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Clinical Utility of the T2Candida NPV

57-year-old male transferred to long-term acute care (LTAC) facility for long-term ventilatory support and rehabilitation.

Discussion

This case highlights how the high negative predictive value (NPV) of the T2Candida Panel enables the ability to rule out the five most common Candida species in a clinical setting. In this case, because of the rapid negative result, antifungal therapy could be de-escalated early in the patient’s course.

Presentation

57-year-old male transferred to long-term acute care (LTAC) facility for long-term ventilatory support and rehabilitation. On Day 6 of admission to LTAC, the patient spiked a fever of 100.9 F with increased oxygen requirements and drainage from enterocutaneous fistula. The patient has a history of penetrating abdominal trauma, tracheostomy, and multiple re-explorations/evacuations of intra-abdominal abscesses, partial gastrectomy, and placement of abdominal wound VACs.

Patient Selection Criteria

Multiple abdominal surgeries, empiric use of micafungin

Evaluation and Treatment

Diagnosis

Sepsis from intra-abdominal infection and/or possible pneumonia

Empiric Therapy

The patient was switched from ceftriaxone to imipenem/cilastatin, vancomycin, and micafungin for suspected abdominal sepsis and possible pneumonia.

Blood Culture Result

No growth

Tracheal Aspirate Culture Result

No growth

Urine Culture

Vancomycin-resistant Enterococcus faecium

T2Candida Panel Result

Negative for the five target pathogens

Decision making based on the T2Candida Result

T2Candida was negative, therefore micafungin was discontinued after only a single dose.

Blood and sputum cultures demonstrated ‘no growth’ after 48 hours. Urine culture was positive for VRE, so vancomycin was switch to linezolid on day 3 of antimicrobial therapy. The patient completed a course of antibacterials x 10 days total.

A patient suffering from status epilepticus and traumatic brain injury was admitted to the ICU

Discussion

In the case presented, the T2Bacteria result enabled clinicians to initiate appropriate antibiotic therapy within three hours from the diagnosis of septic shock and helped to avoid the unnecessary Gram-positive antibiotic coverage while targeting therapy to cover for P. aeruginosa.

Presentation

A 36-year-old male patient suffering from status epilepticus and traumatic brain injury was intubated and admitted to the Intensive Care Unit (ICU). During his ICU stay the patient became febrile and a diagnosis of intubation-associated sinusitis was made. Prior respiratory cultures revealed Klebsiella pneumoniae (KPC-producing) and the patient was started on ceftazidime-avibactam. Over the next 24 hours, the patient deteriorated clinically and fulfilled the criteria of septic shock requiring fluid resuscitation and initiation of vasopressors. The attending physicians obtained new blood cultures and added empiric Gram-positive antibiotic coverage. A T2Bacteria test was also ordered.

Patient Selection Criteria

Critical care patient with septic shock and bloodstream infection suspected.

Evaluation and Treatment Decision

Diagnosis

Septic shock

Empiric Therapy

The patient was on ceftazidime-avibactam at the time of septic shock. This antibiotic selection was based on previous microbiology results (respiratory fluid culture).

T2Bacteria Result

P. aeruginosa

Blood Culture Result

P. aeruginosa (returned 72 hours after T2Bacteria positive result)

Decision making based on T2Bacteria Result

A rapid T2Bacteria result allowed for the timely identification of the P. aeruginosa bacteremia in a patient that was receiving therapy for multidrug-resistant K. pneumoniae infection. This finding prompted the escalation of therapy with the addition of colistin to cover for the P. aeruginosa infection according to local antibiotic resistance patterns and breakthrough infection while on ceftazidime-avibactam. Gram-positive coverage was discontinued and the blood culture result came back positive for P. aeruginosa 72 hours later.

 

A 68-year-old male with fevers, lethargy, and anorexia was admitted.

Discussion

This case highlights not only the benefit of rapid species identification with the T2Canida Panel but also timely diagnosis of Candida endocarditis that may present as culture-negative endocarditis.  It also illustrates the potential role of T2Candida in monitoring clinical response in a persistently positive Candida endocarditis patient.

