, skin, mucous membranes, lower
respiratory, and gastrointestinal and genitourinary tracts.

Pathogenesis:
-increased fungal burden and colonization, such as in the setting of
broad-spectrum antimicrobial agents

-breakdown of normal mucosal and skin barriers, which can occur

with indwelling intravascular devices, recent surgery/trauma or
tissue damage secondary to chemotherapy or radiation

-immune dysfunction secondary to disease states or iatrogenic

conditions.
 The first step in the development of a candidal infection is
colonization of the mucocutaneous surfaces.

 The routes of candidal invasion include;

disruption of a
colonized surface adsorption via the
(skin or mucosa), gastrointestinal wall, which
allowing the may occur following massive
organisms access to colonization with large
the bloodstream numbers of organisms that
pass directly into the
bloodstream
Granulocytopenia Hematologic malignancies

Bone marrow transplantation Foley catheters

Solid organ transplantation (liver, kidney) Solid neoplasms

Parenteral hyperalimentation Recent chemotherapy or radiation therapy

Acute and chronic renal failure Hemodialysis

Premature birth Central intravascular access devices

Gastrointestinal tract surgery Recent surgery
Recent bacterial infection Severe trauma
Prolonged hospitalization Burns

Corticosteroids Broad-spectrum antibiotics

Mechanical ventilation for longer than 3 days
 CAUSES
 Over 200 species of Candida exist in nature; thus far, only a few species
have been associated with disease in humans.

 The medically significant Candida species include the following:

 C. albicans, the most common species identified (50-60%)

 Candida glabrata (previously known as Torulopsis glabrata) (15-20%)
 C. parapsilosis (10-20%)
 Candida tropicalis (6-12%)
 Candida krusei (1-3%)
 Candida kefyr (<5%)
 Candida guilliermondi (<5%)
 Candida lusitaniae (<5%)
 Candida dubliniensis, primarily recovered from patients infected with
HIV
 TYPES OF CANDIDIASIS
Local mucous membrane Invasive candidal infections
infections (systemic)
•Oral candidiasis •candidemia
•Vulvovaginal candidiasis •disseminated candidiasis
•Erosio interdigitalis •deep organ involvement
blastomycetica •endocarditis
•Intertrigo •Endophthalmitis
•Candidal paronychia •Meningitis
•Diaper rash •isolation of Candida from a normally sterile
•Perianal candidiasis body site,including blood, peritoneal fluid,
•Chronic mucocutaneous pleural fluid, intra-articular fluid,
candidiasis or cerebrospinal fluid.
 inflammatory lesion
at the labial commissure,
or corner of the mouth,
Perlèche
and often occurs bilaterally.
(Angular cheilitis)
The condition manifests
as deep cracks or splits

-infection of yeast fungi

of the genus Candida
on the mucous
Oral candidiasis membranes of the mouth.
(Thrush) -frequently caused by
C.albicans

infection of the vaginal mucous

Candidal vulvovaginitis
membranes by C. albicans

infectious of a child's
Diaper candidiasis
diaper area
 infection of the skin by
C. albicans,more specifically
Candidal intertrigo
located between intertriginous
folds of adjacent skin

-inflammation of the nail fold

Candidal paronychia - associated with frequent hand

immersion in water and

diabetes mellitus
skin condition that results in
newborn babies due to premature
rupture of membranes
Congenital cutaneous candidiasis
together with a birth canal
infected with C. albicans

Skin maceration and pruritus are

Perianal candidiasis frequent with frequent
extension to the perineum
 2 primary syndromes:
candidemia and disseminated
Systemic candidiasis candidiasis
(organ infection by Candida species).

an oval-shaped area of
Erosio interdigitalis macerated white skin on
blastomycetica the web between and
extending onto the sides
of the fingers

result from overuse/over-

Antibiotic candidiasis
presciption of broad
(Iatrogenic candidiasis)
spectrum antibiotics

a heterogeneous group
of Candida infections of
Chronic mucocuntaneous the skin, mucous membranes,
candidiasis hair, and nails, which has a
protracted course despite
typical therapy
 TREATMENT
 based on the anatomic location of the infection, the patients'
underlying disease and immune status, the patients' risk factors for
infection, the specific species of Candida responsible for infection,
and, in some cases, the susceptibility of the Candida species to
specific antifungal drugs

