A 70-year-old Man With a Difficult-to-Treat C auris Infection*

Presented by Dr Mohanad M. Al-Obaidi

Case Presentation

A male in his 70s with a history of diabetes mellitus, hypertension, and metastatic gastric adenocarcinoma status post-surgery and chemotherapy develops sepsis and an extended-spectrum beta-lactamases (ESBL) E coli bacteremia. He is instrumented with a peripherally inserted intravenous central catheter (PICC) line for antibiotic delivery. He then presented with abdominal pain and diarrhea due to C difficile colitis. On day 10 of the current hospitalization, blood cultures show Candida yeast, which is tentatively identified as C haemulonii. This is subsequently identified as C auris. Based on the candidemia diagnosis, the patient is started on micafungin (100 mg daily), and the PICC line is removed.

On day 15, the repeated blood cultures from the peripheral line are still positive for C auris, despite the removal of the PICC line and the start of intravenous micafungin (100 mg daily) 5 days prior.

What is be the next step?

  1. Add intravenous liposomal amphotericin B, 5 mg/kg per day
  2. Assess other sources of infection (eg, imaging studies to evaluate deep-seated infection, evaluation of infective endocarditis echocardiogram)
  3. This is not an unusual finding with this infection, and there is nothing to add at the moment
  4. This could be related to the natural history of candidemia, but assessment of other sources is warranted

Click Here to View Answer and Discussion

Discussion:

Answer 4 is correct. C auris candidemia can persist for several days but given the complexity of our presented case and the difficulties in treating C auris, other potential sources of infection should be evaluated.

Answer 1 is reasonable but not ideal. Adding another antifungal can be considered in situations of difficult-to-treat C auris infection. While clinical evidence is not well established, switching to liposomal amphotericin B or adding it to echinocandin therapy may be considered for cases of persistent candidemia lasting more than 5 days.1,2 However, before starting another agent, it would be reasonable to look for other unaddressed sources that explain the persistent candidemia.

Answer 2 is a correct answer but not complete. Assessing different potential sources of candidemia is crucial to providing adequate therapy and control of the infection. Based on the patient’s risk factors and provided clinical history,3 the clinician should use a dedicated imaging modality to evaluate deep-seated infection that can point to source control.

Answer 3 is also reasonable but not complete. While C auris candidemia may persist for several days, the provided case has a complex surgical history, and it is reasonable to evaluate for other possible sources to control and repeat blood cultures until we have negative cultures.

Case Continued

The microbiology laboratory performed antifungal susceptibility testing of the C auris isolate, and the minimal inhibitory concentration (MIC) results are shown in the Table.

Based on the provided MICs, would you change or add a new antifungal agent?

  1. Stop intravenous micafungin and start liposomal amphotericin B 5 mg/kg per day.
  2. Continue intravenous micafungin 100 mg daily
  3. Continue intravenous micafungin and add oral voriconazole
  4. Continue intravenous micafungin and start intravenous liposomal amphotericin B, 5 mg/kg per day

Click Here to View Answer and Discussion

Discussion:

Correct answer: 2. Based on the provided antifungal susceptibilities, it is reasonable to continue intravenous micafungin at this time as long as the candidemia is not persistent and we have good source control.

Answer 1 is not correct. Liposomal amphotericin B can be considered as a treatment option if the echinocandin MIC is elevated1 and if the patient has persistent candidemia for more than 5 days. While there are currently no established susceptibility breakpoints for C auris, breakpoints have been proposed based on those established for closely related Candida species and expert opinion. Therefore, breakpoints should be considered as a general guide. The current Clinical and Laboratory Standards Institute (CLSI) interpretation of antifungal MICs for C auris addresses rezafungin, with a breakpoint of ≤0.5 µg/ml (M27M44S) for susceptible isolates.4 CDC lists tentative breakpoints for amphotericin B (≥2 µg/mL) and other echinocandins, with tentative breakpoints for micafungin and caspofungin of 4 and 2 µg/mL, respectively.5 Therefore, based on the current knowledge of C auris antifungals MICs and breakpoints, and the antifungals MICs provided above, stopping micafungin and changing to liposomal amphotericin B is not warranted.

Answer 3 is not correct. This answer explores the idea of synergistic activity of combining antifungals against C auris. Also, having an oral antifungal (in this case, voriconazole) as an option may facilitate the patient’s care up to hospital discharge. However, the case presents a fluconazole-resistant isolate, and there is limited clinical knowledge about breakpoints for other triazoles in the case of C auris, as well as the clinical efficacy of voriconazole in such cases. CDC guidelines do not list a breakpoint for voriconazole; therefore, this option is not favorable.5

Answer 4 is not correct. Based on the provided MICs, there is no indication to add liposomal amphotericin B. However, in cases of persistent candidemia for several days (≥5 days) or an echinocandin-resistant isolate, switching to liposomal amphotericin B or attempting a combination of different antifungals may be considered. However, very limited clinical data are available to support such a clinical decision.1,2 Another option to explore, especially if the C auris isolate is pan-drug resistant, is to consider an investigational agent through expanded access programs for fosmanogepix or ibrexafungerp.1,6

Case Continued

Twenty-one days into the hospital stay and 6 days after the last positive C auris blood culture (which remained positive for 8 days), blood cultures are finally negative. Dilated ophthalmic examination was negative, and imaging studies did not show any other source for C auris. The patient reports feeling well and states he is ready to leave the hospital.

