1. Rex summary of updated IDSA Candidiasis guidelines.ppt1 2008 IDSA Candidiasis Guidelines John H. Rex, MD Adjunct Professor of Medicine; University of Texas Medical School-Houston Vice President Clinical Infection, AstraZeneca Pharmaceuticals

2. Rex summary of updated IDSA Candidiasis guidelines.ppt 2 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

3. Rex summary of updated IDSA Candidiasis guidelines.ppt 3 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

4. Rex summary of updated IDSA Candidiasis guidelines.ppt 4 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)

5. Rex summary of updated IDSA Candidiasis guidelines.ppt 5 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

6. Rex summary of updated IDSA Candidiasis guidelines.ppt 6 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

7. Rex summary of updated IDSA Candidiasis guidelines.ppt 7 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

8. Rex summary of updated IDSA Candidiasis guidelines.ppt8 A Survey of a Few Other Selected Topics “I don’t want you to make the wrong mistake” —Yogi Berra

9. Rex summary of updated IDSA Candidiasis guidelines.ppt 9 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%

10. Rex summary of updated IDSA Candidiasis guidelines.ppt 10 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)

11. Rex summary of updated IDSA Candidiasis guidelines.ppt 11 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

12. Rex summary of updated IDSA Candidiasis guidelines.ppt 12 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?

13. Rex summary of updated IDSA Candidiasis guidelines.ppt 13 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.

14. Rex summary of updated IDSA Candidiasis guidelines.ppt 14 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

15. Rex summary of updated IDSA Candidiasis guidelines.ppt 15 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)