Presentation

A 68-year-old male with a past medical history of systolic heart failure with ICD placement, ulcerative colitis status post a colectomy, cirrhosis secondary to primary sclerosing cholangitis underwent a liver transplant. A few months later the patient was admitted with fevers, lethargy, and anorexia.  Routine blood cultures were negative, however, Cytomegalovirus (CMV) levels were positive and IV ganciclovir was initiated.  The patient remained in the hospital for five days and was discharged home.  The patient was readmitted ten days later with fever, fatigue, and a blind spot in the right eye with improving CMV. Blood culture and T2Candida were drawn, and anidulafungin was started. T2Candida was reported positive for C. albicans/C. tropical and ophthalmology obtained intravitreal cultures which were positive for C. albicans. A TTE was obtained and was negative for vegetation.  Blood cultures were pending but negative to date.  ID recommended intravitreal voriconazole injections, fluconazole 800mg daily adjusted for renal function for six months and to continue IV anidulafungin for two weeks and discharged home.  The patient was re-admitted for a 3rd time with fevers up to 104° F, dyspnea, and fatigue.  CMV PCR was negative, blood cultures were drawn, and another T2Candida was obtained. T2Candida remained persistently positive whereas the blood cultures were persistently negative to date. The patient was continued on fluconazole and restarted on anidulafungin.

Pleural and pericardial effusions were identified and no organism was detected via multiple different diagnostic tests.  A TEE was done due to the persistently positive T2Candida and mobile vegetation was identified on the pulmonic valve.  The patient was considered to be too high risk for surgical removal of the vegetation thus an angiovac was done by interventional radiology.  Tissue cultures of the vegetation were obtained and C. albicans and S. hominis grew out.  Repeat ophthalmology evaluation showed retinitis improving.

Patient Selection Criteria

Empiric use of an echinocandin

Evaluation and Treatment

Diagnosis: Candida retinitis and Candida infective endocarditis

Empiric Therapy: The patient was started on anidulafungin

T2Candida Panel Result: Positive for C. albicans/C. tropicalis, negative for the remaining three pathogens.

Blood Culture Result: No growth

Decision making based on the T2Candida Result

A rapid and persistent T2Candida positive for C. albicans/C. tropicalis prompted the team start the patient on anidulafungin and fluconazole due to the source of the infection.  Once Candida retinitis was confirmed it lead to the addition of intravitreal voriconazole.  Due to the persistent T2Candida despite being on adequate therapy, it further prompted clinicians to investigate an alternate source of infection leading to the detection of fungal infective endocarditis. Post removal of the vegetation an additional T2Candida was obtained and was negative.  Once stable the patient was discharged home with IV anidulafungin, fluconazole and vancomycin.

A 58-year-old female with a history of metastatic breast cancer presented to the clinic.

Discussion

This case highlights the ability of the T2Bacteria® Panel to provide rapid species identification and detection of the causative organisms when blood cultures do not, including polymicrobial infections.

This high-risk, immunocompromised patient was initially treated with ceftriaxone and azithromycin for empiric treatment of pneumonia. Rapid species identification prompted an escalation of therapy to the anti-pseudomonal antibiotic, cefepime. The patient defervesced the day after therapy escalation and continued to clinically improve with cefepime continuation until hospital discharge. Without the availability of T2Bacteria, the patient may have remained on inappropriate therapy for days until further clinical deterioration may have led to an empiric switch/broadening of therapy

Presentation

A 58-year-old female with a history of metastatic breast cancer presented to the clinic with shortness of breath, fever, and pancytopenia. She was then admitted to the hospital with orders for blood cultures, T2Bacteria, and empiric antibiotics.

Patient Selection Criteria

The patient was admitted to the hematology-oncology unit with a suspected bloodstream infection

Evaluation and Treatment Decision

Diagnosis

Pneumonia

Empiric Therapy

Ceftriaxone and azithromycin

T2Bacteria Result

Positive for P. aeruginosa and E. coli

Blood Culture Result

No growth

Chest x-ray

Evidence of right lower lobe pneumonia

Decision making based on T2Bacteria Result

A rapid T2Bacteria result allowed for the identification of the P. aeruginosa and E. coli bacteremia in a patient with a culture-negative infection. This prompted the prescriber to escalate therapy to cefepime for the coverage of the P. aeruginosa that was not identified via the blood culture.

An immunocompromised patient was admitted after developing fever and rigors.

Discussion

This high-risk, immunocompromised patient was initially treated with ceftriaxone. The rapid T2Bacteria result for pseudomonas allowed for the escalation of therapy to meropenem and amikacin. Additionally, the positive T2Bacteria result prompted the removal of the central line as the suspected source of the infection. The culture from the catheter tip confirmed P. aeruginosa, five days after the initial P. aeruginosa result from T2Bacteria. Rapid species identification allowed for rapid escalation of therapy. Without the availability of T2Bacteria, the patient may have remained on inappropriate therapy for days until further clinical deterioration may have led to an empiric switch/broadening of therapy.

