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 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 admit to LTAC, the patient spiked fever of 100.9 F with increased oxygen requirements and drainage from enterocutaneous fistula. Patient has 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. Patient completed a course of antibacterials x 10 days total.

Critical Care Patient with Septic Shock

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.

 

Candida Retinitis and Candida Infective Endocarditis

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 patient was admitted with fevers, lethargy and anorexia.  Routine blood cultures were negative, however, Cytomegalovirus (CMV) levels were positive and IV ganciclovir was initiated.  Patient remained in the hospital for five days and was discharged home.  Patient was readmitted ten days later with fever, fatigue, and a blind spot in right eye with improving CMV. A blood culture and T2Candida were drawn, and anidulafungin was started. T2Candida was reported positive for C. albicans/C. tropicalis 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.  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. 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 a 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.

Suspected Blood Stream Infection

A 58-year-old female with history of metastatic breast cancer presented to 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 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 history of metastatic breast cancer presented to 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

Patient admitted to hematology-oncology unit with suspected blood stream 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 identification of the P. aeruginosa and E. coli bacteremia in a patient with 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.

Sepsis in an Immunocompromised Patient with a Central Line

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: 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.

Septic Shock in an Immunocompromised Hemodialysis Patient

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 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 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 to 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.

Septic Shock with Fever

An 86 year old patient presented with fevers and lethargy for one week.

Discussion

This case highlights not only the benefit of rapid species identification with the T2Bacteria Panel but also the Panel’s ability to prevent therapy that is not necessary as well as to detect the causative organisms that blood cultures may not due to infection localized within an abscess.

Presentation

An 86 year old patient presented with fevers and lethargy for one week. The patient had a history of ischemic stroke complicated by residual right-sided weakness, type II diabetes, atrial fibrillation, recurrent urinary tract infections (history of Proteus mirabilis, E. coli, ESBL Klebsiella pneumoniae) as well as a known perianal fistula with ischioanal abscess. On arrival, the patient was in septic shock with fever to 103°F, hypotension requiring pressors, and lactate 3.8. The patient was started on vancomycin, meropenem, doxycycline, and a one-time dose of amikacin for empiric coverage based on prior cultures. Four blood cultures were collected in the ED as well as a T2Bacteria Panel.

CT abdomen/pelvis with contrast was performed which showed the increased size of left ischioanal fluid collection compared to CT previously. Urinalysis was sent with >100 WBCs and negative for bacteria.  Urine culture showed no growth, however, urine was obtained after initiation of antibiotics.

Patient Selection Criteria

A septic patient presenting in the Emergency Department

Evaluation and Treatment

Empiric Therapy: The patient was started on vancomycin, meropenem, doxycycline, and a one-time dose of amikacin

T2Bacteria Panel Result: Positive for Klebsiella pneumoniae, negative for the remaining four pathogens.

Hospital Course/Decision Making Based on the T2Bacteria Panel Result

The patient was transferred from the ED to the medical ICU where broad-spectrum antibiotics were continued and ID was consulted.  The T2Bacteria resulted and was positive for Klebsiella pneumoniae. At this point, the patient was not administered an additional dose of amikacin and the doxycycline was discontinued. Blood culture eventually grew Gram-positive cocci pairs & chains but no Gram-negative rods.  Overall, the patient was improving on broad-spectrum antibiotics and given that the T2Bacteria Panel was negative for E. faecium despite having pairs and chains in his blood, the ID consult team felt more comfortable with holding off on empiric VRE coverage based on the T2Bacteria result. Blood cultures ultimately speciated to Streptococcus anginosus a day and a half later, but no Klebsiella. Patient’s perianal fluid collection was subsequently drained by colorectal surgery the next day, as this was likely the source of infection which grew many Proteus mirabilis, moderate Klebsiella pneumoniae, and moderate Streptococcus anginosus.

T2Bacteria picked up the Klebsiella from patient’s abscess but it was never detected in blood culture. Antibiotics were subsequently de-escalated from vancomycin and meropenem to ceftriaxone given that the organisms were highly susceptible (non-ESBL) to complete a fourteen-day course.

Suspected Acute Cholecystitis

An 82-year-old patient presented in the emergency department with a fever.

