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.

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 an 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 and 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 consults 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. The 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 the 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.

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 a 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 the presentation, because the 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 spectrum therapy 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. The 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 a 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 the time of febrile episode. The patient was initiated on cefepime 2g IV q8h at the 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 the 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.

The patient presented with acute onset of pain in his left lower extremity.

Discussion

Rapid molecular diagnostics such as T2MR technology may help with the 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 that 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.