Next-Generation Sequencing in Critically Ill COVID-19 Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study

Leitl, Christoph; Stoll, Sandra Emily; Wetsch, Wolfgang A.; Kämmerer, T; Mathes, Alexander; Böttiger, Bernd W.; Seifert, Harald; Dusse, Fabian

doi:10.3390/jcm12041466

Cited by 4 publications

(6 citation statements)

References 45 publications

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“…Overall, NGS had an impact on antimicrobial therapy in 7.3 % of patients observed in this study. This is lower than in previous studies, in which NGS results were considered clinically relevant in 11-45% of cases [16,27,[39][40][41]. This difference may result from differences in patient selection and the definition of clinical impact, which was limited to actual changes to antimicrobial therapy directly linked to NGS results in our study.…”

Section: Impact Of Ngs On Therapycontrasting

confidence: 67%

The Value of Next-Generation Sequencing in Diagnosis and Therapy of Critically Ill Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study

Overbeek,

Leitl,

Stoll

et al. 2024

JCM

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Bloodstream infection (BSI), a frequent cause of severe sepsis, is a life-threatening complication in critically ill patients and still associated with a high mortality rate. Rapid pathogen identification from blood is crucial for an early diagnosis and the treatment of patients with suspected BSI. For this purpose, novel diagnostic tools on the base of genetic analysis have emerged for clinical application. The aim of this study was to assess the diagnostic value of additional next-generation sequencing (NGS) pathogen test for patients with suspected BSI in a surgical ICU and its potential impact on antimicrobial therapy. In this retrospective single-centre study, clinical data and results from blood culture (BC) and NGS pathogen diagnostics were analysed for ICU patients with suspected BSI. Consecutive changes in antimicrobial therapy and diagnostic procedures were evaluated. Results: 41 cases with simultaneous NGS and BC sampling were assessed. NGS showed a statistically non-significant higher positivity rate than BC (NGS: 58.5% (24/41 samples) vs. BC: 21.9% (11/41); p = 0.056). NGS detected eight different potentially relevant bacterial species, one fungus and six different viruses, whereas BC detected four different bacterial species and one fungus. NGS results affected antimicrobial treatment in 7.3% of cases. Conclusions: NGS-based diagnostics have the potential to offer a higher positivity rate than conventional culture-based methods in patients with suspected BSI. Regarding the high cost, their impact on anti-infective therapy is currently limited. Larger randomized prospective clinical multicentre studies are required to assess the clinical benefit of this novel diagnostic technology.

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Section: Impact Of Ngs On Therapycontrasting

confidence: 67%

The Value of Next-Generation Sequencing in Diagnosis and Therapy of Critically Ill Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study

Overbeek,

Leitl,

Stoll

et al. 2024

JCM

Self Cite

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“…Currently, the positivity of pathogen detection in COVID-19 critically ill patients with BSI using blood culture ranges from 10 to 28% [ 6 ]. However, these studies are often based on small sample sizes.…”

Section: Discussionmentioning

confidence: 99%

“…However, this method is limited by suboptimal sensitivity, ranging from ≤ 10% to about 50% in patients with suspected bacteremia, febrile neutropenia, or sepsis/septic shock [ 5 ]. In COVID-19 critically ill patients, the positivity of pathogen detection using blood culture is 10–28% [ 6 ]. Due to the limited sensitivity of blood culture and weak ability to detect multiple infections, our understanding of the causative pathogens of BSI in COVID-19 patients is limited.…”

Section: Introductionmentioning

confidence: 99%

Clinical evaluation of a multiplex droplet digital PCR for pathogen detection in critically ill COVID-19 patients with bloodstream infections