Discussion

This case highlights not only the benefit of rapid species identification with the T2Bacteria Panel but also the Panel’s ability to detect the causative organisms when blood culture does not.

Presentation

An 82-year-old patient presented in the emergency department with a fever. About three days prior, the patient had an abrupt episode of rigors and was febrile at 103°F at home. The patient was brought to another hospital where workup was negative for infection, including blood culture by her report. Subsequently, the patient was discharged home, although it is unclear if the patient was discharged with or without antimicrobials.  Still having similar chills and rigors the patient presented to an academic medical center and was admitted. The patient was febrile on admission with slight abdominal pain.  A CT scan revealed a severely distended gallbladder but normal common bile duct, with no significant gallbladder wall thickening.  Blood cultures and a T2Bacteria were drawn in the ED and the patient was started on ceftriaxone and flagyl with the abdomen as the suspected source of infection. Patient re-spiked a fever and was broadened to cefepime and given a one-time dose of vancomycin.

Patient Selection Criteria

A septic patient presenting in the Emergency Department

Evaluation and Treatment

Diagnosis: Suspected acute cholecystitis
Empiric Therapy: The patient was started on ceftriaxone and flagyl and broadened to cefepime and vancomycin.
T2Bacteria Panel Result: Positive for E. coli and S. aureus, negative for the remaining three pathogens.
Blood Culture Result: E. coli (4/4 bottles)

Decision making based on the T2Bacteria Result

A rapid T2Bacteria positive for E. coli and S. aureus prompted the team to de-escalate from cefepime to ceftriaxone and add vancomycin.  The high negative predictive value (99.7%) of the T2Bacteria Panel provided important diagnostic information that allowed for more informed treatment decisions, specifically the de-escalation of anti-pseudomonal therapy as well as the addition of vancomycin for the coverage of the S. aureus that was not identified via the blood culture. ID was consulted and they recommended two weeks of ceftriaxone and vancomycin for both organisms identified.  Patient defervesced and improved after 24 hours of therapy and was discharged home with IV antimicrobials for two weeks.

T2Bacteria® Negative De-escalation

67-year-old female admitted for reduced intensity conditioning followed by Stem Cell transplant for acute myelogenous leukemia.

Discussion

Patients undergoing cytotoxic chemotherapy and hematopoietic stem-cell transplantation (HSCT) are at high risk for infection, particularly during the period of neutropenia and are often prescribed antibiotic prophylaxis with fluroquinolones. The majority of patients who develop fever during neutropenia have no identifiable site of infection and no positive culture results. IDSA guidelines recommend that every patient with fever and neutropenia receive empiric antibiotic therapy with an antipseudomonal beta lactam urgently after presentation, because infection may progress rapidly.1

De-escalation of antimicrobials is challenging in these scenarios, where cultures remain negative, and patients are often exposed to extended durations of broad-spectrum antimicrobials as information is not available to target therapy. This puts the patient at risk for collateral damage associated with antimicrobial therapy such as antimicrobial resistance and toxicity. T2Bacteria negative results in 3-5 hours can help clinicians to improve their empiric therapy for bloodstream infections by providing key information to help narrow a patient’s empiric therapy.

At the time of febrile episode in this case, the patient was on levofloxacin 500 mg daily for bacterial prophylaxis. She had blood cultures obtained and T2Bacteria ordered and was then initiated on broad spectrumtherapy with cefepime 2g IV q8h. Due to the patient’s history of recent HSCT, profound immunosuppression and neutropenia, she was at risk for organisms such as P. aeruginosa in addition to other common causes of febrile neutropenia such as Enterobacteriaceae and Gram-positive commensal bacteria.

The patient received 3 doses of cefepime (~24 hours of therapy) then therapy was de-escalated to ceftriaxone based on negative T2Bacteria Panel results to avoid unnecessary continuation of the broad spectrum, antipseudomonal beta-lactam. Ceftriaxone was continued for 4 more days until the patient defervesced, was hemodynamically stable, afebrile and displayed no other sign or symptom of infection. Once treatment of the febrile neutropenic episode was complete, the levofloxacin prophylaxis was reinitiated.

