85. Comprehensive detection of pathogens in immunocompromised children with bloodstream infections by next-generation sequencing
Session: Oral Abstract Session: Identification, Treatment, and Prevention of Pediatric Bacterial Pathogens
Thursday, October 5, 2017: 9:15 AM
Room: 05AB

Background: Bloodstream infection (BSI) is a severe complication in immunocompromised patients. Prompt identification of causative microorganisms would improve the outcome of BSI due to optimization of antimicrobial treatment. Next-generation sequencing (NGS) allows us to analyze comprehensively and quantitatively all microorganisms present in a clinical sample in comparison with blood culture. However, there are currently no established methods to identify causative pathogens by NGS.

Methods: BSI was defined by the following criteria: 1) pathogen isolated from blood culture and 2) fever ≥38.0 Celsius or C-reactive protein >1.0 mg/dL. Thirty-five pediatric patients (12 with BSI and 23 with suspected BSI/negative blood culture) were enrolled. Plasma/serum samples were used for sequencing and the results were compared with those from blood culture. The bacterial reads per million reads of the sequence depth (BR) and relative importance values of the dominant bacteria (P1) were applied to identify causative pathogens.

Results: Sequencing reads of bacteria isolated in blood culture were identified by NGS in all plasma/serum samples at the onset of BSI. Additionally, bacteria isolated in blood culture were identical to the dominant bacteria by NGS in 8 of 12 patients with BSI. Causative microorganisms were detected when the NGS results fulfilled the criteria of BR >200 and P1 >0.5. In two patients with catheter-related BSI, causative bacteria were detected in the plasma/serum at 7 days before disease onset. Causative pathogens (Tatlockia micdadei, Escherichia coli, and human adenovirus 2) were identified in three of 23 patients in the suspected BSI group. A total of 62 resistance genes were detected in nine patients with sequences covering 5-100% of references.

Conclusion: An NGS-based approach has great potential for analysis of causative microorganisms in BSI and may help to diagnose a disease before disease onset. Antimicrobial resistance genes can also be found through sequence data processing.

Kazuhiro Horiba, MD1, Jun-Ichi Kawada, MD, PhD1, Yusuke Okuno, MD, PhD2, Nobuyuki Tetsuka, M.D.3, Takako Suzuki, MD1, Shotaro Ando, MD, PhD1, Yasuko Kamiya, MD, PhD1, Yuka Torii, MD, PhD1, Tetsuya Yagi, M.D., Ph.D.3, Yoshiyuki Takahashi, MD, PhD1 and Yoshinori Ito, MD, PhD1, (1)Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan, (2)Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan, (3)Department of Infectious Diseases, Nagoya University Hospital, Nagoya, Aichi, Japan

Disclosures:

K. Horiba, None

J. I. Kawada, None

Y. Okuno, None

N. Tetsuka, None

T. Suzuki, None

S. Ando, None

Y. Kamiya, None

Y. Torii, None

T. Yagi, None

Y. Takahashi, None

Y. Ito, None

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