Wednesday 13 June 2012

Anidulafungin


Class: Echinocandins
VA Class: AM700
Chemical Name: 1 - [(4R,5R) - 4,5 - dihydroxy - N2 - [[4″ - (pentyloxy)[1,1′:4′,1″ - terphenyl] - 4 - yl]carbonyl] - l - ornithine] Echinocandin B
Molecular Formula: C58H73N7O17
CAS Number: CAS-166663-25-8
Brands: Eraxis

Introduction

Antifungal; echinocandin; lipopeptide synthesized from a fermentation product of Aspergillus nidulans.1 2 4 5 7


Uses for Anidulafungin


Candidemia and Other Invasive Candida Infections


Treatment of candidemia and certain other invasive Candida infections (intra-abdominal abscess, peritonitis).1 5 8 19 21 24 A drug of choice.21 24


For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in such patients, IDSA recommends fluconazole or an echinocandin (caspofungin, micafungin, anidulafungin) for initial therapy;24 amphotericin B (conventional or lipid formulation) is the preferred alternative.24 An echinocandin may be preferred for initial treatment in those who have moderately severe to severe candidemia, are allergic to or intolerant of azole antifungals, have recently received an azole, or have or are likely to have infections caused by Candida glabrata or C. krusei.24 Fluconazole may be preferred for initial treatment in those who are less critically ill and have not recently received an azole and for infections caused by C. parapsilosis.24 If an echinocandin is used initially, transition to fluconazole is recommended for patients who are clinically stable and have isolates likely to be susceptible to fluconazole (e.g., C. albicans).24


For treatment of candidemia in neutropenic patients, IDSA recommends an echinocandin (caspofungin, micafungin, anidulafungin) or amphotericin B (a lipid formulation) for initial therapy;24 fluconazole is the preferred alternative in those who are less critically ill or have not recently received an azole;24 voriconazole can be used as an alternative when broader antifungal coverage is required.24 An echinocandin is preferred for C. glabrata infections;24 fluconazole or amphotericin B (a lipid formulation) is preferred for C. parapsilosis infections;24 an echinocandin, amphotericin B (a lipid formulation), or voriconazole is recommended for C. krusei infections.24 For initial empiric treatment of suspected invasive candidiasis in neutropenic patients, amphotericin B (a lipid formulation), caspofungin, or voriconazole is recommended;24 alternatives are fluconazole or itraconazole.24


Safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.1


Manufacturer states efficacy data are insufficient to date regarding use of anidulafungin for treatment of candidemia or other invasive Candida infections in neutropenic patients.1


Esophageal Candidiasis


Treatment of esophageal candidiasis.1 3 5 11 21 24 26 A drug of choice.21 24


Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).24 26


IDSA recommends oral fluconazole as the preferred drug of choice for the treatment of esophageal candidiasis;24 if oral therapy is not tolerated, IV fluconazole, IV amphotericin B (conventional formulation), or an IV echinocandin (caspofungin, micafungin, anidulafungin) is recommended.24 For fluconazole-refractory infections, preferred alternatives are itraconazole oral solution, oral posaconazole, or IV or oral voriconazole;24 other alternatives are an IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B (conventional formulation).24


For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, National Institute of Health (NIH), and IDSA recommend IV or oral fluconazole as the preferred drug of choice and itraconazole oral solution as the preferred alternative.26 Other alternatives include an IV echinocandin (caspofungin, micafungin, anidulafungin), oral or IV voriconazole, oral posaconazole, or IV amphotericin B (conventional formulation).26 For refractory esophageal candidiasis, including fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;26 alternatives include IV amphotericin B (conventional or lipid formulation), an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.26


Patients with frequent or severe recurrences of esophageal candidiasis, including HIV-infected patients, may benefit from long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or oral posaconazole; however, the potential for azole resistance should be considered.1 3 24 26 Echinocandins not included in recommendations for secondary prophylaxis of esophageal candidiasis.24 26 Patients with fluconazole-refractory esophageal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.26


Oropharyngeal Candidiasis


Treatment of oropharyngeal candidiasis.21 24 26 Considered an alternative, not a drug of choice.24 26


IDSA recommends topical clotrimazole or topical nystatin for mild oropharyngeal candidiasis;24 oral fluconazole is recommended for moderate to severe disease.24 For refractory oropharyngeal candidiasis, including fluconazole-refractory infections, itraconazole oral solution, oral posaconazole, or oral voriconazole is recommended.24 An IV echinocandin (caspofungin, micafungin, anidulafungin) or IV amphotericin B (conventional formulation) also are recommended as alternatives for refractory infections.24


For treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes;26 alternatives for initial episodes include topical clotrimazole or topical nystatin.26 For fluconazole-refractory infections, itraconazole oral solution or oral posaconazole is preferred;26 alternatives include IV amphotericin B (conventional or lipid formulation), an IV echinocandin (caspofungin, micafungin, anidulafungin), or oral or IV voriconazole.26


Patients with frequent or severe recurrences of oropharyngeal candidiasis, including HIV-infected patients, may benefit from long-term suppressive or maintenance therapy (secondary prophylaxis) with oral fluconazole or itraconazole oral solution; however, the potential for azole resistance should be considered.24 26 Echinocandins not included in recommendations for secondary prophylaxis of oropharyngeal candidiasis.24 26 Patients with fluconazole-refractory oropharyngeal candidiasis who responded to an echinocandin should receive voriconazole or posaconazole for secondary prophylaxis until antiretroviral therapy produces immune reconstitution.26


Anidulafungin Dosage and Administration


Administration


IV Administration


Administer by slow IV infusion.1 Do not administer by rapid IV injection.1


Do not admix or infuse concomitantly with other drugs.1


Reconstitution

Reconstitute 50- or 100-mg vials of lyophilized anidulafungin with 15 or 30 mL, respectively, of sterile water for injection to provide a solution containing 3.33 mg/mL.1


Dilution

Dilute total contents of the required number of reconstituted vials in 50, 100, or 200 mL of 5% dextrose injection or 0.9% sodium chloride injection as directed to provide an IV infusion solution containing 0.77 mg/mL.1 (See Table.)


Use strict aseptic technique since drug contains no preservative.1























Instructions for Diluting Reconstituted Vials of Anidulafungin1

Anidulafungin Dose Indicated



Number of Reconstituted Vials Required



Required Volume of Diluent (5% Dextrose Injection or 0.9% Sodium Chloride Injection)



Total Infusion Volume of 0.77-mg/mL Solution



Minimum Duration of Infusion (minutes)



50 mg



One 50-mg vial



50 mL



65 mL



45



100 mg



Two 50-mg vials or one 100-mg vial



100 mL



130 mL



90



200 mg



Four 50-mg vials or two 100-mg vials



200 mL



260 mL



180


Rate of Administration

Administer IV infusions at a rate not exceeding 1.1 mg/minute (1.4 mL/minute).1 More rapid infusion may increase risk of histamine-mediated reactions.1 (See Histamine-mediated Reactions under Cautions.)


Dosage


Adults


Candidemia and Other Invasive Candida Infections (Intra-abdominal Abscess, Peritonitis)

IV

A single 200-mg loading dose on day 1, followed by 100 mg once daily.1 21 24


Duration of treatment is based on clinical response.1 Manufacturer recommends anidulafungin be continued for at least 14 days after last positive culture.1 IDSA and others recommend that antifungal treatment for candidemia (without persistent fungemia or metastatic complications) be continued for 14 days after first negative blood culture and resolution of signs and symptoms of candidemia.21 24


Esophageal Candidiasis

IV

A single 100-mg loading dose on day 1, followed by 50 mg once daily is recommended by the manufacturer and some clinicians.1 21 IDSA recommends a single 200-mg loading dose on day 1, followed by 100 mg once daily.24


HIV-infected adults: A single 100-mg loading dose on day 1, followed by 50 mg once daily.26


Duration of treatment is based on clinical response.1 Manufacturer recommends a minimum of 14 days and at least 7 days following resolution of symptoms.1 IDSA and others recommend that antifungal treatment be continued for 14–21 days.21 24 26


Oropharyngeal Candidiasis

IV

Some clinicians recommend a single 100-mg loading dose on day 1, followed by 50 mg once daily.21 IDSA recommends a single 200-mg loading dose on day 1, followed by 100 mg once daily.24


HIV-infected adults: A single 100-mg loading dose on day 1, followed by 50 mg once daily.26


IDSA and others recommend that antifungal treatment be continued for 7–14 days.24 26


Special Populations


Hepatic Impairment


Dosage adjustment not required in adults with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C).1


Renal Impairment


Dosage adjustment not required.1 Not dialyzable; may administer without regard to dialysis timing.1 2 4 5 7 11


Geriatric Patients


Dosage adjustment not required in adults ≥65 years of age.1 7 11


Cautions for Anidulafungin


Contraindications



  • Known hypersensitivity to anidulafungin, other echinocandin antifungals (e.g., caspofungin, micafungin), or any ingredient in the formulation.1