Presentation

67-year-old female admitted for reduced intensity conditioning followed by Stem Cell transplant for acute myelogenous leukemia. She also received methotrexate and tacrolimus for graft-versus-host disease prophylaxis. Patient's clinical course was complicated by grade 3 nausea, vomiting and mucositis, hyperglycemia and new onset left bundle branch block. Six days after transplant the patient developed febrile neutropenia with profound neutropenia, in which stat blood cultures (x2), T2Bacteria, procalcitonin and lactic acid were drawn, a chest X-ray was taken and cefepime was immediately initiated.

Patient Selection Criteria

Febrile neutropenia in patient with recent HSCT and profound neutropenia.

Evaluation and Treatment Decision

Diagnosis: Neutropenic fever.

Empiric Therapy: The patient was on levofloxacin 500 mg daily for bacterial prophylaxis at time of febrile episode. The patient was initiated on cefepime 2g IV q8h at time of fever spike.

Cefepime was chosen for coverage of common causative pathogens identified in febrile neutropenia.

Procalcitonin, lactic acid, and chest X-ray were benign with no positive findings.

T2Bacteria Panel Result: Negative for all panel pathogens (P. aeruginosa, E. faecium, S. aureus, E. coli and K. pneumoniae.)  

Blood Culture Result: no growth

Decision making based on T2Bacteria Result

A rapid T2Bacteria negative result allowed for ruling out of the most common ESKAPE pathogens. The high negative predictive value (99.7%) of the T2Bacteria Panel provided important diagnostic information that allowed for more informed treatment decisions, including early de-escalation of empiric antibiotic regimen, sparing the patient from unnecessary broad spectrum antibiotics and the potential risks associated with their prolonged therapy.

1. Freifeld AG, et al.  Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52:427-31.

Thrombus in Left Popliteal Artery

Patient presented with acute onset of pain in his left lower extremity

Discussion

Rapid molecular diagnostics such as T2MR technology may help with prognosis of invasive candidiasis. The T2Candida Panel was utilized upon follow up to assess the clearance of candidemia along with clinical symptoms.

Presentation

A 45-year-old man with an extensive history of bicuspid aortic valve disease, aortic valve replacement and multiple cases of bacterial endocarditis was treated with prolonged courses of antibiotics and was placed on chronic suppression with amoxicillin 500 mg orally three times per day. He presented with acute onset of pain in his left lower extremity and was diagnosed with a thrombus in his left popliteal artery.  

Evaluation and Treatment Decision

Surgical Interventions: Left embolectomy with pathology revealing a thrombus with calcification and multiple fungal forms with pseudohyphae, which grew Candida parapsilosis, along with blood cultures and T2Candida Panel positive for Candida parapsilosis. Transesophageal echocardiogram (TEE) revealed trace aortic regurgitation and mild mitral regurgitation.

Initial Antifungal Regimen: Micafungin 150 mg IV daily PLUS fluconazole 600 mg (6 mg/kg) IV daily was started for suspected prosthetic valve endocarditis.

Additional Culture Data and Modified Antifungal Regimen: Blood cultures remained positive for C. parapsilosis after 14 days of antifungal treatment. Treatment was changed to liposomal amphotericin B 5 mg/kg IV daily, flucytosine 2500 mg orally every six hours and fluconazole 400 mg orally daily. All subsequent blood cultures were negative. Due to an episode of acute renal failure, his regimen was finally changed to micafungin 150 mg IV daily and flucytosine 2500 mg PO every 8 hours.

Follow-up Tomography/Angiography: Scan revealed activity on the aortic leaflets and right lateral wall of the ascending aorta three weeks after starting antifungal treatment.

Second T2Candida Panel Result and Modified Antifungal Regimen: T2Candida Panel completed two months after starting antifungal treatment remained positive for C. parapsilosis while blood cultures remained negative. The regimen was narrowed down to flucytosine 2500 mg orally every eight hours and fluconazole 400 mg orally daily. Repeat T2Candida Panel became negative five months after starting antifungal treatment.

