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Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

ABSTRACT: Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs.

SUBMITTER: Gyarmati P

PROVIDER: S-EPMC4800731 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

Gyarmati P P Kjellander C C Aust C C Song Y Y Öhrmalm L L Giske C G CG

Scientific reports 20160321

Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of the ...[more]

PMID: 26996149

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Project description:IntroductionWe aimed to compare the clinical characteristics and outcomes of bloodstream infections (BSI) in cancer patients presenting febrile neutropenia with and without HIV infection, and analyze the prognostic factors for mortality.MethodsBSI episodes in febrile neutropenic patients following chemotherapy were prospectively collected (1997-2018). A case (HIV-infected)-control (non-HIV-infected) sub-analysis was performed (1:2 ratio), matching patients by age, gender, baseline disease, and etiological microorganism.ResultsFrom 1755 BSI episodes in neutropenic cancer patients, 60 (3.4%) occurred in those with HIV. HIV characteristics: 51.7% were men who have sex with men; 58.3% had < 200 CD4; 51.7% had a detectable HIV-1 RNA viral load before the BSI episode; 70.0% met AIDS-defining criteria; and 93.3% were on antiretroviral therapy, with a protease inhibitor-based regimen being the most common (53.0%). HIV-infected patients were younger, more frequently male and more commonly presenting chronic liver disease (p < 0.001 for all). BSI due to Enterococcus spp. was significantly more frequent among patients with HIV (p = 0.017) with no differences in other pathogens. HIV-infected patients with cancer presented with shock more frequently (p = 0.014) and had higher mortality (31.7% vs. 18.1%, p = 0.008). In the case-control analysis, cases (HIV-infected) had chronic liver disease (p = 0.003) more frequently, whereas acute leukemia (p = 0.013) and hematopoietic stem-cell transplant (p = 0.023) were more common among controls. There was a non-significant trend for cases to have higher mortality (p = 0.084). However, in multivariate analysis, HIV infection was not associated with mortality (p = 0.196).ConclusionHIV-infected patients with cancer developing febrile neutropenia and BSI have different epidemiological and clinical profiles, and experience higher mortality. However, HIV infection by itself was not associated with mortality.

Project description:BackgroundThe source of bacterial infection in neutropenic acute leukemia patients is detected in about 20-30% of cases. Bacterial cultures may require a long incubation period and risk false-positive and false- negative results. Therefore, biomarkers distinguishing septic febrile neutropenia from other etiologies in acute leukemia patients play the important role in patient assessment and treatment planning. This study aims to determine the role of procalcitonin (PCT) and presepsin (PSPN) in infectious complication in comparison to C-reactive protein (CRP) on the first and third day at the onset of febrile neutropenia in patients with acute leukemia.MethodsBetween June 2018 and February 2019, 60 acute leukemia patients with febrile neutropenia receiving chemotherapy. The 41 acute myeloid leukemia patients and 19 acute lymphoblastic leukemia patients were recruited in this study. Their ages ranged from 14 to 65 years. PCT and PSPN were measured and were compared to CRP at the onset of febrile neutropenia and after 48 hours. 20 patients had a fever of unknown origin (FUO) and 40 patients had a bacterial infection.FindingsOur results showed that the values of these markers were higher in patients with infection than patients without. The area under the curve (AUC) of PCT were 0.931 and 0.813 on day one and three respectively, which was the best in determination of infection. The cut-off values of PCT were 1.27 and 1.23 ng/mL and the cut off values of PSPN were 1.75 and 2.9 μg/L in the successive days, their clinical sensitivities were high. PCT and PSPN were capable of distinguishing the cause of febrile neutropenia from the onset of infection and predicting its complications (p<0.05). The PSPN level couldn't differentiate gram-positive or gram-negative bacterial infection. Significant differences were found between the mean values of the PSPN during the successive days in all patients and patients with bacteremia. This study illustrated a weak positive correlation between PCT and Sequential Organ Failure Assessment (SOFA) score, the negligible correlation between CRP and SOFA score and no significant correlation between PSPN and SOFA score.InterpretationPCT is an accurate biomarker in identifying infection in acute leukemia patients, its concentration is associated with the severity of bacterial sepsis. PSPN is superior to PCT for follow-up of patients.

Project description:Prior attempts at identifying outcome determinants associated with bloodstream infection have employed a priori determined classification schemes based on readily identifiable microbiology, infection site, and patient characteristics. We hypothesized that even amongst this heterogeneous population, clinically relevant groupings can be described that transcend old a priori classifications.We applied cluster analysis to variables from three domains: patient characteristics, acuity of illness/clinical presentation and infection characteristics. We validated our clusters based on both content validity and predictive validity.Among 3715 patients with bloodstream infections from Barnes-Jewish Hospital (2008-2015), the most stable cluster arrangement occurred with the formation of 4 clusters. This clustering arrangement resulted in an approximately uniform distribution of the population: Cluster One "Surgical Outside Hospital Transfers" (21.5%), Cluster Two "Functional Immunocompromised Patients" (27.9%), Cluster Three "Women with Skin and Urinary Tract Infection" (28.7%) and Cluster Four "Acutely Sick Pneumonia" (21.8%). Staphylococcus aureus distributed primarily to Clusters Three (40%) and Four (25%), while nonfermenting Gram-negative bacteria grouped mainly in Clusters Two and Four (31% and 30%). More than half of the pneumonia cases occurred in Cluster Four. Clusters One and Two contained 33% and 31% respectively of the individuals receiving inappropriate antibiotic administration. Mortality was greatest for Cluster Four (33.8%, 27.4%, 19.2%, 44.6%; P < .001), while Cluster One patients were most likely to be discharged to a nursing home.Our results support the potential for machine learning methods to identify homogenous groupings in infectious diseases that transcend old a priori classifications. These methods may allow new clinical phenotypes to be identified potentially improving the severity staging and development of new treatments for complex infectious diseases.

Dataset Information

Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

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Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

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