Warnings/Precautions


Sensitivity Reactions


Hypersensitivity Reactions

Possible histamine-mediated symptoms (e.g., rash, urticaria, flushing, pruritus, dyspnea, hypotension).1 6 12 Reported infrequently when infusion rate does not exceed 1.1 mg/minute.1


Hepatic Effects


Abnormal liver function test results reported.1 Clinically important hepatic dysfunction, hepatitis, or worsening hepatic failure reported in patients with serious underlying conditions receiving multiple drugs concomitantly; causal relationship not established.1


If abnormal liver function test results occur, monitor for evidence of worsening hepatic function and evaluate benefits versus risks of continuing therapy.1


Selection and Use of Antifungals


Obtain specimens for fungal culture and other relevant laboratory studies (e.g., histopathology) prior to initiation of therapy.1 Therapy may be started pending results; adjust therapy as needed when results available.1


Specific Populations


Pregnancy

Category C.1


Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use only if potential benefits outweigh risks.1


Pediatric Use

Safety and efficacy not established in pediatric patients.1


Has been used in a limited number of neutropenic children 2–17 years of age without unusual adverse effects.18


Some experts state data are insufficient to date to recommend use of anidulafungin for first-line treatment of invasive candidiasis or for treatment of esophageal or oropharyngeal candidiasis in children (including HIV-infected children).25


Common Adverse Effects


GI effects (diarrhea,1 nausea1 3 5 6 8 ), phlebitis/thrombophlebitis,3 5 6 hypokalemia,1 8 12 increased ALT,1 3 increased alkaline phosphatase,1 increased γ-glutamyltransferase (GGT, γ-glutamyl transpeptidase, GGPT),1 3 7 12 headache,1 3 5 6 8 rash,1 3 neutropenia.1 3 5 6


Interactions for Anidulafungin


Does not inhibit or induce and is not a substrate for CYP isoenzymes.1 5 6 7 9 11 27 28


Drugs Metabolized by Hepatic Microsomal Enzymes


Pharmacokinetic interactions unlikely with drugs metabolized by CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A.1 7 28


Drugs Affecting or Affected by P-glycoprotein Transport


Not an inhibitor or substrate of the P-glycoprotein transport system; pharmacokinetic interactions unlikely.11 27 30


Specific Drugs






























Drug



Interaction



Comments



Amphotericin B



No clinically important pharmacokinetic interactions1


In vitro evidence of additive antifungal effects against Candida, including C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis22


In vitro evidence of antagonism against some strains of Aspergillus flavus and A. terreus; in vitro evidence of synergism against some strains of A. fumigatus16



Anidulafungin dosage adjustment not necessary1


Clinical importance of in vitro studies unclear16 22



Fluconazole



In vitro evidence of additive or indifferent antifungal effects against C. albicans, C. glabrata; in vitro evidence of indifference against C. krusei, C. parapsilosis, C. tropicalis22



Clinical importance of in vitro studies unclear22



Flucytosine



In vitro evidence of additive or indifferent antifungal affects against C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis22



Clinical importance of in vitro studies unclear22



Immunosuppressive agents (cyclosporine, tacrolimus)



Cyclosporine: Increased anidulafungin AUC at steady state but no clinically important change in anidulafungin steady-state peak plasma concentrations; no effect on cyclosporine pharmacokinetics1 5 9 11


Tacrolimus: No clinically important pharmacokinetic interactions with oral tacrolimus1 14



Cyclosporine: Anidulafungin and cyclosporine dosage adjustments not necessary1 9 11


Tacrolimus: Anidulafungin and tacrolimus dosage adjustments not necessary1



Itraconazole



In vitro evidence of additive or indifferent antifungal effects against Candida, including C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis22


Synergistic or indifferent antifungal effects against Aspergillus; indifferent effects against Fusarium16



Clinical importance of in vitro studies unclear16



Ketoconazole



In vitro evidence of additive or indifferent antifungal effects against C. albicans, C. glabrata, C. krusei, C. parapsilosis; in vitro evidence of antagonism against C. tropicalis22



Clinical importance of in vitro studies unclear16



Rifampin



No clinically important pharmacokinetic interactions1 6 11



Anidulafungin dosage adjustment not necessary1



Voriconazole



No clinically important pharmacokinetic interactions with oral voriconazole1 7 17