Discharge and Follow-Up Plan: The patient was stable for one year but decided to discontinue his flucytosine, fluconazole, and amoxicillin. He developed low-grade fevers and repeat blood cultures were negative for bacteria but grew C. parapsilosisas did a follow-up T2Candida Panel. The patient was restarted on liposomal amphotericin B, flucytosine, and fluconazole. Blood cultures became negative, and the T2Candida Panel was negative after two weeks of antifungal treatment. TEE was unchanged and did not reveal any vegetations. Liposomal amphotericin B was discontinued after six weeks, and the patient remains stable on flucytosine and fluconazole.

Decision making based on T2Candida Result

The T2Candida Panel was used to assess for the presence of disease and the continuation of antifungal therapy, despite negative blood cultures.

 

Citation: Ahuja T, Fong K, Louie E. Combination antifungal therapy for treatment of Candida parapsilosis prosthetic valve endocarditis and utility of T2Candida Panel®: A case series. IDCases. 2019;15:e00525.  

Neutropenic Fever & P. aeruginosa Bloodstream Infection

A 23-year-old female with a history of acute myeloid leukemia and recent haploidentical stem cell transplant, cytokine release syndrome and severe mucositis following receipt of post-transplant cyclophosphamide therapy.

Discussion:

Upon admission, the patient was initially given cefepime for the treatment of febrile neutropenia. Due to the patient’s history of AML and neutropenia, she was at risk for organisms such as P. aeruginosa in addition to other common causes of febrile neutropenia such as Enterobacteriaceae.

At the time of admission, she had blood cultures obtained and T2Bacteria ordered. At this hospital, patient selection for T2Bacteria testing included onco-hematologic and HSCT patients with suspected bloodstream infections.

Bloodstream infections are a major cause of life-threatening complications in patients with cancer, due to the potential delays in chemotherapy, longer hospital stay, suboptimal treatment, higher mortality rate, and increased healthcare costs. The poor performance of blood cultures has a major impact on clinical management of febrile neutropenic patients, especially in cases of unexplained persistent fever. T2Bacteria direct from blood diagnostic technology provided clinically relevant information for the diagnosis of infection in this case of blood culture-negative febrile neutropenia. Cefepime was continued for a total of 7 days, which was 2 days longer than would have been prescribed based on the negative blood cultures after the patient defervesced and ANC increased to >500.

Presentation 

A 23-year-old female with a history of acute myeloid leukemia and recent haploidentical stem cell transplant, cytokine release syndrome and severe mucositis following receipt of post-transplant cyclophosphamide therapy. The patient developed fever and blood cultures, T2Bacteria and empiric antibiotics were ordered.

Patient Selection Criteria

Febrile neutropenia in a patient with AML

Evaluation and Treatment Decision

Diagnosis: Neutropenic fever

Empiric Therapy: Cefepime

Cefepime was chosen for coverage of common causative pathogens identified in febrile neutropenia.

T2Bacteria Result: Positive for P. aeruginosa and negative E. faecium, S. aureus, E. coli and K. pneumoniae.  

Blood Culture Result: No growth

Decision making based on T2Bacteria Result

A rapid T2Bacteria result allowed for early diagnosis of P. aeruginosa bacteremia and confirmation of effective empiric antibiotic therapy. Identification of P. aeruginosa by T2 also provided important diagnostic information that allowed for more informed treatment decisions, including the continuation of IV antibiotics for longer treatment duration.

 

Pulmonary Edema and Suspected Pneumonia

Patient had a history of multiple myeloma, prostate cancer and CHF.

Discussion

This case highlights not only T2Bacteria’s benefit of rapid identification but also the ability to detect the causative organism in the presence of antibiotics as this patient had received the dose of vancomycin before the T2Bacteria was drawn.

Utilization of the T2Bacteria test allows for directed therapy on the same day as the identification of suspected infection. In this case, it took almost 48 hours from admission to identify S. aureus in the blood (Day 3 of admission). Ordering T2Bacteria at 24 hours after admission allowed appropriate therapy to be started on Day 2. Had T2Bacteria had been ordered simultaneously with blood culture, appropriate therapy could have been started on Day 1.

Initial Presentation

A high-risk patient was admitted with pulmonary edema and suspected pneumonia. The patient had a history of multiple myeloma, prostate cancer, and CHF. Blood cultures were obtained, and the patient was started on intravenous antibiotics for coverage of pneumonia.

