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Yeast Susceptibility to Fluconazole, Voriconazole, and Caspofungin

Yeast Susceptibility to Fluconazole, Voriconazole, and Caspofungin

Test Summary

Yeast Susceptibility to Fluconazole, Voriconazole, and Caspofungin

  

Clinical Use

  • Identify yeast species causing infection (test codes 36268 and 36270)
  • Determine susceptibility or resistance of yeast isolates to fluconazole, voriconazole, and caspofungin

Clinical Background

Fungal infection is a major cause of morbidity and mortality in healthcare settings; candidiasis, an infection caused by Candida yeast species, is one of the most common types of fungal infection. Invasive candidiasis is classically considered to affect the blood, brain, bones, eyes, or heart, whereas mucosal candidiasis generally affects the mouth or throat ("thrush") or vagina ("yeast infections"). In the United States, an estimated 46,000 cases of healthcare-associated invasive candidiasis occur annually. The exact impact of invasive candidiasis can be difficult to determine, because infections often occur in people who already have medical conditions. However, 30-day, all-cause mortality is about 30% among people with candidemia, the most common type of invasive candidiasis.1

Many antifungal treatments are available, and laboratory testing can help guide treatment selection. Available therapies include 2 triazoles (fluconazole and voriconazole) and 1 echinocandin (caspofungin). However, the effectiveness of each drug depends on the species of fungus 2: a particular species can be intrinsically resistant to some drugs and susceptible to others. Inadequate therapy is associated with higher in-hospital mortality.3 Thus, species identification, preferably by culture (other methods can be used as adjuncts),2 can help guide treatment decisions.

Susceptibility testing can also help guide treatment, particularly if resistance to a specific drug is more common in a species or if an isolate does not respond to treatment.4 For example, Candida glabrata resistance to triazoles and echinocandins has become more common, and resistance in Candida tropicalis and Candida parapsilosis has been reported by institutions that commonly use antifungal agents.2 Although rare, antifungal resistance among Candida albicans does occur.2 Susceptibility testing of a yeast isolate can help clinicians optimize therapy by 1) comparing susceptibility to different antifungal drugs, 2) determining the likely outcome of therapy, and 3) identifying drug resistance.4 In general, therapy response rates are 90% for isolates identified as susceptible to a certain drug in vitro and 60% for those identified as not susceptible.4

The susceptibility of a yeast isolate is measured by determining the minimum inhibitory concentration (MIC), which is the lowest drug concentration that prevents growth. An isolate can be categorized as susceptible or resistant by comparing the MIC of an isolate to established clinical breakpoints (CBPs); MICs between the breakpoints for susceptible and resistant are categorized as intermediate (or dose-dependent susceptible). CBPs for each category are specific to each species and drug.

Quest Diagnostics offers testing for antifungal drug susceptibility alone (test code 36271), with culture (test code 36268), and with culture and potassium hydroxide (KOH) testing (test code 36270); KOH testing identifies the presence of fungal infection, but does not provide species identification. Culture testing (test code 20541) and culture with KOH testing (test code 3968) are also offered without susceptibility testing.

Individuals Suitable for Testing

  • Individuals likely to be infected with Candida species that are more commonly associated with an increased frequency of antifungal resistance (eg, C glabrata)

  • Individuals with a Candida infection that fails to respond to initial antifungal treatment

Method

  • Susceptibility testing (test codes 36268, 36270, and 36271): Antifungal susceptibility is tested using a microdilution method. Briefly, an isolate is suspended and distributed to culture media containing different antifungal drugs at premeasured concentrations; the mixtures are incubated and growth is monitored to determine the MICs.
  • Identification testing (test codes 36268 and 36270): Routine culture, isolation, and identification methods are used.
  • KOH testing (test codes 36270): A mixture of KOH, which dissolves human cells, and calcofluor white, which binds fungus and fluoresces, is applied to the specimen. The specimen is examined by microscope for fluorescence, which indicates the presence of fungus.

Interpretive Information

A result of "susceptible" indicates that growth of the isolate is blocked by the corresponding drug(s) (caspofungin, fluconazole, and/or voriconazole) at the prescribed concentration. Because treatment outcomes are influenced by many factors (eg, drug pharmacokinetics, pharmacodynamics, and interactions; the patient's immune response; disease severity),4 a "susceptible" result does not ensure that a patient will respond to the particular drug.

A result of "resistant" indicates that growth of the isolate is not blocked by the corresponding drug(s) (caspofungin, fluconazole, and/or voriconazole) at the prescribed concentration. Because treatment outcomes are influenced by many factors (eg, drug pharmacokinetics, pharmacodynamics, and interactions; the patient's immune response; disease severity),4 a "resistant" result does not ensure that a patient will not respond to the particular drug.

A result of "intermediate" indicates that growth of the isolate is not effectively blocked by the corresponding drug(s) (caspofungin, fluconazole, and/or voriconazole) at the prescribed concentration.

References

  1. Invasive Candidiasis Statistics. Centers for Disease Control and Prevention. https://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html. Updated January 25, 2017. Accessed October 5, 2017.

  2. Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1-50.

  3. Parkins MD, Sabuda DM, Elsayed S, et al. Adequacy of empirical antifungal therapy and effect on outcome among patients with invasive Candida species infections. J Antimicrob Chemother. 2007;60:613-618.

  4. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012;50:2846-2856.
     

Content reviewed 12/2017

 

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