2008 IDSA Candidiasis
Guidelines
John H. Rex, MD
Adjunct Professor of Medicine; University of
Texas Medical School-Houston
Vice President Clinical Infection, AstraZeneca
Pharmaceuticals
Rex summary of updated IDSA Candidiasis guidelines.ppt
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How were they created?
• Current version is from 2004
– Clin Infect Dis 2004;38:161-189
• A group of 14 international authorities began work
a revision in spring 2007.
• There are 15 major topics addressed in the
revised version
– Each recommendation is given a ‘grade’ based on the
strength of evidence (eg, A-I, B-II, C-III)
– An evidence summary follows each recommendation
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Key organism principles
• Helpful to know tiers of progressive difference
– (most virulent, most susceptible): albicans, parapsilosis, tropicalis,
dubliniensis
– (intermediate): glabrata
– (least virulent, least susceptible: krusei
• You often know quickly if C. albicans
– It’s the one that is “germ tube-positive”
• Just knowing species is very helpful
– P = Plastic = parapsilosis. Look for the device!
– Resistance patterns
•
•
•
•
glabrata & krusei: Azoles are dicey. Newer azoles are better
parapsilosis: Echinocandins sometimes a little weaker
lusitaniae: Amphotericin resistance is frequent
guilliermondii: higher azole and candin MICs
– Hint about your patient
• Glabrata and krusei are weaklings. When seen, says much about patient
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Key drug principles
• Voriconazole
– Fatty meal reduces absorption
– IV form uses cyclodextrin: not well cleared by dialysis
– Lots of drug-drug interaction
• Candins
– Very few convincing differences
– Usually cross-resistant – but not always! (emerging data)
• Amphotericins
– Always use trade name for lipid-associated forms
– Do not utter phrase “liposomal amphotericin B”: error very easy
•
•
•
•
Liposomal amphotericin B = AmBisome
Amphotericin B lipid complex = ABLC = Abelcet
Amphotericin B colloidal dispersion = ABCD = Amphotec
(Classic ampho = Amphotercin B deoxycholate = Fungizone)
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Major guideline changes from 2004
• Emphasis on fluconazole and echinocandins as the
‘preferred choices’ for proven/suspected invasive disease
• De-emphasis on amphotericin B and lipid-associated
amphotericin B under most circumstances
• Concept of step down therapy is strongly encouraged
– Voriconazole generally advised as step down therapy for selected
isolates (most notably, C. krusei)
• There is little distinction made among the echinocandins
• Fluconazole prophylaxis in neonatal units is limited to high
risk sites
• Resource-limited environments are acknowledged
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Candidemia & not neutropenic
• If species is unknown, either fluconazole (800mg loading dose, 400
mg daily) or an echinocandin is appropriate initial therapy for most
adult patients (AI)
• An echinocandin is favored if
– Moderately severe to severe illness,
– Recent azole use for treatment or prophylaxis (AIII), or
– Isolate is known to be C. glabrata or C. krusei (BIII)
• Fluconazole for patients who are
– less critically ill and
– who have no recent azole exposure (AIII).
• Move from candin to fluconazole when isolates likely susceptible to
fluconazole (e.g., C. albicans) and patient is clinically stable (AIII)
• Remove or exchange intravenous catheters
• Treat for two weeks after clearance of bloodstream
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Other settings
• Thinking of non-neutropenia as the start point
– The less you know or
– The more the patient scares you
• The more the guidelines point to
– An echinocandin
– A (lipid-associated) amphotericin B
• But, for resource constrained settings…
– The guidelines do note that classic AmB works
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A Survey of a Few Other
Selected Topics
“I don’t want you to make the wrong
mistake” —Yogi Berra
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Candidemia: Who do we treat?
• Answer: Essentially everybody
– Even a single +BC can be relevant
– Concerned about hematogenous seeding
• Spread to the eye
–
–
–
–
Can cause blindness
Lesions are common!
MSG study: 29% rate
Krishna: 26%
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Eye followup
• Krishna et al. Eye 14: 30-34, 2000
–
–
–
–
31 patients with fungemia, followed to 6 mos
Exam by 72h: 5/31 (16%) had a lesion
Exam at 7d: 1/21 (5%) had a new lesion
Exam at 14d: 2/16 (13%) had a new lesion
• All chorioretinitis, no vitreal disease
• Duration of fungemia was a weak clue
– 2.5 vs. 4.3 days (no disease vs. disease)
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Catheter Exchange? Yes!
• Lots of consistent data
– Without catheter removal, 82% had persistent infection
• Lecciones, Clin Infect Dis 1992;14:875-883
– Shortened duration of fungemia from 5.6 to 2.6 days
• P < 0.001 (Rex, Clin Infect Dis 1995;21:994-996)
– Reduced mortality: 41% to 21%
• P < 0.001 (Nguyen, Arch Intern Med 1995;155:2429-2435)
• Especially true for C. parapsilosis
– Very strong link with catheters
• Kojic, Clin Microbiol Rev 2004;17:255-267
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Catheter Exchange? Other Sources
• ~ 15% of candidemia patients have another
obvious source (urine, abscess)
• The gut may
be a cryptic
source
• What does
this imply?
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Catheter Exchange? Definite Maybe
• In non-cancer patients, suspect the catheter
– Unless another source is apparent
• After cytotoxic chemotherapy, think twice
– Gut may be source, effect of removal is less?
• C. parapsilosis is the clear exception
• More data & better tools needed here
– Differential quantitative and time-to-growth central/peripheral BC
• Bouza, Clin Infect Dis 2007;44:820-6.
– We keep wishing for good serodiagnostic tools
– We have several (beta-glucan, PCR) but none have produced
high levels of confidence
• Kedzierska, Eur J Clin Microbiol Infect Dis 2007;26:755-766
• Nett, J Infec Dis 2007;195:1705-1712.
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Empirical Therapy
• In the febrile non-neutropenic patient?
– Early treatment is theoretically attractive
• IDSA Guidelines
– “The specific basis for selecting non-neutropenic patients who
should receive empiric antifungal therapy is unclear, but should be
based on at least one of the following: clinical assessment of risk
factors, serologic markers for invasive candidiasis, and/or culture
data from non-sterile sites (BIII).”
• My rules
–
–
–
–
Antibiotics, lines, no other source, and…
Colonized somewhere with Candida
I don’t distinguish sites: anywhere works for me
The more sites or fungus the better (see work of Pittet)
• Prophylaxis? Even hazier
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Candiduria
• Asymptomatic candiduria
– No treatment unless high-risk dissemination (AIII).
– Focus on elimination of predisposing factors. (BIII).
• High risk for dissemination
– Urologic manipulations (BIII)
• Use short course fluconazole or even amphotericin B
– Neutropenic patients and low birth weight infants
• Treat as for invasive candidiasis.
• Consider imaging kidneys/collecting system (BIII)
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