Evaluation and Treatment Decision

Empiric Therapy: The patient was started on levofloxacin and piperacillin/tazobactam for empiric coverage of pneumonia.

Blood Culture Result: Twenty four hours after admission, the nursing unit was called with a critical result from microbiology: gram-positive cocci in clusters.

Updated Therapy: The physician was notified, and a single dose of vancomycin was ordered.

T2Bacteria Result: The physician was uncertain if the organism might be a contaminating organism such as Staphylococcus epidermidis or a more concerning pathogen such as Staphylococcus aureus. The nurse suggested ordering T2Bacteria, and four hours later, the T2Bacteria resulted as S. aureus prompting the appropriate continued therapy with vancomycin. S. aureus was confirmed by the blood culture result the following morning.

Decision Making Based on T2Bacteria Result

The T2Bacteria Panel was used to detect the presence of S. aureus, allowing appropriate therapy to be initiated one day earlier than using blood culture alone.

Utilizing a Negative T2Bacteria Result

81 year old female admitted with a one-day history of fever, rigors, weakness, and confusion. Blood and urine cultures were ordered as well as IV antibiotics.

Discussion/Decision Making Based on T2Bacteria Result 

At this point in time, the hospital has not adopted T2Bacteria, however, another hospital in their system has. Given the high likelihood that the repeat BCx would be negative, they were asked to draw a blood sample on the day the patient was ready for discharge and send it to the institution that currently utilized the T2Bacteria Panel.

A courier was called and the test was run 4.5 hours after the blood was drawn, and resulted in 3.5 hours with no organisms detected.  The information was relayed to the ordering resident and physician, and the patient was subsequently discharged roughly a day earlier with oral antibiotics.  The clinician noted that even though this was not standard use of this test, it saved a patient a day in the hospital and also potentially spared the patient additional risk of hospital-acquired infections, further confusion, deconditioning, and risk of falls.

Presentation

81 year old female admitted with a one-day history of fever, rigors, weakness, and confusion. Blood and urine cultures were ordered as well as IV antibiotics.

Hospital Course

The patient was started on broad-spectrum IV antibiotics and baseline BCx and UCx grew E. coli.  The patient rapidly defervesced after the initial antibiotics and was de-escalated to IV ceftriaxone and clinically improved. The patient was ready for discharge two days later, though need to wait for repeat BCx drawn that day to show no growth for 48 hours, thus, prolonging their stay an additional two days. It was noted the patient had an identical episode nine years ago, with a very sensitive E. coli in BCx and UCx and was discharged on oral ciprofloxacin.

Candida parapsilosis bloodstream infection1

The T2Candida Panel was used to assess for the presence of disease and continuation of antifungal therapy, despite negative blood cultures.

Discussion


Rapid molecular diagnostics such as T2MR technology may help with prognosis of invasive candidiasis. For our case, the T2Candida Panel was utilized upon follow up to assess clearance of candidemia along with clinical symptoms.

Presentation

A 69-year-old man with history of testicular cancer, chronic kidney disease, anemia, gangrenous gallbladder, status post cholecystectomy, hypertension, hyperlipidemia, type 2 diabetes mellitus, paroxysmal atrial fibrillation, heart failure with reduced ejection fraction and implantable  cardioverter defibrillator (ICD), and aortic valve disease s/p mechanical aortic valve replacement who presented with fatigue, fever, diarrhea, emesis, febrile to 102.3 degree Fahrenheit with a blood pressure of 93/43 mm Hg, heart rate of 64 bpm, and respiratory rate of 18 breaths/min. 

Evaluation and Treatment Decision


Initial Diagnosis: Initially diagnosed with Candida parapsilosis bloodstream infection and treated with liposomal amphotericin B at 5 mg/kg/day. After developing acute kidney injury, therapy was changed to micafungin 150 mg intravenous (IV) daily.


Blood Cultures and Echography: Repeat blood cultures continued to grow Candida parapsilosis 10 days after admission. A trans-esophageal echocardiogram (TEE) revealed fibrin stranding on the mechanical aortic valve. Due to his multiple comorbidities, he was not deemed safe for surgical intervention.