 4 major antifungal agents:

 polyenes
 azole
 Glucan synthesis inhibitors (echinocandins)
 Antimetabolite (flucytosine)
 Polyenes
 broad-spectrum fungicidal agents
 MOA: insertion into fungal cytoplasmic membrane, causing increases in permeability. Membrane
channel activity is increased at lower doses, and pores are formed at higher concentrations.
 Drugs: amphotericin B & Nystatin
 Amphotericin B (Fungizone®)
 MOA: Binds to ergosterol altering cell membrane permeability in susceptible fungi
and causing leakage of cell components with subsequent cell death

 Side effects: Fever, headache, anorexia, weight loss, GI disturbances,malaise,

epigastric pain, dyspepsia, generalized pain, anaemia, abnormal renal function.
Rarely cardiovascular toxicity, haematologic reactions, neurologic reactions, liver
Dosing
failure.
-Adult : 0.25 mg/kg/day (IV infusion), gradually increase if
tolerated to 1 mg/kg/day. Max. in severe cases : 1.5 mg/kg
 Drug interactions:-increased
daily or on alternate daysrisk (blue
of nephrotoxicity-nephrotoxic
book)
antibiotics, cyclosporine, other nephrotoxic
immunosuppressants,
-Paeds:1.5mg/kg in 50ml dex-hep or parenteral
at 2ml/hrpentamidine
(1.5mg/kg/hr)
continuous-may
IV;total doseeffects
enhance 30-35mg/kg over 4-8 weeks (Frank Shann)
of neuromuscular-blocking
drugs
-Renal impairment: if due
-may increase to drug,↓
toxicity doseglycosides
of digitalis by 50% if or dose can
be given every other day (lexi-comp)
 Lipid formulations
-Amphotericin B (Cholesteryl sulfate) (Amphotec®)-colloidal
dispersion
-amphotericin B lipid complex (ABLC, Abelcet®)

-liposomal amphotericin B (L-AMB, AmBisome®).

 Nystatin suspension (100
000u/ml)
 MOA: Binds to sterols in fungal cell membrane, changing the cell
wall permeability allowing for leakage of cellular contents
Dosing
 Side effects:GastrointestinaI
Suspension: Newborn : 50,000 - disturbances, rash.
100,000 units daily.
Child : Up to 5 yrs: 100,000 units 6hrly.
 Counseling 6 - 12 yrs & Adults : 500,000 units qid
points:
Cream/oitment: Apply liberally to affected area bd or as required.
- shake well before use has disappeared continue treatment
After lesion
for 10 about
-should be swished days to prevent
the mouthrelapses
and retained in the mouth for as
Tablet: 1-2possible
long as tab (500,000 to 1,000,000
(several units
minutes) nystatin)
before TDS
swallowing
-Avoid eating for 5-10 minutes after using this medication
-Wash the dropper with hot water before returning it to the bottle
 Azoles
MOA: inhibition of lanosterol 14-alpha-demethylase, an enzyme required
for the synthesis of ergosterol, the main component of fungal cell
membranes.
Imidazoles Triazoles

2 atoms of nitrogen in the azole ring 3 atoms of nitrogen

miconazole, ketoconazole, and clotrimazole fluconazole, itraconazole,

econazole, terconazole,
butoconazole, and tioconazole
Newer triazoles: voriconazole,
posaconazole, ravuconazole

Common s/e: Common s/e:

Clotrimazole- Local irritation, mild burning and stinging of the GI symptoms (nausea, abdominal
skin or vaginal area can occur with topical application. pain, vomiting and diarrhea);Rash
Miconazole -Topical: Allergic contact dermatitis, burning, and headache; Mild elevations in
maceration liver function tests (1-7%) of cases
Ketoconazole- Oral:GI upset (nausea, vomiting, and diarrhea)
and headache and dizziness ;Hepatotoxicity; Pruritus (2%)
Shampoo: Abnormal hair loss, dry/oily scalp or itching may
be seen following the application of the shampoo.
Drugs Clotrimazole Ketoconazole Miconazole
Formulations & -1% Cream - Tablet 200mg -Cream2%
doses Imidazoles
-1% Solution - Shampoo 2% -Powder (nitrate) 2%
-Vaginal Tablet 200mg & 500mg

