T2Bacteria enabled the detection of a polymicrobial infection as well as the detection of Enterococcus faecium in a patient where cultures remained negative. Rapid species identification lead to targeted therapy and eventual discharge.

Klinik Favoriten | Vienna, Austria

Patient History

Age and Sex: 53-year-old male
History: The patient had no history of chronic diseases
Presentation: The patient was admitted to the hospital with COVID-19 and respiratory failure and was mechanically ventilated
Risk Factors: The patient had multiple risk factors for infection.

• Presence in ICU
• Broad spectrum antimicrobial therapy
• Mechanical ventilation

Evaluation and Treatment

Initial presentation
The patient was admitted to the hospital eight days after the onset of symptoms and then admitted to the ICU with COVID-19 and respiratory failure. The patient was mechanically ventilated.

Weaning was complicated due to ventilator-associated pneumonia.

T2Bacteria Result
The T2Bacteria Panel was positive for Staphylococcus aureus and Escherichia coli, and targeted therapy was initiated before culture results were returned.

Culture Result
A bronchoalveolar lavage sample was also positive for Staphylococcus aureus and Escherichia coli.

Patient Deterioration
10 days later, the patient developed septic shock from an unknown source. Several blood, bronchoalveolar, and urine cultures were taken, but no growth occurred.

Another T2Bacteria Panel was run and was positive for Enterococcus faecium, leading to targeted therapy. A transesophageal echocardiogram revealed endocarditis of the native aortic valve.

Day 42
After 42 days in the ICU, the patient was discharged to a rehabilitation facility.

T2Candida enabled the detection of candidemia 29 hours before a positive blood culture was returned. Early detection allowed for the rapid initiation of antifungal therapy in a critically ill COVID-19 patient.

Lee Health | Fort Myers, Florida

Patient History

Age and Sex: Elderly Male
History: Patient was admitted to the hospital with confirmed COVID-19. His past medical history included Type 2 diabetes mellitus and hypertension
Presentation: The patient required oxygen support via nasal cannula. A chest radiograph showed bibasilar infiltrates and initial blood cultures were negative.
Risk Factors: The patient had multiple risk factors for candidemia during hospitalization.

• Presence in ICU
• Broad-spectrum antimicrobial therapy
• Immunosupressing medications

Evaluation and Treatment

Day 1
The patient was initiated on azithromycin and methylprednisolone, was given one dose of convalescent plasma

Day 2
Patient was administered 1 dose of tocilizumab (8mg/kg)

Day 3
Patient was intubated for worsening respiratory status

Day 14
Patient developed new fever, chest x-ray showed increased opacities, broad-spectrum antimicrobial therapy was initiated for suspected bacterial pneumonia

Day 15 & 16
Fever escalates (Tmax 101.9F and 103F, respectively). Additional blood cultures were obtained and T2Candida was ordered. T2Candida was positive for Candida albicans/Candida tropicalis 29 hours before the positive blood culture. On the evening of day 16 anidulafungin was initiated

Day 18
Patient defervesced

Day 30
Patient was discharged to a long-term acute care center

1. Cubillos, A., et al. CAP, 2021

In a study conducted by Lee Health System clinicians at Lee Memorial Hospital, Fort Myers, Florida, T2Bacteria^® Panel research use only (RUO) results were compared to the conventional standard of care culture results. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

Presentation

A 53-year-old immunocompromised, morbidly obese female with a recent history of surgery to drain an intra-abdominal abscess. The patient presented at the emergency department 8 days post-op with fever, chills, and abdominal pain. Sepsis was suspected and the patient was admitted with orders for blood cultures, T2Bacteria, and broad-spectrum antibiotics.

Patient Selection Criteria

SIRS criteria

• Temperature- 103.4
• Heart Rate-133 BP90/62
• Respiratory Rate – 34
• WBC: 6,800/mm³

NEWS Score: 9

QSOFA Score – 2

Evaluation and Treatment Decision

Diagnosis: Suspected Intra-abdominal sepsis

Empiric Therapy: Linezolid, Aztreonam, Metronidazole

Linezolid was chosen for gram-positive coverage due to challenges with vancomycin dosing in obese patients. Aztreonam was chosen for gram-negative coverage due to the patient’s history of penicillin allergy. Metronidazole was chosen for anaerobic coverage.