Updated Therapy: Micafungin 150 mg IV daily and fluconazole 400 mg orally daily


Discharge Plan: A peripherally inserted central catheter (PICC) was placed, and the patient was discharged from the hospital to complete micafungin IV for 12 weeks plus fluconazole oral combination therapy.


T2Candida Panel – Initial Result: Six weeks after negative blood cultures, a T2Candida Panel was ordered, which still detected the presence of Candida parapsilosis. However, all repeat fungal blood cultures remained negative, and the patient had improved overall. 


T2Candida Panel – Second Result: 18 weeks after blood cultures became negative, a repeat T2Candida Panel was negative for any Candida species while on chronic suppression with fluconazole.


One year later, the patient currently remains alive and doing well on oral fluconazole suppressive therapy at 200 mg daily.


Decision making based on T2Candida Result


The T2Candida Panel was used to assess for the presence of disease and the continuation of antifungal therapy, despite negative blood cultures.

 

1. Ahuja, Tania, Karen Fong, and Eddie Louie. "Combination antifungal therapy for treatment of Candida parapsilosis prosthetic valve endocarditis and utility of T2Candida Panel®: A case series." IDCases 15 (2019): e00525.

Urinary Tract Infection: Suspected Sepsis

83-year-old male presented to the emergency department with urinary retention.

Had the T2Bacteria test been performed and result been reported immediately after collection, the patient could have been initiated on effective empiric therapy over 24 hours sooner, and P. aeruginosa bacteremia identified over two days earlier.

Discussion

Upon admission, the patient was initially given ceftriaxone for the treatment of suspected urinary tract infection.  At the time of admission, he had blood and urine cultures obtained, and T2Bacteria ordered. At this institution patient selection for T2Bacteria testing was based on elevated lactate and/or procalcitonin in patients presenting to the emergency department with suspected bloodstream infections.

Empiric therapy was chosen to cover E.coli, the most common cause of urinary tract infection. This patient did not present with usual risk factors for P. aeruginosa; thus effective therapy against P. aeruginosa was not initiated until urine cultures demonstrated the growth of P. aeruginosa over 24 hours after admission (T2Bacteria results were not reported as this case was part of an observational study). Blood culture growth with P. aeruginosa was delayed >48 hours after admission.

Presentation

83-year-old male presented to the emergency department with urinary retention. Sepsis was suspected, and the patient was admitted with orders for blood and urine cultures, T2Bacteria, and antibiotics.

Patient Selection Criteria

Lactic acid 3.29

Evaluation and Treatment Decision

Diagnosis: Urinary tract infection

Empiric Therapy: Ceftriaxone

Ceftriaxone was chosen for coverage of common causative gram-negative pathogens of UTIs.

T2Bacteria Panel Result: Positive for P. aeruginosa and negative E. faecium, S. aureus, E. coli, and K. pneumoniae.  

Blood Culture Result: P. aeruginosa (>48 hours after admission)

Urine Culture Result: P. aeruginosa (24 hours after admission)

Decision making based on T2Bacteria Panel Result:

A rapid T2Bacteria result could have allowed for more informed treatment decisions, including the initiation of earlier effective therapy.

Community Acquired Pneumonia

Patient presented to the emergency department with shortness of breath, cough, fever and chills.

A rapid T2Bacteria result could have allowed for more informed treatment decisions, including the initiation of earlier effective therapy over 30 hours sooner.

Discussion

Upon admission, the patient was initially given ceftriaxone and azithromycin for the treatment of suspected community-acquired pneumonia. Due to the patient’s history of COPD, he was at risk for organisms such as MRSA (methicillin-resistant Staphylococcus aureus) in addition to the more common causes of community-acquired pneumonia such as Streptococcus pneumoniae and atypical organisms.

 

At the time of admission, he had blood cultures obtained, and T2Bacteria ordered. At this hospital, patient selection for T2Bacteria testing was based on elevated lactate and/or procalcitonin in patients presenting to the emergency department with suspected bloodstream infections.