How long do you treat C auris candidemia, and do you recommend placing another central venous catheter (CVC) for the intravenous antifungals and antibiotics?

  1. Place a CVC and continue micafungin for 6 more weeks
  2. Stop all antifungals and discharge the patient home
  3. Do not place any CVC and continue micafungin 100 mg per day for another 3 weeks
  4. Continue micafungin for an additional 8 days. Alternatively, consider prescribing rezafungin, which would not need a CVC and can be given once weekly

Click Here to View Answer and Discussion

Discussion

Correct answer: 4. An echinocandin is needed; micafungin could be continued. Alternatively, rezafungin, which is given once weekly, would eliminate the need for a new CVC placement.7 Also, currently rezafungin has a CLSI breakpoint for antifungal susceptibility (≤0.5 has CLSI µg/ml). While clinical experience with rezafungin to treat C auris is limited, including utility of breakpoints, clinicians may consider obtaining susceptibility testing.

Answer 1 is incorrect. While negative blood cultures permit the placement of CVC, the prolonged duration of therapy is not warranted in this case. The current IDSA guidelines recommend providing therapy for 2 weeks following documented clearance of Candida spp. from the bloodstream and resolution of signs and symptoms attributable to infection.8 Those milestones were reached 6 days ago in this case.

Answer 2 is also incorrect. Stopping therapy at this point is not reasonable, since the patient has 8 more days of therapy to complete, according to the IDSA guidelines.

Answer 3 is incorrect. There are no current recommendations for antifungal use for 4 weeks total after the last positive blood culture for the treatment of candidemia.

*Continuation of Dr Al-Obaidi’s other case.

Click Here to View Resources

Resources

  1. Centers for Disease Control and Prevention. Treatment and Management of C. auris Infections and Colonization. Accessed March 27, 2024, https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html
  2. Hernando-Ortiz A, Eraso E, Jauregizar N, de Groot PW, Quindós G, Mateo E. Efficacy of the combination of amphotericin B and echinocandins against Candida auris in vitro and in the Caenorhabditis elegans host model. Microbiol Spectr. 2024;12(1):e0208623. doi:10.1128/spectrum.02086-23
  3. Bassetti M, Azoulay E, Kullberg BJ, et al. EORTC/MSGERC Definitions of Invasive Fungal Diseases: Summary of Activities of the Intensive Care Unit Working Group. Clin Infect Dis. 2021;72(Suppl 2). doi:10.1093/cid/ciaa1751
  4. Clinical & Laboratory Standards Institute. M27M44S-ED3:2022 Performance Standards for Antifungal Susceptibility Testing of Yeasts, 3rd Edition. 2022. https://em100.edaptivedocs.net/GetDoc.aspx?doc=CLSI%20M27M44S%20ED3:2022&scope=user
  5. Centers for Disease Control and Prevention. Candida auris: Antifungal Susceptibility Testing and Interpetation. Reviewed May 209, 2020. Accessed March 27, 2024. https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html
  6. Treviño-Rangel RJ, González GM, Montoya AM, Rojas OC, Elizondo-Zertuche M, Álvarez-Villalobos NA. Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review. J Fungi (Basel). 2022;8(11). doi:10.3390/jof8111144
  7. Jo J, Tran T, Beyda N, et al. Development of the invasive candidiasis discharge [I Can discharge] model: a mixed methods analysis. Eur J Clin Microbiol Infect Dis. 2022;41(10). doi:10.1007/s10096-022-04473-w
  8. 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 Inf Dis. 2016;62(4). doi:10.1093/cid/civ933

Chair

Jose Vazquez, MD, FACP, FIDSA

Division Chief, Department of Infectious Diseases
Augusta University. Medical College of Georgia
Augusta, Georgia

Faculty

Mohanad M. Al-Obaidi, MD, MPH

Clinical Assistant Professor, Medicine
The University of Arizona College of Medicine
Tucson, Arizona

Justin F. Hayes, MD

Clinical Assistant Professor, Medicine
Co-Director, Antimicrobial Stewardship Program
The University of Arizona College of Medicine
Tucson, Arizona

Sophie Jones Allen, PhD, MSc

Epidemiologist
Centers for Disease Control and Prevention
Atlanta, Georgia

Meghan Lyman, MD

Epidemiology Team Lead
Medical Officer
Mycotic Diseases Branch
Division of Foodborne, Waterborne, and Environmental Diseases
Centers for Disease Control and Prevention
Atlanta, Georgia, USA

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