Anidulafungin and voriconazole dosage adjustments not necessary1 7


Anidulafungin Pharmacokinetics


Absorption


Plasma Concentrations


Linear relationship between dose and peak plasma concentration and AUC.30 31


Steady state achieved on the first day after an IV loading dose.1


Distribution


Extent


Crosses placenta in rats and detected in rat fetal plasma;1 not known whether crosses placenta in humans.1


Distributed into milk of lactating rats;1 not known whether distributed into human milk.1


Plasma Protein Binding


>99%.1


Elimination


Metabolism


Slow chemical degradation at physiologic temperature and pH; metabolite exhibits no antifungal activity.1 5 6 7 12


Elimination Route


Eliminated principally in feces via the biliary tract.5 28 30 Following a single IV dose, 30% recovered in feces over 9 days (<10% as unchanged drug); <1% excreted in urine.1 5 7 28


Half-life


Distribution half-life is 0.5–1 hour;1 terminal elimination half-life is 27–52 hours.1 5 28


Special Populations


Geriatric adults: Median clearance in adults ≥65 years of age slightly less than that in younger adults; dosage adjustments not required.1


Hepatic impairment: Not metabolized in the liver;1 6 7 9 concentrations not increased in adults with mild, moderate, or severe hepatic impairment (Child-Pugh class A, B, or C).1


Renal impairment or end-stage renal disease: Negligible renal clearance; pharmacokinetics not affected by mild, moderate, or severe renal impairment.1


Not removed by hemodialysis.1


Stability


Storage


Parenteral


Powder for IV Infusion

2–8°C;1 do not freeze.1


Following reconstitution with sterile water for injection, store at 2–8°C for ≤1 hour;1 do not freeze.1 Following further dilution in 5% dextrose injection or 0.9% sodium chloride injection to a concentration of 0.77 mg/mL, store at 2–8°C and administer within 24 hours of preparation.1 Do not freeze.1


Compatibility


For information on systemic interactions resulting from concomitant use, see Interactions.


Parenteral


Solution Compatibility





Compatible



Dextrose 5%



Sodium chloride 0.9%


Actions and SpectrumActions



  • Echinocandins (e.g., caspofungin, micafungin, anidulafungin) differ structurally and pharmacologically from other available antifungals.1 2 4 5 6 7 11




  • Inhibits synthesis of β-d-glucan, an essential component of fungal cell walls that is not present in mammalian cells.1 2 3 4 5 7




  • May be fungistatic or fungicidal in action.1 2 3 4 5 7 13




  • Active in vitro against Candida, including C. albicans,1 10 11 29 C. dubliniensis,11 23 C. glabrata,1 10 11 13 C. guilliermondii,1 10 C. keyfri,10 C. krusei,1 10 11 C. lusitaniae,10 C. metapsilosis,37 C. orthopsilosis,37 C. parapsilosis,1 10 37 and C. tropicalis.1 10 11 27 30 31




  • Active against some strains of fluconazole-resistant C. albicans,1 10 C. glabrata,10 29 and C. krusei.10




  • Active in vitro against Aspergillus, including A. fumigatus, A. flavus, A. niger, and A. terreus.2 4 5 6 7 11 12 27 29 30 31




  • Like other echinocandins, not active against Cryptococcus neoformans,2 4 5 11 27 29 30 31 Trichosporon,2 29 31 33 Fusarium,2 4 11 27 31 33 or zygomycetes.2 4 29 30 31 33




  • Potential for development of resistance or for cross-resistance with other echinocandins (caspofungin, micafungin) not known.1 2 6 11 12




  • Active against some strains of C. glabrata resistant to caspofungin13 and C. parapsilosis resistant to caspofungin and micafungin.36



Advice to Patients



  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1




  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1




  • Importance of informing patients of other important precautionary information. (See Cautions.)



Preparations


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.


















Anidulafungin

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Parenteral



For injection, for IV infusion



50 mg



Eraxis



Pfizer



100 mg



Eraxis



Pfizer



Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.


The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


† Use is not currently included in the labeling approved by the US Food and Drug Administration.