Effective therapy against MRSA was not initiated until blood cultures demonstrated the growth of S. aureus over 30 hours after admission (T2Bacteria results were not reported as this case was part of an observational study). Had the T2Bacteria test been performed and result been reported immediately after collection, the patient could have been initiated on effective empiric therapy over 30 hours sooner.

Presentation

A 59-year-old male with a history of rectal cancer and COPD. The patient presented to the emergency department with shortness of breath, cough, fever, and chills. Sepsis was suspected, and the patient was admitted with orders for blood cultures, T2Bacteria, and antibiotics.

Patient Selection Criteria

Lactic acid 2.8 mg/dl

Procalcitonin 59 ng/ml

Evaluation and Treatment Decision

Diagnosis: Community-acquired pneumonia

Empiric Therapy: Ceftriaxone, Azithromycin

Ceftriaxone and azithromycin were chosen for coverage of common causative respiratory pathogens identified in community-acquired pneumonia.

T2Bacteria Result: Positive for S. aureus and negative E. faecium, P. aeruginosa, E. coli, and K. pneumoniae.  

Blood Culture Result: Methicillin-resistant Staphylococcus aureus (36-hour delay in species identification from time of blood culture collection)

Decision making based on T2Bacteria Result

A rapid T2Bacteria result could have allowed for more informed treatment decisions, including the initiation of earlier effective therapy over 30 hours sooner.

Suspected urinary tract infection

91-year-old female presented to the emergency department with several day history of fever, chills, and nausea/vomiting.

Had the T2Bacteria® test been performed and result been reported immediately after collection, the patient could have potentially avoided premature discharge and readmission.

Discussion

Upon presentation to the emergency department, the patient was initially given ceftriaxone for the treatment of suspected urinary tract infection. At the time of admission, she had blood and urine cultures obtained, and T2Bacteria ordered. Patient selection for T2Bacteria testing was based on procalcitonin in at the time of presentation.

The patient was discharged prior to blood culture resulting in positive for growth (T2Bacteria results were not reported as this case was part of an observational study). Had the T2Bacteria test been performed and result been reported immediately after collection, the patient could have potentially avoided premature discharge and readmission.

Presentation

A 91-year-old female presented to the emergency department with several day history of fever, chills, and nausea/vomiting. The patient was admitted with orders for blood cultures, T2Bacteria, urine cultures, and antibiotics.

Patient Selection Criteria

Procalcitonin 1.5 ng/ml in a patient suspected of bloodstream infection.

Evaluation and Treatment Decision

Diagnosis:  Suspected urinary tract infection

Empiric Therapy: Ceftriaxone x 1 dose

Ceftriaxone was chosen for coverage of common causative gram-negative pathogens identified in UTIs.

T2Bacteria Result: Positive for E. coli and negative for S. aureus, E. faecium, P. aeruginosa, and K. pneumoniae.

Blood Culture Result: E. coli on Day 2

Urine Culture Result: E. coli on Day 2

The patient was discharged in the morning of Day 2 prior to the availability of culture results. The patient returned to the ED on the next day with ongoing fever/chills and was readmitted.

Decision making based on T2Bacteria Result

A rapid T2Bacteria result could have allowed for more informed treatment decisions, including the continuation of antibiotic therapy and avoidance of readmission less than 24 hours after her initial premature discharge.

Deep-seated invasive candidiasis in a liver recipient

Patient with insulin-dependent diabetes mellitus, primary sclerosing cholangitis, multiple bacteremic episodes and recent liver transplant was admitted.

In this case, T2Candida® results could have permitted earlier focused therapy and aided with the diagnosis of invasive Candida infection and lead to appropriate antifungal therapy. Unfortunately, the T2Direct Diagnostics results were not in clinical use at the time and not obtained until after patient death.

Discussion

T2Candida retrospectively revealed C. albicans/C. tropicalis, even at the beginning of the process when the patient was asymptomatic. This case highlights the potential advantage of T2Direct Diagnostics aiding in the diagnosis of deep-seated infection in an immunosuppressed patient without confirmed infection, even before the onset of symptoms.

The two key findings were that arteritis and thrombosis of the hepatic graft resulted from an undocumented fungal infection in the explanted liver and that T2Candida was a suitable diagnostic tool for the diagnosis of deep-seated invasive candidiasis in the absence of positive blood culture results.