T2Bacteria Result: Positive for E. coli and P. aeruginosa and negative for S. aureus, E. faecium, and K. pneumoniae. (SA -, PA + & EC +); T2Bacteria results were not reported as this case was part of an observational study.

Blood Culture Result: Negative

Decision making based on T2Bacteria Result

The negative S. aureus result meant that the patient did not have MRSA and therefore linezolid could have been discontinued after the first dose when the T2Bacteria result was available, a 4.5-day reduction in linezolid. The patient’s therapy could have been more targeted gram-negative coverage by switching to meropenem to cover E. coli and P. aeruginosa

Discussion

Upon admission, the patient was initially given the broad-spectrum antibiotics linezolid, aztreonam, and metronidazole for the treatment of suspected intra-abdominal sepsis. Due to the patient’s recent healthcare exposure, she was at risk for organisms such as MRSA (methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa in addition to the more common causes of intra-abdominal infection such as enterobacteriaceae and anaerobic organisms.

At the time of admission, she had blood cultures obtained and T2Bacteria ordered. At Lee Health patient selection for T2Bacteria testing was based on the NEWS (National Early Warning Score) scoring system. The NEWS score was developed to standardize the approach to detection of clinical deterioration in acutely ill patients in the United Kingdom, and a score of 7 or higher puts the patient in the high-risk category. This patient also was positive for 3 of 4 SIRS criteria and had a qSOFA score of 2 indicating a high risk of mortality.

Due to the negative blood culture (T2Bacteria results were not reported as this case was part of an observational study), the patient remained on empiric therapy for 5 days and then was changed to oral therapy and discharged 2 days later. Had the T2Bacteria result been reported, the patient could have been changed to meropenem to cover the E. coli and P. aeruginosa, allowing discontinuation of aztreonam. Given the S. aureus was negative, linezolid could have been discontinued as well. Discontinuation of these two antibiotics within the first 24 hours of admission would have led to ~$6,000 savings in antibiotic charges, and potentially led to earlier discharge on effective oral therapy.

The retrospective approach from a study at Northwestern University Feinberg School of Medicine provided an ideal opportunity for detailed case studies, comparing the results using the available standard of care at the time (culture on blood, urine, and BAL samples) against more sensitive testing, the T2Bacteria^® Panel RUO, five years later. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

The Patient

A 25-year-old female with cerebral palsy diagnosed with duodenal pneumatosis. The patient was admitted to the hospital for gastrointestinal (GI) issues and started on empiric vancomycin and Zosyn.

Day 8 of Treatment

The patient developed tachypnea and hypoxia and was diagnosed with aspiration pneumonia. The patient’s respiratory culture grew 15,000 CFU/mL Pseudomonas aeruginosa and 1,000 CFU/mL Klebsiella pneumoniae, both pan-sensitive, so she was appropriately treated.

• The T2Bacteria Panel RUO result from blood drawn on day 8 was negative
• Blood culture drawn on day 8 was negative

Day 35 of Treatment

The patient was discharged after prolonged GI complications.

Case Study Analysis

The negative T2Bacteria Panel RUO result most likely indicates an appropriately managed infection in the lung that was contained and did not progress, and that did not require a change in antibiotic treatment.

The retrospective approach from a study at Northwestern University Feinberg School of Medicine provided an ideal opportunity for detailed case studies, comparing the results using the available standard of care at the time (culture on blood, urine, and BAL samples) against more sensitive testing, the T2Bacteria^® Panel RUO, five years later. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

The Patient

A 73-year-old female with lymphoma was in the hospital on chemotherapy and diagnosed with pneumonia and septic shock.

Day 1 of Treatment

The blood culture tested positive for Pseudomonas aeruginosa. The patient was given cefepime and ciprofloxacin.