References



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3. Krause DS, Simjee AE, van Rensburg C et al. A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis. Clin Infect Dis. 2004; 39:770-5. [PubMed 15472806]



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7. Raasch RH. Anidulafungin: review of a new echinocandin antifungal agent. Expert Rev Anti Infect Ther. 2004; 2:499-508. [PubMed 15482216]



8. Krause DS, Reinhardt J, Vazquez JA et al. Phase 2, randomized, dose-ranging study evaluating the safety and efficacy of anidulafungin in invasive candidiasis and candidemia. Antimicrob Agents Chemother. 2004; 48:2021-4. [PubMed 15155194]



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10. Pfaller MA, Boyken L, Hollis RJ et al. In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole. J Clin Microbiol. 2005; 43:5425-7. [PubMed 16272464]



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13. Cota J, Carden M, Graybill JR et al. In vitro pharmacodynamics of anidulafungin and caspofungin against Candida glabrata isolates, including strains with decreased caspofungin susceptibility. Antimicrob Agents Chemother. 2006; 50:3926-8. [PubMed 16940061]



14. Dowell JA, Stogniew M, Krause D et al. Lack of pharmacokinetic interaction between anidulafungin and tacrolimus. J Clin Pharmacol. 2007; 47:305-14. [PubMed 17322142]



15. Dowell JA, Stogniew M, Krause D et al. Anidulafungin does not require dosage adjustment in subjects with varying degrees of hepatic or renal impairment. J Clin Pharmacol. 2007; 47:461-70. [PubMed 17389555]



16. Philip A, Odabasi Z, Rodriguez J et al. In vitro synergy testing of anidulafungin with itraconazole, voriconazole, and amphotericin B against Aspergillus spp. and Fusarium spp. Antimicrob Agents Chemother. 2005; 49:3572-4. [PubMed 16048988]



17. Dowell JA, Schranz J, Baruch A et al. Safety and pharmacokinetics of coadministered voriconazole and anidulafungin. J Clin Pharmacol. 2005; 45:1373-82. [PubMed 16291712]



18. Benjamin DK, Driscoll T, Seibel NL et al. Safety and pharmacokinetics of intravenous anidulafungin in children with neutropenia at high risk for invasive fungal infections. Antimicrob Agents Chemother. 2006; 50:632-8. [PubMed 16436720]



19. Reboli AC, Rotstein C, Pappas PG et al. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007; 356:2472-82. [PubMed 17568028]



21. Anon. Antifungal drugs. Treat Guidel Med Lett. 2008; 6:1-8. [PubMed 18157085]



22. Karlowsky JA, Hoban DJ, Zhanel GG et al. In vitro interactions of anidulafungin with azole antifungals, amphotericin B and 5-fluorocytosine against Candida species. Int J Antimicrob Agents. 2006; 27:174-7. [PubMed 16414247]



23. Jacobsen MD, Whyte JA, Odds FC. Candida albicans and Candida dubliniensis respond differently to echinocandin antifungal agents in vitro. Antimicrob Agents Chemother. 2007; 51:1882-4. [PubMed 17307974]



24. Pappas PG, Kauffman CA, Andes D et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009; 48:503-35. [PubMed 19191635]



25. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009; 58:1-166. [PubMed 19730409]



26. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58:1-207; quiz CE1-4. [PubMed 19357635]



27. Estes KE, Penzak SR, Calis KA et al. Pharmacology and antifungal properties of anidulafungin, a new echinocandin. Pharmacotherapy. 2009; 29:17-30. [PubMed 19113794]



28. Damle BD, Dowell JA, Walsky RL et al. In vitro and in vivo studies to characterize the clearance mechanism and potential cytochrome P450 interactions of anidulafungin. Antimicrob Agents Chemother. 2009; 53:1149-56. [PubMed 19029327]



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32. Juang P. Update on new antifungal therapy. AACN Adv Crit Care. 2007 Jul-Sep; 18:253-60; quiz 261-2.



33. de la Torre P, Meyer DK, Reboli AC. Anidulafungin: a novel echinocandin for candida infections. Future Microbiol. 2008; 3:593-601. [PubMed 19072176]



34. Vazquez JA, Schranz JA, Clark K et al. A phase 2, open-label study of the safety and efficacy of intravenous anidulafungin as a treatment for azole-refractory mucosal candidiasis. J Acquir Immune Defic Syndr. 2008; 48:304-9. [PubMed 18545153]



35. Eschenauer G, Depestel DD, Carver PL. Comparison of echinocandin antifungals. Ther Clin Risk Manag. 2007; 3:71-97. [PubMed 18360617]



36. Moudgal V, Little T, Boikov D et al. Multiechinocandin- and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrob Agents Chemother. 2005; 49:767-9. [PubMed 15673762]



37. Lockhart SR, Messer SA, Pfaller MA et al. Geographic distribution and antifungal susceptibility of the newly described species Candida orthopsilosis and Candida metapsilosis in comparison to the closely related species Candida parapsilosis. J Clin Microbiol. 2008; 46:2659-64. [PubMed 18562582]



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