Presentation

A 57-year-old woman with insulin-dependent diabetes mellitus, primary sclerosing cholangitis, multiple bacteremic episodes, and recent liver transplant was admitted for sudden abdominal pain. After identification of intrahepatic abscesses the patient underwent a second liver transplant. Subsequently, non-purulent inflammatory tissue was observed in the liver with extensive clotting of the portal vein and hepatic artery and generalized hepatic ischemia. In the following hours, the patient developed graft failure, severe coagulopathy, and died.  

Evaluation and Treatment Decision

All of the cultures collected before death, including blood (obtained at admission and repeated 3 times during hospitalization), ascitic fluid at admission, and liver and abdominal tissues during the re-transplantation procedure, were sterile.

Final Diagnosis: Liver abscess

Empiric Therapy (May 31, 2017): Vancomycin, meropenem, caspofungin

T2Candida Panel Result: Retrospective T2MR performed on blood samples obtained on May 27th, May 31st, June 9th, June 16th, and June 26th showed C. albicans/C. tropicalis present in all samples.

Histology Result: Histopathology of explanted liver tissue revealed multiple ischemic areas with abundant filamentous fungal structures in their interior, and C. albicans was identified using multiplex PCR.

Decision making based on T2Candida Result

T2Candida result from May 27th (and subsequent results) could have permitted earlier focused therapy and aided with the diagnosis of invasive Candida infection. Unfortunately, the T2Direct Diagnostics results were not in use clinically and not obtained until after death.

Suspected aspiration pneumonia vs HCAP

Patient presents to the Emergency Department from nursing home with fever, dyspnea, and altered mental status.

Discussion

At the time of admission, this patient had blood cultures obtained, and T2Bacteria ordered. At Piedmont Columbus Regional, patient selection for T2Bacteria testing was based on >2 SIRS criteria PLUS suspected source of infection PLUS hypotension or altered mental status. This patient was positive for 2 of 4 SIRS criteria and had a suspected cause of infection and altered mental state, thus meeting criteria for testing.

Determination of the causative organism for this patient’s infection allowed optimization of the antibiotic regimen within 24 hours of presentation. The patient was not improving on empiric therapy and experienced clinical improvement after the switch from ceftazidime to meropenem. Additionally, clindamycin was discontinued on Day 2 and vancomycin was discontinued on Day 3 allowing for 5 days of therapy to be saved for clindamycin and 4 days of therapy to be saved for vancomycin. The patient continued to improve and was discharged back to the nursing home after meropenem therapy was completed.

Presentation

PS is a 69 y/o M who presented to the Emergency Department from a nursing home with a fever, dyspnea, and altered mental status. His initial lactic acid was 4.5. The treating physician saw him, and sepsis was suspected. PS was admitted with orders for labs, blood cultures, T2Bacteria®, and broad-spectrum antibiotics.

Patient Selection Criteria

SIRS criteria:

  • Temperature: 103.5˚F
  • Heart Rate: 130 bpm
  • Respiratory Rate: 20
  • WBC (initial): 19,920/mm3

Evaluation and Treatment Decision

Suspected aspiration pneumonia vs. HCAP

Empiric Therapy: Vancomycin, Clindamycin, Ceftazidime

T2Bacteria scheduled to result at 2030 on second shift. Result: K. pneumonia (time to result: ~5 hours), result reviewed by ID pharmacist next am

Blood Culture Result: Negative after 5-days incubation

WBC next am on Ceftazidime: 24,950/mm3 (worsening)

Decision making based on T2Bacteria Result

  1. Reviewed internal antibiogram. Changed Ceftazidime to Meropenem based on antibiogram percent susceptibility of 88% vs. 99%.
  2. Discontinue Clindamycin and vancomycin
  3. WBC next am after the switch to Meropenem: 10,960/mm3

 

Suspected Intra-abdominal sepsis

Patient presents with suspected sepsis

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.

Presentation

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 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

  • Sign Up for our Blog

  • Media Contact

    Gina Kent
    610-455-2763
    gkent@vaultcommunications.com

    Media Center

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

  • Publications

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

    Read Now!
  • JOIN THE MAILING LIST!