Persistence of Detectable Pathogens by Culture-Independent Systems (T2 Magnetic Resonance) in Patients With Bloodstream Infection: Prognostic Role and Possible Clinical Implications

Peri, Anna Maria; O’Callaghan, Kevin; Rafiei, Nastaran; Graves, Bianca; Sinclair, Holly; Brischetto, Anna; Lim, Karen; Parkes-Smith, Jill; Eustace, Matthew; Davidson, Natalie; Tabah, Alexis; Stewart, Adam; Chatfield, Mark D; Harris, Patrick N A; Paterson, David L

doi:10.1093/cid/ciad663

Cited by 6 publications

(2 citation statements)

References 26 publications

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“…Although BC may be negative from the antimicrobial effect of empirically administered antibiotics, T2B and T2R may still be positive based on the presence of nonviable, nonproliferating, or latent bacteria. The clearance of BCs with the persistence of a positive T2B signal carries potentially important clinical implications of poorer outcomes consistent with ongoing infections ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections

Walsh,

Mencacci,

Paggi

et al. 2024

J Clin Microbiol

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Early initiation of antimicrobial therapy targeting resistant bacterial pathogens causing sepsis and bloodstream infections (BSIs) is critical for a successful outcome. The T2Resistance Panel (T2R) detects the following resistance genes within organisms that commonly cause BSIs directly from patient blood samples: bla KPC , bla CTXM-14/15 , bla NDM /bla /IMP /bla VIM , bla AmpC , bla OXA , vanA , vanB , and mec A/ mec C. We conducted a prospective study in two major medical centers for the detection of circulating resistance genes by T2R in patients with BSIs. T2R reports were compared to antimicrobial susceptibility testing (AST), phenotypic identification, and standard molecular detection assays. Among 59 enrolled patients, 25 resistance genes were identified: bla KPC ( n = 10), bla NDM /bla /IMP /bla VIM ( n = 5), bla CTXM-14/15 ( n = 4), bla AmpC ( n = 2), and mec A/ mec C ( n = 4). Median time-to-positive-T2R in both hospitals was 4.4 hours [interquartile range (IQR): 3.65–4.97 hours] in comparison to that for positive blood cultures with final reporting of AST of 58.34 h (IQR: 45.51–111.2 hours; P < 0.0001). The sensitivity of T2R to detect the following genes in comparison to AST was 100% for bla CTXM-14/15 , bla NDM /bla / IMP /bla VIM , bla AmpC , mec A/ mec C and 87.5% for bla KPC . When monitored for the impact of significant antimicrobial changes, there were 32 events of discontinuation of unnecessary antibiotics and 17 events of escalation of antibiotics, including initiation of ceftazidime/avibactam in six patients in response to positive T2R results for bla KPC . In summary, T2R markers were highly sensitive for the detection of drug resistance genes in patients with bacterial BSIs, when compared with standard molecular resistance detection systems and phenotypic identification assays while significantly reducing by approximately 90% the time to detection of resistance compared to standard methodology and impacting clinical decisions for antimicrobial therapy. IMPORTANCE This is the first reported study to our knowledge to identify key bacterial resistance genes directly from the bloodstream within 3 to 5 hours in patients with bloodstream infections and sepsis. The study further demonstrated a direct effect in modifying initial empirical antibacterial therapy in response to T2R signal to treat resistant bacteria causing bloodstream infections and sepsis.

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Section: Discussionmentioning

confidence: 99%

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections

Walsh,

Mencacci,

Paggi

et al. 2024

J Clin Microbiol

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“… 26 , 27 A prolonged duration of either positive microbial cell-free DNA or T2 magnetic resonance was associated with increased risk of metastatic infection in both S. aureus BSI and GN-BSI. 27 , 28 Conversely, shorter durations of positivity may permit earlier cessation of antibiotics through a precision-medicine approach.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study

Ong,

Luo,

Fridman

et al. 2024

Journal of Antimicrobial Chemotherapy

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Objectives The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. Methods We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2–5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. Results In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29–2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24–1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. Conclusions Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.

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Incidence and predictors of complications in Gram-negative bloodstream infection

Mondal,

Warren,

Bookstaver

et al. 2024

Infection

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Background The incidence of metastatic complications in Gram-negative bloodstream infection (GN-BSI) remains undefined. This retrospective cohort study examines the incidence and predictors of complications within 90 days of GN-BSI. Methods Patients with GN-BSIs hospitalized at two Prisma Health-Midlands hospitals in Columbia, South Carolina, USA from 1 January 2012 through 30 June 2015 were included. Complications of GN-BSI included endocarditis, septic arthritis, osteomyelitis, spinal infections, deep-seated abscesses, and recurrent GN-BSI. Kaplan–Meier analysis and multivariate Cox proportional hazards regression were used to examine incidence and risk factors of complications, respectively. Results Among 752 patients with GN-BSI, median age was 66 years and 380 (50.5%) were women. The urinary tract was the most common source of GN-BSI (378; 50.3%) and Escherichia coli was the most common bacteria (375; 49.9%). Overall, 13.9% of patients developed complications within 90 days of GN-BSI. The median time to identification of these complications was 5.2 days from initial GN-BSI. Independent risk factors for complications were presence of indwelling prosthetic material (hazards ratio [HR] 1.73, 95% confidence intervals [CI] 1.08–2.78), injection drug use (HR 6.84, 95% CI 1.63–28.74), non-urinary source (HR 1.98, 95% CI 1.18–3.23), BSI due to S. marcescens, P. mirabilis or P. aeruginosa (HR 1.78, 95% CI 1.05–3.03), early clinical failure criteria (HR 1.19 per point, 95% CI 1.03–1.36), and persistent GN-BSI (HR 2.97, 95% CI 1.26–6.99). Conclusions Complications of GN-BSI are relatively common and may be predicted based on initial clinical response to antimicrobial therapy, follow-up blood culture results, and other host and microbiological factors.

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Persistence of Detectable Pathogens by Culture-Independent Systems (T2 Magnetic Resonance) in Patients With Bloodstream Infection: Prognostic Role and Possible Clinical Implications

Cited by 6 publications

References 26 publications

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections

Prospective observational pilot study of the T2Resistance panel in the T2Dx system for detection of resistance genes in bacterial bloodstream infections

Epidemiology and clinical relevance of persistent bacteraemia in patients with Gram-negative bloodstream infection: a retrospective cohort study

Incidence and predictors of complications in Gram-negative bloodstream infection

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