Indications Cutaneous candidiasis, Tinea Tablet 200mg Cream:

corporis, Tinea cruris, Tinea i) Pityriasis versicolor i) Fungal infections: Tinea pedis,
pedis and Tinea versicolor ii) Systemic mycosis (other Tinea corporis, Tinea capitis and
skin mycoses) other dermatophyte infections
caused by Trichophyton and
iii) Nail infections
Epidermophyton species.
ii) Antifungal agent that has been
in various candida infections
including vaginal
candidiasis.
Powder: Skin infections caused by
dermatophytes or Candida

Dose & Topical:Rub in gently onto i) 200 mg with meal once Cream:
durations affected and surrounding skin dly for 14 days. i)Skin Infection: Apply sparingly
bd-tds; continuing for 14 days ii) 200 - 400 mg dly for 4 and rub gently onto affected area
after lesions have healed. wks - 12 mths. once daily or bd continuing for
Tablet:200mg pessary for 3 iii) 200 - 400 mg dly for 6 - 10 days after lesions have
days 12 mths. Max 400 mg dly. healed.
ii) Apply BD continuing for 10
days after lesions have healed
Powder: Dust powder over infected
area OD or bd.
Drugs Fluconazole Itraconazole Voriconazole
Formulations & -capsule 50mg, 100mg -Oralsolution 10mg/ml -Tablet 200mg, 50mg
doses Triazoles
-injection 2mg/ml -Capsule 100mg - Injection 200mg

Indications i)Oropharyngeal candidiasis, Oral solution: - Invasive aspergillosis

atrophic oral candidiasis
associated with dentures, other i) oral or oesophageal - Candidemia in nonneutropenic
candidal infections of mucosa candidiasis patients and the following
ii) Tinea pedis, corporis,cruris, ii) fluconazole resistant Candida infections:
versicolor and dermal disseminated infections in
and/or oesophageal
candidiasis skin and infections in
candidiasis
iii) Invasive candidal & abdomen, kidney, bladder
cryptococcal infections wall, and wounds
(including meningitis) Capsule:
iv) Prevention of relapse of i)Dermatomycosis
- Esophageal candidiasis
cryptococcal meningitis in including Pityriasis
AIDS patients after completion versicolor
of primary therapy ii) Oral Candidosis - Serious fungal infections
caused by Scedosporium
v) Prevention of fungal iii)Palmar Tinea manus
apiospermum (asexual form
infections in and plantar Tinea pedis
of Pseudallescheria boydii)
immunocompromised patients iv) Fingernail and Fusarium spp.
considered at risk as a onychomycosis including Fusarium solani,
consequence of HIV infections v) Toenail in patients intolerant of, or
or neutropenia following onychomycosis refractory to, other therapy
cytotoxic chemotherapy,
vi) Vulvovaginal
radiotherapy or bone marrow
candidosis
transplant
Drugs Fluconazole Itraconazole Voriconazole
Dose &
durations Triazoles
i)50-100 mg daily for 7-14 day (Max. Oral solution:
14 days) except in severely i) 200 mg dly in 2 intakes, or in
Children > 12 y/o & adults;
-Loading dose: 6 mg/kg IV
immunocompromised patients. 1 intake, for 1 wk. If no q12h infused over 2 h for 2
-Atrophic oral candidiasis response after 1 wk, doses
associated with dentures : 50 mg continue treatment for another -Maintenance: 4 mg/kg IV
daily for 14 days. -Other candidal wk. q12h infused over 2 h;
infec tions of mucosa : 50 -100 mg ii) Fluconazole resistant or switch to 200 mg PO q12h
daily for 14-30 days. Child :3-6 mg/kg oesophageal candidiasis- 100 -
on first day then 3 mg/kg daily when able to tolerate; may
200 mg bd for 2 increase to 300 mg PO
(every 72 hrs in Neonate up to 2 wks. If no response after 2 wks
wks old, every 48 hrs in neonate 2-4 continue treatment for another
q12h if inadequate
wks old ) response
2 wks.
ii)50 mg daily for 2-4 wks, max. 6 wks. The 400 mg daily dose should - If <40 kg: Average
iii)400 mg initially then 200-400 mg maintenance dose is 100
not be used for >14 days. mg PO q12h (may increase
daily for 6-8 wks. Child: 6-12 mg/kg
daily to 150 mg PO q12h)
Capsule:
(every 72 hrs in Neonate up to 2
wks old, every 48 hrs in neonate 2-4 i) 200 mg once dly for 7 days. Renal impairment:
wks old ) ii) 100 mg daily for 15 days Crcl<50ml/min-after IV loading
iv)100 - 200 mg daily. iii) 200 mg bd for 7 days dose, oral voriconazole
v) 50-400 mg daily. Child: 3-12 mg/kg iv) 200 mg bd for 1 wk/mth should be administered
daily (every 72 hrs in Neonate up to 2 v) 200 mg bd for 1 wk/mth for 3 Hemodialysis: no oral dosage
wks old, every 48 hrs in neonate mths adjustment needed, IV not
2-4 wks old). vi) 200 mg morning and recommended
evening for 1 day or 200 mg *accumulation of IV vehicle
once daily for 3 (sulfobutylether-β-
days. cyclodextrin) (SBECD).
Glucan synthesis inhibitors (echinocandins)