This case highlights how T2Bacteria can guide early treatment by rapidly identifying the causative pathogen in sepsis cases that are missed by blood cultures. T2Bacteria may be particularly useful in hematology/oncology patients with new-onset of bloodstream infection and/or sepsis due to the heavy antibiotic pre-exposure and the critical importance of getting therapy right on Day 1.

Presentation

An immunocompromised patient was admitted after developing fever and rigors approximately three months after stem cell transplant for treatment of AML. He was given ceftriaxone empirically upon admission. He had been diagnosed with AML the previous year and successfully underwent a stem cell transplant with a normal post-transplant course.

Patient Selection Criteria

Sepsis in an immunocompromised patient with a central line

Evaluation and Treatment Decision

Diagnosis

Sepsis

Empiric therapy

Initially ceftriaxone in addition to the continuation of prophylactic trimethoprim/sulfamethoxazole and posaconazole.

T2Bacteria Result

Positive Pseudomonas aeruginosa

Blood Culture Result

No growth; CVC tip culture: P. aeruginosa

Decision Making Based on T2Bacteria Results

The rapid T2Bacteria result supported the rapid escalation of therapy from ceftriaxone to meropenem and amikacin. The patient also received antibiotic lock therapy with amikacin preceding removal of the central line. The patient completed therapy and was discharged home with no complications.

27-year-old male admitted after developing fever and increased white blood cell count during hemodialysis.

Discussion

This high-risk, immunocompromised patient was initially treated with broad-spectrum antimicrobials. When he developed septic shock, micafungin was initiated immediately as candidemia accounts for 3-10% of all septic shock and each hour delay in instituting an active antimicrobial reduces survival in both septic shock and candidemia. Ideally, T2Candida would have been collected prior to giving micafungin. However, testing after antifungal dosing retains value because T2Candida positivity is significantly less likely to be impacted by treatment than are blood culture results.

This case highlights how T2Candida can identify candidemia cases that are missed by blood cultures and guide early treatment. T2Candida may be particularly useful in targeting antifungal treatment in patients with septic shock and other risk factors for candidemia.

Presentation

A 27-year-old male was admitted after developing fever and increased white blood cell count during hemodialysis. He was given vancomycin at hemodialysis and meropenem upon admission. He had a distant history of a double-lung transplant due to cystic fibrosis and a history of tacrolimus induced renal failure as well as line-associated bloodstream infections due to Enterococcus faecalis, coagulase-negative Staphylococcus, Candida glabrata, and S. aureus over the preceding two years. He had been discharged from the hospital 5 days earlier after receiving treatment for Enterobacter cloacae through a peripherally inserted central catheter (PICC).

Shortly after admission, he developed hypotension and respiratory failure requiring vasopressor therapy and mechanical ventilation. Micafungin was initiated within 2 hours, the PICC was discontinued and blood cultures and T2Candida were collected concurrently at 4 hours after the micafungin dose. The T2Candida was positive 4.5 hours later for C. albicans/C. tropicalis.

Patient Selection Criteria

Septic shock in an immunocompromised hemodialysis patient

Evaluation and Treatment Decision

Diagnosis

Septic Shock

Empiric therapy

Initially, broad-spectrum antibiotics with the addition of micafungin when the septic shock occurred

T2Candida Result

Positive for C. albicans/C. tropicalis

Blood Culture Result

No growth (from hemodialysis and admission); PICC tip: No growth

Ophthalmologic Exam (Day 5)

Consistent with Candida chorioretinitis

Decision Making Based on T2Candida Results

The rapid T2Candida result supported the continuation of antifungal therapy as well as PICC removal while blood cultures remained negative. The finding of chorioretinitis confirmed a diagnosis of deep-seated infection due to hematogenously disseminated candidiasis and justified both the switch from micafungin to fluconazole after 2 weeks and the total duration of therapy of 6 weeks.

 

1. Clancy, Cornelius J., and M. Hong Nguyen. “Diagnosing candidemia with the T2Candida panel: an instructive case of septic shock in which blood cultures were negative.” Diagnostic microbiology and infectious disease 93.1 (2019): 54-57.

According to the CDC, of the 154 million prescriptions for antibiotics written in doctors’ offices and emergency departments each year, 30% are unnecessary.12

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Over 200 studies published in peer-reviewed journals have featured T2MR in a breadth of applications.