• Subsequent blood cultures were negative, but the patient deteriorated, developed septic shock, and required intubation.

Day 17 of Treatment

The patient’s bronchoalveolar lavage (BAL) cultures showed 100 CFU/mL Achromobacter and 100 CFU/mL Pseudomonas aeruginosa, below the threshold for clinically relevant titer level of 10,000 CFU/mL set by the laboratory. The results were not alarming, and the antibiotic regimen was not changed.

• T2Bacteria Panel RUO identified Pseudomonas aeruginosa from blood drawn on day 17
• Blood culture drawn on day 17 was negative

Day 20 of Treatment

The BAL cultures grew significantly to 100,000 CFU/mL Achromobacter and 100,000 CFU/mL Pseudomonas aeruginosa.

Day 23 of Treatment

The patient expired under palliative care.

Case Study Analysis

The T2Bacteria Panel RUO’s identification of Pseudomonas aeruginosa 3 days earlier than the BAL cultures and in the absence of positive blood cultures likely indicates the progression of infection due to both ineffective source control and inappropriate antimicrobial therapy. The T2Bacteria Panel RUO result may have led to faster-targeted therapy, such as the addition of an aminoglycoside to better treat this patient’s septic shock, potentially impacting the outcome.

In a study conducted by Lee Health System clinicians at Lee Memorial Hospital, Fort Myers, Florida, T2Bacteria^® Panel research use only (RUO) results were compared to the conventional standard of care culture results. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

The Patient

84-year-old male with diabetes, prostate cancer, and end-stage renal disease on hemodialysis.

Presentation

The patient was experiencing chills during dialysis. The patient had not been feeling well for a week and was complaining of weakness, nausea, and vomiting. The patient was found to have a fever of 101.7 and lactic acid of 3.2, while urinalysis was negative.

Empiric Therapy Decision

The patient was started on vancomycin and piperacillin-tazobactam. Piperacillin-tazobactam was discontinued on day 3 based on the blood culture result.

Culture Result

Blood culture was positive for S. aureus on day 3.

Paired T2Bacteria Result

Positive for S. aureus, negative for E. coli, E. faecium, P. aeruginosa, and K. pneumoniae.

Case Study Analysis

T2Bacteria^® would have accelerated the clinical care pathway for this patient. With the T2Bacteria results in hours, piperacillin-tazobactam could have been discontinued two days earlier, on day 1. The S. aureus positive confirmed that the infection was being appropriately managed with the vancomycin.

An early T2Bacteria result could have reduced other health risks through appropriate discontinuation of unnecessary antibiotic therapy. For example, extended antibiotic treatment is associated with an increased risk of a Clostridium difficile infection. In addition, many patients with extended antibiotic treatment experience an increased risk of nephrotoxicity, though in this case study, the patient was already on dialysis.

In a study conducted by Lee Health System clinicians at Lee Memorial Hospital, Fort Myers, Florida, T2Bacteria^® Panel research use only (RUO) results were compared to the conventional standard of care culture results. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

The Patient

53-year-old immunocompromised, morbidly obese female with a recent history of surgery to drain an intra-abdominal abscess

Presentation in the Emergency Room

The patient presented at the emergency department 8 days post-op with fever, chills, and abdominal pain. She was started on empiric antibiotics and admitted to the emergency room. The patient continued on empiric IV antibiotic therapy for 5 days, then transitioned to 2 days of oral antibiotics prior to discharge.

Empiric Therapy Decision

The patient was started on linezolid, aztreonam, and metronidazole. Linezolid was chosen for gram-positive coverage because vancomycin dosing is very difficult for obese patients. The patient had allergies to penicillin and bactrim. Aztreonam was chosen for gram-negative coverage as the piperacillin-tazobactam substitute because of the patient’s allergy. Metronidazole was chosen for anerobic coverage.

Culture Results

Blood and urine cultures were negative.

Paired T2Bacteria Result

Positive for E. coli and P. aeruginosa and negative for S. aureus, E. faecium, and K. pneumoniae.