 MOA:inhibit the formation of fungal cell wall.

 Drugs: caspofungin, micafungin, and anidulafungin.

 Indications:have been approved for complicated forms of invasive

candidiasis, candidemia, disease refractory to other systemic
antifungals, and intolerance to amphotericin B.

 Spectrum activity: They are broad spectrum and fungicidal against

most Candida species, except C parapsilosis and C guilliermondii.
Drugs Caspofungin Micafungin Anidulafungin
Formulations & Injection (Acetate) 70mg, 50mg Injection (Sodium) 50mg, Injection 50mg
doses Echinocandins 100mg

Indications i)candidemia, invasive i) prophylaxis of i) esophageal candidiasis

candidiasis, refractory Candida infections in
invasive aspergillosis patients undergoing ii)candidemia, and other forms
hematopoietic stem cell of candidal infections (eg,
transplantation,
ii) esophageal candidiasis. intra-abdominal abscesses,
peritonitis).
iii) Also approved as empiric ii) esophageal
therapy for presumed fungal candidiasis, candidemia,
and invasive candidiasis
infections in febrile
neutropenic patients

Dose & i) I.V.: Initial dose: 70 mg i) 50 mg daily; median i) I.V: 100 mg loading dose on
durations on day 1; subsequent duration of therapy (from day 1, followed by 50 mg daily
dosing: 50 mg/day clinical trials) was 18 for at least 14 days and for at
days least 7 days after symptom
resolution
ii) I.V.: 50 mg/day
ii) I.V.: 150 mg daily;
iii) I.V.: Initial dose: 70 mg median duration of ii) I.V: 200 mg loading dose on
therapy (from clinical day 1, followed by 100 mg daily
on day 1; subsequent
trials) was 14 days for at least 14 days after last
dosing: 50 mg/day; may
increase up to 70 mg/day if positive culture
tolerated, but clinical
response is inadequate.
 Antimetabolite
Flucytosine

MOA: deaminated to 5-fluorouracil in the fungal cell by an enzyme not present

in mammalian cells, and inhibits RNA and protein synthesis

Spectrum activity: against Candida and Cryptococcus species and generally

used in combination with amphotericin B

Formulations: injection 2.5g/250ml, tablet 500mg

Indications: indicated only in the treatment of serious infections caused by

susceptible strains of Candida and/or Cryptococcus.

 Candida: Septicemia, endocarditis and urinary system

infections; Limited trials in pulmonary infections justify the use
of flucytosine.

 Cryptococcus: Meningitis and pulmonary infections; Studies in

septicemias and urinary tract infections are limited, but good
responses have been reported
Flucytosine

Dosing;
 Injection: Adult : 100 - 200 mg/kg daily in 4 divided doses by IV infusion over
20 - 40 mins not more than 7 days. For neonates, used primarily with
Amphotericin. (Blue Book)

 Tablet: Adult : 50 - 100 mg/kg/day in 4 divided doses. 250 mg/kg/day have

been recommended in severe infection
(only for the treatment of fungal meningitis-blue book)

 Renal impairment:
Crcl 20-40ml/min- 37.5mg/kg every 12 hours
10-20ml/min-37.5mg/kg every 24 hours
<10ml/min -37.5mg/kg every 24-48 hours (lexi-comp)

