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Karius Medical Case Reports: The Race to Diagnose Sepsis

Sepsis affects more than 1.5 million Americans annually, with about 250,000 of these patients dying each year from this extreme response to infection. It can be caused by common conditions such as pneumonia, bloodstream infections, and infections of the urinary tract, gastrointestinal tract, and skin.(4)

In sepsis, time is of the essence for making a diagnosis and initiating early, life-saving treatment. Rapid identification of the causative pathogen is critical to targeting early, effective antimicrobial therapy, which directly impacts morbidity and mortality.

When blood cultures are negative and the infection is unable to be identified, patients have more comorbidities and acute organ dysfunction, as well as higher in-hospital mortality -- 34.6% vs 22.7% -- compared to patients with positive blood cultures.(2)

Sepsis also carries a high economic burden. The total annual cost for hospitalization of patients with severe sepsis is estimated to be nearly $17 billion USD, with the mean costs per hospital stay being $26,820 for standard care, $36,218 if an ICU stay is required, and $38,036 if surgery is needed.(1)

There is a clear need for comprehensive infectious disease diagnostic tests that accurately identify a breadth of potential pathogens to inform more effective therapy. This is especially true for sepsis, since in many cases a causative pathogen is never identified.

We have demonstrated the use of the Karius™ plasma NGS test for the detection of pathogens in patients with suspected sepsis. A complete list of 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 patients with sepsis.


Case Report: Sepsis and Respiratory Failure

Clinical Scenario: A 72 year-old male with ischemic cardiomyopathy requiring left ventricular assist device (placed a few months prior) was admitted to the hospital with respiratory failure requiring intubation and mechanical ventilation. He worsened clinically despite broad-spectrum antibiotics.

Chest imaging revealed bilateral pulmonary infiltrates. BAL fluid was obtained via bronchoscopy, and routine cultures were negative. AFB smears were also negative, and AFB cultures were pending at the time a Karius test was ordered.

Karius Test Result: Mycobacterium tuberculosis complex

Karius testing returned the M. tuberculosis result within one day of sample receipt.

The patient was started on 4-drug treatment for pulmonary tuberculosis and showed steady improvement.

The AFB culture from BAL fluid turned positive for M. tuberculosis after 3 weeks, and a bone marrow biopsy showed granulomas consistent with disseminated tuberculosis.

The patient was able to initiate targeted tuberculosis treatment without waiting for the AFB culture.


Case Report: Sepsis and Endocarditis

Clinical Scenario: An 8-year-old female with a history of rheumatic heart disease and severe mitral insufficiency underwent a mitral valve replacement with a St. Jude valve in early 2014.

In the summer of 2017, the patient presented with prolonged fever and tachycardia, and had echocardiographic findings of a vegetation on her prosthetic mitral valve. She was started on intravenous vancomycin and rifampin. Initial blood cultures were negative, but antibiotics were continued for presumptive infective endocarditis.

A higher-resolution echocardiogram showed destruction of the mitral valve with severe mitral insufficiency, severe mitral stenosis, and an associated vegetation. The patient was started on linezolid and gentamicin. Bacterial, fungal, and AFB blood cultures were also negative, as were the following lab tests: Q fever serology, Bartonella PCR, Brucella serology, Tropheryma whipplei PCR, ASO/Anti-DNAse B.

The patient was switched from linezolid/gentamicin to linezolid/doxycycline, and a Karius test was ordered.

Karius Test Result: Kingella kingae (HACEK group)

The Karius result prompted an antibiotic change to cefazolin while the patient was still in the hospital. Antibiotics were ultimately switched to ceftriaxone for ease of dosing to complete a 6-week outpatient course, and the patient eventually underwent surgery to replace the diseased valve. 

Following valve replacement surgery, pathology of the explanted mitral valve showed diffuse eosinophilic necrosis with dystrophic calcification. Bacterial PCR of the explanted valve ultimately turned positive for Kingella species.

In this case, Karius testing identified the causative organism of the culture-negative endocarditis prior to surgical intervention and valve tissue diagnosis, allowing for early, targeted antibiotic treatment.


Case Report: Sepsis, Altered Mental Status, and Respiratory Failure

Clinical Scenario: An adult male with a history of asplenia was admitted to the ICU with hypotension, altered mental status, and Acute Respiratory Distress Syndrome. Broad empiric antimicrobial treatment was initiated.

Blood cultures were initially negative, but Gram stain of the buffy coat revealed Gram-negative rods. A Karius test was also ordered.

Karius Test Result: Capnocytophaga canimorsus

The antibiotic regimen was optimized to treat this pathogen. Blood cultures eventually grew GNRs which were identified as C. canimorsus more than one month later.

Karius testing enabled this patient to receive targeted treatment sooner than would have been possible with blood cultures alone.


This post is part of a series of Karius Medical Case Reports. We will discuss additional cases in future posts.

References

  1. Chalupka, A. & Talmor, D. The Economics of Sepsis. Crit Care Clin 28 (2012) 57-76.
  2. Gupta et. al. Culture-Negative Severe Sepsis: Nationwide Trends and Outcomes. CHEST (2016) 150(6):1251-1259.
  3. Mancini et. al. The Era of Molecular and Other Non-Culture-Based Methods in Diagnosis of Sepsis. Clinical Microbiology Reviews (2010) 23(1):235-251.
  4. https://www.cdc.gov/sepsis/datareports/index.html

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.