Case Study Analysis

The T2Bacteria Panel result could have been a powerful aid in stewardship through the identification of E. coli and P. aeruginosa and the rule out of S. aureus (and therefore rule out of MRSA).

While the empiric choice was effective and the patient responded well, it was also broader than necessary, as it covered MRSA, a primary species of concern at this community hospital.

The negative S. aureus result meant that the patient did not have MRSA and therefore linezolid could have been discontinued after the first dose when the T2Bacteria result was available. The 4.5-day reduction in linezolid ($289 per dose and two doses per day) amounts to an estimated savings of $2,600 as these antibiotics were not needed.

The patient’s therapy could have been more targeted by switching to meropenem to cover E. coli and P. aeruginosa, as well as providing the anaerobic coverage needed. The penicillin allergy history precluded the utilization of a more narrow beta-lactam or beta-lactam agent combination.

The retrospective approach from a study at Northwestern University Feinberg School of Medicine provided an ideal opportunity for detailed case studies, comparing the results using the available standard of care at the time (culture on blood, urine, and BAL samples) against more sensitive testing, the T2Bacteria^® Panel RUO, five years later. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

The Patient

25-year-old female with cerebral palsy diagnosed with duodenal pneumatosis. The patient was admitted to the hospital for gastrointestinal (GI) issues and started on empiric vancomycin and Zosyn.

Day 8 of Treatment

The patient developed tachypnea and hypoxia and was diagnosed with aspiration pneumonia. The patient’s respiratory culture grew 15,000 CFU/mL Pseudomonas aeruginosa and 1,000 CFU/mL Klebsiella pneumoniae, both pan-sensitive, so she was appropriately treated.

• The T2Bacteria Panel RUO result from blood drawn on day 8 was negative
• Blood culture drawn on day 8 was negative

Day 35 of Treatment

The patient was discharged after prolonged GI complications.

Case Study Analysis

The negative T2Bacteria Panel RUO result most likely indicates an appropriately managed infection in the lung that was contained and did not progress, and that did not require a change in antibiotic treatment.

The retrospective approach from a study at Northwestern University Feinberg School of Medicine provided an ideal opportunity for detailed case studies, comparing the results using the available standard of care at the time (culture on blood, urine, and BAL samples) against more sensitive testing, the T2Bacteria^® Panel RUO, five years later. This comparison allows an analysis of how the use of the T2Bacteria Panel could have potentially changed clinical practice and outcomes.

The Patient

A 73-year-old female with lymphoma was in the hospital on chemotherapy and diagnosed with pneumonia and septic shock.

Day 1 of Treatment

The blood culture tested positive for Pseudomonas aeruginosa. The patient was given cefepime and ciprofloxacin.

• Subsequent blood cultures were negative, but the patient deteriorated, developed septic shock, and required intubation.

Day 17 of Treatment

The patient’s bronchoalveolar lavage (BAL) cultures showed 100 CFU/mL Achromobacter and 100 CFU/mL Pseudomonas aeruginosa, below the threshold for clinically relevant titer level of 10,000 CFU/mL set by the laboratory. The results were not alarming, and the antibiotic regimen was not changed.

• T2Bacteria Panel RUO identified Pseudomonas aeruginosa from blood drawn on day 17
• Blood culture drawn on day 17 was negative

Day 20 of Treatment

The BAL cultures grew significantly to 100,000 CFU/mL Achromobacter and 100,000 CFU/mL Pseudomonas aeruginosa.

Day 23 of Treatment

The patient expired under palliative care.

Case Study Analysis

The T2Bacteria Panel RUO’s identification of Pseudomonas aeruginosa 3 days earlier than the BAL cultures and in the absence of positive blood cultures likely indicates the progression of infection due to both ineffective source control and inappropriate antimicrobial therapy. The T2Bacteria Panel RUO result may have led to faster-targeted therapy, such as the addition of an aminoglycoside to better treat this patient’s septic shock, potentially impacting the outcome.