Side effects:
 Leucopenia, thrombocytopenia, headache, drowsiness, confusion,
hallucinations, nausea, vomiting, diarrhoea, elevated liver function tests, and
cutaneous reactions.
 REFERENCES
 E., E., Nwokedi & A., Omele-Ohonsi 2007. Current Clinical Review of
Vulvovaginal Candidiasis. Journal of Medicine and Rehabilitation.
1(1): 28-32
 Peter G. Pappas, Carol A. Kauffman, David Andes, Daniel K.
Benjamin, Jr., Thierry F. Calandra, John E. Edwards, Jr., Scott G.
Filler, John F. Fisher, Bart-Jan Kullberg, Luis Ostrosky-Zeichner,
Annette C. Reboli, John H. Rex,Thomas J. Walsh & Jack D. Sobel.
2009. Clinical Practice Guidelines for the Management of Candidiasis:
2009 Update by the Infectious Diseases Society of America. Clinical
Infectious Diseases 48:503–35
 Ministry of Health Drug Formulary 2008
 Drug information Handbook 2008-2009, 17th edition
 http://en.wikipedia.org/wiki/Candidiasis
 Jose A Hidalgo & Jose A Vazquez. 2008. Candidiasis.
http://emedicine.medscape.com
 A. Damian Dhar. 2008. Candidiasis. The Merck Manuals Online
Medical Library. http://www.merck.com/mmpe
 C glabrata and C albicans account for approximately 70-80% of Candida species
recovered from patients with candidemia or invasive candidiasis. C glabrata has
recently become very important because of its increasing incidence worldwide, its
association with fluconazole resistance in up to 20% of clinical specimens, and its
overall decreased susceptibility to other azoles and polyenes.
 C krusei is important because of its intrinsic resistance to ketoconazole and
fluconazole (Diflucan); it is also less susceptible to all other antifungals, including
itraconazole (Sporanox) and amphotericin B.
 Another important Candida species is C lusitaniae; although not as common as
other Candida species, C lusitaniae is of clinical significance because it may
be intrinsically resistant to amphotericin B, although it remains susceptible to azoles
and echinocandins.
 C parapsilosis is also an important species to consider in hospitalized patients. It is
especially common in infections associated with vascular catheters prosthetic
devices. Additionally, in vitro analyses have shown that echinocandins have a higher
minimum inhibitory concentration (MIC) against C parapsilosis than other Candida
species. The clinical relevance of this in vitro finding has yet to be determined.14
 C tropicalis has frequently been considered an important cause of candidemia in
patients with cancer (leukemia) and in those who have undergone bone marrow
transplantation.
 Alternative options for candidemia include the following:
 Caspofungin (Cancidas) can be initiated as a 70-mg loading dose, followed by 50 mg/d intravenously to complete a
minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared. Caspofungin is a broad-
spectrum semisynthetic echinocandin. It is an effective alternative for severe mucosal infections and systemic infections
due to Candida, especially those due to non-albicans
non-albicans Candida species such as C glabrata.
glabrata.
 Anidulafungin can be initiated as a 200-mg loading dose, followed by 100 mg intravenously to complete a minimum of 2
weeks of antifungals after improvement and after blood cultures have cleared. Anidulafungin is a broad-
spectrum echinocandin. It is an effective alternative for severe mucosal infections and systemic infections due to
Candida, especially those due to non-albicans
non-albicans Candida species such as C glabrata.24
glabrata.24
 Micafungin can be administered at 100 mg/d intravenously to complete a minimum of 2 weeks of antifungals after
improvement and after blood cultures have cleared. Micafungin is a broad-spectrum echinocandin. It has been shown to
be an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to
non-albicans
non-albicans Candida species such as C glabrata.25
glabrata.25
 Voriconazole can be initiated at 6 mg/kg intravenously or orally twice per day, followed by 3 mg/kg orally twice per day or
200 mg orally twice per day. Based on the findings from a global multicenter clinical trial, voriconazole has also
been approved for use in candidemia in patients who are not neutropenic.26
 Amphotericin B deoxycholate can be administered at 0.7 mg/kg/d intravenously for a total dose of 1-2 g over a 4- to 6-
week period.
 Liposomal preparations of amphotericin B may also be options if (1) the infection is refractory to fluconazole or at least
500 mg of standard amphotericin B, (2) the patient has severe infusion-related toxicity, or (3) the patient develops renal
insufficiency while on amphotericin B (generally with an increase in creatinine level >2.5 mg/dL).
 Chronic mucocutaneous candidiasis: This condition is generally treated with oral azoles, such
as fluconazole at a dose of 100-400 mg/d or itraconazole at a dose of 200-600 mg/d until the patient
improves. The initial therapy for acute infection is always followed by maintenance therapy with the same
azole for life.