Li,

Huang,

Yin

et al. 2023

Infection

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Background Nosocomial bloodstream infections (nBSI) have emerged as a clinical concern for physicians treating COVID-19 patients. In this study, we aimed to evaluate the effectiveness of a multiplex ddPCR in detecting bacterial pathogens in the blood of COVID-19 critically ill patients. Methods This prospective diagnostic study included RT-PCR-confirmed COVID-19 patients admitted to our hospital from December 2022 to February 2023. A multiplex ddPCR assay was used to detect common bacterial pathogens and AMR genes in blood samples of the patients, along with antimicrobial susceptibility testing (AST). The diagnostic performance of the ddPCR assay was evaluated by comparing the results with those obtained through blood culture and clinical diagnosis. Additionally, the ability of ddPCR in detecting bacterial resistance was compared with the AST results. Results Of the 200 blood samples collected from 184 patients, 45 (22.5%) were positive using blood culture, while 113 (56.5%) were positive for bacterial targets using the ddPCR assay. The ddPCR assay outperformed blood culture in pathogen detection rate, mixed infection detection rate, and fungal detection rate. Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens in COVID-19 critically ill patients, followed by Enterococcus and Streptococcus. Compared to blood culture, ddPCR achieved a sensitivity of 75.5%, specificity of 51.0%, PPV of 30.9%, and NPV of 87.8%, respectively. However, there were significant differences in sensitivity among different bacterial species, where Gram-negative bacteria have the highest sensitivity of 90.3%. When evaluated on the ground of clinical diagnosis, the sensitivity, specificity, PPV and NPV of ddPCR were 78.1%, 90.5%, 94.7%, and 65.5%, respectively. In addition, the ddPCR assay detected 23 cases of blaKPC, which shown a better consistent with clinical test results than other detected AMR genes. Compared to blaKPC, there were few other AMR genes detected, indicating that the application of other AMR gene detection in the COVID-19 critically ill patients was limited. Conclusion The multiplex ddPCR assay had a significantly higher pathogen detection positivity than the blood culture, which could be an effective diagnostic tool for BSIs in COVID-19 patients and to improve patient outcomes and reduce the burden of sepsis on the healthcare system, though there is room for optimization of the panels used.- Adjusting the targets to include E. faecalis and E. faecium as well as Candida albicans and Candida glabrata could improve the ddPCR' s effectiveness. However, further research is needed to explore the potential of ddPCR in predicting bacterial resistance through AMR gene detection.

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“…So far, this technology has only been used in pilot studies and in small series of high-risk patients, e.g. hematologic cancer patient, patients with septic shock or critically ill patients with suspected secondary bloodstream infections [5][6][7]. A major methodological limitation is the lack of detection of RNA viruses.…”

Section: Introductionmentioning

confidence: 99%

Metagenomic next-generation sequencing as a diagnostic tool in the clinical routine of an infectious diseases department: a retrospective cohort study

Kalbitz,

Ermisch,

Kellner

et al. 2024

Infection

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Background Metagenomic next-generation sequencing (mNGS) of circulating cell-free DNA from plasma is a hypothesis-independent broadband diagnostic method for identification of potential pathogens. So far, it has only been investigated in special risk populations (e.g. patients with neutropenic fever). Purpose To investigate the extent to which mNGS (DISQVER® platform) can be used in routine clinical practice. Methods We collected whole blood specimens for mNGS testing, blood cultures (BC), and pathogen-specific PCR diagnostics. Clinical data and pathogen diagnostics were retrospectively reviewed by an infectious disease expert panel regarding the adjustment of anti-infective therapy. Results In 55 selected patients (median age 53 years, 67% male) with heterogeneous diagnoses, a total of 66 different microorganisms and viruses were detected using mNGS (51% viruses, 38% bacteria, 8% fungi, 3% parasites). The overall positivity rate of mNGS was 53% (29/55). Fifty-two out of 66 (79%) potential pathogens detected by mNGS were found in patients with primary or secondary immunodeficiency. The concordance rates of BC and pathogen-specific PCR diagnostics with mNGS testing were 14% (4/28) and 36% (10/28), respectively (p < 0.001). An additional bacterial pathogen (Streptococcus agalactiae) could only be detected by BC. Therapeutic consequences regarding anti-infective therapy were drawn from 23 pathogens (35% of detections), with 18 of these detections occurring in patients with immunodeficiency. Conclusions We conclude that mNGS is a useful diagnostic tool, but should only be performed selectively in addition to routine diagnostics of infectious diseases. The limited number of patients and the retrospective study design do not allow any further conclusions.

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Next-Generation Sequencing in Critically Ill COVID-19 Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study

Cited by 4 publications

References 45 publications

The Value of Next-Generation Sequencing in Diagnosis and Therapy of Critically Ill Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study

The Value of Next-Generation Sequencing in Diagnosis and Therapy of Critically Ill Patients with Suspected Bloodstream Infections: A Retrospective Cohort Study

Clinical evaluation of a multiplex droplet digital PCR for pathogen detection in critically ill COVID-19 patients with bloodstream infections

Metagenomic next-generation sequencing as a diagnostic tool in the clinical routine of an infectious diseases department: a retrospective cohort study

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