Karius Medical Case Reports: Invasive Fungal Infections in Immunocompromised Patients | Karius
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Karius Medical Case Reports: Invasive Fungal Infections in Immunocompromised Patients

Invasive fungal infections (IFIs) are associated with significant morbidity and mortality in immunocompromised patient populations, particularly in those with prolonged neutropenia, hematologic malignancies, graft-vs-host disease (GVHD), recipients of allogeneic hematopoietic stem cell transplants (HSCTs) and solid organ transplants (SOTs), and patients on immunosuppressive therapy.

Fungal infections frequently diagnosed in these high-risk patients include candidiasis, aspergillosis, cryptococcosis, coccidioidomycosis, and other endemic fungi. Patients with IFIs have a significantly higher mortality rate (up to 28.6% vs 5%), longer length of hospital stay (18.7 days vs 7.3 days), and higher hospitalization costs ($44,726 vs $15,445) compared to similar patients without IFIs.(1, 2)

Diagnosis of IFIs in a timely manner can be a challenge because clinical symptoms are often non-specific, currently available noninvasive diagnostic approaches have poor sensitivity (biomarkers such as galactomannan and serum β-D-glucan), and cultures from invasive diagnostic procedures are often slow and have limited sensitivity.(3) Additional diagnostic challenges include difficulty obtaining sufficient sample volumes and the need for anaesthesia with some diagnostic procedures.(4)

There is a clear need for rapid, sensitive, noninvasive methods for accurate diagnosis of IFIs to enable early, precisely targeted antifungal therapy.

We have demonstrated the use of the Karius™ plasma NGS test for the detection of IFIs in immunocompromised patients. A complete list of fungal pathogens that the Karius test can detect is located here.

The following are selected medical case reports that illustrate the efficacy and utility of the Karius test for these high-risk patient populations.


CASE REPORT: DETECTION OF INVASIVE FUNGAL INFECTION POST-BMT

Clinical Scenario: Following bone marrow transplant (BMT), a 12yo female with severe GVHD of her digestive tract and liver developed a large pulmonary lesion visible on chest CT. Galactomannan results were negative.

She was too ill to undergo a bronchoscopy or a lung biopsy. Her clinicians suspected an invasive fungal infection.

Karius Test Result: Aspergillus fumigatus

A. fumigatus is a ubiquitous fungus that lives on organic debris in soil and produces airborne spores. When these spores are inhaled into the lungs, they can cause infection, particularly in immunocompromised hosts.

After this result, the patient was started on liposomal amphotericin B. She began to improve on the new treatment.


CASE REPORT: PROLONGED FEBRILE NEUTROPENIA DURING CHEMOTHERAPY

Clinical Scenario: A 5yo female was admitted with fever and neutropenia. The patient was on consolidation chemotherapy for high-risk pre-B cell ALL. She had a positive blood culture for Klebsiella pneumoniae, which was treated with cefepime.

She initially defervesced on cefepime but then became febrile again, although she was still looking well. Vancomycin and micafungin were added. Repeat blood cultures and fungal blood culture came back negative, as did tests for galactomannan, β-D-glucan, Coccidiodes antibody, cryptococal antigen, and Histoplasma antigen.

Karius Test Result: Rhizopus oryzae

R. oryzae is a parasitic fungus known to be found in soil and some fruits. It is part of the Mucorales group of fungi, and is the most common cause of mucormycosis.

Based on the Karius result, a CT of the lungs was performed, which revealed a large pulmonary lesion.

The patient was successfully treated with liposomal amphotericin B and posaconazole. Pathology testing after a resection of the lung lesion later came back showing fungal elements consistent with Rhizopus, although biopsy fungal cultures were negative.


CASE REPORT: TREATMENT CHOICE CLARIFIED FOR RELAPSED AML PATIENT

Clinical Scenario: A 21yo female with relapsed AML on reinduction chemotherapy presented with a cough. The patient had a history of pulmonary Aspergillosis that had improved with posaconazole. After months of the antifungal therapy, she developed this new cough and was found to have a new right upper lobe pulmonary nodule. Due to the need for BMT, the decision was made to perform wedge resection of the right upper lobe.

The antifungal therapy was changed from posaconazole to liposomal amphotericin B after resection. Her galactomannan testing was positive. While cultures and pathology from the wedge resection were pending, the Karius result came in.

Karius Test Result: Lichtheimia ramosa

L. ramosa is a fungus most commonly found in decaying plants and other organic debris. It has the potential to be angioinvasive in immunocompromised hosts.

The Karius result provided reassurance that wedge resection was necessary and that liposomal amphotericin B was the right choice for therapy. The Lichtheimia was also found after a lung biopsy by fungal PCR and Sanger sequencing


CASE REPORT: TARGETED ANTIFUNGAL TREATMENT FOR LEUKEMIA PATIENT

Clinical Scenario: A 9yo male with a history of relapsed leukemia was admitted to the hospital after two weeks of fever, cough, and thigh pain. He received a BMT 18 months prior and had a history of an undiagnosed infection in his lungs and thighs a year ago that responded well to broad-spectrum antifungal treatment. For these new symptoms, the patient was given broad-spectrum antibiotics and antifungals.

A chest CT showed multiple lung nodules and MRI of his legs showed microabscesses. Bronchoalveolar lavage cultures were initially negative. Coccidioides serology, β-D-glucan, and galactomannan were also negative.

Karius Test Result: Coccidioides posadasii

C. posadasii is a fungus that can cause coccidioidomycosis, or Valley Fever, when the spores are inhaled. It lives in the arid or semi-arid soil environments of the southwestern United States and parts of Mexico and Central America.

Based on this result, the patient was placed on early targeted antifungal treatment. Bronchoalveolar lavage cultures eventually turned positive for Coccidioides posadasii.


In these cases, the Karius test was able to accurately identify specific IFIs within a clinically relevant timeframe, enabling the clinicians to provide more timely and precise treatment to their patients. We will discuss additional case reports in future posts.

REFERENCES

  1. Menzin et. al. Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients. Clinical Report. Am J Health-Syst Pharm (2009) 66: 1711–1717.
  2. Hahn-Ast et. al. Overall survival and fungal infection-related mortality in patients with invasive fungal infection and neutropenia after myelosuppressive chemotherapy in a tertiary care centre from 1995 to 2006. J Antimicrob Chemother (2010) 65: 761 –768.
  3. Cornely, O.A. Aspergillus to Zygomycetes: Causes, Risk Factors, Prevention, and Treatment of Invasive Fungal Infections. Infection (2008) 36: 296.
  4. Warris, A. & Lehrnbecher, T. Progress in the Diagnosis of Invasive Fungal Disease in Children. Curr Fungal Infect Rep (2017) 11: 35–44.

DISCLAIMER: Case descriptions have been modified to protect patient privacy and, while every attempt has been made to provide accurate information, errors may occur. This information is provided for educational purposes only, and is not intended to be used as medical advice.